30 day supply: 60 capsules
Complete multinutrient protects visual and whole body health with meaningful levels of over 30 key nutrients.
Offers a diverse array of antioxidants, such as 6 mg of FloraGLO® lutein, zeaxanthin, lycopene, vitamins C and E and taurine.
New! Now with trans-resveratrol!
Made from premium ingredients and manufactured according to the highest quality standards.
Recommended dose: two capsules per day (one capsule taken orally, twice daily).
Suggested Use: take a total of two capsules daily, with meals (one capsule taken orally, twice daily).
Note: pregnant or lactating women or individuals with medical conditions should consult a physician before using.
New! Now with trans-resveratrol!
ScienceBased Health (SBH) continually evaluates emerging scientific evidence
and SBH products reflect the most current science available. Select a category
below to view science information for this product:
Now with trans-resveratrol!
Vitamins C (400 mg) and E (100 IU)
Vitamin C is the major water-soluble antioxidant concentrated in ocular
tissues. Concentrations in the lens are up to 60 times the level found
in blood. Fat-soluble vitamin E is the major chain-breaking antioxidant
that protects lipid-rich retinal cell membranes against free radical
A link between vitamin C intake and macular
health has been established. Tufts Nutrition and Vision Project
notes that long-term vitamin C supplementation (360 mg on average),
can significantly lower the odds of developing age-related clouding
of the central portion of the eyes lens. OcularEssentials provides
vitamin C at levels consistent with these findings.
Some studies also report that higher vitamin
E intakes or blood levels may improve ones chance of prolonging
lens and macular health. OcularEssentials provides a basic level of
vitamin E that is appropriate for healthy people. Natural source vitamin
E (tocopherol) is used, as studies show it is better absorbed and
retained. It also delivers broad spectrum vitamin E from alpha to
gamma tocopherol, that together play a health-protective role.
FloraGLO® Lutein (6 mg) and
Zeaxanthin (300 mcg)
Lutein and zeaxanthin are two similarly structured carotenoids that
compose the pigment of the macula, the area in the center of the retina
where the sharpest central vision occurs. Macular pigment filters
out blue (visible) light that can cause photo-oxidative damage to
the retina. Lutein and zeaxanthin are also the only carotenoids detected
in the eyes lens. Many, though not all, studies link higher
intake of these carotenoids with a significantly lower prevalence
of lens opacity or likelihood of undergoing cataract surgery.
Population-health studies have examined
the relationship between lutein and macular health. In studies where
lutein intake was minimal, no apparent association was seen. However
in studies where the range of intake was wider, those eating the greatest
amount of lutein (6-7mg daily) were more likely to maintain macular
health. Macular pigment density is positively associated with macular
function. Both elevated serum levels and consumption of the two carotenoids
(up to 6.5 mg daily) are related to greater pigment density. OcularEssentials
provides levels of lutein and zeaxanthin consistent with these findings.
Zinc (30 mg)
Zinc is an essential mineral selectively concentrated in the eye,
and found in the retina and choroid, ciliary body, iris, optic nerve,
sclera, cornea and lens. Within these ocular structures, zinc is believed
to interact with vitamin A and taurine to modify photoreceptor membranes,
regulate the light-rhodopsin reaction, help nerve transmission and
to serve as an antioxidant. OcularEsentials provides bioavailable
zinc at a level that is appropriate for eye-healthy individuals.
More Eye-Essential, Health-Promoting Ingredients:
Vitamin A is
provided both as pre-formed vitamin A (retinyl palmitate) and beta-carotene,
which functions as an antioxidant and is converted to vitamin A as
required by the body. Vitamin A protects night vision and is vital
for the health of the eyes cornea. It also interacts with zinc
and the amino acid taurine within retinal photoreceptors.
required for the proper function of glutathione peroxidase, an antioxidant
enzyme found in the eyes lens and localized in photoreceptor
and retinal pigment epithelial cells. Low selenium levels have been
detected in lenses of patients with age-related cataract.
is an amino acid that is made in the body and selectively concentrated
in eye tissues. Taurine helps stabilize cell membranes in the retina
and may act as an antioxidant in the lens.
Trans-resveratrol is an important component of red wine believed
to contribute to wines heart healthy effects. It is a potent
antioxidant with potential anti-inflammatory properties. It has been
referenced in over 2,000 research citations, including studies at
Harvard and The National Cancer Institute. It is also currently being
studied as a possible anti-aging agent. OcularProtect now provides
the amount of trans-reservatrol found in approx two 4 oz. glasses
of pinot noir, a wine with one of the highest trans-resveratrol contents.
is the antioxidant pigment that gives tomatoes their vivid color.
Greater intakes have been linked to a better chance of retaining prostate
and pancreatic health. This formula provides 600 mcg of lycopene,
which makes a good contribution to overall dietary intake.
And More ... Plant
compounds with antioxidant activity such as the flavonoids contribute
to the health benefits of eating 5 or more fruit and vegetable servings
daily. OcularEssentials contains flavonoids from billberry and quercetin.
As antioxidants, they support healthy retinal circulation and ocular
Antioxidants & Cancer; Supporting Mental Function
Antioxidant Trio & Pancreatic Cancer Risk
Awareness of pancreatic cancer rose last month with the news that astronaut Sally Ride, the first U.S. woman in space, lost her battle with this disease. Pancreatic cancer, which also claimed the life of Apple co-founder Steve Jobs last year, is relatively rare. The number of people affected by pancreatic cancer yearly is fairly low: a little more than 250,000 globally. It has, however, the worst survival rate of any cancer.
While genes, smoking and type-2 diabetes are all major risk factors for pancreatic cancer, it’s thought that diet, too, could play a role. In support of that idea are new findings that increasing dietary intake of certain antioxidants may help cut the risk of developing this cancer by up to two-thirds (1).
Findings from the ‘EPIC’ Study
U.K researchers tracked the health of nearly 24,000 people who took part in the European Prospective Investigation of Cancer (the EPIC study). Participants completed comprehensive food diaries that detailed the types and amounts of every food they ate, including the methods used to prepare it. The researchers analyzed the nutrient intakes of those who developed pancreatic cancer within 10 years of entering the study, and compared that with the intakes of about 4,000 healthy people to see if there were any differences.
They found that those with the highest intake of vitamins C, E and selenium were 67% less likely to develop the disease than those consuming the least. If this association holds true, 1 in 12 of these cancers might be prevented, according to the researchers.
Tips for Staying Mentally Sharp
There are many factors that can affect our ability to concentrate and be mentally sharp on any given day. Examples include: what we eat, whether we are physically active, how we manage stress, and whether or not we’ve had a good night’s sleep.
Drinking caffeinated coffee is probably the most popular way to gain a temporary mental boost. (Research also suggests that this morning routine may have even more enduring effects on mental well-being and health. Moderate coffee consumption – 2-3 cups daily – has been linked to lower risk of depression, Parkinson’s, and ischemic stroke, as well as a significantly reduced risk for type 2 diabetes).
Aside from taking coffee or tea breaks, the results of two new studies suggest some other ways to help support mental focus:
Keep Your Water Bottle Handy. According to studies in both young men and women, even mild dehydration can alter mood and the ability to think clearly, leaving subjects feeling “cranky” and tired (2,3). In the most recent evaluation, researchers compared the results of cognitive tests taken when participants were not dehydrated, and when they were mildly dehydrated – either from gentle walking or simply from being sedentary.
In women, mild dehydration caused headaches, fatigue, and difficultly concentrating. While the symptoms were not as pronounced for men, mild dehydration also caused some difficulty with mental tasks, as well as fatigue, tension and anxiety.
Try Aroma Therapy. Researchers report that the scent given off by the essential oils of the herb rosemary may improve mental performance (4). Subjects in the experiment were exposed to varying levels of the rosemary aroma, and blood levels of one of rosemary’s main chemicals (1,8-ceneole) was measured.
Results indicate that blood levels of the compound absorbed from the scent were related to mental performance. Higher blood levels resulted in improved results on speed and accuracy tests.
In the news: Vitamin C & Exercise, Veggies & Breast Health
Vitamin C May Help Overweight Exercisers
If you are cutting calories and moving more to shed some weight, the findings of a new study might be news you can use. The study reports that daily supplements of vitamin C may decrease heart rate during moderate exercise, helping exercisers feel less exertion and fatigue (1).
In this small but carefully conducted trial, 20 obese men and women were put on a calorie-restricted diet and assigned to receive either 500 mg of vitamin C daily or a placebo over a 4 week period. The diet was also controlled for vitamin C content.
At the beginning and end of the trial, the volunteers used a treadmill for 60 minutes at 50% intensity of predicted maximal oxygen consumption – the maximum capacity of an individual’s body to transport and use oxygen during exercise.
There was no difference in breathing between the groups, and they both lost similar amounts of weight. However the vitamin C takers had, on average, 11 fewer heartbeats per minute during exercise compared to those taking a placebo.
The group getting vitamin C also reported feeling that the treadmill session took less effort and that they felt less fatigue, as assessed by a questionnaire and by a scale that rates perceived exertion.
Perceived exertion – how hard you feel like your body is working – typically correlates with heart rate: If one is lower, the other is likely to be lower too. The researchers suggest that their findings could be a factor in helping people stick to their exercise routine, since both calorie cutting and physical activity are needed for effective weight loss.
Cruciferous Veggies May Improve Survival For Breast Cancer Patients
Members of the cabbage family, called cruciferous vegetables, include greens like mustard, collard, kale, and bok choy, cauliflower, broccoli, Brussels sprouts, turnips, watercress, radishes and more.
These veggies are well known for providing nutrients that we’re all familiar with, such as fiber, carotenoids (e.g. lutein) and folic acid. But they are also a unique source of lesser-known compounds called glucosinolates.
When digested, glucosinolates are turned into other compounds (isothiocyanates and indoles) that have anti-cancer properties. High intakes of crucifers have been associated with a lower risk of lung and colorectal cancer in some population-health studies.
Evidence linking these veggies to breast or prostate cancer has been limited. However, the newly published findings of a collaborative research project between Vanderbilt University and scientists at Shanghai Centers for Disease Control and Prevention, suggest that eating more of these veggies may benefit women who’ve had breast cancer (2).
The researchers monitored nearly 4,900 Chinese breast cancer survivors, analyzing their diets at 6, 18 and 36 months post-diagnosis.
They found that women who ate higher amounts of crucifers during the first 3 years after being diagnosed with cancer had a higher rate of survival.
Compared to women eating the least crucifers, those who had the highest daily intake had a 62% lower risk of dying from breast cancer, and a 35% reduced risk of breast cancer recurrence.
Chinese women typically eat higher amount of crucifers than do their American counterparts. They also eat different kinds of crucifers – more bok choy, turnips and greens, while broccoli and Brussels sprouts are the most common crucifers eaten by American women. Putting more crucifers on the menu might benefit all of us, especially women with a history of breast cancer.
Getting a Handle On Blood Pressure
Blood Pressure Basics
About 1 in 3 U.S. adults have high blood pressure according to the Centers for Disease Control, which increases the risk for heart disease, stroke, and kidney disease. It’s also been linked to a higher risk of eye conditions such as diabetic retinopathy and some types of cataract.
Blood pressure doesn’t stay the same all the time, dipping during the night, and rising when we’re excited, nervous or active. But levels that stay above 120/80 mmHg most of the time can raise the risk of health problems. (Systolic pressure is the first number, and diastolic the second number). Blood pressure also tends to go up with age, but there are ways to delay or prevent this.
Blood Pressure-Lowering Strategies
Some people with hypertension will require medication to keep their blood pressure under control. But for most of us, making healthy choices can mean avoiding, delaying or reducing the need for drugs. The key to control is losing weight, being physically active, and watching your diet.
Shedding extra weight – even just 10 pounds – can reduce blood pressure. And, generally, the more weight you lose, the greater the blood pressure reduction. Since carrying too much weight around the waist raises the risk for elevated blood pressure, watching your waistline is important too.
Regular physical activity – about 30-60 minutes on most days – can lower blood pressure by as much as 9 points. Boosting your intake of potassium and magnesium-rich foods while lowering sodium-containing foods and added salt can reduce blood pressure by another 2-9 mmHg.
Research on Nutrients & Blood Pressure
Research suggests that other nutrients may also be helpful in keeping blood pressure levels in check.
Vitamin B2 (riboflavin). From Ireland comes a report that about 1 in 10 people could significantly lower their blood pressure by raising their intake of vitamin B2. Hypertension is often linked to a particular genetic or inherited factor found in around 10% of the population.
The researchers found that for these people, B2 was able to lower blood pressure to target levels while having no adverse effects on those who didn’t have the gene (1). They saw this response even in people already taking blood pressure-lowering drugs.
The test to determine whether you fall within this genetically-at-risk group may not always be readily available. But it’s safe, say the authors, for anyone to get more of this B-vitamin from dairy or fortified foods, and/or taking a B-containing multivitamin supplement.
Vitamin C. Researchers from Johns Hopkins recently analyzed 29 controlled trials looking at vitamin C’s effect on blood pressure (2). The analysis revealed that vitamin C supplementation (median level of 500 mg) was associated with reductions of almost 4 mmHg for systolic pressure, and about 1.5 mmHg for diastolic readings. For those who already had hypertension, the benefits were even better: a decrease of nearly 5 and 2 mmHg for systolic / diastolic pressures, respectively.
Cocoa-Rich Chocolate. A research team from the UK, Australia and Harvard, analyzed 42 studies (1,297 total participants) that examined the effects of cocoa-rich chocolate on blood pressure and other cardiovascular risk factors (3).
They concluded that consuming chocolate has mild blood-pressure lowering effects, as well as other heart-healthy benefits. Some research (4) suggests that 1-2 ounces daily of dark, cocoa-rich chocolate (at least 50% cocoa) is sufficient to achieve these effects while still keeping calorie intake reasonably low.
Latest Cataract Research
The “ABCs” of Cataract
A cataract is the clouding of the eye’s lens due to clumping of lens protein and discoloration of the lens because of age, smoking, sunlight exposure, the use of certain drugs, and diabetes.
The lens consists mostly of water and protein. When the protein clumps up, it clouds the lens and reduces the light that reaches the retina, causing blurred vision. Most age-related cataracts develop from protein clumping.
The clear lens also slowly colors with age. This gradual darkening doesn’t affect the sharpness of the image transmitted to the retina, but it can make it more difficult to distinguish between colors such as blues and purples.
Nuclear cataract, which occurs in the central portion of the lens, is the most common type of cataract among older people, especially women. Cataract can develop in other locations too. Cortical cataract is found at the outside edge of the lens, while posterior subcapsular cataract (PSC, the least common type) forms at the back surface of the lens beneath the lens capsule.
Helping to Keep Cataracts at Bay
Damage to lens proteins can happen gradually from a variety of causes, including the formation of free radicals due to light exposure. Antioxidants such as vitamin C and lutein / zeaxanthin are believed to play an important role in mopping up those free radicals or filtering out harmful blue light.
Two recently published studies suggest that there are steps we can take to help protect the eye’s lens. One study identifies risk factors that we can do something about, while the other report adds weight to the idea that lutein and zeaxanthin may play a protective role.
Lutein & Zeaxanthin Tied to Cataract Risk
Finnish researchers recently looked at whether blood levels of lutein and zeaxanthin are related to nuclear cataract in over 1,600 older participants (1).
People who had the highest blood levels of lutein and
zeaxanthin had a 40% lower risk of having nuclear cataract, compared with the group who had the lowest blood levels.
Risk Factors linked to Cataract Types
University of Southern California researchers tracked risk factors for different types of cataract in nearly 6,000 people participating in the Los Angeles Latino Eye Study (2).
It’s no surprise that older age increased the risk for most of the cataract types except PSC, where higher systolic blood pressure and a history of diabetes were identified as risk factors.
For cortical cataract, a history of diabetes and higher hemoglobin A1c raised risk, while smoking and myopia (myopic refractive error) emerged as risk factors for nuclear type cataract. Myopia is nearsightedness, where distant objects appear out of focus. Hemoglobin A1c is the best measure of blood sugar control over time.
Finally, myopic refractive error, history of diabetes, higher systolic blood pressure, and presence of large drusen were independent risk factors for mixed cataract, where more than one lens location was involved. The presence of large drusen is predictive of developing advanced macular degeneration (AMD).
Steps We Can Take
In addition to getting regular eye exams and not smoking, make sure to:
In the News: Vitamin C in Heart Failure, Diabetes Risk; Vitamin D & Rhinitis
Vitamin D and Chronic Rhinitis: A Connection?
Chronic rhinitis is a common condition with multiple causes, and is characterized by inflammation of the inner lining of the nose. People with rhinitis suffer from symptoms such as a runny and itchy nose, nasal congestion, and sneezing. And chronic rhinosinusitis (CRS), inflammation of the nose and sinuses, is actually one of the most common health challenges, affecting an estimated 14% of US adults.
When it comes to vitamin effects on the immune system, vitamin D is one that takes center stage. Researchers are interested in this vitamin because it directly affects many cells (e.g. dendritic cells and macrophages) that are involved in immune and other processes underlying nasal and sinus inflammation.
Studies (1) have found low levels of vitamin D in patients with CRS and allergic fungal rhinosinusitis, and those low levels correlated with elevated levels of dendritic cells. Insufficient blood levels of vitamin D have also been observed in Afro-Americans with CRS compared with age and sex matched healthy controls.
More research is needed to better understand the relationship between vitamin D and CRS, allergic and chronic rhinitis. But in the meantime, it’s a good idea to get enough vitamin D for many reasons including bone and possibly heart health.
Low Vitamin C Linked to Inflammation in Heart Failure, Plus Diabetes Risk
Low intake of vitamin C is not uncommon, and can adversely affect our health. Just last year, for example, researchers found that heart failure patients who didn’t consume enough vitamin C had higher levels of inflammation as measured by the biomarker CRP (2).
Those heart failure patients with low C intake and more inflammation were twice as likely to die of cardiovascular disease within a one-year follow-up. Nearly 40% of the patients had inadequate intake of the vitamin.
Getting adequate vitamin C has also been linked to the risk of developing diabetes.
In the most recent study to explore this relationship, researchers looked at blood levels of vitamin C and hemoglobin A1c (one of the best measures of diabetes risk) among non-diabetic participants in the U.S. National Health and Nutrition Examination Survey (NHANES) (3).
The investigators saw a clear relationship between low blood levels of the vitamin and higher risk for diabetes (higher A1c) that was more pronounced in people 18-44 years old, in women, and in those of Hispanic origin.
Vitamin C and D Interact
In the same study, blood levels of vitamin D were also examined, since high rates of vitamin D deficiency have been found in people that are obese, and past studies have also linked low vitamin D levels to type 2 diabetes.
The link between poor vitamin C status and diabetes risk was even more pronounced in younger and female NHANES participants who additionally had lower vitamin D blood concentrations.
Interactions between these two vitamins have been identified in other studies: Vitamin C is needed to turn vitamin D into its active form within the body. The current findings suggest that this interaction may be important. So be sure to get some sunshine, eat lots of vitamin C-rich fruits and vegetables, and take a daily multi-nutrient supplement that includes both vitamins C and D.
Young hearts & omega-3s; Antioxidants & Stroke Risk; Diet & genetic risk of AMD
Omega-3s & Heart Health in Young Women
The cardiovascular health benefits of omega-3 fatty acids are well-documented in men and older men and women. But whether a fish-rich diet is important for heart health in younger women is an area that – until recently – has received little attention.
Now, the first study to focus exclusively on women of child-bearing age reports that diets plentiful in omega-3s may help protect younger women’s hearts too (1).
The research team analyzed data from nearly 49.000 initially healthy pregnant women (average age of 30), whose dietary habits were assessed at 3 intervals over an 8 year period. The women were then followed by checking hospital records for cardiovascular-related admissions. Because very few of these women were found to take fish oil supplements, those that did were excluded from the analyses.
Women who rarely or never ate fish had 50% more cardiovascular problems than those who consumed fish regularly. And compared to women who ate fish high in omega-3s weekly, the risk of cardiovascular disease (CVD) was 90% higher for those who rarely ate these omega-3 fish sources. Because they saw a strong association with CVD in women who were still in their late 30’s, the team advises younger women to eat fish as a main meal at least twice a week.
Dietary Antioxidants & Stroke Risk in Women
In more good news for women, Swedish researchers have found a link between a diet high in fruits, veggies and whole grains (antioxidant rich foods) and the risk of stroke (2). The researchers used dietary information from more than 31,000 women without heart disease and 5,000 with a history of CVD to determine the women’s total antioxidant capacity – the power of the food’s antioxidants to reduce free radicals in cells.
Healthy women with the highest antioxidant intake had a 17% risk reduction for all forms of stroke (hemorrhagic and ischemic) compared to those with the lowest intake. A 57% lower risk of hemorrhagic stroke was seen in women with a history of CVD who fell within the highest ¾ of antioxidant intake.
Reducing the Genetic Risk of Early AMD
Can younger people with an inherited genetic risk for age-related macular degeneration (AMD) delay or even prevent this vision-disabling condition with the right diet? Science has no conclusive answer to this question yet, though higher intakes of lutein/zeaxanthin, as well as EPA/DHA have been linked to AMD risk reduction in a number of studies.
Dutch researchers have also found a strong link between dietary zinc, antioxidants (beta-carotene and lutein/zeaxanthin) and omega-3s, and AMD development in people who carry two of the more common gene forms (variants) known to increase susceptibility to this disease (3).
Carriers of one or both of these genetic variants who consumed more of these nutrients had a significantly reduced risk of developing early AMD. Researchers estimate that, together, these variants probably contribute to late AMD in more than 80% of cases.
The study’s authors urge younger people with family members who have AMD – to consume diets that provide good intakes of these nutrients. In addition to choosing cold water fish for EPA/DHA, zinc can be found in fortified cereals, meats, dairy products, nuts and seeds. Dark green leafy veggies such as spinach and kale, and orange veggies like pumpkin and carrots, are good sources of lutein and beta-carotene.
In the News: Omega-3s & IHD in Women; Physicians’ Supplement Use; B-Vitamins & Mental Function
Long Chain Omega-3s Lower IHD Risk
There are different members of the omega-3 family of fatty acids. One member, called alpha-linolenic acid, can be converted to the longer chain omega-3s EPA and DHA which are found in cold-water fish. However, the conversion of alpha-linolenic acid to EPA/DHA is limited, with only about 8-20% actually converted.
Present in flaxseeds and other plant sources, alpha linolenic acid may not be the best omega-3 choice for heart health in women according to results of a newly published trial (1).
In this prospective Danish study, dietary intake data was analyzed from over 3,200 healthy volunteers. During 23 years of study, 471 cases of ischemic heart disease (IHD) occurred.
IHD, the most common type of cardiovascular disease, refers to problems with the circulation of blood to the heart muscle. A partial blockage of one or more of the coronary arteries can result in too little oxygenated blood (ischemia), thus causing symptoms such as chest pain or shortness of breath. A complete blockage of an artery can cause a heart attack.
The researchers found that high intakes of EPA and DHA were associated with a 38% reduction in IHD risk for women. In contrast, high intakes of alpha-linolenic acid did not significantly lower the risk of IHD among women.
Do Physicians Use Supplements?
According to a newly published survey (2), a majority of US physicians within certain medical specialties appear to use supplements and recommend them to their patients.
Nine hundred physicians were surveyed; 300 cardiologists, 300 orthopedists, and 300 dermatologists. The survey results obtained were in line with the prevalence of use reported among the general public in the most recent National Health and Nutrition Examination survey, where 54% of adults said they had taken supplements in the past month.
Fifty-seven percent of cardiologists said they use dietary supplements at least occasionally, as did 75% of dermatologists and 73% of orthopedists. Regular dietary supplement use was reported by 37% of cardiologists, 59% of dermatologists, and 50% of orthopedists.
The product most commonly reported to be used was a multivitamin, but over 25% in each specialty said they used omega-3 fatty acids and over 20% said they used some botanical supplements. Seventy-two percent of cardiologists, 66% of dermatologists, and 91% of orthopedists reported recommending supplements to their patients.
B-vitamins May Slow Mental Decline
In the February issue of Staying Healthy (Protecting our Brain: Recent Research), scientists reported that a daily combination of folic acid and vitamins B6 and B12 slowed the rate of brain shrinkage or atrophy in people with mild cognitive impairment (MCI). Brain atrophy is a common sign of MCI, and can be an early warning to signs of dementia.
In a follow-up report, the Oxford and Oslo-based researchers looked specifically at participants in this intervention trial who had elevated homocysteine levels at the study’s start. Two years of B-vitamin treatment reduced levels of this amino acid, which has been previously linked to dementia.
Compared to placebo takers, people in the B-vitamin group with high initial homocysteine levels fared better on mental tests such as correct word recall, semantic memory (which refers to meaning, understanding and other concept-based knowledge), and global cognition which tests a range of cognitive functions.
In the News: Omega-3s & Mood, Vitamin E & Lung Health, Resveratrol & Insulin
Fish Oil May Ease Depression and Anxiety
The findings of two new studies add to the growing body of evidence suggesting that fish oil may positively affect mood, behavior and mental well-being.
In the first study (1), university researchers from Australia recruited 50 people aged 65 and older with mild cognitive impairment to participate in a 6-month long trial. Volunteers received supplements of EPA-rich fish oil, DHA-rich oil, or linoleic oil daily.
Those assigned to the predominately EPA fatty acid group scored better than the linoleic acid group on the Geriatric Depression Scale – a validated questionnaire commonly used to identify depression in older people. The DHA-rich group, on the other hand, displayed improvements in verbal fluency.
These results, according to the study’s authors, indicate that both EPA and DHA omega-3 fatty acids are important for fighting symptoms of depression and boosting neurological function. Since symptoms of depression may increase the risk of progressing from mild cognitive impairment to dementia, the researchers also call for larger and longer trials to see whether fish oil can reduce the risk of dementia in this population.
Evaluating the effects of fish oil in healthy young adults was the objective of the second study (2). Ohio State University investigators enlisted 68 medical students who were given either high dose EPA plus DHA or a placebo.
Results showed a 14% reduction in levels of an inflammatory biomarker, and a 20% decrease in anxiety symptoms with the omega-3 supplement. Inflammation is believed to be involved in hormonal stress responses, and those hormones could influence a key brain region for fear and anxiety.
Vitamin E Could Decrease Lung Disease Risk
Daily supplements of vitamin E might reduce the risk of chronic obstructive pulmonary disease (COPD) by about 10% in women over 45, according to a study from Cornell University (3). COPD, which causes wheezing, shortness of breath, chest tightness and other symptoms, affects about 12 million Americans according to the National Institutes of Health.
Oxidative stress in lung tissue, the result of oxidants outnumbering antioxidants, is believed to contribute to COPD. In addition, population health studies consistently report that higher antioxidant blood levels are associated with lower risk of COPD and asthma.
The researchers analyzed data from over 38,500 women who took part in the Women’s Health Study (WHS). In the WHS, women received either 600 IU of vitamin E every other day plus 100 mg of aspirin every other day, or placebos. The finding of a 10% risk reduction was observed in both smokers and non-smokers.
Resveratrol May Boost Insulin Sensitivity
Could an antioxidant found in red wine, grapes and peanuts affect the efficiency of insulin? Though more study is needed, results from a pilot study (4) conducted in 19 type 2 diabetic men, suggests that resveratrol could prove to be helpful.
The patients took 5 mg of resveratrol or placebo twice daily for 4 weeks. Those getting resveratrol had far fewer signs of oxidative stress, and higher levels of a protein that triggers cells to take up and use the sugar glucose. Oxidative stress is thought to be a factor in insulin resistance, which renders cells less able to absorb glucose circulating in the blood stream.
In the News:
Vitamin D & AMD Risk
Flavonoids are a “Hot” Research Topic
Flavonoids, also referred to as bioflavonoids, are polyphenol antioxidants found naturally in plants. Flavonoids are nutrients found in fruits, vegetables, herbs, wine, cocoa and teas. There are many different families of flavonoids, and various families are thought to have protective effects against chronic diseases.
We consume an estimated 190 mg of flavonoids daily, and researchers are trying to better understand their contribution to health and to determine optimal intakes. The results of two new studies, which focus on citrus flavonoids, illustrate the potential benefits of flavonoids and suggest that higher intakes are warranted.
Citrus Flavonoids Lower Blood Pressure
Researchers studied the effects of orange juice (OJ) and its major flavonoid, hesperidin, on blood pressure and blood vessel function in overweight but otherwise healthy men (1). About 1/3 of the men had elevated blood pressure, but were taking no anti-hypertensive medications.
During 3 successive 4 week periods, the men drank either 17 oz of orange juice daily, a control drink with 300 mg hesperidin capsules (the same amount as the orange juice contained), or a control drink along with a placebo capsule.
At the end of both the OJ and hesperidin test periods, diastolic pressure was significantly lower than after the placebo period. Diastolic pressure (the second number in blood pressure readings) measures the pressure in blood vessels between heart beats, when the heart is resting. Even a decrease of just 3-4 points in diastolic pressure could translate into a 20% reduction in the incidence of coronary heart disease.
The researchers also tested a variety of measures of blood vessel activity, including the ability of vessels to dilate. Both OJ and hesperidin showed positive effects compared to placebo.
More Flavonoids, Less Inflammation
In another study (2), researchers examined flavonoid intake and blood markers of inflammation in a large group of women. The investigators found that women eating the highest amount of total flavonoids had the lowest blood levels of one marker (IL-8). Among foods, higher intakes of grapefruit were linked to lower levels of two more markers (CRP and TNF-R2). Finally, citrus flavonoids in particular were associated with lower levels of another inflammatory marker (IL-18).
Why is this finding important? Well, most people are aware of acute inflammation – the redness, swelling and pain encountered with injury. However, it’s long-term unresolved inflammation that is believed to underlie many chronic diseases, including ocular conditions such as age-related macular degeneration (AMD), dry eye and glaucoma.
Vitamin D May Protect Against AMD in Women
Higher blood levels of vitamin D are associated with a lower risk of developing AMD, according to new research (3). Looking at vitamin D and AMD status in over 3,000 postmenopausal women, investigators found that higher blood levels of this “sunshine vitamin” decreased the risk of early AMD in women under 75. For those over 75, the association was borderline.
In terms of vitamin D intake from supplements and foods, those consuming the highest amount (on average about 600 IU) daily, had a 59% lower risk of AMD compared to those getting the least (about 300 IU on average).
This is the second study to report a relationship between vitamin D and AMD. The vitamin has anti-inflammatory actions, and inflammation plays a role in AMD development. Specifically, the vitamin may interfere with the destructive inflammation that happens in the early stages of the disease at the interface of the retina’s blood supply (choroid) and the pigment-containing cells of the retina.
In the News:
Berries & Vitamin D
Think Purple and Red. Think Health.
Can putting more purple and red produce on the menu really help maintain good health? Mounting evidence says that it can.
Certain red and purple fruits and vegetables owe their color to a type of naturally occurring bioflavonoid called anthocyanins. Bilberries, blueberries, and blackberries are loaded with this flavonoid. Other good contributors include grapes, cherries, raspberries, strawberries, plums, cranberries, and blood oranges. Choosing red cabbage, red onions, and red wines will boost your intake too.
Consuming more anthocyanins, according to two newly published studies, may reduce the risk of developing Parkinson’s as well as support healthier blood pressure.
An Anthocyanin-Rich Diet and Parkinson’s
Experimental studies suggest that anthocyanins may help protect nerve cells and enhance the connections between these cells. Now, Harvard School of Public Health investigators say that if their findings are confirmed, anthocyanins may be one way to reduce the risk of Parkinson’s (1).
A degenerative disease affecting movement and balance, Parkinson’s involves nerve cells in several parts of the brain and nervous system – particularly those that use the chemical messenger dopamine.
After more than 20 years of tracing nearly 50,000 men from the Health Professional Follow-up Study and over 80,000 women from the Nurses’ Health Study, the Harvard team reports that men eating the most flavonoids lowered their risk by 35%. Risk reduction was observed in both women and men who regularly consumed anthocyanin-rich foods specifically.
Anthocyanins Linked to Reduced Blood Pressure
Also led by Harvard researchers, a second study found that the highest intake of anthocyanins – mainly from blueberries and strawberries – reduced the risk of high blood pressure by 12% among people over 60 (2).
The information about blood pressure and diet came from about 150,000 U.S. health professionals. After crunching the numbers, the researchers found that the highest average intakes of anthocyanins ranged from 16 to 21 mg per day – a rather modest amount since a normal serving of blueberries provides in excess of 500 mg. What’s needed now, says this team, are studies that test whether optimal doses of anthocyanin-rich foods can prevent hypertension.
Anthocyanins seem to help regulate blood pressure by influencing the flow of blood through vessels, and the vessels’ ability to expand and contract as needed.
A Role for Vitamin D in Urinary Tract Health?
Adequate vitamin D may increase the body’s immune response, and in doing so, help protect against urinary tract infections (UTIs), according to preliminary but intriguing research from Sweden (3). After menopause, women are more prone to UTIs. And they often have low blood levels of vitamin D as well.
The Swedish scientists measured amounts of a protective, anti-microbial substance made by bladder cells in postmenopausal women before and after they were given vitamin D supplements for 3 months.
Levels of the protective substance went up when the vitamin D enriched bladder tissue was exposed to E. coli bacteria, suggesting that vitamin D prepares the bladder to mount a stronger and faster immune response when bacteria enter the bladder.
In light of the emerging resistance to antibiotics that are used to treat UTIs, we need to fully explore whether improving vitamin D in older women really helps fight off these infections.
Protecting our Brain: Recent Research
Brain Volume and Mental Function
With age, the brain tends to atrophy and shrink in volume. For those over 70, 16% experience mild cognitive impairment (MCI), characterized by issues with memory, language and other mental functions. And over ½ of those with MCI progress to Alzheimer’s.
Two new studies suggest that there may be steps we can take to help protect our mental abilities like thinking, reasoning and remembering – all part of what’s termed cognitive function.
Walking To Help Preserve Mental Function
Findings from a University of Pittsburgh study provide more evidence that physical activity can play a key role in protecting our brain as we grow older (1).
The investigators did additional research on nearly 300 of the 1,400+ people who are part of the long term Cardiovascular Health Study. The participants, who were all cognitively normal at the beginning of the study, underwent MRI brain scans 9 years later. After 13 years, they were tested for MCI or dementia.
Based on weekly walking distances, participants were divided into four groups. The average number of blocks walked per week was 8, 21, 45 and 156 in the groups.
After the brain scan, only those in the group with the highest amount of walking showed significantly greater volumes in three gray matter areas of the brain.
At the 13 year mark, about 39% of the participants had developed some degree of MCI while the rest still had normal cognition. The researchers found that the larger gray matter volume observed with physical activity reduced the risk of cognitive impairment 2-fold.
This study was conducted in people with an average age of 78 – a time of life when the risk for brain deterioration and dementia are greatest. So, it’s tempting to think that starting a walking program even earlier in life may be a good way to help preserve our brain as it ages. For certain, physical activity will benefit the heart, help keep weight down, and reduce the risk of getting a number of chronic diseases.
Extra B-Vitamins May Slow Dementia
Though not all studies examining the effects of B-vitamins in cognitive impairment have reported benefit, recent findings (2) from Oxford University’s Project to Investigate Memory and Aging are heartening. They suggest that supplemental B-vitamins can slow the progress of dementia.
The trial enrolled individuals over 70 with MCI who were given 3 B-vitamins (folic acid, vitamins B6 and B12) or placebo. Of the 271 participants, 168 had MRI brain scans at the start and end of the two-year study.
The brain scans showed that the B-vitamin group had a significantly slower rate of brain atrophy and shrinkage over time compared to placebo. The researchers also reported that at the end of the trial, a greater rate of brain deterioration was linked with lower test scores measuring cognitive function.
The B-vitamins lowered levels of homocysteine – the artery damaging compound once thought to raise the risk of heart disease and stroke. There is evidence, though, that homocysteine is a likely culprit in dementia and some eye diseases like AMD and glaucoma. In this study, among those with the highest homocysteine levels at the study’s start, taking B-vitamins reduced the rate of brain shrinkage by ½ compared to taking placebo.
Accelerated brain atrophy is often seen in people with MCI who go on to get Alzheimer’s. More studies will be needed to see whether B-vitamins can delay the progression of MCI to Alzheimer’s disease.
Trio of Nutrients May Help Combat Type 2 Diabetes
Take Positive Steps to Counter Type 2
When it comes to preventing type 2 diabetes – or controlling blood sugar in those who already have it – the factors with the biggest punch by far are pretty straight forward: lose weight if you need to, exercise regularly, and eat a healthy Mediterranean or low glycemic index diet.
In addition, researchers continue to explore the contribution of individual nutrients in combating type 2. This issue of Staying Healthy highlights recent findings related to omega-3 fats, magnesium and cinnamon.
New Understanding of Omega-3 Benefits
The American Diabetes Association (ADA) already recommends that people with diabetes eat 2-3 servings of fish weekly. That’s because studies have shown that consuming more omega-3s can help stave off coronary heart disease in diabetics, who have a greater risk of developing cardiovascular conditions than non-diabetics.
New research also points to a potential role for the omega-3 fatty acids EPA and DHA in helping to activate anti-diabetic genes (1). The study, carried out in animals, found that these omega-3 fatty acids activate genes that help regulate fat cells and maintain blood sugar balance. The factor activated by the omega-3s (transcription factor PPARy) is one that’s targeted by a number of anti-diabetic drugs. If the findings hold true in humans, it may mean additional benefits for those meeting ADA guidelines for omega-3 intake.
Study Underscores Importance of Magnesium
Low blood levels of magnesium occur in about 25-30% of people with type 2, and are more common in those with poorly controlled diabetes. Many studies have also reported that a better intake of this mineral can lower the risk of developing type 2. Results from a long term study appear to confirm that association (2).
Led by investigators at the University of North Carolina at Chapel Hill, the study recruited nearly 4,500 young adults 18-30 years of age who were free of diabetes and assessed their intake of dietary magnesium.
Three hundred and thirty cases of diabetes developed over the next 20 years of follow-up.
People with the highest magnesium intake were 47% less likely to acquire type 2 compared to those eating the least. Those getting the most averaged about 200 mg of magnesium for every 1,000 calories consumed compared with the lowest intake group who got about 100 mg of the mineral per 1,000 calories.
High magnesium consumers also had lower blood levels of inflammatory markers, and less insulin resistance (the inability of some cells to respond to insulin). One of magnesium’s jobs is to help insulin move glucose out of the blood stream and into cells.
As mentioned in the March Staying Healthy, a recently published survey found that less than ½ of US adults consume recommended magnesium levels. Dietary sources include beans, whole grains, broccoli, squash, and green leafy veggies, seeds, and nuts (especially almonds). Dairy, meats, chocolate, and coffee also provide magnesium, as does "hard" water.
Cinnamon Useful for Some Diabetics
From the UK comes a study suggesting that cinnamon may be useful in patients with poorly controlled type 2 diabetes (3). Fifty eight type-2 patients with high HbA1c (a key measure of glucose control) were given 2 grams of cinnamon or placebo daily for 3 months. Compared to placebo-takers, those supplemented with cinnamon experienced a significant reduction in HbA1c as well as a decrease in blood pressure (both systolic and diastolic values).
According to the researchers, this spice could be a useful addition to conventional drugs for diabetics who have trouble controlling their blood sugar levels.
In the News: Blueberries & Metabolic Syndrome, Cancer Risk & HDL, Caffeine & IOP
Healthful Blueberries: Bang for the Buck
Metabolic syndrome is a constellation of disorders that can raise the risk of developing diabetes and cardiovascular disease (CVD). High blood pressure, high triglycerides, abnormal cholesterol, obesity and lots of fat in the abdomen and waist area are among the associated problems. What’s alarming is that up to 25% of Americans are thought to fit the profile for metabolic syndrome, mostly due to the obesity epidemic we face.
Weight loss and exercise are our biggest weapons in the fight against metabolic syndrome. Results of a new study (1) now suggest that regularly eating blueberries can also help reduce some of the adverse health risks associated with this syndrome.
In the study, overweight people with the syndrome who consumed a beverage providing 50 g of freeze-dried blueberries daily for 8 weeks had greater decreases in their blood pressure and biomarkers for inflammation compared to people getting a placebo beverage. Oxidized LDL cholesterol in the blood, which can directly damage the lining of arteries, was also significantly decreased in the “blueberry” group.
Blueberries, like bilberries, are very high in polyphenols – compounds that are believed to be responsible for the berries’ heart-healthy benefits. The volunteers in this study consumed the equivalent of a little more than 12 ounces of blueberries daily – an amount that is fairly easy to achieve.
Higher HDL May Mean Lower Cancer Risk
According to an analysis of 24 randomized, controlled trials, HDL cholesterol (the so-called “good” cholesterol) might reduce the risk of cancer (2). The authors, from Tufts University, report that cancer risk dropped 36% for every 10 mg/dl increase in HDL.
It’s not understood how HDL might help combat cancer. One theory is that it could have antioxidant and anti-inflammatory effects. Or HDL may help the immune system search out and destroy abnormal cells with the potential of growing into tumors. The researchers point out that their study can’t prove that low HDL levels up the risk of cancer. However while we await further findings, it’s still a good idea to keep HDL levels as high as possible since it’s already known to help protect against heart disease. Optimum levels for cardio-protection are at least 60 mg/dl, with higher levels even better.
How can we boost HDL? Regular exercise, weight loss (for those overweight), and not smoking have the biggest impact on bolstering HDL levels. Moderate alcohol consumption has a modest effect, and omega-3 might be helpful as well. A recent study found an association between omega-3 intake and HDL, with a 2.5 mg/dl increase in HDL observed for every 1% increase in omega-3 consumption (3).
High Eye Pressure & Caffeine: Bad Combo?
Moderate coffee intake – about 2-3 cups daily or the caffeine equivalent of about 250 mg – appears to be safe for most people. At that level of intake, the bulk of the evidence indicates that caffeine isn’t cancer-causing, doesn’t cause or worsen CVD or hyper-tension, and doesn’t raise the risk of fibrocystic breast disease or bone loss. Caffeine may even have some benefits: it’s been linked to a lower risk of type-2 diabetes, gallstones in men, and Parkinson’s disease.
For people with glaucoma and elevated intraocular pressure (IOP) however, regular or excessive caffeine intake may not be a great idea. In an analysis of 6 trials, the IOP of normal individuals did not go up when measured 30, 60 and 90 minutes after ingesting caffeine (4). IOP did, however, rise significantly at these time points when people with glaucoma or ocular hypertension were given caffeine.
In the News: Folic Acid & Hearing Loss, Meat & Heart Disease, B6 & Colon Health
Folic Acid May Help Preserve Hearing
Low blood levels of folate are associated with a 35% increased risk of hearing deficits, according to a recent study that strengthens the link between B vitamins and protection against hearing loss. Loss of hearing is the most common sensory disorder in the US, affecting more than 36 million people.
The Blue Mountains Hearing Study (1), based on a population of nearly 3,000 people aged 50+, found that low blood levels of folate (below 11 nanomoles per liter) correlated with a greater risk of age-related hearing loss. In addition, higher blood levels of the naturally occurring compound homocysteine (over 20 micro-moles per liter) were linked with a 64% higher risk. An elevated level of homocysteine may adversely affect blood flow in the inner ear, and studies have shown that levels of folic acid, as well as vitamins B6 and B12, can influence homocysteine concentration in the blood.
This is not the first time folic acid has been linked to the prevention of hearing loss. In 2007, researchers reported that folic acid supplements delayed age-related hearing loss in the low frequency range in a study of 700+ men and women 50-70 years of age (2).
In addition, Boston-based researchers have just reported that men over 60 with high folate intake from foods and supplements had a 21% lower risk of developing hearing loss (3). Scientists now need to conduct large trials to assess these associations.
Watch Your Intake of Processed Meats
The findings of a new review and meta-analysis (4) provide some good and bad news for meat lovers. Researchers from the Harvard School of Public Health looked at 20 prior studies that examined red and processed meat intake and the risk of coronary heart disease (CHD), stroke and type-2 diabetes. The analysis involved more than 1.2 million people from 10 different countries.
They found that eating processed meat is associated with a higher risk of CHD and diabetes, but that consumption of red meat such as beef, pork or lamb is not linked to these conditions.
Processed meats were defined as any meat preserved by smoking, curing, salting, or chemical preservatives. That includes meats such as bacon, sausage, salami, luncheon meats and hot dogs. In fact, eating just 1.8 ounces of processed meat per day (about 1 hot dog or 2 slices of salami) was associated with a 42% greater risk of CHD, and increased the risk of diabetes by 19%.
Prior studies did not separately evaluate unprocessed red versus processed meats, which may explain why these studies came up with conflicting results on the health effects of red meat. While we’ve tended to blame the saturated fat in red meats for heart disease, the results of the Harvard study suggest it might not be that simple. Processed and unprocessed red meats contain similar amounts of saturated fats and cholesterol, but the processed kind have about 4 times more sodium and 50% more nitrate preservatives. It may be that the salt and preservatives are more the culprits, rather than simply the fats.
Low B6 Levels Could Impact Colon Health
The results of a new Swedish study add to the mounting evidence that maintaining high blood levels of vitamin B6 may help reduce the risk of colorectal cancer (5). Researchers pooled and analyzed the results of 13 studies that examined the relationship between vitamin B6 and colorectal cancer. They found that people with the highest blood levels of the vitamin were less likely to develop the disease. When one study with inconsistencies was excluded, analysis of the remaining 12 studies showed a 48% reduction in risk for every 100 picomole per milliliter increase in blood levels of B6.
Nutrition Support in Inflammatory Bowel Disease
What is Inflammatory Bowel Disease (IBD)?
About 1 million people in the US suffer from IBD (which is different than the more common irritable bowel syndrome). Most new cases of IBD develop in people 15 to 25 years of age, but it can occur in older adults too. There are two different forms of IBD: Crohn's disease and ulcerative colitis. Both cause inflammation in the bowel, but they often affect different parts of the bowel and to a different degree.
Many experts believe that IBD is an autoimmune disease, with genetic, immune and environmental factors all likely to be involved.
In terms of dietary supplements, a daily multi-nutrient is often recommended because IBD patients can have difficulty absorbing nutrients from their diet. Also, ‘multis’ usually contain folic acid, and one of the medications (sulfasalazine) used to treat IBD, can reduce absorption of this B-vitamin in the intestine. Other dietary supplements have been investigated in IBD, and several have shown some initial promise.
Vitamin D May Help Stave Off Relapse
In those with IBD, symptoms (diarrhea, abdominal pain and weight loss) come and go in a pattern of relapse and remission. Patients with IBD often experience long periods without symptoms, but then get acute attacks that can last from several weeks to months. The anti-inflammatory activity of vitamin D led researchers to examine its effect on the rate of remission in IBD patients.
In this study, patients with Crohn’s who were in remission received 1200 IU vitamin D or placebo daily for 12 months (1). Those taking vitamin D had a lower rate of relapse: Only 13% of those in the vitamin D group relapsed compared with the 29% in the placebo group. According to the researchers, a larger trial is needed to confirm that vitamin D can make a significant difference in holding off relapse.
Can Omega-3s Help Calm Inflammation?
Fish oils have been studied for IBD in clinical trials, but results haven’t always been consistent. One trial reported that taking 2.7 grams of omega-3s for 12 months can reduce rate of relapse in Crohn's disease patients who are in remission (2), while another clinical study failed to show a difference in relapse rate (3).
In ulcerative colitis patients, preliminary clinical research suggests that taking fish oil along with soluble fiber and antioxidant vitamins C and E might reduce the need for corticosteroids (4), a medication that is sometimes given in moderate and severe disease.
Probiotics May Be an Adjunct to Medications
Supplements of “friendly” bacteria are often used to help re-colonize the GI tract in patients who are given certain antibiotics. But in addition to helping restore normal bacteria, probiotics might also work to modulate the immune system.
A probiotic mixture of several species of Bifidobacteria, Lactobacillus, and Streptococcus, has been studied in people with IBD. One trial reports this probiotic combination helped keep pathogenic bacteria in check and reduced relapse in ulcerative colitis patients intolerant to 5-aminosalicylic acid (5-ASA) (5) – a drug often used to treat mild disease. Other clinical evidence suggests adding a probiotic may help some patients with active mild-to-moderate ulcerative colitis who don't respond adequately to conventional treatment alone (6).
Finally, if you have IBD, it’s always best to work with your physician in deciding whether and when to try a dietary supplement for nutritional support.
Emerging Vitamin D Research: Immunity, Muscle Function
Emerging Areas of Vitamin D Research
As many as a billion people worldwide, including more than 30% of Americans, have low levels of vitamin D (1). Those figures are fairly stunning since insufficient blood levels of vitamin D may well contribute to a spectrum of health conditions such as osteoporosis, certain cancers, cardiovascular disease and diabetes. [See Staying Healthy newsletters March, 2010 and November, 2007].
The Institute of Medicine (IOM) has been conducting a review of the available vitamin D science, and is due to deliver its findings later this year. Many experts expect the IOM to recommend daily intakes much above the current levels of 400 IU.
In the meantime, researchers are delving deeper into the potential benefits of getting enough vitamin D, as well as how this vitamin works throughout the body. Two areas receiving attention are the role of vitamin D in the immune system and its possible contribution to maintaining strong, healthy muscles.
Promise Against Seasonal Flu
That vitamin D is involved in regulating the immune system is not a new idea. But researchers from the University of Copenhagen believe they have figured out how: it’s crucial for activating key immune defense cells. The Danish scientists report that vitamin D is necessary to trigger the action of T-cells (2) – the immune system’s killer cells. Too little vitamin D means these cells remain inactive and unable to mobilize against foreign invaders.
Researchers recently tested the effects of vitamin D in a placebo-controlled trial among 300+ school children in Japan (3). They found that supplemental doses of vitamin D reduced the incidence of seasonal flu (influenza A) by over 40% compared to the placebo group over the course of 4 months. The benefits were even more noticeable in children who had low levels of vitamin D at the start of the study.
Canada’s Public Health Agency also confirmed last year that it is partnering with universities and hospitals to find out whether there’s a correlation between severe seasonal flu and low vitamin D levels and/or a person’s genetic make-up. The bottom line is to continue getting seasonal flu shots and practice preventive hygiene. But it’s also a good idea to get adequate vitamin D for a healthy immune response.
Strong Muscles and Vitamin D Linked
A study by researchers from McGill University and University of Southern California is one of the first to show a clear link between vitamin D levels and the accumulation of fat in muscle tissue (4) – a factor in muscle strength and overall health. They found that the lower the levels of vitamin D the more unwanted fat was present in subjects' muscles.
A remarkable 59% of the study subjects had too little vitamin D in their blood, and nearly 25% of the group had serious deficiencies (less than 20 ng/ml). These results are surprising, because the subjects – all healthy young women living in California – could be expected to benefit from ample exposure to sunshine, the trigger that causes the body to produce vitamin D.
The authors of the study are not yet sure what’s causing vitamin D insufficiency in these women. Better levels of vitamin D might be helping to keep fat from infiltrating muscles. Or also it’s possible that in overweight people more vitamin D is retained in fat tissues leaving a shortage in blood.
Studies in the elderly, though, have led scientists to believe that vitamin D is essential for muscle strength. Older, bedridden patients, for example, have been shown to gain strength when given vitamin D. And a recent study reports that fatty degeneration of thigh muscles in elderly adults is associated with low levels of the vitamin in blood and poor balance and gait (5).
In the News: Nuts, Hibiscus Tea and Vitamin E
Adding Nuts to a Healthy Diet Has Rewards
A newly published review offers the best evidence yet that eating nuts can reduce LDL cholesterol and triglycerides, especially in people with elevated levels of these blood lipids (1). The analysis, which examined data from 25 different clinical trials, found that eating an average of a little over 2 oz. of nuts daily cut LDL cholesterol by about 7% and triglycerides by 10%.
According to the study authors, the type of nuts eaten did not seem to make a difference to the overall heart-healthy effect. They did find, though, that the cholesterol-lowering effects of nuts were strongest in thinner compared to overweight people, and added that more research is needed to understand why.
Nuts are naturally low in sodium and sugar, and are a good source of healthy fats as well as fiber, protein, B-vitamins and minerals. That makes them a good hunger-quenching snack. Nuts like walnuts, pecans, pistachios and almonds can also be tossed with vegetables and added to salads. It’s best to choose unsalted nuts, and to keep intake at a maximum of about 3 oz daily (roughly 2/3 cup) since they provide around 150-200 calories per oz. Because of their fat content, nuts are best stored in the refrigerator.
Hibiscus Tea May Lower Blood Pressure
Next time you have your mid-afternoon snack, try having a cup of hibiscus tea along with your handful of walnuts. According to a new study from Tufts University, a few cups of hibiscus tea a day may reduce blood pressure and offer benefits for those at risk of developing hypertension (2).
In this clinical trial, 65 adults aged 30-70 with pre-hypertension or mildly elevated blood pressure were randomly assigned to consume either 3 servings of the brewed tea (roughly 8 oz or 1 cup per serving) or a placebo drink for 6 weeks. None of the participants were taking blood pressure-lowering medications.
At the end of the study, people in the hibiscus tea group had an average reduction of 7.2 points (mmHg) in their systolic blood pressure compared to a 1.3 drop in the placebo group. A slight decrease in diastolic pressure was also noted in the tea drinkers. Systolic pressure is the top number, and diastolic the bottom number in blood pressure readings. Pre-hypertension is defined as a blood pressure reading that’s between 120/80 mmHg and 139/89 mmHg, and signals that a person is at risk of developing hypertension.
The blood-pressure lowering effects of hibiscus tea, according to the researchers, may be due to its relaxing action on blood vessels or to the vessel-protecting effects of its flavonoid (anthocyanin) content. There is also some indication that Hibiscus tea may act as a diuretic.
Vitamin E Helps Fight Fatty Liver Disease
NASH (non-alcoholic steatohepatitis) is a disease where excess fat in the liver causes inflammation and damage. The disease, which is linked to weight gain and obesity, can lead to cirrhosis and liver cancer.
An NIH-funded clinical trial published in the New England Journal of Medicine found that 43% of non-diabetic people with NASH showed significant improvement in their liver cells when given 800 IU of vitamin E daily compared to only 19% of those receiving a placebo and 34% of those given a medication (pioglitazone) over a 96-week period (3).
Fatty liver disease is a growing problem in the U.S and we currently have no approved medication to offer patients, according to one of the study’s investigators. Vitamin E may hold promise for those with NASH, and people who are overweight may lower their risk of this disease by slimming down.
In the News: Magnesium, Flavonoids and Vitamin D
Magnesium May Improve Lung Function
Observational studies have reported beneficial effects of magnesium on the occurrence and management of asthma. To test whether this mineral could bolster lung function in asthmatics, researchers at Bastyr University in Washington recruited 55 people with mild to moderate asthma who received either 340 mg of magnesium or a placebo pill daily for 6 ½ months (1).
The supplemented group showed a greater improvement in lung function compared to those receiving placebo pills. In order to determine the ability of the airways to stay open, both groups were given a drug that causes the airways to constrict and narrow, as they do during an asthma attack. The magnesium group needed 20% more of the drug to constrict the airways to the same degree as seen in the placebo group. Finally, quality of life, assessed by questionnaire, improved only in the magnesium takers.
Americans Face Dietary Magnesium Gap
Magnesium has anti-inflammatory actions that could improve asthma control, and it may enhance the capacity of the lungs to expand by favorably affecting cell membranes. While not all trials have reported a beneficial response to magnesium, these findings support its use for those with mild to moderate asthma. That’s important because less than half of US adults consume recommended levels of this mineral, according to the last National Health and Nutrition Examination Survey.
Flavonoids May Lower Stroke Risk in Women
Increased intakes of flavonol-rich foods may reduce a woman’s risk of stroke by 20%, according to a new review of studies involving over 110,000 people (2). Flavonols (also known as flavonoids) make up a sub-group of the bioflavonoid family, and are found in a variety of fruits and vegetables such as onions, apples and broccoli – as well as tea.
Dutch researchers conducted a meta-analysis (a review of studies) using data from people who were free of cardiovascular disease or stroke when the studies started. People in these studies were followed from 6 to 28 years, during which time the incidence of stroke was documented. Strokes occur when blood clots or an artery bursts in the brain and interrupts the blood supply to part of the brain. It is the leading cause of disability and the 3rd leading cause of death in the US.
While the researchers caution that more clinical research is needed, they conclude that accumulating evidence supports a role for flavonol-rich foods in maintaining vascular health.
Vitamin D Helps Fend Off Heart Disease and Diabetes in Older People
British researchers conducted the first ever review of studies looking at the relationship between blood levels of vitamin D and cardiovascular disease (CVD), type-2 diabetes and metabolic syndrome. Twenty eight studies were included providing data on nearly 100,000 people (3).
The analysis found that the highest blood levels of vitamin D were associated with a 33% risk reduction in CVD, a 55% reduction in type-2 diabetes, and a 51% drop in the risk of metabolic syndrome, compared with the lowest blood levels.
These findings add to a rapidly expanding body of science supporting the benefits of adequate vitamin D levels. A review that may lead to the establishment of higher recommended intakes is being conducted by the Institute of Medicine.
In the News: Anti-aging effects of Blueberries, Omega-3s & Salt Reduction
Can Blueberries Aid Memory in Older Adults?
The Blueberry – and its Scandinavian counterpart, the Bilberry – are rich sources of flavonoids, particularly the kind known as anthocyanins. Researchers have long been interested in the effects of these flavonoids on brain functioning. Studies, for example, have shown positive mental gains in older animals when blueberries were added to their diet. [See: Staying Healthy, Jan, 2008 at sciencebasedhealth.com]. Now, results from a small pilot study conducted by the US Department of Agriculture and Tufts University suggest that these berries may support brain function in people too (1).
In this study, the first of its kind, older people with early memory problems and an increased risk of dementia and Alzheimer’s, took a daily drink of about 500 ml (17 ounces) of blueberry juice for a 3 month period. Results showed significant improvements in learning and word-list recall, a measure of short-term memory. A trend toward reduced symptoms of depression was also observed.
While the investigators stressed that these findings need to be confirmed in a larger and controlled trial, they were encouraged that consistent supplementation with blueberries could be a way to forestall brain aging. It’s believed that the flavonoids in blueberries and bilberries may enhance connections and communication between nerve cells, and stimulate nerve cell regeneration.
Omega-3 Linked to Younger Biological Age
Telomeres are the genetic material at the end of chromosomes that shorten as cells replicate (the process by which cells divide and make copies of themselves). With each replication telomeres get shorter, and when they are used up, the cells are destroyed. Many experts believe that telomere length may be a marker of biological aging.
Previous studies have shown that telomeres are vulnerable to oxidative stress, and certain antioxidant nutrients have been linked to maintaining telomere length. [See: Staying Healthy, Nov, 2009].
Researchers from the University of California, San Francisco recently reported that higher blood levels of the omega-3 fatty acids EPA and DHA are linked to a lower rate of telomere shortening over a 5 year period in people with stable coronary artery disease (2). Telomeres shortened more rapidly in those with the lowest blood levels of EPA and DHA, while they grew shorter more slowly in those with the highest levels of these 2 fatty acids. Omega-3s have been shown to reduce markers of oxidative stress and increase levels of antioxidant enzymes, which may account for their protective effect.
The researchers noted that several studies have shown that high dietary intake of marine omega-3s is associated with longer survival in people with cardiovascular disease. While it’s not established that the omega-3 and telomere connection plays a role in the better survival rate, it could be a contributing factor.
Less Salt, Big Benefits
A new report published in the New England Journal of Medicine concludes that lowering the amount of salt people eat by even a small amount could meaningfully reduce cases of heart disease, stroke and heart attacks (3). The report found that everyone would benefit from less salt, but people at higher risk for heart problems would benefit the most. If everyone consumed even ½ a teaspoon less salt daily, there would be between 54,000 and 99,000 fewer heart attacks each year according to the estimates.
The idea that only certain people need to limit salt is a misconception, since blood pressure increases with age. Nearly 1/3 of adults have hypertension, and another 1/3 currently have pre-hypertension. To cut back on salt intake use the salt shaker less, and more importantly, read the sodium content on labels of processed foods – the source of about 75% of our dietary salt intake.
A Daily Dose of Color
for Good Health
Color Counts When it Comes to Produce
When the current Dietary Guidelines for Americans were released in 2005, the recommendation for daily fruit and vegetable consumption was increased from
5-9 to 5-13 servings per day for adults. Despite the known health benefits of eating enough fruits and vegetables, many of us find it hard to meet these recommended intakes.
While eating a wide variety of produce is a worthwhile goal, eating a variety of different colors of fruits and vegetables is a new way of thinking about meeting that goal. Color can be just as important – maybe even more so – than quantity when it comes to fruits and veggies. That’s because colorful produce contains phytonutrients – unique plant-derived nutrients that contribute to good health.
About 80% of Americans fail to eat a diet rich in specific colorful fruits and veggies according to a new study entitled America’s Phytonutrient Report. While scientists continue to identify plant-based nutrients, this report focused on 14 select phytonutrients that were grouped into color categories.
The five color categories included:
Using data from the National Health and Nutrition Examination Surveys, the US Department of Agriculture and other published surveys, the authors calculated the phytonutrient gap by comparing intakes of the 14 phytonutrients among the sub-group of Americans who do meet the daily fruit and veggie recommendations with intakes of average Americans.
Based on this analysis, Americans are falling short in virtually every color category of phytonutrients:
Phytonutrient Index Could Prove Helpful
Researchers from the University of Florida developed a phytonutrient index that ranks the amount of calories consumed from plant-based foods with overall daily calorie intake. In their study, they broke young adult volunteers into normal weight and overweight/obese groups and calculated their “index”. Normal weight adults had a higher phytonutrient index (23.5), almost twice that of the overweight group (13.2).
Although both groups ate about the same amount of calories, the overweight and obese adults consumed fewer plant based foods and therefore less protective trace minerals and phytonutrients – and more saturated fats. The overweight group also had higher levels of oxidative stress and inflammation. According to the researchers, the phytonutrient index could prove to be a useful tool to optimize diets for disease prevention.
Sample the Spectrum
To help you choose richer and more vibrantly colored foods whenever possible, here are just a few examples of foods from different color categories:
Vincent HK, et al. Relationship of the dietary phytochemical index to weight gain, oxidative stress, and inflammation in overweight young adults. J of Human Nutr Dietetics [Epub ahead of print, September, 2009]
Nutrition, Aging and Telomeres
How Do We Age?
There is, of course, no simple answer to this complex and intriguing question. However scientists are exploring a number of hypotheses that attempt to explain the underlying mechanisms that affect the aging process. Recent research suggests that there may be a limited number of these mechanisms, providing hope that scientists’ efforts may one day lead to strategies that could help us lead longer, healthier lives.
A number of ‘aging’ hypotheses are being hotly pursued. One hypothesis involves the complex connections between the brain and nervous system and our endocrine glands – the neuro-endocrine system. This system becomes impaired as we age, and can lead to high blood pressure, poor sugar metabolism and sleep problems. Researchers are focusing on a pathway that involves insulin and a substance called insulin-like growth factor. Though reducing levels of insulin-like growth factor extends the lifespan of several species, it’s not yet clear whether it might have the same effect in humans.
Another hypothesis hinges upon free radicals and oxidative damage. Free radicals are one of the by-products of normal cell metabolism, and are normally mopped up and neutralized by antioxidants. But those that escape this clean-up process can damage DNA, proteins and mitochondria – the tiny energy-producing structures in our cells. Mitochondria from the cells of older people tend to be less efficient than those from younger individuals, and too much damage to mitochondria can cause cell death. Because oxidative damage is linked with so many of the problems associated with aging, it remains one of the hottest areas of aging research.
With age, our proteins, DNA and other molecules develop unwanted attachments to one another, referred to as cross-links. The cross-linking hypothesis holds that these attachments disable the function of important proteins and DNA. One of the main offenders is glucose (sugar), which can stick to proteins and form injurious links. Cross-linking of proteins is thought to be partly responsible for wrinkling of the skin as well as age-related cataract.
Another hypothesis arose from the observation that human cells can undergo only a limited number of divisions to make new cells. Most scientists believe that what determines this limit on cell division is the length of a structure called a telomere. Telomeres are positioned at the end of our cells’ chromosomes, and they play an important role in cell division by ensuring that chromosomes don’t fuse together or get rearranged, which can lead to cancer. Every time a cell divides, telomeres get a little bit shorter. And when they are totally gone, the cell self-destructs. Telomere length is believed to be one marker of biological aging.
Nutrition, Aging and Telomeres
Diet can have a profound effect on many aspects of health, including aging. We’ve learned, for instance, that restricting calories can lead to greater longevity in primates. We know that the right diet and lifestyle can help maintain healthy glucose levels, and that dietary antioxidants can help counter oxidative stress. Research is also beginning to shed light on how nutrients affect the expression of our genes.
Preliminary findings from two recent population health studies now raise the question of whether nutrients might be a factor in maintaining telomeres. In the first study (1), investigators examined multivitamin use, nutrient intakes and telomere length in 586 women aged 35-74. They found that telomeres were modestly longer in multivitamin users compared to non-users. They also observed a positive relationship between dietary intake of vitamins C and E and telomere length.
The second study (2) also looked at the dietary habits and telomeres in nearly 2,000 Chinese participants over 65. The researchers report that the telomeres of people who drank an average of 3 cups of tea (mostly green tea) daily were longer than those drinking on average only a quarter cup per day. Telomeres have been shown to be highly susceptible to oxidative stress, and antioxidant vitamins C, E and the polyphenols in tea could be protective of these structures. While it’s premature to draw conclusions from these findings, they will prompt a new and exciting research direction.
Foundations of a Heart-healthy Lifestyle
It’s clear that the foundation for a healthy heart includes getting enough physical activity, keeping our weight down, and sticking as much as possible to a Mediterranean style diet which emphasizes fish, nuts, whole grains, fruits, vegetables, olive oil and moderate red wine, while limiting red meat and sugars. But there’s often a divide between what we know and what we actually do. Americans tend to eat an insufficient amount of fish, for example, and to go overboard on sugary foods and beverages.
Several papers published last month focus on the cardiovascular (CV) benefits of the omega-3 fats from fish and the perils of excess sugar. A third study gets to the heart of how vitamin D (from sunlight, oily fish and egg yolks) contributes to CV health in diabetics.
Review Endorses CV Benefits of Fish Oil
A new review – probably the most extensive ever – concludes that the evidence from three decades of research supports fish oils as beneficial for everyone (1). This applies to healthy people as well as those with heart disease – including patients who have had a heart attack, those with heart failure, atherosclerosis and those with many kinds of heart arrhythmias. One of the most significant benefits is seen in atrial fibrillation, the most common form of abnormal heart rhythm.
Though fish oil, or more specifically the omega-3 fats they contain, can both prevent and treat many aspects of cardiovascular disease, it is not promoted often enough by physicians to their patients, according to the authors of the review.
The authors also echo the recommendations of the American Heart Association (AHA) in advising that healthy people get at least 500 mg of EPA and DHA per day – equal to around 2 fatty fish meals weekly – and that those with coronary heart disease or heart failure get about 1000 mg daily. Fish oil supplements free of mercury and other contaminants are a good alternative, note the authors, as few people are going to consume therapeutic doses of fatty fish.
AHA Urges Major Cutbacks in Sugar Intake
Americans are swallowing 22 teaspoons of sugar each day on average, and it’s time to cut way back according to the AHA (2). The heart organization distinguished between naturally occurring sugars and sugars added to foods during processing, and picked out the later for attack. Added sugars are likely contributors to the obesity crisis and are associated with increased risks of high blood pressure and elevated triglyceride levels, as well as other causes of heart disease and stroke.
Women should be getting no more than 6 teaspoons of added sugar daily, according to AHA guidelines, while 9 teaspoons is the limit recommended for most men. Regular soft drinks are one of the biggest culprits for adding sugars, followed by candy, cakes, cookies and pie. The sugar in just one 12-ounce can of regular soda exceeds the daily limit for women! So sit back with a glass of water with a twist of lime and sprig of mint, and learn more about the amount of added sugars in common foods at the US Dept. of Agriculture database.
How Vitamin D Helps Diabetic Heart Health
Regular readers of this newsletter know that vitamin D research is booming, and that low blood levels of this essential nutrient are common in people, including diabetics who have a higher risk of heart disease. New research with diabetic subjects has found that vitamin D inhibits the ability of cholesterol to be taken up by cells called macrophages (3).
With vitamin D deficiency, macrophage cells gobble up more cholesterol than they can eliminate. Once they’re clogged with cholesterol, macrophages become foam cells – one of the earliest markers of atherosclerosis. This eventually leads to stiffened blood vessels and blocked blood flow. The researchers noted that it may be possible to delay or reverse the development of atherosclerosis by helping diabetics regain adequate vitamin D levels.
New Findings on Nutrients & Mental Function
Diet, Exercise Help Preserve Brain Function
Cognition refers to our ability to process,
retrieve and apply information. Cognitive skills are those that
people use every day such as memory, learning, reasoning, and
decision-making. Though a gradual decline in cognitive function
occurs naturally as we grow older, evidence indicates that staying
physically active and getting a good supply of essential nutrients
are both critical factors in staying mentally sharp.
Studies, for example, have shown that older
adults who maintain their level of physical activity with age
can slow down their rate of cognitive decline, and that low blood
levels of vitamins
B12 and folic
acid can compromise brain function. Now, preliminary
findings from several new studies suggest a potential role for
fatty acids, vitamin
D and flavonoids in helping to counter age-related
Omega-3 Boosts Memory for Healthy Adults
The results from two studies were presented
in July at the Alzheimer's Association 2009 International Conference
in Vienna. One of the studies, which examined the effects of the
omega-3 fatty acid DHA
in healthy older people with age-related memory complaints, reported
improved memory function and heart health.
Nearly 500 people took part in this double-blind,
6 month, multi-site trial. Compared to those receiving a placebo,
participants taking supplemental DHA
had almost double the reduction in errors on a test that measures
learning and memory performance (1).
In addition, the researchers noted a decrease in heart rate in
group, while blood pressure and weight did not change.
In contrast to the improvements observed
in healthy older individuals, a second study presented at the
Conference found that DHA
did not benefit mental function in patients with Alzheimer's compared
to those getting a placebo (2). The
investigators did, however, observe a slower rate of decline on
a sub-group of people who carried a gene (the e4 version of ApoE
gene) that increases the risk of developing Alzheimer's but doesn't
affect progression of the disease. Though more research is needed,
it may be that nutritional interventions must occur very early
in the disease to make any real difference.
Vitamin D & Mental Function in Older Men
Several recent studies have linked low blood
levels of vitamin
D with reduced cognitive abilities in older adults.
Newly reported results from the European Male Aging Study are
in agreement with these previous findings (3).
In this study, over 3000 men age 40-79 underwent evaluation of
their cognitive skills and vitamin
Lower blood concentrations of vitamin
D were associated with poorer performance on a test
that measures how fast information is processed and visual short-term
memory. This observation underscores the need for health professionals
to routinely test blood levels of vitamin
D, especially in older people.
Wine, Chocolate & Tea for Better Cognition?
Foods like fruits, wine, tea and chocolate
are high in polyphenols, particularly flavonoid compounds. Intakes
of flavonoids have been linked to a lower risk for age-related
cognitive decline and dementia. In a newly published study (4),
about 2000 men and women took a battery of tests evaluating learning,
memory, attention, and verbal fluency. Their intake of wine, chocolate
and tea was also determined.
Performance on the cognitive tests was higher
in people consuming up to 10 grams per day of chocolate (typically
less than of a chocolate bar) and 2-3 ounces of wine, with the
effects stronger for wine consumption. Importantly, the effects
were most pronounced for people consuming all three foods.
Dietary Tips from New Cancer Prevention Research
100th Meeting of AACR Highlights Diet's Role
New findings from science and medical institutions
worldwide were presented at the 100th meeting of the American
Association for Cancer Research (AACR) recently, and many underscore
the role of lifestyle and diet in preventing cancer. We know that
a healthy diet overall lowers the risk for many kinds of chronic
diseases - and cancer is no exception. Here, briefly, are a few
of the takeaways from research presented at this meeting or published
in the latest scientific journals.
Put More Fruits & Veggies on Your Plate
Coinciding with the AACR meeting was a newly
published study (1) that provides
yet another reason to shop the produce aisle. An analysis of the
European Prospective Investigation into Cancer and Nutrition trial
with over 452,000 participants, found a 24% reduction in colorectal
cancer risk for those consuming the most produce. The findings
did not hold true for smokers, so now's the time to give up smoking
if you do, and go for a produce-rich diet.
More Broccoli for Stomach Health
Broccoli, which already has a reputation
as a "superfood", contains a compound called sulforaphane.
This compound has anti-bacterial activity, and is found in even
higher concentration in broccoli sprouts. In this trial, presented
by Dr. Jed W. Fahey at AACR, people infected with H. pilori bacteria
consumed either 2.5 ounces of broccoli sprouts daily or the same
amount of alfalfa sprouts. H. pilori can cause ulcers and gastritis,
and has been implicated in stomach cancer. Participants eating
the broccoli sprouts were found to have lower levels of H. pilori
at the end of the 8 week study.
Walnuts Might Help Reduce Breast Cancer Risk
Dr. Elaine Hardman and her research team
reported at the AACR meeting that lab mice bred to develop breast
cancer had a significantly lower risk of breast cancer if fed
the human equivalent of a handful of walnuts a day. Half of the
mice, which normally always develop breast cancer, got the human
equivalent of two ounces of walnuts per day and half got a normal
diet. The mice eating the walnuts had fewer and smaller breast
tumors and those that did get tumors got them later than the other
mice. Walnuts contain multiple ingredients that, individually,
have been shown to slow cancer growth including omega-3 fatty
acids, antioxidants and phytosterols. While the study was done
with lab animals, it's likely the same mechanism would be at work
Pass Up Overcooked Meat at the Next BBQ
At the AACR meeting, Dr. Kristen Anderson
presented findings that a preference for very well-done steak
increased the risk of pancreatic cancer by 60% compared to those
eating less charred meat among 62,500 healthy subjects. A 70%
greater risk was seen with the highest intake of very well-done
meat of all kinds. Although not all studies have seen this link,
So turning down the heat when grilling, frying
or barbecuing to avoid excess burning or charring may be a smart
way to help prevent pancreatic cancer - a cancer for which treatments
are very limited. Previous research has also suggested that marinating
meat in beer or wine before cooking can cut down on the cancer-causing
compounds (heterocyclic amines) that form when meat is cooked
and charred at high temperatures.
Eat Flavonoid-Containing Foods
Flavonoids acts as antioxidants, and are
believed to protect cells from free radical damage. Writing in
the International Journal of Cancer, Dr. Margaret Gates and colleagues
reported that apigenin, a flavonoid found in such foods as parsley,
tomato sauce, kumquats and red wine, may help protect women from
ovarian cancer (2). The link was
seen in studying the flavonoid intake of 1,100 + women with ovarian
cancer, and about the same number of healthy women. These findings
are yet another reason to a wide variety of fruits and veggies.
In the News: Omega-3s, Antioxidants and GLA
Omega-3s, Zinc & "C" May Ease
Results of new research suggest that a combination
of fish oil, zinc
C can improve the symptoms of bronchial asthma in children
(1). Asthma, which affects nearly
20 million Americans, is on the rise according to the American
In this double-blind study, 60 asthmatic
children were supplemented with 300 mg of EPA
15 mg of zinc,
200 mg of ascorbic acid, a combination of all the nutrients or
a placebo for 6 week periods. Lung function was measured, as were
markers of inflammation. Symptoms such as wheezing, shortness
of breath and the use of rescue inhalers were measured in a standardized
The researchers found significant improvement
in all the tests when the nutrients were given one at a time.
However all three nutrients combined produced the best results.
Omega-3s & Better Blood Pressure in Dieters
One of the many benefits of weight loss is
often blood pressure reduction, and results of a recent study
suggest that the omega-3s can result in even better reductions
- at least in those who have low levels of the omega-3 DHA
stored in their cell membranes (2).
Low levels of cellular omega-3 are believed to reflect infrequent
intake of these important fatty acids.
All of the 324 overweight study participants,
aged 20-40, were put on weight loss diets and divided into 4 different
groups. One group ate salmon 3 times weekly, while another consumed
cod, which is lower in omega-3 content. The third group was given
supplements providing about 495 mg of EPA
daily, while the forth group was assigned to a placebo and ate
All of the study subjects lost weight - a
little over 11 pounds on average. Blood pressure also went down
overall, but reductions were greater in those eating salmon or
receiving the daily omega-3 supplement compared to people in the
cod-consuming group and in placebo-takers who had low stores of
the omega-3 to begin with. These observations are in line with
a number of other study findings that indicate blood pressure
reductions with greater EPA
GLA Makes Contact Wear More Comfortable
Contact lens wearers commonly experience
a feeling of dryness in their eyes. As a result, many people wear
their lenses less often or discontinue their use altogether. A
recent double-blind, placebo-controlled study examined the effects
of 300 mg of supplemental GLA
daily in 76 women with contact lens-related dry eye (3).
The participants all wore soft contact lens.
The women in the GLA
group experienced significant improvement in the sensation of
dryness and overall lens comfort at 3 months and at 6 months,
when the study ended. Tear meniscus height - a relatively new
measurement of tear production - was also greater in the GLA
supplementers compared to placebo.
Antioxidants, Exercise Boost Bones in Women
The results of a pilot study in 34 post-menopausal
women suggest that a combination of antioxidant supplements and
resistance training may help protect against bone loss. The women
were assigned to 1 of 4 groups: 1) antioxidants plus exercise;
2) antioxidants and no exercise; 3) placebo plus exercise; or
4) placebo and no exercise. The antioxidants consisted of 600
E and 1,000 mg of vitamin
At the end of 6 months, measures of bone
density revealed that only those women not exercising and getting
the placebo experienced significant bone loss in the spine. In
contrast, the bone density of those who exercised or took the
antioxidants remained constant. These preliminary findings are
promising and lend support to previous links seen between higher
intake of antioxidants (e.g. lycopene) and better bone density
in the spine of women and, for men, in the hip.
AMD Forecasters Call for Wider Vitamin Use
In a newly published analysis
(1), researchers predict that cases of age-related macular
degeneration (AMD) will nearly double in the coming decades, increasing
from 9.1 million in 2010 to 17.8 million in 2050. The study also
found that newer therapies have the potential to reduce AMD-related
visual impairment and blindness by as much as 35%.
According to the authors, the use of antioxidant
vitamins - specifically those used in the Age-Related
Eye Disease Study (AREDS) - is a key preventive strategy in
slowing the progression of AMD from early to late stages. The
authors point out that AREDS
formulas are not widely used among patients with early-stage disease,
and suggest that public prevention efforts should focus on expanding
the use of antioxidant vitamins in people with early AMD, and
making sure those people are getting the correct vitamin doses.
So for those who have been diagnosed with
AMD, a first step is to talk with your eye care professional about
high dose antioxidants, and to be consistent with supplementation
when it is recommended.
Genetic Risk Factors May Be Critical
It's now understood that those with a family
history of AMD have a greater risk of getting the disease. Scientists
have identified a number of genes that seem to make some people
more susceptible to AMD by creating inflammation or increasing
oxidative damage (2). Adopting good
dietary and lifestyle habits early may help prolong health and
save eyesight later in life, especially for susceptible individuals.
Food Combinations Reduce AMD Risk
Foods provide many nutrients that may work
together to help counter AMD from developing. Researchers from
Tufts University developed a scoring system to examine the combined
effect of nutrients, and applied this to the diets of people in
trial. Those whose diets were high in protective nutrients and
low-GI (glycemic index) foods had a much lower risk of getting
early and advanced AMD (3).
A food's GI value is based on how fast its carbohydrates raise
the body's blood sugar levels; low GI foods like whole grains
have less impact on blood sugar fluctuations.
Protective foods included good sources of
trial nutrients: vitamin
E and zinc,
as well as the nutrients being tested in AREDS 2: the omega-3s
from fish oil - DHA
(Another antioxidant included in the original AREDS
clinical trial, beta-carotene,
did not affect AMD risk levels).
Putting it All Together: Preventive Actions
Red Wine and Heart Health
The potential health benefits of wine received
wide- spread attention in 1991, when 60 minutes reported on the
"French Paradox" - an observation that the French enjoy one of
the lowest heart attack rates, despite their penchant for eating
lots of saturated fats. While more recent statistics suggest that
heart disease in France may have been underestimated in those
years, support for alcohol and red wine's apparent heart-healthy
role has grown. We're also learning more about how the individual
components in wine may contribute to its overall effects.
The Rise of Polyphenols and Resveratrol
The most abundant antioxidants in our diets
aren't the ones we're most familiar with, according to Dutch researchers
(1). The most plentiful are compounds called polyphenols.
About 6000 different flavonoid polyphenols are known, and we may
consume as much as a gram of them daily. In contrast, intake of
combined often amounts to less than 100 mg a day. It is increasingly
clear that polyphenols are major contributors to the antioxidant
actions of fruits and vegetables.
Wine contains an array of polyphenols, including
flavonoids, primarily from the skins of the grapes (which are
removed in making white wine). Studies generally show a positive
link between dietary flavonoid intake and good health overall,
and with cardiovascular health especially (2).
A recently published study (3)
suggests that enjoying a glass of wine with fish (both featured
in the Mediterranean diet) might maximize omega-3s
and explain one way that wine reduces heart disease risk. Moderate
wine consumption - 1 glass a day for women, 2 daily for men -
was found to boost levels of omega-3 in cell membranes. Because
wine had a stronger link with omega-3s
than other alcoholic drinks, the scientists think that the polyphenols
are key, possibly protecting EPA and DHA from oxidation or stimulating
the body to produce more of them.
Trans-resveratrol is another intriguing polyphenol
found in grape skins, red wines, and grape juice. In plants, resveratrol
acts like an antibiotic, defending the grapevine from disease.
Investigators are interested in resveratrol's antioxidant and
other properties, as evidenced by its reference in over 2,000
research citations in the National Library of Medicine, including
studies at the National Cancer Institute and the National Institute
of Aging. One theory holds that polyphenols like resveratrol can
help protect the aging brain (4).
Another hypothesis is that resveratrol could influence the aging
process itself and lead to longer life. Both of these theories
need to be confirmed.
Studies have shown that restricting calories
increases the lifespan of various animals. It's not clear whether
this might hold true in humans where longevity is determined by
complex mechanisms, but interest in resveratrol surged when it
was found to trigger effects in animals like those prompted by
calorie restriction (5).
The Growing Promise of Pomegranates
Pomegranate juice is also chocked full of
polyphenols with the capacity to mop up free radicals and interfere
with chronic inflammation. This juice, in fact, contains more
polyphenols than blueberries, cranberries, green tea, orange juice
or even red wine.
Most of the clinical studies exploring the
effects of pomegranate juice have been small, but with promising
results that warrant further investigation (6,7).
Drinking about 2 ounces daily for a year has been shown to reduce
the intimal-media thickness of the carotid artery - a measurement
of artery walls that's used to track the progression of atherosclerotic
disease. In another study, daily intake of about 8 ounces is reported
to decrease stress-induced ischemia in patients with heart disease
compared to a placebo. It may be that pomegranate polyphenols
help protect blood vessels or influence inflammation in artery
Latest Findings are Encouraging
Four new studies reinforce previous findings
for some essential nutrients, while suggesting potential new benefits
for others. Calcium, vitamin
D and three of the B-vitamins
are featured in a quartet of studies published in the Archives
of Internal Medicine.
The Calcium and Cancer Connection
Some previous population-health studies have
found a link between calcium intake and cancer, but the evidence
has been inconsistent. The calcium-cancer relationship appears
to be affirmed in the large National Institutes of Health AARP
Diet and Health Study which followed nearly 294,000 men and 199,000
women aged 50-71 for seven years (1).
Women consuming up to 1,300 mg of calcium
daily from foods and supplements had a decreased risk of any type
of cancer. A 23% lower risk for digestive types of cancer, particularly
colorectal cancer, was seen for those women in the top 20% of
calcium intake compared to those consuming the least. The highest
consumers among men also had a 16% lower risk of cancer in the
digestive cancer category.
Higher Vitamin D for Fewer Broken Bones
Though calcium may prove important in cancer
prevention, the results of another study suggest that calcium
may play second fiddle to higher levels of vitamin
D when it comes to protecting bones. Harvard researchers
performed a meta-analysis (review) of 12 clinical trials involving
D supplements in over 42,000 adults aged 65 or older
(2). They found that supplemental
D was associated with a 14% decrease in the risk of
non-vertebral fractures and a 9% decrease in the risk of hip fractures.
More importantly, when they looked at 9 of the studies using doses
over 400 IU per day, the supplements were associated with a 20%
and 18% reduction in non-vertebral and hip fractures, respectively.
The researchers noted that while calcium was protective, the mineral
did not have an additional effect in individuals taking high doses
Risk of Colds Influenced by Vitamin D?
D deficiency has resurfaced in recent years, resulting
in diseases such as rickets in children. Vitamin
D research has also exploded, with better blood levels
D now linked to lower incidences of cancer, multiple
sclerosis and heart disease. Another line of inquiry under hot
pursuit is vitamin
D's role in the immune system.
In an analysis of the 3rd National Health
and Nutrition Examination Survey (3),
researchers found that people with low blood levels of this vitamin
were more likely to have an upper respiratory tract infection
(URTI) which can include colds, sinusitis, pharyngitis and flu.
Compared to people with higher vitamin
D blood levels (30 ng/mL or more), those with lower
values (under 10 ng/mL) were 36% more likely to have had a recent
URTI. People with intermediate values (10-29 ng/mL) had 24% higher
odds. Whether getting more vitamin
D will actually help prevent URTIs needs to be confirmed
in controlled trials.
B-Vitamins Lower AMD Risk in Women
Previous studies have suggested an association
between age-related macular degeneration (AMD) and elevated blood
levels of homocysteine - a compound that can be lowered by folic
To determine whether B-vitamins
might help prevent AMD, about 5,400 female health professionals
who already had, or were at high risk for, heart disease were
given very high doses of these 3 B's or a placebo (4).
After more than 7 years of follow-up, the
women assigned to the supplemental B-vitamin group lowered their
risk of developing any AMD by 34%. The risk for visually significant
AMD was reduced by a solid 41%. These findings are exciting, and
the next step is to test whether lower, more reasonable levels
of the B's are just as effective when supplemented over time.
Diet & Antioxidants 'Eyed' for Cataract
A cataract is a clouding of the eye's lens that
eventually interferes with vision, and requires surgical removal for vision to
be restored. Age, genetics and the environment - as well as injury, trauma and
medications such as corticosteroids - are all factors that may contribute to
cataract development, a common condition in people over age 65. Results from
recent studies suggest that your intake of antioxidant nutrients, as well as the
type of carbohydrates that you eat, may also play a role.
Antioxidants Reduce Cataract Risk over Time
Antioxidants may help prevent age-related cataracts,
according to a new study published in the American Journal of Clinical Nutrition
The Blue Mountains Eye Study included 3,654 people over
48 years old. Initially, each participant had an eye exam and their dietary
intake and antioxidant supplement use including
zinc; and vitamins
E was assessed.
People with the highest
vitamin C intake from diet and supplements had a significantly reduced
cataract risk after 10 years compared with those consuming less.
Those with above-average intakes of combined
antioxidants, including vitamins
zinc, also had a reduced cataract risk compared with those consuming fewer
The authors point out that the study participants overall
ate lots of fruits and vegetables and had "fairly healthy diet habits." Around
1/3 of the people were taking vitamin supplements at the baseline exam, with a
vitamin C intake of 500 mg among supplement users."
Lutein and Zeaxanthin are Important Too
Results of a prospective study from Harvard Medical
School add to the body of evidence suggesting that
vitamin E may also help delay cataract formation (2).
zeaxanthin are present in the human lens, where they filter out harmful blue
light. In this study, dietary intake was assessed in over 35,000 women health
professionals who were free of cataract. Information was gathered on the women's
antioxidant intake from food and supplements, and they were followed for about
10 yrs. Women with the highest daily intake of
zeaxanthin (6.7 mg, on average), cut their risk of developing cataract by
18% compared to those eating the least (about 1.2 mg a day).
vitamin E, a 14% risk reduction was noted in the group with the highest
intake overall. Those in the highest group consumed a mean of about 260 IU daily
from food and supplements, while those in the lowest group got an average of 4-5
IU a day.
Make Your Carbohydrates the Complex Type
The glycemic index (GI) is a measure of how quickly
carbohydrates raise blood sugar levels. In general, complex carbs like whole
grains, brown rice and cereals raise blood sugar levels more slowly than sugary
and processed foods like white breads. Several studies indicate that high GI
diets raise the risk for early AMD, and that low GI patterns might be protective
for nuclear cataracts, the most common cataract type (3,4).
Researchers from Tufts think that eating too many of the
"fast" carbs can cause 'double trouble'. First, proteins that are directly
needed for the visual function of the lens and retina may be damaged. Secondly,
this eating pattern may also cause indirect damage by compromising pathways that
usually identify and remove those damaged proteins.
The take-home message from all of this research is to
make your diet high in antioxidant-rich produce and to eat sugary and processed
Scientists Examine Lutein's Effect on Glare
New research indicates that the carotenoids
zeaxanthin may help our vision when we
have difficulty seeing due to the glare encountered in very bright light
These two carotenoids have been shown to slow down
the progression of moderate to advanced age-related macular degeneration) in
the AREDS trial. But in this new study,
zeaxanthin appear to improve visual
function even in healthy people with normal vision.
Researchers from the University of Georgia recruited
40 healthy young people (average age of about 24 years), and examined their
reaction to glare. Glare is commonly encountered in bright sunlight, when
staring at a computer monitor, and when facing the bright beams of oncoming
The investigators determined lutein and
zeaxanthin's effects on glare by
studying how the carotenoids affected macular pigment density. The eye's
macula is made up of lutein and
zeaxanthin, which help filter out
certain damaging light waves. When the concentration of these carotenoids in
the macula is higher, the macula is better able to absorb these light waves.
Taking lutein and
zeaxanthin increased the density of
macular pigment significantly after six months of supplementation.
When the study volunteers performed visual tasks
following exposure to glare, lutein and
zeaxanthin supplements significantly
reduced the damaging effects of the exposure for both of the visual
performance tasks that were measured.
Improved Visual Performance under Glare
The researchers concluded, "Four to six months of 12
mg daily lutein plus
zeaxanthin supplementation significantly
increases macular pigment density and improves visual performance in glare
for most subjects."
How can we achieve the level of
zeaxanthin tested in this study? By
consuming good sources of these carotenoids such as leafy green vegetables,
corn, egg yolks, squash, broccoli and peas, and augmenting those foods with
daily supplementation of lutein and
Vitamin D Status Linked to Artery Health
Increased levels of
vitamin D may improve cardiovascular health and reduce the prevalence of
peripheral arterial disease, or "PAD", suggests a new study
(2). People who suffer from PAD often
experience decreased blood flow in their legs. PAD occurs when arteries in
the legs become narrowed or clogged with fatty deposits. According to 2008
statistics from the American Heart Association, PAD affects about 8 million
Americans and is associated with significant disease and death.
In the new study, researchers looked at over 4,800
participants of the National Health and Nutrition Examination Survey
(NHANES). They found that people with higher blood levels of
vitamin D were far less likely to have
Blood samples from the NHANES participants were
divided into 4 groups according to the concentration of
vitamin D in the samples. The
investigators found that the higher the level of
vitamin D, the lower the risk for this
artery disease. In fact, PAD was 64% more common in the group with the
lowest compared with the highest blood levels of the vitamin.
How Might Vitamin D Lower Risk for PAD?
According to the study's lead author,
vitamin D might directly affect blood
vessels. We know that in laboratory animals
vitamin D regulates one of the hormone systems that effects blood
pressure. It may affect this same hormone system in humans too. The authors
also point out that the study does not prove that increased levels of
vitamin D protect against PAD directly.
However, they called for large randomized clinical trials to test whether
vitamin D supplementation offers
protection against PAD.
Consistent 'Multi' Use Has Multi-Benefits
A number of recent studies add to the body of
evidence that taking a multiple vitamin and mineral supplement daily is an
important and healthful habit.
In the first study, U.S. Department of Agriculture
researchers confirm that diet alone cannot ensure that people 50 and older
meet their vitamin and mineral needs (1). The
investigators found that less than 1/2 of the 4,384 adults studied took
supplements daily. Those who did met recommended levels for most nutrients
including vitamins A and
B-vitamins, zinc and iron. In
contrast, many non-users had low intakes for a variety of nutrients.
Multi Users May Lower Their Cataract Risk
A number of studies have reported a lower occurrence
of cataract in regular users of multi-vitamin and mineral supplements. Even
though the high dose antioxidants tested in the cataract portion of the
Age-Related Eye Disease Study (AREDS)
failed to show a benefit, a recent analysis of this trial shows that multis
may delay cataract progression (2).
In addition to getting a placebo or high dose
antioxidants, 2/3 of AREDS participants
elected to take a multi vitamin and mineral supplement containing RDA-level
potencies that was offered to everyone. After accounting for factors that
might bias the results, the researchers found that multi users had a 16%
lower risk of developing any type of cataract, or of cataract progressing.
For the most common type of age-related cataract, nuclear cataract, a 25%
risk reduction was seen. The risk reduction for cortical cataract was
similar, though it didn't reach statistical significance.
Multis May Help Reduce Hunger in Dieters
Preliminary findings also suggest that multi-vitamins
and minerals could reduce the appetite of women on weight-loss programs
(3). In this study, 45 overweight people were put on a
calorie-restricted diet and assigned to take a multi or placebo. Both groups
lost weight at the end of 15 weeks, but women who took the supplements had
reduced hunger ratings. The investigators point out that many vitamins and
minerals are involved in producing hormones and neurotransmitters that
regulate food intake and control appetite. However, more research in this
area is needed to confirm and understand these findings.
Multis May Uplift Mood in Older Individuals
A daily multi could improve the mental health of
hospitalized elderly patients, according to a study from the University of
Sheffield. Researchers recruited 225 hospitalized patients and randomly
assigned them to receive a normal hospital diet plus a multi or placebo for
a 6-week period.
The research team assessed depression by
administering a standardized questionnaire, and found that those taking the
multi had significantly better outlooks compared to non-users at the end of
the study. The benefit was seen regardless of the patients' initial level of
depression - ranging from no depression to severe. The authors attributed
the beneficial effect of the multi primarily to its
folic acid components. Levels of both vitamins increased in the
multi-takers, but declined in the placebo group. Both of these nutrients are
important for the nervous system, and deficiencies of them are common even
among relatively healthy older people.
Choose a Comprehensive Multi with "Phytos"
These studies demonstrate that good intake of many
vitamins and minerals can support visual and mental health, and possibly aid
weight loss efforts. But beyond essential vitamins and minerals, mounting
evidence suggests that our consumption of "phyto" or plant nutrients is also
important. When choosing a multi, look for one that provides meaningful
contributions of such key phytonutrients as
lycopene, lutein, and the compounds
in green tea, ginkgo and berries.
More Vitamin D = Better Public Health
From a nutritionist's point of view, 2007 should be
declared the Year of
Vitamin D. Over the past year alone, there have been three major conferences
on this topic and a multitude of research papers published. Now, a consensus
among experts is emerging: We're not getting enough of this nutrient for optimal
What Does the Research Tell Us?
Many studies have linked higher intakes or blood levels
vitamin D with a lower risk of cancer. The evidence shows a protective
effect against colon cancer, and suggests that
vitamin D may also help reduce cancers of the breast and prostate.
Vitamin D has been found to help prevent falls and preserve bone density in
older people. In addition, researchers are exploring the role of
vitamin D in such diverse conditions as MS and macular degeneration.
One recent and skillfully done study
(1) looked at 18 clinical trials of
vitamin D, each of which reported results for total mortality - an accurate
measurement of poor health effects. "The results were remarkable" wrote
Harvard's Dr. Edward Giovannucci in an accompanying editorial. Those who
vitamin D in these studies had a significant 7% reduction in death from any
cause. Importantly, no "negative surprises" were seen from the doses given,
which ranged from 300-2000 IU
vitamin D daily.
More compelling evidence comes from a recent trial that
supplemented postmenopausal women with 1,100 IU
vitamin D plus calcium or calcium alone for 4 years
(2). Women who received
vitamin D had significantly fewer cancers of all types.
How Much Vitamin D Is Needed?
Experts from Tufts and Harvard put their heads together
to tackle this question. They examined studies which looked at dental health,
risk of falls, fractures and colon cancer, and that also reported blood levels
vitamin D. It was clear that blood levels associated with beneficial health
outcomes began at 75 nmol/L. Calculations showed that at least 1000 IU
vitamin D daily is needed to bring half the population into that healthy
range (3). These findings led to a safety
vitamin D (4), and eventually to
vitamin D experts urging that the RDA be raised (5).
The "D" Dilemma: How Do We Get More?
Getting enough of this important vitamin can be
challenging since very few foods contain significant amounts. The best sources
are fatty fish such as mackerel, salmon, sardines and tuna, as well as fortified
milk, which contains about 100 IU per glass. Diet alone, however, can't provide
the amounts that researchers suggest we need to achieve.
vitamin D is produced when skin is exposed to sunlight, specifically
ultraviolet B radiation (UVB), most people follow advice to apply UVB blocking
sunscreen when outdoors. Making sufficient levels of the "sunshine vitamin" is
even more difficult for Afro-Americans who need longer sun exposure to produce
the same amount of "D"
generated within lighter skin.
In fact the American Academy of Dermatology is concerned
that reports about
vitamin D's health benefits could lead to higher rates of skin cancer.
People should avoid unprotected sun exposure, and take a multivitamin or drink a
few glasses of
vitamin D fortified milk every day, according to the Academy. But there's
one glaring problem with that advice.
Sound Supplementation Can Bridge the Gap
"The amount of
vitamin D in supplements isn't nearly enough," states Creighton University's
Dr. Robert Heaney who has conducted nearly 2 decades of research on vitamin D.
The response of a forward-thinking, responsible
supplement company might be to provide 800-1000 IU in supplements for adults.
Along with a healthy diet and lifestyle that includes fish, whole foods, low-fat
dairy, and regular exercise, supplementation based on good science can help
improve public health.
Enter the Diverse World of Flavonoids
polyphenols, are a class of compounds present in a wide array of vegetables,
fruits, beverages such as tea and red wine, and some members are found in beans
and whole grains. The health effects of
flavonoids have been intensively investigated over the last 10 years, and
nutrition scientists urge us to consume more of them.
It has been proposed that
flavonoids help protect against damage in blood vessels, thus decreasing the
risk of cardiovascular diseases. In addition, they may have a role in cancer
prevention, in enhancement of the immune system, and even in eye health. While
they act as antioxidants, many flavonoids
work in diverse ways to influence cellular functions. Actually,
flavonoids represent thousands of compounds
that have been categorized into subclasses-often with funny-sounding, complex
names. But our goal is simple: Eat a wide variety of foods that are rich in
flavonoid family members:
Past issues of Staying Healthy newsletter have reported
research findings on flavonoids such as green tea catechins and brain function (April,
2006) or the anti-aging effects of blueberry anthocyanins (February,
2002). Recent studies also illustrate how the potential health effects of
flavonoids are as diverse as the compounds that make up this healthful class of
Flavonoids, Lignans and Breast Health
Results of the Long Island Breast Cancer Study project
suggest that higher consumption of some
flavonoids may decrease the risk of this disease (1).
Comparing data from 1,434 breast cancer patients with 1,440 women without the
disease revealed that the risk for developing breast cancer was reduced for
those with the highest vs. the lowest total
flavonoid intake. Risk was about 45% lower among post-menopausal women,
though no benefit was seen for younger women. Specific
flavonoids - including flavones, flavonols
and lignans - were associated with risk reductions ranging from 26 to 39%, while
the flavanones, soy isoflavones and anthocyanins, showed no relationship.
"These results are consistent with other studies
conducted among Mediterranean women," according to the lead investigator. "Few
epidemiologic studies have examined whether there is a relationship between
breast cancer and dietary flavonoids. Our study proposes that dietary flavonoids
can help American post-menopausal women reduce their risk of breast cancer,
though further research is needed."
Quercetin and Eye Health
Evidence suggests that chronic oxidative stress may
damage retinal pigment epithelial (RPE) cells, making them more susceptible to
developing age-related macular degeneration. In a recent study, all 6 classes of flavonoids were tested to see if they could
protect cultured human RPE cells (2). Quercetin,
fisetin, luteolin and EGCG were especially effective. These promising results
now need to be confirmed in clinical trials.
The CAREDS Study
A number of studies have looked at the relationship
between dietary lutein and zeaxanthin intake and the risk for age-related
macular degeneration (AMD). Many - though not all - of the findings from these
population health studies suggest that eating more lutein-rich foods is
The authors of the Carotenoids in Age-Related Eye Disease
Study (CAREDS) now report that a stable intake of these nutrients over time
could reduce the risk of AMD by 43% in healthy women under 75.
CAREDS, an off shoot of the Women's Health Initiative
(WHI), looked at over 1780 women aged 50-79 who had either high or low intake of
lutein plus zeaxanthin when they entered the WHI study. These women were later
asked to participate in CAREDS, and researchers determined which of them had
developed AMD using special photographic techniques.
Regular Lutein Intake Supports Visual Health
Women with higher intakes of lutein plus zeaxanthin (at
least about 3 milligrams or more daily) had a substantial 43% lower risk for
intermediate AMD compared to those eating about ¾ of a milligram or less every
day. This protective effect was seen in women 75 years and younger who had
stable intakes of these nutrients.
Safely Achieving a Lutein-Rich Diet
If a higher and consistent intake of lutein and
zeaxanthin is important, how do we go about achieving it?
A commonly eaten, concentrated source of lutein is green
leafy vegetables such as spinach. Some people are leery of eating
fresh spinach because of the recent contamination of certain fresh
spinach brands with the illness-causing, bad bug E. coli 0157:H7.
Information about the brands and batches that were recalled can
be found at the Center for Food Safety and Applied Nutrition (CFSAN)
According to CFSAN, no frozen or canned spinach was
implicated in this most recent outbreak.
Should an E. coli 157:H7- related outbreak occur in the
future, CFSAN indicates that cooking fresh spinach at 160 degrees Fahrenheit for
at least 15 seconds will kill any E. coli O157:H7 present.
Eat a Variety of Lutein-Containing Foods
While terrific, spinach isn't the only source of lutein
and zeaxanthin. These nutrients can also be obtained from eating corn, broccoli,
peas, squash and other green leafy vegetables like kale, collards and mustard
greens. Consuming a wide variety of produce is healthful overall, and the CFSAN
website offers a handy booklet of general safety tips for storing and preparing
fresh produce and juices called Safe Handling.
Eggs yolks are another excellent source. Though they
contain considerably less of these nutrients than spinach, the lutein and
zeaxanthin they do contain is very well absorbed according to several recent
studies. The good bioavailability is likely due to the fats found in egg yolk.
Lutein and zeaxanthin are fat-soluble, so absorption is enhanced when fat is
present. While eggs contain 213 mg of cholesterol - and the recommended intake
of dietary cholesterol is 300 mg. daily - eggs can fit into the daily
cholesterol budget several times weekly if you limit cholesterol from other
sources such as meats, poultry and dairy products.
Lutein Supplements Can Also Play a Role
While the ideal intake of lutein has not been pinned
down, we do know that the typical American intake of 1-2 mg daily from foods
falls short of the 3-7 mg daily that studies suggest may be beneficial.
Supplements of lutein and zeaxanthin can also be of help in closing this dietary
gap and ensuring regular intake.
Moeller SM et al. Age-Related Macular Degeneration
and Lutein and Zeaxanthin in the Carotenoids in Age-Related Eye Disease Study
(CAREDS). Archives of Ophthalmology 124:1151-1162, 2006.
Vitamin C Helps Lutein
Higher intakes of lutein have been linked to a lower risk of
developing age-related macular degeneration. Since the levels of
lutein associated with eye health are much
higher than the amounts we typically get from our diet, many people now take
lutein supplements to close that dietary
gap. Results from a recent study suggest that it may be better to take
supplements of lutein along with
vitamin C (1).
To learn whether other
antioxidants affect the absorption of lutein
from supplements, researchers from the University of Wisconsin gave young
healthy men and women supplements of lutein
alone, or combined with vitamins C or
E. Whether given alone or with one of the
vitamins, absorption of lutein varied
greatly among individuals. However lutein
was absorbed significantly faster when given simultaneously with
Calcium Works Against
In 1999, Dartmouth Medical
School researchers reported that participants in the Calcium Polyp Prevention
Study who took calcium supplements lowered their risk of all colorectal cancers
by 20%. In that study, 930 adults took either 1200 mg. of supplemental calcium
or a placebo over a four-year period. Just recently, the researchers updated
their findings on the 822 study participants who continued to be monitored.
More than five years after
the original study concluded, the benefits from calcium were even greater than
during the treatment phase, with a 41% drop in the risk of polyps and a 35% fall
in the risk of all colorectal cancers. The protective effect persisted for up to
five years after the group stopped taking supplements, though it didn't last
beyond five years. According to lead investigator, there appears to be a delayed
and pronounced effect of calcium in suppressing new polyp or tumor formation.
Even though the benefits
of calcium seem to be long-lasting for the colon, other studies have reported
that gains in bone density from calcium are lost a year or two after stopping
supplementation. So remember to take calcium supplements daily for consistent
benefits to bone as well as colon health. Taking
vitamin D along with calcium is the best bet, since
vitamin D also works against colon cancer
Vitamin D Recommendations Could Be Too Low
We become less able to
absorb vitamin D as we grow older
(4). Older individuals also get less of this vitamin from foods and
become less efficient at making their own
vitamin D from sunlight exposure. These age-related effects led the
Institute of Medicine to increase the RDA for
vitamin D to 600 IU for elderly people several years ago. Now a new review
suggests that even 600 IU may be too low for that age group
The review included 12
double blind trials of vitamin D with and
without calcium to determine the effectiveness of the vitamin in preventing
fractures of the hip and other bones in older persons. No significant effect of
400 IU vitamin D was seen in the analysis,
while 700-800 IU vitamin D daily was found
to reduce the risk of hip fracture by 26% in older individuals. It appears that
those 60 years and older should aim for at least 700 IU
vitamin D daily.
Vitamin B12 Basics
Vitamin B12 is the largest and most complex
of all the vitamins. It is also unique among vitamins because it is the only one
that contains a metal - cobalt - as part of its structure. For this reason
cobalamin is the term used to refer to compounds having
B12 activity. The type of cobalamin used in
most dietary supplements, cyanocobalamin, is readily converted to active forms
of vitamin B12 in the body.
B12 is needed to help maintain healthy nerve
and red blood cells, and to make DNA, the genetic material in all cells.
Another unusual feature of
this vitamin is the multi-step process required for its absorption.
Vitamin B12 is bound to the protein in food.
Hydrochloric acid in the stomach is needed to release
B12 from its protein bonds during digestion.
Once released, B12 must combine with a
substance called gastric intrinsic factor, which is secreted by specialized
stomach cells. This B12-intrinsic factor
complex can then be absorbed by the intestinal tract with the help of calcium.
Who Is at Risk for
Vitamin B12 Shortfalls?
B12 deficiency can occur as a result of an
inability to absorb B12 from food. Most
people are familiar with the autoimmune condition pernicious anemia, which
results from an inability of stomach cells to secrete intrinsic factor. People
with this condition usually receive B12 by
injection and large oral doses. Aside from pernicious anemia, older people in
general can have difficulty absorbing B12
due to lower levels of stomach acid. Sometimes the only symptom of this limited
absorption is subtly reduced mental function resulting from early
B12 deficiency. Anemia, dementia or nerve
problems may follow.
Up to 40% of older adults
may have atrophic gastritis, an overgrowth of intestinal flora, and be unable to
normally absorb vitamin B12 in food.
Atrophic gastritis, an inflammation of the stomach, not only decreases gastric
acid secretion but can also result in overgrowth of normal bacterial flora in
the small intestines. The bacteria may take up
vitamin B12 for their own use, further contributing to
B12 deficiency. Older individuals with
atrophic gastritis are, however, able to absorb the
B12 added to fortified foods and
supplements, and these may be the best sources of
vitamin B12 for people over 50.
Strict vegetarians and
vegans are another group at risk for developing
B12 deficiency because natural sources of
vitamin B12 are limited to animal foods such as meat, poultry, fish, eggs
and dairy. Fortified cereals are one of the few non-animal sources of
B12. The use of certain medications such as
the diabetic drug Metformin, can also interfere with
B12, Brain Function and
Researchers have long been
intrigued by the connection between vitamin B12
deficiency and dementia. One review examined the relationships between cognitive
skills, homocysteine levels, and blood levels of folate,
B12 and B6.
The authors suggest that vitamin B12
deficiency may decrease levels of substances needed for the metabolism of
neurotransmitters, the chemicals that transmit nerve signals
(1). Reduced levels of neurotransmitters may result in cognitive
Another area rapidly
gaining attention is the observed link between
B12 and osteoporosis. B12 has been
associated with bone cell activity and bone formation. Recently, researchers
from Tufts measured bone mineral density (BMD) and
B12 levels in more than 2,500 men and women
participating in the Framingham Osteoporosis Study (2).
They found that those with low B12 had
significantly lower average BMD, a measure of bone quality used to assess
fracture risk. These results follow two earlier studies, which reported similar
findings in women (3,4). The Tufts authors conclude that low
B12 may be a risk factor for osteoporosis -
one that could be remedied by consuming more B12
from supplements and fortified foods.
Taurine: A Unique Amino
Amino acids, when strung
together, make up the proteins found in our diet. The bonds connecting these
building blocks of protein are broken during digestion, releasing amino acids
for absorption. Once absorbed, the amino acids can be re-assembled to form
proteins of different shapes, sizes and properties that the body needs to repair
tissue, form muscle, manufacture enzymes, produce immune cells and perform a
host of other functions.
A few amino acids are also
manufactured within the body in addition to being provided by the protein foods
we consume. Taurine is one example. This amino acid occurs naturally in foods
such as seafood, meats, poultry and eggs - although it can also be synthesized
internally from two sulfur-containing amino acids, methionine and cysteine, in
the presence of
vitamin B6. Unlike most proteins, however, taurine is not incorporated into
proteins or enzymes but is found as a free amino acid in body tissues. The
chemical structure of taurine is also unique, making it well-suited to perform
its physiologic functions.
Taurine "Wears Many
Hats" in the Body
Taurine's role in the body
is diverse: from working with bile acids to help digest and absorb fats, to its
involvement in regulating water balance by helping to transport magnesium and
potassium into cells. Taurine is found throughout the body, but is concentrated
in muscle, where it is thought to help regulate heart beat and muscle
contraction. Taurine has antioxidant activity, and is gaining attention for its
potential clinical use in ischemia-reperfusion injury - the free radical damage
that can occur when blood flow is restored to oxygen deprived tissue, such as
after heart valve or coronary artery bypass surgeries. Researchers are also
investigating taurine's involvement in mediating the inflammatory response.
Because taurine is needed
for the development of retinal and nervous tissue, dietary sources are important
for premature and newborn infants who can't manufacture sufficient amounts on
their own and obtain taurine through breast milk. For those with chronic kidney,
liver or heart failure, taurine is often considered a "conditionally essential"
amino acid, which means that under certain conditions, diseases or injury, the
body may not be able to make enough taurine to meet demands.
The Role of Taurine in
Taurine plays a role in
the visual system of adults: it interacts with
zinc to stabilize membranes and helps make photoreceptors (rods) in the
retina, resistant to injury. Some also postulate a role for antioxidant taurine
in helping to maintain clarity of the eye's lens, though this remains
In addition to taurine's
function in the adult eye, new research has shed some light on how this amino
acid helps to initially develop rod photoreceptors - the specialized
light-gathering cells that line the retina. In the early 1990s, it was found
that adding taurine to immature retinal cells could get more of them to turn
into rods. Yet it was unclear what was making the cells susceptible to taurine's
instructions. New findings from Harvard suggest that taurine works its
transforming effects through neurotransmitter receptors, with similar findings
reported by UC San Francisco researchers. According to the Harvard team, this
discovery provides information that someday could lead to new methods of
restoring or replacing these delicate cells, which are lost in various retinal
diseases and decline with age.
Immunity and Nutrition
in Older Individuals
respiratory infections, are common in older individuals. Infections can
interfere with daily activities, prolong recovery time from illnesses and result
in more frequent complications. Contributing to that greater susceptibility to
respiratory infections is the decline in immune response that occurs as we grow
older. Good nutrition plays an important role in keeping the immune system
functioning efficiently, especially getting adequate amounts of protein and a
variety of nutrients such as
zinc and vitamins
While we've long known
that various nutrients are needed for proper immune performance - and that
deficiencies of them can lower disease resistance - researchers only began in
the late '80's and '90's to ask whether supplemental amounts might improve
immune function in the elderly. Results from the long-term placebo-controlled
studies that were conducted showed that giving a complete multi-nutrient to
healthy, even well nourished, older people could boost immune function, although
it wasn't clear whether those improvements always translated into meaningful
disease-fighting effects (1).
In 1997, Dr. Simin Meydani
and her team of researchers from Tufts University reported in the Journal of the
Medical Association (JAMA) that
vitamin E could enhance immunity (2). In that
study, older subjects taking
vitamin E supplements in doses of 60, 200 and 800 IU said they experienced
fewer respiratory infections - about a 30% reduction compared to placebo takers.
Subjects taking the 200 IU
vitamin E levels showed the greatest response in immune function.
Vitamin E Protects
Against Colds in "Real Life" Situations
To test whether those
findings would hold up, Meydani and her colleagues enrolled over 600 people who
were at least 65 years old and living in nursing homes. Residents of long-term
care facilities are more prone to infections than elderly who live
independently. All of the study volunteers received a multi-nutrient supplement,
while half of them took an additional 200 IU
vitamin E and the other half a placebo for a one-year period. The results
were reported in the August issue of JAMA (3).
After controlling for
other factors that could influence immunity, the researchers found that the
vitamin E group had significantly fewer colds, and less of them acquired 1
or more upper respiratory tract infections (mostly colds) during the study
period. In contrast,
vitamin E did not appear to significantly impact the overall incidence of
different upper and lower respiratory tract infections combined (influenza,
pneumonia, acute bronchitis, sinusitis and others). However, the number of
episodes of these infections was low in both groups, and the authors also point
out that the use of multi-nutrient supplements by all participants could have
blunted the impact of
The protective effect of
vitamin E against colds is noteworthy for a number of reasons. First, colds
were the most common upper respiratory infection encountered in this study.
Colds are also frequently seen in the elderly population as a whole, and often
lead to increased disease in this age group. Finally, combating the common cold
among nursing home patients is particularly important because the number of
elderly residing in long-term care facilities has increased and is expected to
grow steadily in the coming years.
New Study Shows Lutein
Improves Eyesight for AMD Patients
Lutein Antioxidant Supplement Trial (LAST) is the first study to report
actual improvement in key visual functions among patients who already have "dry"
age-related macular degeneration (AMD), the most common form of this disease.
Prior to the publication of LAST in April (1),
studies had linked greater consumption of
lutein solely to a lower risk of AMD in healthy people.
This double-blind, year
long study looked at the effects of 10 mg of
lutein alone or combined with other antioxidants, on a number of visual
measures in 90 patients with atrophic AMD. The amount of
lutein supplemented in LAST is equivalent to eating about 3-4 ounces of
spinach each day. While
lutein is concentrated in dark green leafy vegetables such as spinach,
collards and kale, the U.S. intake is estimated to be only 1-2 mg daily.
Compared to those getting
a placebo, the lutein/antioxidant supplemented group experienced
a 50% increase in macular pigment density, indicating an improved
ability to filter out damaging UV light. Patients taking
lutein or the combination showed improvement in quality of vision
(measured by contrast sensitivity) and glare recovery, a test of
macular function. They were also better able to distinguish near
object details and shape (near visual acuity). According to lead
author Dr. Stuart Richer, patients taking
lutein were able to see the equivalent of one line more on standard
eye tests at the end of the year, while those receiving placebo
continued to decline-- a clinically meaningful finding for those
trying to preserve their vision.
Vitamin C Fights
Inflammation-Risk Factor for Heart Attack
A second study published
in April is also a "first" of its kind--the first to report that
vitamin C can lower C-reactive protein (CRP). CRP is a biomarker for
inflammation that has garnered increasing attention as a new way to identify
those at risk for heart attack (2). It's now
understood that chronic inflammation can lead to heart attack and stroke by
making cholesterol-laden artery plaque less stable and more likely to rupture
(See newsletter issues for
CRP levels can rise up to
a 100 fold for short periods during illness, because inflammation occurs as part
of the body's normal defense against infection. However a persistent, moderately
elevated level of CRP in the blood reflects chronic inflammation, and has been
linked to increased risk of heart disease, diabetes, Alzheimer's disease, and
even age-related macular degeneration.
In this double-blind
study, researchers at University of California at Berkeley tested 160 healthy
adults who either smoked or were exposed to second hand smoke. Those who had
greatly elevated CRP likely due to existing illness were excluded from the
study. The remaining participants were assigned to receive placebo, 500 mg of
vitamin C, or a mixture of antioxidants (C, E and alpha-lipoic acid). Plasma
levels of CRP in the volunteers were measured before and at the end of the two
Levels of CRP decreased a
significant 24% among those supplementing with
vitamin C compared to placebo takers. CRP levels also declined for those
taking the antioxidant mixture, but not as much as
vitamin C group. The researchers noted that much higher levels of
vitamin E than were utilized in this study have previously been reported to
lower CRP in diabetics and healthy individuals (3).
These same investigators will be conducting a second trial in an attempt to
replicate these findings. According to lead author Dr. Gladys Block, "If our
vitamin C's ability to lower CRP is confirmed,
vitamin C could become an important public health intervention."
Nearly half of all Americans take supplements regularly,
most commonly multi-vitamin and mineral formulations (1).
That's good news, since the American Medical Association now recommends at least
one multivitamin daily for all adults, and new research continues to support
their benefit. A recent population-health study from Sweden, for example,
indicates that the use of multi supplements can lower the risk of heart attack
(2). Most importantly, the findings from this study
- the largest of its kind to date - underscore the need for supplementing with a
wide array of nutrients to promote healthy aging. Since choosing a multi can be
challenging, here are some basic questions to ask when evaluating a multi
Ginkgo May Slow Visual Field Loss in Normal Tension Glaucoma
Glaucoma and Altered Ocular Blood Flow
There are two leading theories to explain the mechanisms underlying glaucoma. The first, a mechanical theory, postulates that increased intraocular pressure (IOP) stretches the lamina cribrosa and damages retinal ganglion cell axons. The second theory suggests that an inadequate vascular supply, such as reduced blood flow to the optic nerve, results in ganglion cell damage.
Although there’s agreement that IOP reduction is a beneficial treatment in both high and normal tension glaucoma (NTG), the vascular theory may be more relevant in explaining NTG pathogenesis. In support of this idea is the observation that glaucoma continues to progress in many patients despite IOP reductions, and the fact that a reduction in blood flow often precedes optic nerve damage. Additionally, risk factors for NTG – such as low blood pressure, orthostatic hypotension, nighttime hypotension, migraine and sleep apnea – result in reduced blood flow to the brain.
Ginkgo biloba: Mechanisms & Research Findings
Ginkgo biloba leaf extracts have been used in Chinese traditional medicine for 5000 years. In recent times, Ginkgo has been reported to be neuroprotective for retinal ganglion cells in animal models of chronic glaucoma, and clinically shown to increase ocular blood flow and reduce visual field damage in NTG patients in the short term. Ginkgo has demonstrated antioxidant activity, and may increase blood flow by changes in blood viscosity and inhibition of platelet activating factor.
The current study (1) was conducted to evaluate the long-term effects of G. biloba extract on progression of visual field defects in patients with NTG.
In this retrospective study, 42 eyes of 42 NTG patients were evaluated for more than a 4-year period before and 4 years after receiving 80 mg of Gingko biloba extract twice daily (total of 160 mg per day). Patients had at least 5 visual field (VF) tests in the 4 years prior to and after supplementation. The VF tests were routinely preformed at diagnosis, 3 months later, and every 6-12 months thereafter with the Humphrey VF Analyzer. The change of progression rate was evaluated using mean deviation, pattern standard deviation, and visual field index. The time course of mean total deviation in 10 zones corresponding to the glaucoma hemifield test was analyzed using a linear mixed effects model with unequal random effects variance.
The mean follow-up period was 12.3 years. After Ginkgo treatment, the regression coefficients of the mean deviation (MD), pattern standard deviation (PSD) and visual field index (VFI) change improved significantly (p<0.001). Before and after treatment regression coefficient values were as follows:
In zone 1, after Ginkgo biloba administration, visual field damage was significantly slowed (rate of the regression coefficient of mean total deviation change significantly increased; p<0.05).
The authors conclude that Ginkgo biloba extract slowed the progression of visual field damage in patients with NTG, especially in zone 1 which corresponds to the superior central field. A number of studies have shown that the superior central field is the main location of visual field defects in NTG, whereas high tension glaucoma defects tend to be more diffuse (2,3).
No ocular or systemic adverse effects were reported among patients during follow-up in this retrospective study cohort. This appears to be the first study to compare visual field progression in the same patients after Ginkgo supplementation, and the results suggest that Ginkgo biloba may be useful as a complementary treatment for glaucoma.
Lutein & Zeaxanthin Protect Lens Cells from Oxidative Damage
Background: Lutein, Zeaxanthin & Cataract
Epidemiologic studies indicate that high dietary intake or blood levels of lutein or zeaxanthin may decrease the risk of cataract. The most recent study reports that subjects with the highest plasma concentrations of lutein and zeaxanthin had 42% and 41% lower risk of nuclear cataract, respectively (see EduFacts Vol 13, No 5).
Lutein and zeaxanthin are the only carotenoids detected in the lens. While their role in the lens and the mechanism by which they may reduce the risk for cataract aren’t fully understood, it has been proposed that the benefit of these two carotenoids is related, at least in part, to their antioxidant properties.
Oxidative stress is, in fact, a major risk factor for age-related cataract, particularly nuclear cataract. One of the major oxidants in the lens and aqueous humor is H202 (hydrogen peroxide), and levels of H202 in the aqueous humor of those with cataracts have been shown to be higher than in the aqueous humor of normal individuals.
In a recently published study, researchers from Tufts University and Sun Yat-sen University in China used cultured lens epithelial cells exposed to H202 as a model system to study the effects of supplemental lutein or zeaxanthin on oxidative damage, and their interaction with intracellular glutathione – an antioxidant enzyme that prevents damage by peroxides.
Human lens epithelial cells were pre-incubated with or without 5 μM lutein, zeaxanthin, or α-tocopherol for 48 hours, and then exposed to 100 μM H202 for 1 hour. Alpha tocopherol ( vitamin E) was used as a positive control because the same researchers previously demonstrated that adding α-tocopherol to cultured rabbit lens epithelial cells can improve cellular redox status and restore the resistance of glutathione-depleted cells to H202. Markers of damage to proteins (protein carbonyls), lipids (maldonaldehyde) and DNA (damaged nuclei), were assessed by western-blotting analysis, HPLC, and comet assay, respectively. Glutathione (reduced and oxidized) were measured by HPLC.
Exposure of the lens cells to H202 significantly increased levels of oxidized proteins, lipid peroxidation, and DNA damage. Pre-incubation with lutein, zeaxanthin, or α-tocopherol dramatically reduced the levels of H202 -induced protein carbonyl, MDA, and DNA damage.
The addition of lutein, zeaxanthin, or α-tocopherol increased glutathione levels and the ratio of reduced to oxidized glutathione, particularly in response to oxidative stress. Alpha tocopherol, but not lutein or zeaxanthin, partially restored the resistance of glutathione-depleted cells to H202.
These findings imply that sufficient intake of lutein and zeaxanthin may reduce the risk for senile cataract via protecting the lens from oxidative damage. They also suggest that vitamin E is important in protecting lens cells when glutathione levels are depleted.
Plasma Lutein & Zeaxanthin Tied to Cataract Risk
Oxidative Stress, Carotenoids and Cataract
Cataracts can be defined as clouding of the lens in the eye due to clumping of lens protein and coloration of the lens because of age, smoking, sunlight exposure, use of oral corticosteroids, estrogen replacement therapy, and diabetes. Nuclear cataract is the most common type of cataract among older individuals, especially women.
The inability to sufficiently defend against or repair accumulated damage from a variety of environmental stressors, including photochemical formation of free radicals, can lead to cataract development. Reactive oxygen species, for example, can damage lens proteins and fiber cell membranes.
Lutein and zeaxanthin are the most abundant carotenoids that accumulate in the lens of the eye, where they appear to filter phototoxic blue light and neutralize reactive oxygen species. Many, though not all, longitudinal studies that have looked at dietary intake or plasma levels of lutein and zeaxanthin and cataract incidence have reported a relationship between these carotenoids and cataract.
In the present investigation, Finnish researchers examined whether plasma concentrations of lutein and zeaxanthin are related to age-related nuclear cataract in elderly participants of the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.
The KIHD Study is an ongoing population-based, cohort study designed to investigate risk factors for CVD and other degenerative disease in a sample of middle-aged men and women. Plasma concentrations of carotenoids were determined in 1689 participants (1557 men and 783 women), aged 61-80 years. Nuclear cataract diagnoses were determined by an ophthalmologist using lens photography and grading.
Nuclear cataracts diagnosed were classified into tertiles according to plasma concentrations of lutein and zeaxanthin. The association of plasma lutein and zeaxanthin concentrations with age-related nuclear cataract was assessed using the Cox proportional hazards model.
A total of 113 cases of incident age-related cataracts were confirmed, of which 108 cases were nuclear cataracts.
Subjects in the highest tertiles of plasma concentrations of lutein and zeaxanthin had 42% and 41% lower risks of nuclear cataract, respectively, compared with those in the lowest tertiles. (Relative risk (RR) 0.58, 95% CI 0.35, 0.98; p = 0.041 for lutein. For zeaxanthin, RR 0.59, 95% CI 0.35, 0.99; p= .0.046).
These associations were observed after adjustment for age, examination year, sex, BMI, smoking, alcohol consumption, serum LDL-cholesterol, serum HDL-cholesterol, years of education, use of oral corticosteroids, history of diabetes and history of hypertension with current use of antihypertensive medication.
These results suggest that higher plasma levels of the carotenoids lutein and zeaxanthin are associated with risk reduction for nuclear cataract in the elderly. According to the authors, “there may be other protective factors of the diet (e.g. synergism of carotenoids with vitamin C or other antioxidants) that may partly explain the observed results”.
The researchers also note that both compounds appear to provide similar levels of protection from cataracts, an observation that challenges the hypothesis that dietary zeaxanthin intake is more important for lens health.
In the News Folic acid, B12 & Vision in Astronauts | Omega-3s & Brain Volume
Visual Changes Post-Space Flight May be Due to Altered Folic Acid & B12 Metabolism
About 20% of astronauts who’ve been on International Space Station (ISS) missions have developed ophthalmic changes after flight, including optic disc edema, globe flattening, choroidal folds, hyperopic shifts, and cotton wool spots. But why are some but not other astronauts affected? NASA researchers in collaboration with several universities have conducted experiments on ISS since 2006 to answer this question.
The investigative team found biochemical differences in crewmembers with vision issues, which strongly suggest that their folate and vitamin B12 dependent 1-carbon transfer metabolism was affected before, during, and after flight. One-carbon metabolites, including homocysteine, were 25-45% higher (P, 0.001) in those with ophthalmic changes than in those without them, and crewmembers with vision issues had consistently lower serum folate during flight. Pre-flight levels of homocysteine and cystathionine, and in-flight levels of folate, correlated with changes in refraction observed after flight (1).
The researchers believe that common polymorphisms in enzymes of this pathway (e.g. MTHFR 677C/T) interact with the shift in cranial fluids encountered at “zero” gravity in space to cause these ophthalmic changes.
While it’s not likely that you’ll encounter an astronaut in your waiting room anytime soon, these findings may have clinical import to those on Earth as well.
One of the most studied polymorphisms in this pathway is MTHFR 677C/T, which has an allele frequency of 30% in many ethnic groups. Heterozygotes (C/T) have a 30% decrease in the activity of the enzyme MTHFR and homozygotes (T/T) a 60% decrease in this critical enzyme. Evidence suggests that individuals with these polymorphisms may require more folic acid to maintain their status of this B-vitamin.
While Americans are getting more dietary folic acid than ever due to food fortification, getting some extra folic acid via a multi-vitamin supplement may be a good idea considering the high frequency of the polymorphisms, and that elevated homocysteine is a risk factor for ischemic stroke, inter-cranial aneurysms, migraine headaches, and possibly occlusive retinal vascular disease and some types of glaucoma. Many could also benefit from supplemental B12 due to the difficultly of its absorption in older people.
Brain Volume Tied to Omega-3 Intake
According to new findings, low blood concentrations of the omega-3s are associated with smaller brain volume and poorer performance on mental acuity tests (2).
Researchers from UCLA looked at the fatty acid content of red blood cells from over 1,500 men and women who were free of dementia and averaged 67 years of age. MRI scans were used to measure brain volume and white matter hyperintensities, a radiological finding that indicates vascular damage.
Study participants in the lowest quartile of omega-3 blood levels were observed to have significantly smaller total cerebral brain volume compared to those in the top quartile – a finding that held even after adjusting for age, smoking, body mass index and other variables.
Those with low omega-3 also fared poorer on tests of visual memory, abstract memory and executive function, defined as the control and management of other cognitive processes.
The investigators believe that the omega-3’s reduce vascular pathology and thus slow down the rate of brain aging. Too little omega-3 could promote accelerated brain aging.
Few people in the study used fish oil supplements, so the benefits were due to consuming more oily, cold-water fish. It may be that omega-3 supplementation could benefit brainpower – as well as cardiovascular health and perhaps vision maintenance – for those getting insufficient omega-3s from diet alone.
Antioxidants, Zinc & Omega-3s Reduce Genetic Risk of Early AMD
Introduction: Genes, Nutrients and AMD Risk
AMD is clearly a complex disease with multiple environmental and genetic risk factors. In terms of genetics, two of the more prominent AMD susceptibility genes identified to date are Complement Factor H (CFH) and LOC387715 / HTRA1.
There are several different forms (variants) of these genes that significantly raise the risk of AMD. Carrying the CFH Y402H variant increases risk of AMD up to 11 times. For carriers of the variant LOC387715 A69S, the risk is up to 15 times greater.
Together, these variants may contribute to late AMD in more than 80% of cases. Thus finding ways to counter these major gene effects is of public health importance.
The only protective factors for AMD known to date are nutrients. Zinc and antioxidants were shown in the AREDS trial to reduce the risk of progression from intermediate to advanced AMD. Population based studies have also found a reduction in AMD risk progression with higher intakes of lutein/zeaxanthin, or with higher intakes of the omega-3 fatty acids EPA and DHA.
Is the protection afforded by these nutrients sufficient to reduce AMD risk in carriers of well-known risk variants? To address this question, authors of The Rotterdam Study have explored the relationship between a healthy diet, genetic risk and early AMD in a nested, case-control study (1).
Dietary intake was assessed at baseline using a food frequency questionnaire for 2167 participants (> 55 years) at risk of AMD from the population-based Rotterdam Study. Genetic variants were determined using TaqMan assay. Incident early AMD was determined by fundus photography at 3 follow-up visits.
The synergy index was used to evaluate biological interaction between risk factors; Hazard ratios were calculated to estimate risk of early AMD in strata of nutrient intake (stratified by tertiles) and genotypes.
During a median follow-up of 8.6 years, 517 participants developed early AMD. Significant synergy indices supported a biological interaction between:
Homozygotes of CFH Y402H with zinc intake in the highest tertile reduced their hazard ratio of early AMD from 2.25 to 1.27. For intakes of beta carotene, lutein / zeaxanthin, and EPA / DHA, these risk reductions were from 2.54 to 1.47, 2.63 to 1.72, and 1.97 to 1.30, respectively. (See table).
Graphic courtesy of Archives of Ophthalmology
Carriers of LOC387715 A69S with the highest intake of zinc and EPA / DHA reduced their risk from 1.70 to 1.17 and 1.59 to 0.95, respectively (all p trends < .05).
These results suggest that higher dietary intake of zinc, carotenoids and EPA/DHA can attenuate the incidence of early AMD in those carrying important genetic variants. The authors conclude that “clinicians should provide dietary advice to young, susceptible individuals to postpone or prevent the vision-disabling consequences of AMD”.
It’s well established that complement activation and inflammation play an important role in development of AMD. The CFH gene is a key regulator of complement, and the Y420H variant impairs its regulatory function. As for LOC387715, evidence suggests that the A69S variant may jeopardize mitochondrial function and lead to free radical formation and apoptosis.
There are plausible mechanisms that could explain the effect of these nutrients in carriers of both variants. For example, antioxidant nutrients can counter oxidative damage, an activator of the complement cascade, while omega-3s act as anti-inflammatory agents in the retina. Dysfunctional mitochondria may increase complement activation which, evidence suggests, zinc may counter.
Ho L, et al. Reducing the genetic risk of age-related macular degeneration with dietary antioxidants, zinc, and ω-3 fatty acids. The Rotterdam Study. Arch Ophthalmol 129:758-66, 2011.
Low Antioxidant Status Seen in Glaucoma
Oxidative Stress & Development of Glaucoma
Primary open-angle glaucoma (POAG) is a chronic, slowly-progressing optic neuropathy characterized by a distinctive pattern of visual field defects. Psuedoexfoliation syndrome (PEX) is distinguished by abnormal extracellular fibrillar material that accumulates in the anterior segment of the eye and in other organs. PEX is the most common identifiable cause of open-angle glaucoma worldwide.
Oxidative stress – the presence of increased levels of reactive oxygen species relative to antioxidant defenses – may contribute to the development of both POAG and psuedoexfoliation glaucoma (PEG). Greater oxidative damage to trabecular meshwork cells has been reported in POAG and PEG vs. non-glaucoma patients (1), for example, and oxidative stress has been implicated as an underlying mechanism of retinal ganglion cell death (2).
In the present study, researchers examined the antioxidant status and established the presence of oxidative stress in patients with POAG and PEG3 (3).
The study enrolled 23 POAG patients, 24 PEG patients, and 19 healthy control subjects; all 3 groups included men and women within the same age range.
As indicators of antioxidant status, the total antioxidant capacity of serum and total activity of superoxide dismutase were determined by spectrophotometry. Total antioxidant status represents the cumulative action of all antioxidants present in serum.
Total oxidant status, nitric oxide, protein carbonyl levels, and maldonaldehyde were also measured from blood sample by spectrophotometry as indicators of oxidative stress. Maldonaldehyde and protein carbonyl reflect the level of lipid peroxidation and protein oxidation, respectively.
Antioxidant Status Indicators: Mean total antioxidant capacity in the POAG and PEG groups was about half that of controls (p = 0.001).
Mean superoxide dismutase levels were significantly higher in both glaucoma groups compared to the control group (p = 0.001). Concentrations of superoxide dismutase are known to rise as a consequence of oxidative stress, and in accordance with the degree of stress conditions.
Oxidative Stress Indicators: Mean total oxidant status was significantly higher in both glaucoma groups compared to controls (p = 0.001), as was maldonaldehyde (p = 0.001). The POAG group showed higher serum nitric oxide levels than controls
(p = 0.005), although the PEG group did not.
Those with PEG had higher serum protein carbonyl levels than both the POAG and control groups (p = 0.001), while protein oxidation in the POAG group was no different from controls.
These results add to the growing body of evidence supporting a role for oxidative stress in POAG and PEG. The finding of lower antioxidant defense systems in the glaucoma patients are also consistent with reports from other researcher groups (4,5).
The relatively small number of subjects assessed can be considered a study limitation. However, the breadth of biomarkers measured is certainly one of the study’s strengths, since no one biomarker of antioxidant or oxidant status gives a full picture of the oxidative state. The consistency of results observed between the various biomarkers that were measured lends credence to the findings overall.
In the News: Vitamin C & Retinal Cell Function, Metformin & Vitamin B12 Depletion, Meta-analysis: Lutein & AMD
Background: Role of GABA in Retina
GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the central nervous system (CNS). GABA receptors modulate the rapid communication between brain cells by acting as an inhibitory ‘brake’ on excitatory nerve cells.
There are different types of GABA receptors: The ‘a’ type, for example mediates fast inhibition, while the ‘c’ receptor mediates slow and sustained responses. GABAc receptors are expressed in many regions of the brain, with prominent distribution on retinal neurons. These receptors are thought to play important roles in retinal signal processing.
Vitamin C Needed for Retinal Neuron Function
Researchers at Oregon Health and Science University report this month that the function of both retinal GABAa and c receptors is regulated by vitamin C (1).
According to the authors, “the cells need to be bathed in relatively high doses of vitamin C inside and out” for proper receptor function. Conversely, the receptors failed to function in the absence of the vitamin.
Vitamin C appears not only to play an indispensible role in retinal nerve cells, it may also be important for brain function. “Because the retina is part of the CNS, this suggests there’s likely an important role for vitamin C throughout our brains, to a degree we had not realized before”, explained the lead investigator. Vitamin C stores in the brain are known to be the last to be depleted during times of vitamin C deprivation.
The findings may also have implications for other conditions involving malfunctioning nerve cells in the retina and brain, such as glaucoma and epilepsy, the investigators theorize, and it “may be that a vitamin C-rich diet could be neuroprotective for the retina”.
Metformin and Vitamin B12 Depletion
There’s been increasing concern over the risk of vitamin B12 deficiency in type 2 diabetics taking the common diabetes medication metformin (2) (e.g. Glucophage®). According to some studies, 10-30% of people taking this drug show evidence of decreased B12 absorption. Since people over 50 are generally less efficient at absorbing B12, this drug-nutrient interaction could exacerbate levels that are already low. Vitamin B12 depletion is more common in people who’ve been taking metformin the longest, and/or at high doses.
Clinicians suggest that patients who’ve used the medication for several years or who take a high dose, should have their B12 levels tested. Checking blood levels of B12 should always be done with signs of deficiency, especially those related to nerve problems such as numbness, pain or tingling in the hands or feet.
Lutein Reduces Risk of Late Stage AMD
Lutein and zeaxanthin are thought to decrease the incidence of AMD; however, findings have not always been consistent. A team of Chinese researchers from Peking University recently conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk (3).
Six longitudinal cohort studies met the strict inclusion criteria, and their results were pooled for analysis. The researchers excluded studies that examined the use of supplemental carotenoids.
Comparing the highest with lowest category of intake showed that higher intakes of these carotenoids were associated with a 26% reduction in the risk of late-stage AMD, and a risk reduction of 32% for neovascular AMD.
Little effect of lutein and zeaxanthin in the early stages of this disease was found.
Meta-Analysis: Antioxidants Lower HbA1c In Type 2 Diabetes
Role of Oxidative Stress in Type 2 Diabetes
For almost 25 years, oxidative stress has been considered to play a central part in the type 2 disease process, with over 6,000 related articles published over that time.
Some articles reflect growing evidence that cellular oxidative stress triggers cascades (p38 MAPK) that, in turn, interfere with signaling from the insulin receptor. Other findings suggest that diabetic complications arise from oxidative stress, which is defined as an imbalance of oxidants and antioxidants in the favor of oxidants. Hyperglycemia underlies the development of diabetic complications, most likely due to a greater production of free radicals, more specifically reactive oxygen and nitrogen species.
Combating Oxidative Stress
To combat oxidative stress, a number of trials have investigated administering vitamins C and/or E, since plasma levels of these nutrients are often reduced in those with type 2. In addition, epidemiological studies have found that type 2 individuals with reduced plasma status of vitamins C and E are at increased risk for cardiovascular events.
Antioxidant intervention trials in diabetic patients have not been uniform, however, and this has hindered their interpretation. Recently, researchers conducted a meta-analysis to clarify whether a defective antioxidant network contributes to insulin resistance in diabetes, or to its complications (1).
Databases were searched for randomized, placebo-controlled trials examining the effect of supplemental vitamins E and/or C on glycemic control markers in non-pregnant adults with type 2 diabetes.
The analysis focused upon the effects of these nutrients on 1) plasma glucose and insulin concentrations as an indicator of the ability of the antioxidant to interfere with disease process, and 2) on glycated hemoglobin A1c (HbA1c) as a measure of antioxidant effects on protein modification implicated in disease complications.
Fourteen vitamin E or C intervention studies were identified that met the study inclusion criteria. Collectively, these studies included 572 participants and ranged from 4 weeks to 12 months in duration.
Vitamin C supplementation was from 100 mg to 2 grams daily, while vitamin E supplementation ranged from 200 IU to 1800 IU per day.
Combined analysis revealed that antioxidant supplementation did not affect plasma glucose or insulin levels. However, HbA1c levels (reported in 13 of the 14 studies) were significantly reduced by the supplemental nutrients, suggesting that antioxidants have benefit in protecting against complications of the disease.
Key: Random effects model of meta- analysis of weighted mean difference of HbA1C compared to control group, showing the mean difference for each study and 95% confidence intervals, with the pooled meta-statistic shown as a diamond.
DL pooled effect size = -0.571078 (95% CI = -0.934883 to -0.207273)
HbA1c is the gold standard marker of long term glucose control, and a surrogate for risk of diabetic complications. This analysis found an overall improvement in HbA1c in patients receiving antioxidants (see figure), with the most pronounced effects seen in those getting higher dose vitamin E for at least 2 months.
While some concerns about high dose vitamin E safety have been previously reported, the most recent analysis (Cochrane review) does not support any negative or positive effects on mortality (2).
Research Briefs: Vitamin D, AREDS Antioxidants & Citrus Flavonoids
Introducing EduFacts Research Briefs
While EduFacts will continue to highlight a newly published study or review article on nutrition and ocular health, it will now occasionally present Research Briefs: short summaries of several studies from various journals.
Vitamin D Again Linked to Reduced AMD Risk
Researchers from the University of Wisconsin and elsewhere examined the relationship between serum vitamin D and the prevalence of early AMD among 3000+ postmenopausal women (1). Higher serum vitamin D concentrations (> 38 nmol/L) were found to be significantly associated with a 48% decreased odds of early AMD and a 57% decreased risk of pigmentary abnormalities in women under 75 yrs. For those over 75, the association was of borderline significance.
In terms of vitamin D intake from supplements and foods, those consuming the highest amount (on average about 600 IU) daily, had a 59% lower risk of AMD compared to those obtaining the least (about 300 IU on average). This is the 2nd study to report a relationship between vitamin D and AMD. Because vitamin D has known anti-inflammatory and immune modulating actions, the authors speculate this nutrient may suppress destructive inflammation that occurs at the RPE-choroid interface in early stage disease.
AREDS, Ocular Blood Flow & Endothelial Function
Oxidative stress is a contributor to ocular diseases such as diabetic retinopathy, cataract, AMD, uveitis, and possibly glaucoma. The presence of increased oxygen radicals in vascular tissue is believed to cause endothelial dysfunction, leading to decreased dilation, more inflammatory cell and platelet adhesion, and increased coagulation activity. The retina is especially vulnerable to oxidative stress because of its high oxygen consumption, its high concentration of poly-unsaturated fatty acids, and its direct exposure to light.
Using an experimental protocol, clinicians from the Medical University of Vienna showed that systemic
inflammation diminishes the retinal vascular response to hyperoxia. (The protocol uses an endotoxin to reduce the response of retinal blood flow under conditions of excess oxygen). The reduced response is due to endothelial dysfunction caused by oxidative stress. In a double-blind, placebo-controlled parallel study (2), 21 healthy volunteers were given the AREDS formula or a placebo for two week periods. At the beginning and end of each period, retinal blood flow and retinal blood flow reactivity to hyperoxia was assessed.
The investigators found that the AREDS antioxidants restored retinal vascular reactivity. According to the authors, this was likely due to oxygen radical scavenging by the antioxidants. The results suggest that this model might be a good approach to screening antioxidants for their relative beneficial effects in the retina.
Flavonoids, Inflammation and Blood Pressure
Researchers studied the effects of orange juice (OJ) and its major flavonoid, hesperidin, on blood pressure and blood vessel function in overweight but otherwise healthy men (3). About 1/3 of the men had elevated blood pressure but were taking no anti-hypertensive medications. During 3 month-long periods, the men drank either 17 oz of OJ daily, a control drink with 300 mg hesperidin capsules (the same amount as the OJ contained), or a control drink plus a placebo capsule. At the end of both the OJ and hesperidin test periods, diastolic pressure was significantly lower than after the placebo period. Studies suggest that even a decrease of just 3-4 points in diastolic pressure could result in a 20% reduction in the incidence of coronary heart disease. Hypertension also appears to raise the risk of retinopathy in non-diabetics (4).
The researchers also tested a variety of measures of blood vessel activity, including the ability to dilate. Both OJ and hesperidin showed positive effects compared to placebo. This finding is consistent with recent data linking higher intake of citrus flavonoids with lower markers of inflammation and endothelial dysfunction in participants of the Nurses Health Study (5).
Selenium Found to Improve Mild Graves’ Orbitopathy
Treating Milder Forms of Graves’ Orbitopathy
The most common form of hyperthyroidism is Graves’ disease, and about 1/2 of patients with this disease have ocular involvement in the form of Graves’ orbitopathy (GO). An autoimmune inflammatory disorder affecting the orbit around the eye, GO is characterized by upper eyelid retraction, swelling, redness, conjunctivitis, and bulging eyes. Moderately severe and active forms of this disease can be effectively treated with glucocorticoids and/or orbital irradiation.
Since milder forms may improve spontaneously, the usual treatment is use of artificial tears, ointments, and prisms simply to control symptoms. However, a ‘wait-and-see’ strategy in which patients are monitored until symptoms worsen, can be challenged.
First, many patients with even mild forms of GO have a substantial decrease in their quality of life, as assessed by a Graves’ orbitopathy-specific quality-of-life questionnaire. Second, a natural history study of mild GO, found that spontaneous improvement occurred in about 20% of patients, while the disease remained static in 65% and progressed in 15%. Thus, some believe that therapy would be justified.
Oxidative Stress, Selenium and Graves’
A number of in vitro studies have suggested that increased generation of oxygen free radicals and cytokines play a role in GO. Because the trace mineral selenium is a co-factor for antioxidant enzymes and has an important effect on the immune system, researchers representing the European Group on Graves’ Orbitopathy investigated whether selenium or the anti-inflammatory agent pentoxifylline might be beneficial in patients with mild GO. Their findings, published in the May 19th issue of NEJM, indicate that selenium is clinically useful in this condition.
This randomized, double-blind, placebo-controlled trial was carried out in 159 patients with mild Graves’ orbitopathy. The patients received 2x daily: selenium (100 µg), pentoxifylline (600 mg), or placebo for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, & a GO–specific quality-of-life questionnaire, completed by the patient.
At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (p<0.001), less eye involvement (p = 0.01), and slower disease progression (p = 0.01), compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months.
Two patients assigned to placebo and 1 assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems.
Graph courtesy New England Journal of Medicine
In this study, supplemental selenium significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease, suggesting clinical utility of this mineral in treating milder forms of GO.
Lutein, Zeaxanthin & Omega-3s Shown to Protect Against Blue Light Damage
Lutein, Zeaxanthin, Omega-3 and AMD Risk
The low values of macular pigment density seen in some people, coupled with the age-related decline of natural defenses in the retina and RPE can increase oxidative stress, a risk factor for AMD. AMD risk is thought to be further increased by exposure to blue (short-wavelength) light, although the results of observational studies have been conflicting.
One of the observational studies reports that estimated lifetime blue light exposure increased the risk of neovascular AMD specifically in individuals with low plasma levels of antioxidants, including zeaxanthin. However, experiments to evaluate the relationship of the macular pigment xanthophylls (lutein and zeaxanthin) to light damage and macular disease have been few, due to a lack of appropriate animal models. Only higher primates have a macula lutea, with its high foveal concentration of macular pigment.
Working with a unique set of rhesus monkeys raised on lutein and zeaxanthin-free diets, a research team has now looked at the effects of macular pigment absence – followed by xanthophyll supplementation – on blue light damage. The researchers also examined whether a deficiency of omega-3 fatty acids affects sensitivity to blue light as well.
Study Design and Methods
The study included 8 rhesus monkeys with no lifelong intake of xanthophylls and no detectable macular pigment. Four of the monkeys had low omega-3 intake and 4 had adequate dietary intake.
Retinas received 150 µm-diameter exposures of low-power 476 nm laser light either at 0.5 mm [~2(o)] eccentricity, adjacent to the macular pigment peak, or parafoveally at 1.5 mm [~6(o)]. Exposures of xanthophyll-free animals were repeated after supplementation with pure lutein or zeaxanthin for 22-28 weeks.
Visible lesion areas were plotted as a function of exposure energy, with greater slopes of the regression lines indicating greater sensitivity to damage. The results were compared to data from control animals with typical levels of xanthophylls and omega-3 in their diets and retinas.
For control animals with normal macular pigment, the fovea was less sensitive to blue light damage than the parafovea. However in the monkeys lacking macular pigment, fovea and parafovea were equally vulnerable.
After supplementation, foveal protection in xanthophyll-free animals did not differ from controls. And, like controls, the fovea was now less sensitive to damage than the parafovea.
In the parafovea (but not the fovea), animals low in omega-3 fatty acids showed greater sensitivity to damage compared to those with adequate omega-3.
These findings confirm the photo-protective effect of lutein and zeaxanthin in the fovea where their con-centration is greatest, and indicate that omega-3 fatty acids lessen damage in the parafovea. Although the study showed protection against acute blue light damage, it seems probable that these nutrients would also protect the macula against chronic blue light exposure.
The omega-3 fatty acid DHA is present at exceptionally high levels in the retina, particularly in photoreceptor outer segment membranes. There are a number of ways by which DHA could act to lessen blue light damage: it serves as the precursor for neuroprotective factors and helps counter inflammation. In addition DHA helps block abnormal vessel growth (see EduFacts Vol. 12 No. 1).
“Our results”, conclude the study authors, “offer hope that good nutrition, augmented by supplementation when appropriate, can contribute to reduction of risk for AMD, especially for persons with reduced macular xanthophyll levels due to retinal disease, poor diet, or genetic predisposition”.
Barker FM, et al. Nutritional Manipulation of Primate Retinas. V: Effects of Lutein, Zeaxanthin and n–3 Fatty Acids on Retinal Sensitivity to Blue Light Damage. IOVS Papers in Press. Published on January 18, 2011 as Manuscript iovs.10-5898
Polyphenols Bolster Drug Effects in Ocular Hypertension
Ocular Hypertension and Risk of Glaucoma
Ocular hypertension is a leading risk factor for the development of primary open angle glaucoma (POAG), and is the only modifiable risk factor acknowledged at present.
It’s estimated that 4 to 7% of Americans over 40 years of age have ocular hypertension. The Ocular Hyper-tension Treatment Study (OHTS) clearly showed that lowering IOP is effective in delaying or preventing the onset of POAG in individuals with ocular hypertension. Recent results from a long-term study by the OHTS group indicates that those at high risk of POAG can benefit from early preventive treatment (1).
Spurred by previous findings that a combination of polyphenols (anthocyanins and procyanidins) could improve IOP and blood flow in ocular hypertension, the same researchers recently compared the effects of those polyphenols alone and with latanoprost in ocular hypertensive patients with no signs of POAG (2).
The study recruited 79 men and women, mean age 49 yrs, with diagnosed elevated IOP (> 35 and < 40 mmHg). All subjects had complete eye exams, showing no signs of POAG. Patients were randomly divided into 3 groups to receive latanoprost (Xalatan, one drop per eye daily), one tablet of the polyphenol combination, or both.
The supplement tablet contained a daily dose of about 28 mg anthocyanins (Bilberry extract) and 28 mg procyanidins (French Maritime Pine Bark Extract). IOP was consistently measured at the same time in the a.m. by the same investigator, and in triplicate. High resolution color Doppler imaging was used to measure the peak systolic flow velocity, and the end diastolic flow velocity of the central retinal artery.
The polyphenol and drug combination was more effective for lowering IOP, and the combination yielded better retinal blood flow. Evidence suggests that bilberry anthocyanins may act by countering increased permeability of blood capillaries, while the procyanidins may improve endothelial function. These promising results warrant further research with a larger patient group, according to the authors.
Healthy Eating Lowers
Cataract Risk in Women
Dietary Components and Cataract Risk
Individual components of the diet have been associated with cataract risk over the past few decades. Antioxidants, for example, may lower risk for nuclear cataract by lowering oxidative stress or systemic inflammation (which can lead to oxidative stress). Having high intakes or blood levels of lutein and zeaxanthin and the use of multivitamin supplements have been most consistently related to lower risk for cataract. Less consistently, high dietary intake or blood levels of vitamins C and/or E have been associated with reduced risk.
A few studies have also associated other dietary components with lower risk for nuclear cataract or cataract extraction, including high intake of long-chain omega-3 fatty acids or low intake of refined carbohydrates (as indicated by a low glycemic index score). Only one previous study has directly evaluated the overall impact of a healthy diet on the occurrence of cataract. In that study, adherence to a Healthy Eating Index over a 10-year period was linked to a lower risk for early nuclear lens opacities (1).
The Carotenoids in Age-Related Eye Disease Study (CAREDS), part of the Women’s Health Initiative (WHI), previously found that high intake and blood levels of lutein and zeaxanthin lowered the risk for nuclear cataract in this cohort. CAREDS researchers now report that an overall healthy dietary pattern is related to a low prevalence of nuclear cataract (2).
Presence of nuclear cataract was determined from slit-lamp photographs and self-reports of cataract extractions were assessed in 1,808 CAREDS participants. Scores on the 1995 Healthy Eating Index, which reflect adherence to 1990 guidelines, were assigned from responses to food frequency questionnaires at the WHI baseline.
Having a high Healthy Eating Index score was the strongest predictor of low prevalence of nuclear cataract among numerous risk factors examined. The multivariate-adjusted odds ratio for high vs. low
quintile for diet score was 0.63 (95% confidence interval, 0.43-0.91).
Higher prevalence of nuclear cataract was also associated with other modifiable factors (smoking and marked obesity) and non-modifiable factors (having brown eyes, myopia, and high pulse pressure).
Healthy Eating Index scores in the highest quintile were associated with a 37% lower risk for nuclear cataract after adjusting for non-dietary risk factors. These women ate diets that were lower in fat, saturated fat and sodium, and higher in lutein and zeaxanthin, vitamins C and E, and all other vitamins and minerals compared with women whose overall scores were in the lowest quintile. The authors conclude that “eating foods rich in a variety of vitamins and minerals may contribute to postponing the occurrence of the most common type of cataract in the U.S”.
While there is a large body of observational studies linking multivitamin use with lower risk of nuclear cataract, no association was found in the present study. The lack of a protective association could have resulted from the relatively healthy diets of the women sampled, according to the authors. It is also possible that multi-vitamins may protect against nuclear cataract only in people who have poor diets.
If that is the case, many Americans could potentially benefit from a multi-vitamin supplement to ensure adequate micronutrient intake. A newly published study (3) which examined the dietary habits of over 16,000 individuals found that more than 80% of those 70 and older, and more than 90% of all other groups of both sexes, consumed too many calories from fats, added sugars and alcohol. Nearly everyone failed to meet recommendations for dark green and orange vegetables, and whole grains.
Lutein & Vitamin A May Slow Mid-Peripheral Vision Loss in Retinitis Pigmentosa
Lutein and Vitamin A in Retinitis Pigmentosa
Retinitis pigmentosa (RP) causes progressive vision loss to about 1 in 4000 people worldwide. Patients typically report deficient night vision in adolescence, and loss of mid-peripheral and then far peripheral field in adulthood with development of tunnel vision. Central vision is usually lost after age 60.
The previous EduFacts (Vol. 11, No. 1) summarized an investigation that found macular pigment optical density (MPOD) to be independently related to serum lutein in patients with retinitis pigmentosa (1). Provocative results from a new clinical trial suggest daily supplementation with lutein and vitamin A may help preserve mid-peripheral vision in RP (2).
The objective of this randomized, controlled, double-masked trial was to determine whether lutein supplementation slows visual function decline in patients with RP also receiving vitamin A at a level previously reported by the same investigators to slow the rate of RP progression.
225 non-smoking patients, aged 18 to 60 years, were evaluated over a 4-year interval. Patients received 12 mg of lutein or placebo daily in addition to 15,000 IU/day of vitamin A palmitate. Randomization took into account genetic type and baseline serum lutein level.
The primary outcome was the total point score for the Humphrey Field Analyzer (HFA) 30-2 program. Secondary outcomes were the total point scores for the 60-4 program and for the 30-2 and 60-4 programs combined, 30-Hz electroretinogram (ERG) amplitude, and Early Treatment Diabetic Retinopathy Study acuity.
There was no difference between groups in the rate of loss for the primary outcome measure, or in the secondary outcome measures between groups for rates of loss of the HFA 30-2 plus 60-4 total point score, ERG amplitude, or visual acuity. However, a significant effect of treatment on the rate of loss for the HFA 60-4 total point score (p=.05) was observed. Mean decline with the 60-4 program was slower among those with the highest serum lutein level or with the highest increase in MPOD at follow up (p=.01 and p=.006, respectively). Those with the highest increase in MPOD also had the slowest decline in HFA 30-2 and 60-4 combined field sensitivity (p=.005).
The researchers conclude that their data support the use of 12 mg / day of lutein to slow visual field loss among nonsmoking adults with RP taking vitamin A. They estimate that, based on the randomized comparison, the benefit in preserving mid-peripheral field sensitivity would be 3 additional years. Based on MPOD observational results, they estimate that the benefit would be 10 additional years. In the latter case, a patient taking vitamin A who begins supplemental lutein at age 40 could expect to lose mid-peripheral field by age 61 compared to age 51 for those not taking lutein according to the authors. Patient follow-up would be needed to confirm these estimates.
In an accompanying editorial (3), Massof and Fishman point out that this study, as well as 2 previous trials conducted by the same researchers produced no clear-cut results. One trial tested vitamin A, while the other evaluated vitamin A with 1,200 of DHA daily. According to the editorial, while all 3 trials were well designed and executed, they raise 2 issues: 1) the risk of misinterpreting outcomes because of assumptions built into the data analysis, and 2) the question of how much weight should be placed on clinical recommendations that are based on secondary analyses.
Although some might argue that there is no other viable treatment for RP and the conclusions drawn by the investigators are reasonable, the editorial concludes that neither vitamin A with lutein nor with a diet high in omega-3 have been convincingly shown to slow the rate of progression of RP.
Serum Lutein and Macular Pigment Density in Retinitis Pigmentosa
Lutein Studied in Retinitis Pigmentosa
It has been suggested that increasing macular pigment optical density (MPOD) with lutein supplementation might shield cone photoreceptors from UV-related oxidative damage and possibly slow the rate of cone degeneration over the long term. Previous studies have raised the possibility that lutein may be a potential treatment for retinitis pigmentosa, with one trial showing that supplemental lutein helped preserve visual function (1).
However it has also been reported that macular pigment optical density (MPOD) is not directly related to serum lutein in patients with retinitis pigmentosa, as it is in healthy individuals. This report led researchers from Harvard Medical School and the USDA Human
Nutrition Research Center on Aging at Tufts University to further investigate the relationship between MPOD and serum lutein in retinitis pigmentosa patients (2). Their findings shed light on what factors influence MPOD in people with this disease.
The authors measured MPOD with heterochromatic flicker photometry, serum lutein and serum zeaxanthin by high performance liquid chromatography and central foveal retinal thickness by optical coherence tomography in 176 patients aged 18–68 years with typical forms of retinitis pigmentosa. Thirty seven (21%) of these patients had cystoid macular edema (CME).
The researchers adjusted for potentially confounding variables such as age, sex, iris color, central foveal thickness and, in some analyses, serum total cholesterol.
MPOD increased with increasing serum lutein (P =
0.0017, see figure 4) and decreased with increasing serum total cholesterol (P = 0.0025) but was unrelated to serum zeaxanthin.
MPOD was higher in patients with brown rather than lighter irises (P = 0.014). MPOD was also related to central foveal retinal thickness (P < 0.0001), being lower in eyes with more photoreceptor cell loss and in eyes with moderate to marked CME.
The relationship between MPOD and serum lutein tended to be stronger in men than in women, which is compatible with some previous results in healthy subjects based on measurements of serum lutein.
In summary, this study found MPOD to be independently related to serum lutein, serum total cholesterol, iris color, and central foveal retinal thickness in patients with retinitis pigmentosa.
The authors offer some possible explanations for a number of their observations. The lack of an association between MPOD and serum zeaxanthin, for example, may be explained by the observations that lutein is more abundant in the diet, and that about half of the zeaxanthin in the center of the fovea is derived from lutein. This raises the possibility that it may be easier to increase macular pigment in the axons of cone photoreceptor in patients with retinitis pigmentosa by focusing on supplemental lutein rather than zeaxanthin.
The inverse relationship between MPOD and serum cholesterol suggests that higher serum cholesterol levels impede transport of lutein into the retina.
Finally, the linear relationship observed between MPOD and central foveal thickness when data from patients with CME were excluded, could mean that moderate to marked edema hinders the uptake of lutein into the macula or distorts the radial arrangement of the foveolar cone axons.
Serum Levels of Vitamin C & Uric Acid in Normal Tension Glaucoma
Oxidative Stress & Normal Tension Glaucoma
The occurrence of normal-tension glaucoma (NTG) varies worldwide. In the US, up to 15-25% of people with primary open-angle glaucoma (POAG) experience NTG. It is considerably more prevalent in Japan, with NTG comprising more than 70% of glaucoma cases.
In NTG, progressive damage can occur even with intraocular pressure (IOP)-lowering intervention. The cause of optic nerve damage in NTG is not fully understood, but oxidative stress is believed to be one contributing factor. Current evidence, for example, points to the association between oxidative stress and ganglion cell death without elevated IOP. In addition, there are some reports of lower levels of circulating antioxidants such as the major cellular antioxidant glutathione, in POAG patients.
These and other findings led Japanese researchers to examine serum levels of antioxidant vitamins A (beta-carotene), C and E, as well as folic acid and endogenous uric acid in NTG patients.
Beta-carotene and vitamin A are fat soluble antioxidants, while water soluble ascorbic acid and uric acid are strong reducing agents and potent antioxidants. In humans, over half the antioxidant capacity of plasma comes from uric acid, and vitamin C is highly concentrated in the aqueous humor. While not an antioxidant, folic acid insufficiency results in microvascular-damaging levels of homocysteine.
Sixty patients with newly diagnosed POAG were consecutively screened for inclusion in this study. After diagnosis of POAG, patients underwent 24-hr IOP measurements, and 47 newly diagnosed consecutive NTG patients (18 males, 29 females; mean age 59.5 years) were enrolled. The control subjects were recruited from subjects who came to the clinic for annual refractive check-up. The 44 consecutive control subjects (16 males, 28 females; mean age 62.7 years) had no ocular diseases.
Serum levels of vitamins A, folic acid, C, E, and uric
acid were measured, and the values compared between the NTG and control groups by the Mann-Whitney U test.
Serum levels of vitamin C were significantly lower in
NTG patients than in normal healthy controls (P=0.04; NTG 4.6±4.0 µg/ml, and control 6.3±3.9 µg/ml).
Uric acid concentrations were significantly higher in NTG patients compared to controls (P=0.01; NTG 5.8±1.5 mg/dl, and control 4.9±1.4 mg/dl).
No statistically significant differences were observed in the other vitamins measured.
The results of this study indicate that uric acid levels were increased and vitamin C levels were decreased in NTG patients. The authors speculate that higher serum uric acid and lower serum vitamin C may change the trabecular meshwork physiology. In turn, this may decrease the outflow facility of aqueous humor, causing eventual IOP elevation and glaucomatous optic neuropathy.
The diurnal IOP of the NTG patients in this study was under 21 mmHg, yet significantly higher than that of the normal controls (P=0.001). According to the authors, low vitamin C levels may cause modest IOP elevation and optic neuropathy even in NTG patients.
Vitamin C is thought to play an important role in reducing reactive oxygen species in the trabecular meshwork. Recent studies suggest that oxidative stress accelerates trabecular meshwork cell death. Further, in vitro studies indicate that interactions between uric acid and vitamin C can change the viscosity of some glycosaminoglycans, which are found in the trabecular meshwork.
The authors call for placebo-controlled trials to investigate the effects of vitamin C on IOP and visual field change in patients with NTG.
Review: Lutein & Zeaxanthin Metabolism
Metabolism is Key to Lutein’s Protective Role
Growing evidence suggests lutein and zeaxanthin play an important role in protection against AMD by filtering out blue light or quenching free radicals. While much remains to be learned, researchers from Waterford Institute and Regional Hospital in Ireland and the University of Utah’s Moran Eye Center have reviewed mechanisms involved in absorption and transport of these carotenoids, their uptake by the retina and how they are stabilized (1). Below are highlights of these findings, along with editorial comment on implications for diet, lifestyle and supplement use.
Absorption of Lutein and Zeaxanthin
Dietary fat is important for the absorption of xanthophyll carotenoids like lutein and zeaxanthin. Fat stimulates bile flow from the gall bladder to emulsify fat-soluble vitamins into lipid micelles – microscopic fat droplets – so they can be absorbed in the small intestine. Inadequate fat intake can result in reduced absorption of carotenoids, even if the diet is carotenoid-rich. Experimental data suggest absorption of lutein is mediated by a non-specific transporter protein (this protein, scavenger receptor class B type I, appears to play a primary role in intestinal absorption, but other proteins or passive diffusion may also be involved). Of note, some competition for absorption is seen when similarly structured carotenoids like beta-carotene and lutein are consumed together.
Comments: Though different carotenoids compete for absorption, some evidence suggests that balanced amounts of various carotenoids consumed together over time don’t interfere with each other in terms of bioavailability (2). Importantly, doses of lutein (10 mg) and zeaxanthin (2 mg) now being used in the AREDS 2 trial, did not reduce serum levels of other important carotenoids in a dosing study (3).
Transport of Lutein and Zeaxanthin
Dietary lutein and zeaxanthin are delivered to the retina via plasma lipoproteins, chiefly LDL and HDL cholesterol. While LDL is the primary carrier for most carotenoids, LDL and HDL carry about equal amounts of lutein and zeaxanthin. Several studies suggest relatively low HDL levels could hinder transport and capture of these carotenoids. Lower HDL levels have been found in overweight and obese individuals, for example, and higher body fat percentage is linked to risk of AMD progression as well as to lower macular pigment density. Lipoproteins also include protein components known as apolipoproteins. Researchers are investigating whether a person’s apolipoprotein profile might influence transport and delivery of these carotenoids to the retina. Of many apolipoproteins types, ApoE has the strongest link with AMD.
Comments: Lower levels of HDL have been found in overweight individuals, consistent with the possibility that a relative lack of HDL may impair transport and/or retinal capture of the carotenoids. Obesity has been identified as a risk factor for AMD. Take home message? Aerobic exercise, which aids weight loss and increases HDL, may prove useful in lowering AMD risk.
Retinal Uptake of the Xanthophyll Carotenoids
The mechanisms governing retinal capture and accumulation of lutein and zeaxanthin to the exclusion of other carotenoids are still poorly understood. However, retinal capture of xanthophyll carotenoids is performed by xanthophyll-binding proteins (XBP). XBPs may also be involved in: a) stabilizing xanthophylls in cell membranes, the cytosol or the cytoskeleton, b) mediating inter-conversion of lutein, zeaxanthin and various metabolites within the retina, and c) facilitating antioxidant activity of macular carotenoids. Importantly, it has been found that XBPs can become saturated, with implications for xanthophyll carotenoid supplementation.
Comments: Macular pigment density often increases dramatically in the first 4 weeks of supplementation, and then levels off. In a number of studies testing 10-12 mg of lutein, macular pigment density reached a plateau after the first month. This may be due to saturation of binding proteins, and suggests higher doses may not further enhance macular pigment over time.
Retina is Vulnerable to Effects of Blue Light
While wavelengths in the UV radiation range are largely absorbed by the cornea and lens, the retina is exposed to visible light, including blue light. Animal and laboratory studies have shown that blue light damages the retinal pigment epithelium and choriocapillaris through generation of reactive oxygen species and may be a factor in the pathogenesis of age related macular degeneration (AMD).
Protection against the harmful effects of blue light is provided by the retinal antioxidant defense system, which includes antioxidant enzymes supported by vitamins C and E, lutein and zeaxanthin, and zinc. Lutein and zeaxanthin are highly concentrated in the macula, where they act as scavengers of reactive oxygen species and filter blue light.
Only a few studies have investigated associations of sunlight exposure with AMD in human populations, and the results have been inconsistent. Up to now, however, studies have paid little attention to possible interactions between antioxidant levels and light exposure, though the adverse effects of sunlight may be attenuated by the protective effects of antioxidants.
Now, the European Eye (EUREYE) Study has examined the association of sunlight exposure and antioxidant levels with AMD. The study was designed to maximize a diversity of sunlight exposure and antioxidant levels by selecting study centers throughout Europe.
Four thousand seven hundred fifty-three participants 65 years or older in the EUREYE Study underwent fundus photography, were interviewed for adult lifetime sunlight exposure, and gave blood for antioxidant analysis. Blue light exposure was estimated by combining meteorological and questionnaire data.
Data on sunlight exposure and antioxidants were available in 101 individuals with neovascular AMD, 2182 with early AMD, and 2117 controls. No link was found between blue light exposure and neovascular or early AMD. However significant associations were found between blue light exposure and wet AMD in participants in the lowest quartile of individual antioxidant levels - vitamin C, zeaxanthin, vitamin E, and dietary zinc - with an odds ratio (OR) of about 1.4, or a 40% higher risk, for 1 standard deviation unit increase in blue light exposure.
Low blood levels of certain antioxidant combinations showed higher ORs of blue light exposure compared with single antioxidants. Higher odds ratios for blue light were observed with low levels of vitamin C, zeaxanthin and vitamin E, especially (odds ratio, 3.7; 95% CI 1.6-8.9), which were also associated with early AMD stages.
These results suggest that higher UV exposure may contribute to AMD in those with sub-optimal levels of select antioxidants. The authors conclude that … " people in the general population should use ocular protection and follow dietary recommendations for the key antioxidant nutrients."
Reference Fletcher AE, et al. Sunlight exposure, antioxidants, and age-related macular degeneration. Archives Ophthalmology 126:1396-1403, 2008.
Inflammation and Chronic Diseases
Inflammation is a complex series of reactions designed to prevent ongoing tissue damage and activate repair processes and defense mechanisms against infectious diseases. Prolonged inflammation, however, contributes to the pathogenesis of chronic such as Alzheimer's, diabetes, cancers, and CVD. Chronic inflammation is also believed to contribute to such eye diseases as AMD, dry eye, diabetic retinopathy and glaucoma.
Dampening inflammation may help retard the development of such diseases. Inflammatory injury may be mediated by reactive oxygen species (ROS) or their reaction products, and antioxidant therapy has been shown to prevent in vivo tissue injury during inflammation.
Role of NF-kB in the Inflammatory Response
The transcription factor nuclear factor-kB (NF-kB) controls expression of genes involved in the inflammatory response and is activated by oxidative stress and other pro-inflammatory stimuli. Activation of NF-kB results in coordinated expression of inflam-matory genes and secretion of pro-inflammatory chemokines and cytokines, which are associated with increased risk of disease and poor outcome of chronic inflammatory diseases. Thus, dampening NF-kB activation has been suggested as a strategy to prevent chronic inflammatory diseases.
Anthocyanins Dampen Inflammation
Anthocyanins are water-soluble red and blue flavonoid pigments responsible for the dark color of grapes, plums, black currants, blueberries and bilberries. The anthocyanins are effective antioxidant compounds in vitro, and have also been shown to suppress cancer, cataract, and neurodegeneration in animal models.
These data led researchers from the University of Oslo to examine whether bilberry and blackcurrant anthocyanins could inhibit NF-kB activation in vitro and in humans. The results of this study suggest that anthocyanin supplementation may have a role in pre-venting or treating chronic inflammatory diseases by inhibiting NF-kB trans-activation and deceasing plasma concentrations of pro-inflammatory chemokines, cytokines, and inflammatory mediators.
The researchers studied whether anthocyanins inhibit LPS-induced NF-kB activation in cultured monocytes. Monocytes were pre-incubated with a combination of black currant and bilberry anthocyanins or placebo (dimethylsulfoxide). NF-kB activity was induced by LPS.
In the parallel-designed, placebo-controlled clinical study, 120 participants were randomly assigned to receive 300 mg of anthocyanins or placebo for 3 weeks. The amount of anthocyanins provided corresponded to 100 g of fresh bilberries. The subjects maintained their regular diet during the intervention period.
Blood samples from fasting at baseline and after the intervention period were collected and analyzed for cytokines [IL-1b, IL-1 receptor antagonist (IL-1Ra), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, TNFa, IFNa, IFNg, granolyte/macrophage colony-stimulating factor (GMCSF), and others were measured in plasma by a sandwich immunoassay-based protein array system.
In the cultured cells incubated with anthocyanins, NF-kB activation was suppressed by 28% compared with cells incubated with vehicle only (p = 0.003). Anthocyanins also decreased the LPS-induced p65 DNA binding, another assay for NF-kB-activation, by 18% (p =.041).
In the clinical trial, differences were observed in several NF-kB related inflammatory mediators in the anthocyanin group compared to placebo.
Decreases from baseline in the NF-kB controlled pro-inflammatory chemokines IL-8, ''regulated upon activation, normal T cell expressed and secreted,'' and IFNa (an inducer of NF-kB activation) in the anthocyanin group differed significantly from those in placebos.
Similarly, decreases from baseline in IL-4 (60%) and IL-13 (38%) in the active group differed significantly from the slight decreases seen in placebos. Both of these cytokines mediate pro-inflammatory responses and activate NF-kB.
Reference Karlsen A , et al. Anthocyanins Inhibit Nuclear Factor-kB Activation in Monocytes and Reduce Plasma Concentrations of Pro-Inflammatory Mediators in Healthy Adults. Journal of Nutriton. 137: 1951-1954, 2007.
Italian-American Trial of Multi Use & Cataract
A recent prospective cohort analysis of the National Eye Institute (NEI)-supported Age-Related Eye Disease Study (AREDS) reported that consistent use of a multi-vitamin and mineral supplement may delay the progression of lens opacities [See EduFacts Vol. 8 No. 4]. That analysis found a 25% reduction in risk of nuclear cataract, a similar - though non-significant - risk reduction for cortical cataract, and no beneficial effect for posterior subcapsular opacity.
The NEI has also supported The Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract (CTNS), a 13-year, single-center clinical trial designed to evaluate whether multi use can affect the development or progression of lens opacities in a well-nourished Western population.
Results from the CTNS trial (1), published in the April issue of the journal Ophthalmology, support multivitamin supplementation for preventing or delaying the more common nuclear, and perhaps cortical opacities as well.
In this double-blind, placebo-controlled trial, a total of 1,020 subjects aged 55-70 with early or no cataract were randomized to receive a multivitamin/mineral supplement or placebo daily, and were followed for an average of 9 years. Baseline and annual lens photographs were graded for severity of lens opacities according to a modification of the Age-Related Eye Disease Study system for classifying cataracts.
The primary outcome was a pre-specified increase from baseline in nuclear, cortical, or posterior subcapsular cataract (PSC) opacity grades or cataract surgery. Secondary outcomes included an increase in type-specific opacity grades, cataract surgery, and visual acuity loss from baseline > or = to 15 letters. The statistical analyses yield estimates of hazard ratios (HRs) that can be interpreted as relative risks.
There was an overall benefit and a decrease in total lens events in participants assigned to the multivitamin and mineral formulation compared with those assigned to the placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.68 - 0.98; P= 0.03). Participants assigned to the multi were 34% less likely to experience a nuclear opacity event than participants assigned to a placebo (HR, 0.66; 95% CI, 0.50-0.88; P= 0.004). Multi users were also 22% less likely to experience a cortical event, although the difference did not reach statistical significance (HR, 0.78; 95% CI, 0.60 -1.02; P= 0.07).
First, there was no significant decrease in cataract removal or benefit for visual acuity. Is a larger or longer trial necessary for an adequate evaluation of the effects of multivitamins on visual acuity and/or cataract surgery rates? It should also be noted, however, that the multi tested in the CTNS trial did not contain lutein or zeaxanthin. These carotenoids are being examined in AREDS 2, and have been consistently linked to lower cataract risk, particularly nuclear opacity, and reduced risk for cataract surgery in observational studies.
Secondly, the benefits seen for the most common types of cataract, nuclear and cortical, are consistent with the findings from a number of observational trials, and the Linxian, China randomized trial, which reported a 36% reduction in the risk of nuclear cataract with multivitamin supplements. This implies that supplementation could help delay cataract and result in public health savings.
Lastly, the increased risk for PSC is puzzling, as most studies to date have shown no benefit but also no higher risk for PSC from supplemental antioxidants or multis. PSCs are less common than cortical or nuclear, and are often associated with eye trauma and steroid use. It is possible that the mechanisms involved in nuclear or cortical cataract formation are more susceptible to the level of oxidative stress than are PSC. Further research is needed.
Nuclear Cataract, Lutein and Zeaxanthin
Nuclear cataract is the most common type of cataract among older Americans, and the most common type for which cataract surgery is performed. It occurs more often in women than men and among Caucasian individuals.
The pathogenesis of nuclear cataract is known to involve the inability to sufficiently defend against or repair the damage due to a variety of environmental stressors, including photochemical formation of free radicals. Lutein and zeaxanthin are the most abundant lens carotenoids. They scavenge superoxide and hydroxyl radicals, protect against UV B-induced lipid peroxidation, and may play a role in membrane stability. Diets high in lutein plus zeaxanthin have also been inversely associated with nuclear cataract or cataract extraction in several previous observational studies.
The Carotenoids in Age-Related Eye Disease Study (CAREDS) is an ancillary study of the Women's Health Initiative (WHI). The authors of CAREDS previously found that a stable intake of lutein and zeaxanthin over time could reduce the risk of AMD by about 43% in healthy women under 75 (1) [see EduFacts Vol. 6 No. 9]. The CAREDS investigators now report that diets high in lutein and zeaxanthin are also linked to a lower prevalence of nuclear cataract (2).
A total of 1802 women aged 50 to 79 years with intakes of lutein and zeaxanthin above the 78th (high) and below the 28th (low) percentiles in the WHI were recruited 4 to 7 years later into CAREDS. The primary outcome was nuclear cataract, defined as a nuclear sclerosis severity score of 4 or greater in the worst eye and/or a history of cataract extraction in either eye.
Nuclear cataract was determined from slit lamp photographs. Dietary estimates were made from responses to a validated, semi-quantitative food frequency questionnaire. Serum levels of lutein, zeaxanthin, and tocopherols were determined at Tufts University by a reverse-phase HPLC analysis.
Women in the group with high dietary levels of lutein and zeaxanthin had a 23% lower prevalence of nuclear cataract (age-adjusted odds ratio, 0.77; 95% CI, 0.62-0.96) compared with the low level group. (Table 2)
Women in the highest quintile category of diet or serum levels of lutein and zeaxanthin as compared with those in the lowest quintile category were 32% less likely to have nuclear cataract (multivariable adjusted odds ratio, 0.68; 95% CI, 0.48-0.97; P for trend=.04; and multi-variable-adjusted odds ratio, 0.68; 95% CI, 0.47-0.98; P for trend=.01, respectively). The associations were similarly strong for serum concentrations of the combined carotenoids.
The observed association between these carotenoids and nuclear opacity was stronger when examining intake of lutein plus zeaxanthin across all of the levels of intake in this sample (by quintile categories) than when comparing the 2 groups of women sampled who had lutein and zeaxanthin intakes above the 78th and below the 28th quintiles. The results from CAREDS are consistent with a body of evidence that supports a protective relationship between lutein and zeaxanthin and nuclear cataract.
Oxidative Stress and AMD
Oxidative stress is one of the pathogenic mechanisms in AMD. The retina is thought to be highly susceptible to oxidative stress given its high oxygen consumption, high concentration of polyunsaturated fatty acids and photosensitizers, and exposure to light. Phagocytosis by the retinal pigment epithelium also leads to oxidative stress.
AREDS provided evidence that high dose zinc and antioxidant vitamin supplementation can slow AMD progression in relatively advanced early AMD cases (1). Additionally, the Rotterdam Study reported that above-median dietary intake of all 4 of the nutrients studied in the AREDS trial was associated with a statistically significant 35% reduction in incident AMD risk (2).
The Blue Mountains Eye Study is a population-based cohort study of vision, common eye diseases, and other health outcomes in an urban Australian population. A new analysis from this study confirmed the AREDS result that zinc is protective against AMD, and found that higher intake of lutein and zeaxanthin reduced the risk of long-term incident AMD (3).
Of the 3,654 participants in the study at baseline, 2,454 were re-examined after 5 years, 10 years, or both. The Wisconsin Grading System was used to evaluate stereoscopic retinal photographs. Risk ratios and 95% confidence intervals were calculated after adjusting for age, gender, smoking and other factors. Energy-adjusted intakes of vitamins A, C, and E; alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein and zeaxanthin; lycopene; iron and zinc were assessed via food frequency questionnaires.
Those in the highest decile of total zinc intake (> or = 15.8 mg/day) were found to be significantly less likely to develop early or any AMD compared with the remaining population (RR 0.54; CI 0.30-0.97 and RR 0.56; CI 0.32-0.97 respectively).
Similarly, for dietary lutein and zeaxanthin intake, those in the top tertile (> or = 972 mcg/day) had a 65% reduced risk of incident neovascular AMD (RR 0.35; CI 0.13-0.92). For those with above-median intakes, 34% reduction in risk of incident indistinct soft or reticular drusen was noted (RR 0.66; CI 0.48-0.92).
In contrast, the highest vs. the lowest tertile of total beta-carotene intake from diet predicted incident neovascular AMD in both smokers and non-smokers (RR 2.68; CI 1.03-6.96).
These results suggest a possible threshold effect of total zinc intake on risk of early or any AMD. A protective effect from high intakes of zinc is biologically plausible. Zinc is concentrated in the retina and is a cofactor for many enzymes, including the antioxidant enzymes present in human retinal pigment epithelium. Zinc is also a cofactor for vitamin A metabolism and is essential for the synthesis of retinol binding protein. In AREDS, the protective effect shown with combined zinc and antioxidants seemed driven largely by zinc. The recently reported findings from the Rotterdam Study also seemed to be driven by zinc, and perhaps vitamin E.
These results also suggest a possible threshold protective effect of dietary lutein and zeaxanthin intake on the risk of neovascular AMD or indistinct soft drusen. Lutein and zeaxanthin are the only carotenoids that concentrate in the macula, where they are the main components of macular pigment.
The finding of a link between higher intake of beta-carotene and increased risk of AMD are inconsistent with other reports. In addition to the previously mentioned findings of AREDS and the Rotterdam Study, the Eye Disease Case-Control Study Group also reported a reduced risk for AMD with higher dietary intakes of carotenoids, particularly beta-carotene, lutein and zeaxanthin.
Oxidative Theory of Cataract Formation
The oxidative hypothesis of cataract formation holds that reactive oxygen species can damage lens proteins and fiber cell membranes, and that nutrients with antioxidant actions can protect against these changes. Results of laboratory and animal studies generally support this theory, though findings from epidemiologic studies have varied.
Results of a new prospective study from Brigham and Women's Hospital and Harvard Medical School add to the body of evidence suggesting that lutein, zeaxanthin and vitamin E may help delay cataract formation (1). The study was published in the January issue of Archives of Ophthalmology.
Dietary intake was assessed at baseline in 39,876 female health professionals by using a detailed food frequency questionnaire. Information on antioxidant nutrient intake from food and supplements was obtained from a total of 35,551 women who were free of a diagnosis of cataract.
The main outcome measure was cataract, defined as incident, age-related lens opacity responsible for a reduction in best-corrected visual acuity in the worse eye to 20/30 or worse based on self-report, and confirmed by medical record review.
A total of 2031 cases of incident cataract were confirmed during a mean 10 years of follow-up.
Women with the highest daily intake of lutein and zeaxanthin, averaging about 6.7 mg, had an 18% lower risk of developing cataract compared to women consuming the least, or a mean of 1.2 mg a day. The multivariate relative risk of cataract was 0.82 (95% confidence interval, 0.71-0.95; test for trend, P =.04) for combined intake of lutein and zeaxanthin.
Comparing women in the extreme quintiles for vitamin E from food and supplements combined, a 14% risk reduction was noted. Those in the highest quintile consumed a mean of 262 mg vitamin E daily, while those in the lowest quintile consumed an average 4.4 mg. The multivariate relative risk of cataract was 0.86 (95% confidence interval, 0.74-1.00; test for trend, P =.03).
No relationship was observed between cataract risk and intakes of other carotenoids and antioxidants, including beta-carotene, beta-cryptoxanthin, lycopene and alpha-carotene.
lutein and zeaxanthin are the only carotenoids detected in the human lens, where they filter harmful short-wave blue light. The presence of oxidation products of lutein and zeaxanthin in the lens further supports a functional role for these carotenoids in maintaining lens clarity. Findings from observational epidemiologic studies also generally support a possible beneficial effect of lutein and zeaxanthin.
The association of vitamin E with lower cataract risk in this study comes in the wake of an intervention trial that reported no benefit of 600 IU vitamin E (every other day) on cataract in women (2).
Though speculative, it is possible that moderate amounts of antioxidants such as vitamins C and E and lutein along with B-vitamins, might have beneficial effects beyond that of a single nutrient administered at high levels. This notion is consistent with the findings from several prospective epidemiologic studies reporting a lower occurrence of cataract in regular users of multi-vitamin and mineral supplements (see EduFacts Volume 8, Number 4). A recent analysis of AREDS for example, linked consistent use of a multi-nutrient supplement with a lower risk of cataract even though the high dose antioxidants studied in that trial showed no benefit (3).
Multi-Nutrient Supplements and Cataract
A number of prospective epidemiologic studies have reported a lower occurrence of cataract in regular users of multi-vitamin and mineral supplements (1-3).
The Physicians' Health Study noted significantly fewer self-reported cataracts or confirmed cataract surgery in multi users during 5 years of follow-up. The Longitudinal Study of Cataract found that regular multi users reduced their risk of nuclear opacification by one-third. Finally, taking a multi for 10 years or more was reported to lower the risk of nuclear and cortical cataracts in the Beaver Dam Eye Study. In contrast, the Nurses' Health Study found no association between multi-supplement use and incidence of cataract extraction (4).
The cataract portion of the AREDS trial also failed to show an effect of high dose antioxidants on the risk of development or progression of lens opacities. However, a recent prospective cohort analysis of AREDS has found that consistent use of a multi-vitamin and mineral supplement may delay the progression of lens opacities (5).
There were 4596 participants enrolled in the AREDS cataract trial, half of whom were assigned to high-dose antioxidants and half to no antioxidants. Two-thirds of the subjects elected to take a multi vitamin and mineral supplement containing RDA-level potencies that was offered to all participants.
Lens photographs at baseline and at 5 to 6 years follow-up were compared. An "any" lens opacity event was defined as the occurrence of change from baseline of specified amounts of nuclear, cortical, or posterior subcapsular opacity, or the performance of cataract surgery.
The AREDS researchers used a propensity score approach to provide a means of adjusting for selection bias that may have occurred with the elective use of the multi supplement and for confounding. The use of propensity scores tends to produce unbiased estimates of treatment effects. It balances the covariates between treatment groups, much as trials use randomization to achieve balance. Risk of progression to a lens event was assessed by odds ratios (OR) with 95% confidence intervals (CI).
With adjustment for propensity score and baseline covariates, the risk of development of or progression to any cataract was reduced by 16% in regular multi takers (OR = 0.82, CI = 0.71-0.95, p = 0.025). For nuclear cataract, a 25% risk reduction was observed in the multi-supplement users (OR = 0.75, CI = 0.61-0.91, p = 0.004). (See Table)
There was a similar reduction in risk of cortical lens events, although significance was not reached. No beneficial effect was seen for posterior subcapsular opacities.
Individual nutrients have been linked to a lower risk of various cataract types including vitamins C and E, lutein, and the B-vitamins riboflavin and thiamin. Rather than supplementing with only a few, high-dose antioxidants, it may be that supplementation with a broad-spectrum of nutrients is a more effective strategy. The NEI in fact, is currently supporting a controlled trial of more than 1000 subjects in Italy to assess the effect of multi use on development and progression of cataracts. Median follow-up is 7 years, with completion likely this year. References
Women's Antioxidant & Folic Acid Study
Results from the vision component of the Women's Antioxidant and Folic Acid Cardiovascular Study, also known as WACS, were presented at the ARVO 2007 Annual Meeting. Researchers from the Brigham and Women's Hospital and the National Eye Institute concluded that the data from this randomized trial indicate that supplementation with folic acid, vitamins B6 and B12 reduced the risk of AMD in women with cardiovascular disease (CVD) (1).
These three B-vitamins, particularly folic acid, have been shown to reduce high levels of the naturally occurring compound, homocysteine. Research has implicated elevated plasma levels of homocysteine in the development of vascular diseases including choroidal neovascularization in exudative AMD.
A total of 8,171 female health professionals, 40 years or older with pre-existing CVD or having at least three risk factors for the disease were enrolled in the trial. The women were randomized to receive vitamin C (500 mg daily), vitamin E (600 IU every other day), beta-carotene (50 mg every other day) or placebo in the WACS secondary prevention trial.
Of this group, 5,422 women were subsequently randomized to also receive a placebo or folic acid (2.5 mg), vitamin B6 (50 mg) and vitamin B12 (1 mg) daily. Of these women, 5,205 did not have a diagnosis of AMD, and were included in this analysis. There were two primary outcome measures: a) confirmed AMD (self reported and supported by medical record evidence of an AMD diagnosis after randomization) and b) confirmed AMD with vision loss - defined as vision to 20/30 or worse which was attributable to this condition.
A total of 137 cases of AMD were documented, including 69 cases of AMD with vision loss, during an average of 7.3 years of treatment and follow-up. Fifty-five cases occurred in the treatment group, while the placebo group had 82 documented cases. Relative risk was 0.66 (95% confidence interval, p = 0.02). For AMD with vision loss, there were 26 cases in the B-vitamin group compared to 43 among placebo takers. Relative risk was 0.60 (95% confidence interval, p = 0.04). In summary, women taking supplemental B vitamins were 34% less likely to develop AMD and 40% less likely to have AMD-related vision loss than women in the control group.
While very high doses of the 3 B vitamins were tested in this group of women with CVD, lower doses may well have been effective. For example, a placebo-controlled, randomized dose response study in people with a history of CVD found that the decrease in homocysteine was proportionate to the folate dose up to - and not beyond - 800 mcg daily (2). This dose achieved an average 23% drop in plasma homocysteine compared to placebo - a drop of about the same magnitude found in trials using up to 5,000 mcg folate daily (3). Additionally, excessive amounts of folic acid have recently been implicated in colorectal tumor growth (4,5).
Antioxidant - CVD Outcomes in WACS
The WACS authors report that vitamins C, E or beta-carotene had no overall effects on CVD events in these high-risk women (6), pointing out that antioxidants are no magic bullets for the secondary prevention of this disease. However, the study did confirm the safety of high potency antioxidants, and women who received both vitamins C and E experienced fewer strokes. The same research group is following up to determine whether the combination of vitamins C and E affect the biomarkers in blood that strongly predict stroke. That work will use blood samples from 300 participants taken at the beginning and end of the WACS study.
Vitamin D: Beyond Bone Health
Most people think of vitamin D simply as a regulator of calcium homeostasis and bone mineralization. Over the past decade, however, it has become clear that the active or hormonal form of this vitamin also plays a significant role in xenobiotic metabolism, in the immune system, and in cellular proliferation and differentiation. As a result, adequate vitamin D status is viewed as important for reducing the risk of many malignancies and autoimmune diseases. Now, a recent study suggests that vitamin D is also involved in protecting macular health.
The objective of the study was to evaluate the association between levels of vitamin D (25-hydroxyvitamin D) in serum and prevalence of both early and advanced age-related macular degeneration (AMD) among participants of the 3rd National Health and Nutrition Examination Survey (NHANES III). NHANES III, which is conducted by the Centers for Disease Control, is a representative sampling of the general population. Of 7,752 people (> 40 years) analyzed from this survey, 11% had AMD as determined by non-mydriatic fundus photographs. Questionnaires assessed dietary and supplemental intake, and blood samples were taken to determine vitamin D serum levels.
Protective Effect Seen for Higher Serum D
When participants were split into five groups based on serum vitamin D levels, those in the highest quintile had a 40% lower risk for early AMD compared to those in the lowest quintile (see table). An inverse association between AMD and greater vitamin D-fortified milk consumption was observed. The researchers also found a significantly reduced prevalence of AMD among consistent vitamin D supplement users who did not consume milk daily.
Anti-Inflammatory Role is Likely Connection
A growing body of epidemiologic evidence suggests that inflammation underlies AMD pathology, and the authors of this study speculate that vitamin D may reduce AMD risk by its anti-inflammatory actions. Studies report that vitamin D decreases proliferation of T helper cells, T cytotoxic cells, and natural killer cells, while enhancing T suppressor cell activity. Vitamin D also decreases the production of pro-inflammatory interleukins such as IL-6 and 8. In addition, a recent study has shown that vitamin D intake reduces C-reactive protein, a marker of systemic inflammation.
There is growing evidence for the benefits of supplementing zinc and lutein in those with signs of AMD. This issue of EduFacts explores the benefit of these nutrients beyond macular health.
Supplemental Zinc and Immunity
Many eye care professionals advise their patients with at least moderate AMD to take the high dose zinc and antioxidant combination found to slow vision loss and disease progression. In subsequent analyses, AREDS authors reported that subjects receiving zinc (alone or with antioxidants) had improved survival time from all causes (1). The positive association of zinc with increased longevity did not appear to be due to a reduction in deaths from circulatory disease or cancer. Instead, a possible protective effect for respiratory causes of death was observed. The authors noted that zinc's effect on mortality could be related to an improved immune response, which declines with aging. Results from a recent study lend credence to that postulation.
Fewer Infections, Less Oxidative Stress
Investigators from the University of Michigan and Wayne State University Medical School examined whether zinc supplements could improve immunity in fifty healthy seniors aged 55 to 87 (2). Zinc is essential to optimal immune function, and low plasma zinc is common in older individuals. At baseline, subjects had lower serum zinc and higher levels of oxidative stress compared to younger adults. Study participants received 45 mg of zinc or placebo daily for 1 year. The zinc group had significantly fewer infections (Table 3), lower oxidative stress markers, and reduced ex-vivo generation of pro-inflammatory cytokines (TNF-alpha) than placebo.
Lutein and Skin Health
In the controlled, year-long LAST trial, lutein was found to increase macular pigment density and improve measures of visual function such as glare recovery and near visual acuity in men with atrophic AMD (3). Since lutein filters potentially damaging UV light in the macula, scientists have theorized that lutein plays a similar protective role in the skin. Now, results of a double-blind trial from the University of Naples suggest that those taking supplemental lutein for ocular concerns might also derive a skin-protective effect (4).
Reduction in UV-Induced Skin Damage
One hundred twenty women with different skin types, but each exhibiting signs of premature aging, were followed for 12 weeks after assignment to one of four groups: A) oral placebo and topical placebo; B) oral placebo plus topical treatment with lutein and zeaxanthin; C) 10 mg of oral lutein with .06 mg zeaxanthin and topical placebo; or D) the oral supplement combined with topical lutein and zeaxanthin.
Photo-protection was calculated from skin surface redness after a 2 minute exposure to UV radiation on forearms and from susceptibility to sunburn, defined as the minimum erythematous dose. Photo-protection was increased in all the lutein and zeaxanthin treated groups (Fig). Oral supplements provided a 4-fold increase in protection, while the combined topical and oral intervention provided a 6-fold increase in photo-protection compared to controls. Surface lipids and skin hydration were significantly improved in all lutein-treated groups, while peroxidation of skin lipids decreased. Skin elasticity improved only in those topically treated.
Effect of Lutein and Zeaxanthin Upon Photoprotective Activity by Treatment Group Over the Study Period * p < 0.05 vs. placebo treatment at the same week; # p < 0.05 vs. the week 2 treatment value within the same treatment group.
The Rotterdam Study Findings
The Rotterdam Study is an ongoing population-based, prospective cohort study of the factors influencing cardiovascular, neurologic and ophthalmologic diseases. Unlike AREDS, which focused on antioxidant supplementation for people who already had signs of AMD, the current investigation examined whether regular dietary intake of antioxidants could impact the risk of developing AMD in an older Dutch population free of clinical signs of the disease at baseline.
The results, reported in the December 28, 2005 issue of JAMA, strongly suggest that regular intake of antioxidants can markedly lower the risk of developing AMD, in this case by approximately one third (1).
Dietary intake was assessed at baseline for 4,170 people who were at risk of AMD and who completed the follow-up. This at risk population was 55 or older and had no AMD in either eye. Participants had no drusen or pigment irregularities, hard drusen only, or soft drusen without pigment changes.
Incident AMD until final follow-up in 2004 was determined by grading fundus color transparencies. Potential for bias was minimized by grading the photographs in a blinded manner. The main outcome measure was incident AMD, defined as soft distinct drusen with pigment changes, indistinct or reticular drusen, geographic atrophy, or choroidal neo-vascularization.
After a mean follow-up of 8 years (0.3-13.9 years), AMD occurred in 560 participants. After adjusting for known confounders such as atherosclerosis and smoking, dietary intake of vitamin E and zinc were found to be inversely associated with incident AMD. A dose-response relationship between both vitamin E and zinc intake and a reduced risk of AMD was noted.
The researchers also analyzed the combined intake of all 4 antioxidants studied in the AREDS trial: vitamins E and C, zinc and beta-carotene. An intake above the median for all 4 nutrients reduced AMD risk by 35%.
While no relationship between lutein consumption and risk of AMD risk was seen, the difference in intake levels among the lowest and highest quartiles of dietary intake (1.4 vs. 3.6 mg) was small.
These findings may have important public health implications, for they strongly suggest that long-term consumption of antioxidants could prevent or delay the development of early AMD. Recent data, in fact, suggests that oxidative modification of retinal proteins play a critical role in the formation of drusen, implying that antioxidants may have their strongest effect at the initiation of AMD (2).
Risk reduction was observed for dietary intake above the RDA for all 4 antioxidant nutrients compared to each one alone. This indicates that the combination acted synergistically in exerting a protective effect, and underscores the need to maintain a regular, above-RDA intake of all of 4 nutrients over time.
The majority of people in this Dutch cohort appeared to consume a healthy diet. Additionally, the independent relationship between antioxidant supplements and AMD could not be examined in this study since the number of antioxidant supplement users was relatively small, and the necessary data on dose and duration of use was lacking. However supplementation may be helpful in US populations where subgroups fail to consistently consume adequate amounts of antioxidant nutrients.
The Scottish Heart Health Study is an ongoing prospective cohort study of men and women carried out to evaluate risk factors for various coronary heart disease (CHD) events. Patient accrual took place between 1984 and 1987. Reports quantifying various risk factors for prevalent CHD at baseline have been published. Furthermore, preliminary evaluation of risk factors for incident coronary events during long-term follow-up and all-causes mortality have been published. The authors of the present article point out that in the preliminary evaluation, intake levels of antioxidant vitamins were evaluated as risk factors unadjusted for total energy intake and that low intake of antioxidants did not rank as high as the "classic" risk factors for coronary heart events with respect to level of risk. In the present evaluation, the authors re-examined intake of antioxidant vitamins adjusted for total energy intake, age, and other CHD risk factors.
11,629 participants were recruited through general practitioners from 25 Scottish districts. These were men and women aged 40-59 at baseline. Along with sociodemographic data, "classic" risk factor baseline data included Rose Chest Pain Question responses, medical record evaluation, ECG, BP, and serum total cholesterol. A semi-quantitative food frequency questionnaire was used and specifically validated for antioxidant levels against plasma levels. Nutrient intakes were calculated using standard tables. Dietary carotenoids were calculated as beta-carotene equivalents. Participants were flagged on the Scottish National Health Service Register and followed through hospital discharge data for coronary events and all-causes mortality, including through death certificate data. Mean current follow-up was 7.7 years.
The total energy-adjusted consumption of vitamins C and E, beta-carotene, and fiber were higher among women than men.
Among men, energy adjusted intake levels of vitamin C, beta-carotene and fiber in the upper quartile were associated with decreased risks of incident CHD (shown in graph). For fiber and vitamin C, intake level in the 3rd quartile was also associated with decreased risk of CHD. There were similar decreases in risk of all-causes mortality. Higher vitamin E intake was mildly associated with decreased risk of all-causes mortality (38% decrease, 95% CI=8,58) and, the authors concluded, with decreased risk of CHD (note: This reviewer noted that the tables reported in the article indicated weaker associations for vitamin E and CHD than found for vitamin C). Among women, whose overall intake of fiber and anti-oxidant vitamins was higher, only increased fiber intake was associated with decreased risk of CHD or all-causes mortality.
Currently there are strong recommendations and advisories for adequate intake of the B-vitamin, folic acid, among women of childbearing age to prevent neural tube defects. Government mandated folate fortification of cereal grain products has been in place since 1998. Many current studies continue to evaluate use of nutritional supplements to reduce the risk of birth defects. A recent case-control study carried out by researchers at Harvard and Boston Universities evaluated the effect of periconceptual multivitamin supplementation on risk of specific birth defects.
This evaluation was part of a large case-control birth defects study carried out in the Boston area. Births of infants with major malformations detected prior to 5 months (cases) were ascertained in birth and tertiary care hospitals. Cases also included pregnancies terminated due to malformations. There were 8 case groups (with N's ranging from 31 to 186): cleft lip with or without cleft palate, cleft palate only, conotruncal defects, ventricular septal defects, urinary tract defects, limb reduction defects, congenital hydrocephaly, and pyloric stenosis. Control groups were infants totally without birth defects (N=521) and those with birth defects other than those in the case groups (N=442). Mothers were interviewed in their homes regarding factors under study. Daily multivitamin supplementation was evaluated according to gestational timing categories including periconceptual. A multivitamin was defined as a supplement that contained at least 2 water soluble and 2 fat soluble vitamins. 90% of non-prenatal and 100% of prenatal vitamins contained folic acid.
Subjects were divided into groups based on quintile level of the lipid-standardized plasma vitamin E levels. Adjusted Odd's Ratios were computed, (adjusting for age, sex education, BMI, diabetes, smoking, and various cardiovascular parameters), using the lowest quintile as the reference group. After multivariate adjustment, lipid-standardized vitamin E was inversely associated with risk.
When Cases with limb reduction and urinary tract defects were compared with non-malformation controls, use of multivitamins during the periconceptual period (28 days before through 28 days after last menstruation) was higher among controls. The percent decrease in risk for each of these 2 defects is shown in the figure. Results were similar when cases were compared with malformed controls (defects other than the ones under study - a method of protecting against recall-bias in the interview).
The investigators also found a substantial decreased risk of cleft palate alone (no cleft lip) and of urinary tract defects when multivitamins were initiated in the second lunar month of pregnancy. The authors concluded that periconceptual vitamin supplementation may extend benefits beyond a reduction in neural tube defect risk. In this study, specific nutrient or nutrient combinations of benefit could not be discerned.
Reference Werlar MM, Hayes C, Louik C et al. Multivitamin Supplementation and Risk of Birth Defects. Am J Epidemiol 1999;150:675-682.
In a previous
EduFacts, some results from the Nurses' Health Study were reported,
which indicated an inverse relationship between lutein/zeaxanthin
intake and risk of cataract extraction. The authors had presented
this data at the 1998 annual meeting of the Society for Epidemiologic
Research. The meeting abstract indicated a 22% decrease in risk
of cataract extraction with higher intake of lutein/Zeaxanthin.
The full results were recently published (1) and clarified that the
22% decreased risk was among those in the upper decile (10th percentile)
intake level (energy-adjusted) of lutein/Zeaxanthin
compared with the lower quintile (20th percentile) intake level.
Furthermore, there was a significant linear trend (p=0.04) of decreasing
risk of cataract extraction with increasing intake level. In a separate
publication2, the same authors have evaluated the relationship between
vitamin supplement intake and risk of cataract extraction in the
same study cohort.
The incidence of cataract extraction was determined during 720,082 person-years of follow-up in a total cohort of 73,956 women nurses aged 45 or older and free of cancer. Over half were followed for 12 years. Vitamin Supplement intake (multivitamins and, A, C and E) was determined at baseline (1980) and every 2 years afterward. Use was categorized as 'never', 'past use', and 4 categories of current use (<2, 2-4, 5-9, and ≥10).
There were 1377 cataract extractions. Age-adjusted relative risk (RR) associated with <2 years duration of use of vitamin A was elevated and risk of cataract decreased with increasing duration of current vitamin use. However these relative risks were attenuated with control for cigarette smoking.
Among 'never-smokers', duration of use of vitamins C and E of at least 10 years was associated with decreased risk of cataract extraction (relative risks of 0.71 and 0.79 respectively). Risk among 'never-smokers' using vitamin A could not be evaluated due to small numbers.
Despite the decreased risks of cataract extraction demonstrated among non-smokers taking vitamins C and E long-term, the authors concluded that their findings suggested little overall benefit of supplement use. However another interpretation of this study suggests that when eliminating the strong smoking risk factor for cataract, the use of certain supplements may in fact provide additional decreased risk of cataract.
ScienceBased Health's OcularProtect® is a robust multinutrient formulation containing the antioxidant vitamins A, C, and E and other micronutrients for visual and whole body health.
In a previous
EduFacts we summarized results from the prospective Pathologies
Oculaires Liées á l'Age (POLA) Study, which demonstrated
a high level of antioxidant enzymes in patients with AMD and cataract.
The authors suggested that elevated levels of antioxidant levels
may be a marker of oxidative stress in AMD patients. These same
investigators recently published an evaluation of the relationship
between prevalence of AMD and plasma levels of vitamins E, retinol
and vitamin C to determine if a lower plasma level of these antioxidants
was associated with higher risk of AMD.
During 1995 through 1997, participants were recruited in the French city of Séte on the Mediterranean. At the baseline evaluation, presence of AMD was determined by fundus-photograph grading using the Wisconsin system in 2584 patients. Classification was collapsed for analysis into: none, early or late (neovascular) AMD.
Statistical Evaluation: Subjects were divided into groups based on quintile level of the lipid-standardized plasma vitamin E levels. Adjusted Odd's Ratios were computed ( adjusting for age ,sex education, BMI, diabetes, smoking, and various cardiovascular parameters), using the lowest quintile as the reference group. After multivariate adjustment, lipid-standardized vitamin E was inversely associated with risk of late AMD (exudative/ atrophy). The relative risk of late AMD in the highest quintile level was 0.18 (p=0.004). This suggests a decreased risk of late AMD of over 80%. Lipid standardized plasma vitamin E level was also inversely associated with early signs of AMD ( any kind of soft drusen, hyperpigmentation). The Odd's Ratio was 0.72 (28% decreased risk) in the highest vs lowest quintile level.
The authors stated that these results suggest that vitamin E may provide protection against AMD but that randomized interventional studies were necessary to establish such an effect.
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Complete is a powerful formulation for macular and whole
body health, based on the AREDS
clinical trial, and also includes a complete multinutrient component.
It is generally believed that oxidative mechanisms play a major etiologic role in the development of age-related macular degeneration (AMD) and cataract. The etiology is a decrease in efficiency of the body's natural antioxidative mechanisms, including enzymatic, and non-enzymatic (antioxidant micronutrients). However, ophthalmologists continue to debate both the value of, and the best method for, optimizing anti-oxidative processes in the eye. For example, critics of recommending use of supplemental antioxidants sometimes suggest, even insist, that the epidemiologically studied associations between level of intake (both dietary, supplemental, or both) of antioxidant micronutrients and risk of cataract or AMD may not be causal - that decreased risk may be due to other factors in the food. One way of evaluating the role of oxidative stress in the disease process is to measure and evaluate the serum level of antioxidant enzymes in healthy patients and those with ocular disease. High systemic levels could be indicative of an increased level of oxidative stress. Investigators from the prospective Pathologies Oculaires Liées á l'Age (POLA) Study evaluated the association of age-related ocular pathologies with two antioxidant enzymes (1).
During 1995 through 1997, participants were recruited in the French city of Séte on the Mediterranean. At the baseline evaluation, presence of AMD was determined by fundus-photograph grading using the Wisconsin system in 2,196 patients. Classification was collapsed for analysis into: none, early, or late (neovascular) AMD. LOCSII was used to determine presence of cataract (none, mild, moderate, severe). Erythrocyte superoxide dismutase (SOD) activity and plasma level of glutathione peroxidase (GPx) were measured using accepted laboratory technique. Percentiles of SOD and GPx were determined. Logistic regression was used to obtain adjusted Odd's ratios (high vs. low percentile of antioxidant enzyme) for presence of disease. Age, sex, and potential confounders were included in the statistical models.
Cataracts: A strong association was found between plasma GPx and prevalence of severe cataract. Subjects in the highest quintile of GPx had over a 6-fold higher prevalence of cortical cataract, and about a 2-fold higher prevalence of nuclear or mixed cataract. The Odd's ratios were all significant. AMD: Subjects in the highest 4 quintiles of GPx had a 10-fold greater prevalence of late AMD compared with the lowest quintile level. Excess risk was not found for early AMD. Highest quintile level of erythrocyte SOD activity was associated with about a 2-fold increased prevalence of nuclear cataract but not other cataract types or AMD.
Adjusted Odd's Ratios (1) (Highest vs lowest quintile level)
GPx Odd's Ratio*
SOD Odd's Ratio*
*Odd's of increased prevalence of disease among subjects in highest vs lowest quintile level of SOD or GPx ** The 4 higher vs the lowest quintile
The authors concluded that age-related eye diseases are linked to high levels of antioxidant enzymes, particularly GPx - which reduces mainly hydrogen peroxide and organic hydroperoxides. They suggested that a high concentration of antioxidant enzymes might be a marker that oxidative stress is present.
In earlier EduFacts communiqués we have summarized reports
in the literature evaluating the relationships between dietary intake
levels/serum levels of dietary carotenoids and risk of age-related
macular degeneration and cataract. A recent evaluation of the Third
National Health and Nutrition Examination Survey (NHANES III) data
explored the relationship between diabetes mellitus and serum carotenoid
The article points out that diabetes is a condition characterized by oxidative stress. This etiology is hypothesized based on demonstrated increased reactive oxygen species and, lipid peroxidation and increased free radical activity. The authors hypothesize that oxidative stress may result in a lowering of antioxidant concentrations in glucose-intolerant patients.
Phase I of NHANES III was conducted between 1988 and 1991. This was a cross sectional survey using a sophisticated design enabling generalization of results to the non-institutionalized U.S. civilian population. Of the phase I subjects, 1665 had oral glucose tolerance tests yielding valid glucose tolerance status. Patients were classified as: 1) normal, 2) impaired glucose tolerance, and 3) newly diagnosed diabetes according to World Health Organization criteria. Five carotenoids were assayed at the CDC laboratory: alpha-carotene, beta-carotene, cryptoxanthin, lutein /zeaxanthin and lycopene. Covariate-adjusted geometric means of these carotenoids were computed for the 3 groups. The covariates included socio-demographic variables, physical activity, alcohol consumption, dietary intake (single 24-hour recall), vitamin use, serum cholesterol, HDL, BP, body mass index and activity levels.
Beta-carotene levels and lycopene levels (adjusted geometric means) decreased linearly with glucose tolerance status.
The authors concluded that the NHANES III data suggest that serum carotenoid concentrations are associated with insulin-resistance and glucose tolerance status. The ordinal status from normal to impaired to new diabetes showed a linear trend with respect to the levels of beta-carotene and lycopene.
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