• Research Summaries - Multinutrients

• OcularProtect Monograph

New! Now with trans-resveratrol, pomegranate extract, and more B12!

Vitamins C (400 mg) and E (200 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 attack.

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 eye’s lens. OcularProtect provides vitamin C at levels consistent with these findings.

Studies also report that higher vitamin E intakes or blood levels may improve one's chance of prolonging lens and macular health. OcularProtect provides the amount used in the Age Related Eye Disease Study (AREDS), an appropriate level for healthy people. Natural vitamin E (tocopherol) is used - shown to be better absorbed and retained - plus broad spectrum alpha to gamma tocopherol, that together play a health-protective role.

FloraGLO^® Lutein (7 mg) and Zeaxanthin (1 mg)
Lutein and zeaxanthin are similarly structured carotenoids that compose the macular pigment, the area of the retina's center where the sharpest central vision occurs. Macular pigment filters out blue (visible) light that can cause photo-oxidative damage. Lutein and zeaxanthin are also the only carotenoids detected in the eye's lens. Higher intake is linked with significantly lower risk of lens opacity or likelihood of undergoing cataract surgery.

Population-health studies have examined lutein's relationship with macular health. In studies with low lutein intake, no association was seen, while in studies with wider ranges of intake, those eating the highest lutein (6-7 mg daily) were more likely to maintain macular health. Macular pigment density is linked with improved macular function. Both elevated serum levels and consumption of the two carotenoids (up to 6.5 mg daily) are related to greater pigment density. OcularProtect provides levels of lutein and zeaxanthin consistent with these findings, and in a balanced ratio reflecting dietary intake.

Zinc (25 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 eye 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. OcularProtect provides bioavailable zinc at about 1/3 the therapeutic dose administered in AREDS, a prudent level 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 eye’s cornea. It also interacts with zinc and the amino acid taurine in retinal photoreceptors.

Selenium is required for proper function of glutathione peroxidase, an antioxidant enzyme found in the lens and localized in photoreceptor and retinal pigment epithelial cells. Low selenium levels have been detected in lenses of patients with age-related cataract.

New! Trans-resveratrol is an important component of red wine believed to contribute to wine’s 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 four 4 oz. glasses of pinot noir, a wine with one of the highest trans-resveratrol contents.

New! Pomegranate extract – Fruit of Punica granatum (pomegranate) has a long history of use in several systems of medicine. The synergistic action of pomegranate components appears better than individual components alone (polyphenols, punicalagins, & others). Pomegranate extracts are shown to exhibit antioxidant properties and their components also have anti-inflammatory properties. The antioxidant activity of pomegranate juice can be as much as three times higher than red wine or green tea. Limited clinical data indicate blood pressure lowering effects and artery benefits.

N-Acetylcysteine contributes the major building block for glutathione peroxidase, enabling the body to produce its own supply of the enzyme, which is poorly absorbed from foods.

Taurine is an amino acid made in the body and selectively concentrated in eye tissues. Taurine helps stabilize retinal cell membranes and may act as an antioxidant in the lens.

Alpha Lipoic Acid is a fat and water-soluble antioxidant that can scavenge free radicals and help recharge other antioxidants such as glutathione and vitamin C. Experimentally, alpha lipoic acid protects against oxidative stress in the retina.

Lycopene 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 2 mg of lycopene, which increases typical dietary intakes by 40%.

Green Tea Extract delivers the unique polyphenols found in 1 cup of tea. Absorption of green tea polyphenols and their antioxidant activity in blood is enhanced when taken in capsules versus drinking the beverage. Green tea works with vitamin C to decrease formation of compounds that cause abnormal cellular changes.

Broccoli Sprout Extract contains standardized levels of sulforaphane. Extensively researched, sulforaphane plays a role in boosting the body’s natural defense system that detoxifies substances before they can damage cells. Regular consumption of cruciferous vegetables like broccoli is critical to protecting cellular health.

OptiBerry ^® Mixed Berry Blend is a rich source of healthful anthocyanins, and is equivalent to consuming 1/2 cup of berries daily. This unique blend of 6 different berries scored highest among many berry combinations tested for their antioxidant capacity and ability to thwart the unwanted growth of vessels (anti-angiogenesis).

And More ... Plant compounds with antioxidant activity such as the flavonoids contribute to the health benefits of eating five or more fruit and vegetable servings daily. Additional flavonoids are derived from a wide variety of sources: billberry, citrus, grape seed, Ginkgo biloba and quercetin found in apples and onions. As antioxidants, they support healthy retinal circulation and ocular health.

1. Fletcher RH and Fairfield KM. Vitamins for chronic disease prevention in adults: Clinical Applications. JAMA 287: 3127-129, 2002.
2. Chandra RK. Effect of vitamin and trace element supplementation on immune responses and infection in elderly subjects. Lancet 340: 1124-1127, 1992.
3. Chandra RK. Effect of vitamin and trace-element supplementation on cognitive function in elderly subjects. Nutrition 17: 709-712, 2001.
4. Kuzniarz M, et al. Use of vitamin supplements and cataract: The Blue Mountains Eye Study. Am J Ophthalmol 132: 19-26, 2001.
5. Christen WG, Glynn RJ, Chew EY, Albert CM, Manson JE. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med 169: 335-341, 2009.
6. Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Intern Med 129: 517-524, 1998.
7. Clark LC, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 276: 1957-1963, 1996.
8. Anderson RA. Review: Chromium in the prevention and control of diabetes. Diabetes Metab 26: 22-27, 2000.
9. Jacques PF, et al. Long-term nutrient intake and early age-related nuclear lens opacities. Arch Ophthalmol 119: 1009-1019, 2001.
10. Jacques PF. The potential preventive effects of vitamins for cataract age-related macular degeneration. Int J Vitam Nutr Res 69: 198-205, 1999.
11. AREDS Report No. 8. A randomized, placebo-controlled clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss. Arch Ophthalmol 119: 1417-1436, 2001.
12. Weinstein SJ. Serum alpha-tocopherol and gamma-tocopherol in relation to prostate cancer risk in a prospective study. J Natl Cancer Inst. 97: 396-399, 2005.
13. Morris MC, et al. Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. A J Clinc Nutr 81: 508-14, 2005.14.
14. Stahl. W. Review: Macular carotenoids: lutein and zeaxanthin. Dev Ophthalmol 38: 70-88, 2005.
15. Moeller SM, et al. The potential role of dietary xanthophylls in cataract and age-related macular degeneration. J Am Coll Nutr 19: 522S-527S, 2000.
16. Ribaya-Mercado JD, et al. Lutein and zeaxanthin and their potential roles in disease prevention. J Am Coll Nutr. 23: 567S-587S, 2004.
17. Alves-Rodrigues A, et al. The science behind lutein. Toxicology Lett 150: 57-83, 2004.
18. Seddon JM, et al. Dietary carotenoids, vitamin A, C and E and advanced age-related macular degeneration. JAMA 272: 1413-1420, 1994.
19. Beatty S, et al. Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population. Invest Ophthalmol Vis Sci 42: 439-446, 2001.
20. Curan-Celentano, et al. Relationship between dietary intake, serum concentrations, and retinal concentrations of lutein and zeaxanthin in adults in a Midwest population. Am J Clin Nutr 74: 796-803, 2001.18
21. Grahn BH, et al. Review: Zinc and the eye. J Am Coll Nutr 20: 106-118, 2001.
22. van Leeuwen R, et al. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 2034: 3101-3107, 2005.
23. Karakucuk S, et al. Selenium concentrations in serum, lens and aqueous humor of patients with senile cataract. Arch Ophthamol Scan 73: 329-332, 1995.
24. Keys SA, Zimmerman WF. Antioxidant activity of retinol, glutathione, and taurine in bovine photoreceptor cell membranes. Exp Eye Res 68: 693-702, 1999.
25. Obrosova IG. Early changes in lipid peroxidation and antioxidative defense in diabetic rat retina: effect of alpha lipoic acid. Eur J Pharmacol 398: 139-146, 2000.
26. Campbell JK, et al. (Review) Tomato phytochemicals and prostate cancer risk. J Nutr 134: 3486S-3492S, 2004.
27. Nkondjock A, et al. Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr 135: 592-597, 2005.
28. Henning SM, et al. Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea or a green tea extract supplement. Am J Clin Nutr 80: 1558-1564, 2004.
29. Veermeer IT, et al. Effect of ascorbic acid and green tea on endogenous formation of N-nitrosodimethylamine and N-nitrosopiperidine in humans. Mutat Res 428: 353-361, 1999.
30. Keck AS, et al. Cruciferous vegetables: cancer protective mechanism of glucoinolate hydrolysis products and selenium. Integr Cancer Ther 3: 5-12, 2004.
31. Bagchi D, et al. Anti-angiogenic, antioxidant and anti-carcinogenic properties of a novel anthocyanin-rich berry extract formula. Biochemistry 69: 75-80, 2004.
32. Heber D. Review: Vegetables, fruits and phytoestrogens in the prevention of diseases. J Postgrad Med 50: 145-149, 2004.

Drink to your Health: Red Wine and Pomegranate Juice
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 vitamins C, E and beta-carotene 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 walls.
References

1. Geleijnse JM, et al. Flavonoids and cardiovascular health: which compounds, what mechanisms? Am J Clin Nutr 88:12, 2008.
2. Erdman JW, et al. Flavonoids and heart health: proceedings of the ILSI North America Flavonoids Workshop, 2005, Washington, DC. J Nutr 137(3 Suppl 1):718S-37S, 2007.
3. de Giuseppe R, et al. Alcohol consumption and n-3 poly-unsaturated fatty acids in healthy men and women from 3 European populations. Am J of Clin Nutr 89:354-62, 2009.
4. Vingtdeux V et, al. Therapeutic potential of resveratrol in Alzheimer's disease. BMC Neurosci 9 Suppl 2:S6, 2008.
5. Barger JL, et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.
6. Basu A, et al. Review, Emerging Science. Pomegranate juice: A heart-healthy fruit juice. Nutr Rev 67:49-56, 2009.
7. Jurenka JS. Review: Therapeutic applications of pomegranate. Altern Med Rev 13:128-44, 2008.
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Four New Studies Underscore Vital Role of Vitamins & Minerals
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 vitamin D supplements in over 42,000 adults aged 65 or older (2). They found that supplemental vitamin 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 of vitamin D.
Risk of Colds Influenced by Vitamin D?
Vitamin 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 of vitamin 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 acid, B6 and B12. 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.
References

1. Park Y, et al. Dairy food, calcium and risk of cancer in the NIH-AARP Diet and Health Study. Arch Int Med 169:391-401, 2009.
2. Bischoff-Ferrari HA, et al. A meta-analysis of randomized controlled trials Prevention of non-vertebral fractures with vitamin D and dose dependency. Arch Int Med 169:551-61, 2009.
   
3. Ginde A, et al. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection the Third National Health and Nutrition Examination Survey. Arch Int Med 169:484-90, 2009.
   
4. Christen W, et al. Folic acid, pyridoxine, cyanocobalamin combination treatment and age-related macular degeneration in women. Arch Int Med 169:335-4, 2009.
   
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In the News: B12 & the Brain, Omega-3 & Broccoli for Ailing Hearts
B12 May Help Retain Brain Volume with Age
Maintaining optimal blood levels of vitamin B12 is important, as low levels appear to increase the risk for impaired mental function and neurological disorders. A new study now indicates that failure to get enough B12, or absorb it well, may actually cause the brain to shrink.
The participants in this study, who had an average age of 73 with no mental impairments at the beginning, were divided into 3 groups based on their B12 levels. They underwent MRI scans to measure brain volume and physical and mental exams annually. At the end of the 5-year study period, the group with the lowest B12 levels (below 308 pico-moles/L) lost twice as much brain volume as those with the highest levels. The same researchers are now conducting a study to see whether improving B12 levels will actually prevent brain shrinkage.
It's estimated that up to 25% of the elderly may be B12 deficient. Poor dietary intake or absorption of this vitamin, found only in foods of animal origin including meat, milk, eggs, as well as some fortified cereals, is usually the problem. Most commonly, the age-related decline in stomach acid makes it difficult to digest B12. In addition, some people don't make enough of a small protein called intrinsic factor, which is needed for efficient B12 absorption. The Institute of Medicine recommends supplemental B12 for those over 50, and those with a lack of intrinsic factor often need medical intervention.
Fish Oil Helps Survival Rates in Heart Failure
According to new research, a daily supplement of fish oil omega-3 reduced mortality and cardiovascular-related hospital admissions for patients with heart failure, while statin drugs had no beneficial effect in the same group of patients.
Years ago, a group of Italian researchers (the GISSI) documented the preventive benefits of fish oil in those who had a heart attack by reducing their subsequent risk of sudden death. This same research group has recently published the results of the first large-scale double blind trial investigating the effectiveness of fish oil in chronic heart failure.
In the first trial, 6,975 patients with symptomatic heart failure were randomized to receive either 1 gram daily of omega-3 (EPA and DHA in ethyl ester form) or placebo. After nearly 4 years of follow-up, the risk of mortality was reduced by 9% and hospitalization for cardiovascular causes decreased by 8%.
In contrast, chronic heart failure patients assigned to get 10 mg of a statin drug (rosuvastatin) fared no better in terms of survival or hospitalization rates than those getting placebo. Even though the statin lowered LDL cholesterol and the inflammation marker CRP, the investigators theorize that once heart failure is established, statins may not allow patients to escape the underlying heart-disease process.
Broccoli May Reverse Heart Vessel Damage
Researchers report that compounds such as sulforaphane in broccoli may help counter processes thought to lead to vascular disease in diabetes. The investigators concluded that sulforaphane may function as a "dietary activator", preventing dysfunctional responses of endothelial cells that line the interior of blood vessels caused by elevated blood sugar. Endothelial cell dysfunction is common in diabetics.
The research team found a 73% in reduction in free radicals, which are known to increase in diabetics. While this study was conducted in cultured human endothelial cells, it may help explain why large-scale studies have linked high intake of broccoli, Brussels sprouts and cabbage to a lower risk of developing diabetes.
References

1. Vogiatzoglou A, et al. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology 71:826-32, 2008.
2. GISSI-HF Investigators. Effect of n-3 poly-unsaturated fatty acids in patients with chronic heart failure: a randomized, double-blind controlled trial. Lancet Aug. 29, 2008 [epub ahead of print].
3. GISSI-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure: a randomized, double-blind placebo-controlled trial. The Lancet 372:1231-9, 2008.
4. Xue M, et al. Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes 57:2809-17, 2008.
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Recent Research on Diet, Antioxidants & Cataract
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 (1).
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 beta-carotene; zinc; and vitamins A, C and, 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 C and E, beta-carotene, and zinc, also had a reduced cataract risk compared with those consuming fewer antioxidants.
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 median 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 lutein, zeaxanthin and vitamin E may also help delay cataract formation (2). Lutein and 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 lutein and 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).

For 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 foods infrequently.
References

1. Tan AG, et al. Antioxidant nutrient intake and the long-term incidence of age-related cataract: the Blue Mountains Eye Study. Am J Clin Nutr 87:1899-905, 2008.
2. Christen WG, et al. Dietary carotenoids, vitamins C and E, and risk of cataract in women: A prospective study. Arch of Ophthalmol 126:102-109, 2008.
3. Chiu C-J, et al. Long-term dietary carbohydrate intake, glycemic index and odds for early nuclear and cortical lens opacities. Am J Clin Nutr 81:1411-6, 2005.
4. 4. Chiu C-J, et al. Association between dietary glycemic index and age-related macular degeneration in nondiabetic participants in the Age-Related Eye Disease Study. Am J Clin Nutr 86:180-88, 2007.
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Update: Green Tea & Health
Green Tea Research Expands
Over the past decade, many experimental and population-health studies have linked green tea to a variety of health benefits such as the prevention of cardiovascular disease, cancer, and the decline in brain function that occurs with aging. A 2007 review indicates that, while not all the findings have been consistent, cardiovascular and metabolic health benefits can be obtained by regular consumption of 5-6 or more cups of green tea daily (1).
Buoyed by these findings, researchers are now studying green tea or green tea extracts in a more systematic manner by conducting controlled intervention trials. Three of these clinical trials, highlighted below, suggest that green tea may indeed have a beneficial effect on heart health.
Green Tea Supports Blood Vessel Health
Scientists studied the effects of 6 grams of green tea (the amount typically in 3 tea bags), 125 mg of caffeine (the amount contained in 6 grams of tea), or hot water on flow-mediated dilation of the brachial artery in healthy subjects (2). Flow-mediated dilation is a measure of the artery's ability to relax and expand, and is considered to be an independent predictor of cardiovascular risk.
Artery dilation increased significantly after tea, while it did not change with caffeine or the hot water placebo. This indicated that green tea's positive effects were not related to caffeine, rather that green tea's polyphenols were more than likely responsible for its effects on blood vessel health.
Response to Insulin Improved by Green Tea
Green tea has been shown to promote fat oxidation (fat burning) in humans, and to prevent obesity and improve the response to insulin in mice. This led researchers at the Human Performance Laboratory, University of Birmingham, to examine the effect of high dose green tea extract on glucose tolerance and fat oxidation in healthy men undergoing moderate intensity exercise (3).
Healthy young men underwent a glucose tolerance test and fat oxidation was measured before and after 30 minutes of cycling. In the 24 hour period before these tests, participants were given green tea extract containing about 366 mg of EGCG (the main polyphenol in green tea) or a placebo pill.
Average fat oxidation rates were 17% higher after the men took green tea extract compared to the test when they took the placebo. The scientists also observed an increase of 13% in insulin sensitivity after taking the green tea extract and cycling. Insulin sensitivity is a measure of how well the body responds to insulin's job of getting sugar into cells and out of the blood stream. Insulin sensitivity is one measure of one's risk for heart disease. The more insulin sensitive one is in general, the lower the risk for diabetes and heart problems.
Green Tea Protects LDL Cholesterol
In this study, researchers evaluated the effect of antioxidant green tea catechins (polyphenols) on LDL cholesterol in healthy adults (4). When LDL particles become damaged by oxidation they contribute to the process of atherosclerosis or clogged arteries.
The subjects were randomly divided into two groups, a control group and a group that received 500 mg of catechins, equivalent to about 6 or 7 cups of green tea. After 4 weeks, the green tea group had significantly lower levels of oxidized or damaged LDL cholesterol.
References

1. Wolfram S. Review. Effects of green tea and EGCG on cardiovascular and metabolic health. Journal American College of Nutrition 26:373S-88S, 2007.
   
2. Alexopoulos N, et al. The acute effect of green tea consumption on endothelial function in healthy individuals. European Journal of Cardiovascular Prevention Rehabilitation 15:300-5, 2008
   
3. Venables MC, et al. Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans. American Journal of Clinical Nutrition 87:778-84, 2008.
   
4. Inami S, et al.Tea catechin consumption reduces circulating oxidized low-density lipoprotein. International Heart Journal 48:725-32, 2007.
   
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Anti-Glare Effects of Lutein, Zeaxanthin; Vitamin D for Artery Health
Scientists Examine Lutein's Effect on Glare
New research indicates that the carotenoids lutein and zeaxanthin may help our vision when we have difficulty seeing due to the glare encountered in very bright light (1).
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, lutein and 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 headlights.
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 lutein and 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 zeaxanthin.
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 PAD.
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.
References

1. Stringham JM, Hammond BR. Macular pigment and visual performance under glare conditions. Optometry Vision Science 85:82-8, 2008.
2. Melamed VL, et al. Serum 25-hydroxyvitami D levels and the prevalence of peripheral arterial disease. Results from NHANES 2001-2004. Arteriosclerosis, Thrombosis and Vascular Biology Epub April, 2008.
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Four Good Reasons to Take a "Multi" Regularly
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 C, the 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 B-12 and 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.
References

1. Sebastian R, et al. Older adults who use vitamin/mineral supplements differ from nonuser in nutrient intake adequacy and dietary attitudes. J Am Dietetic Assoc 107(8):1322-32, 2007.
   
2. AREDS Research Group. Centrum use and progression of age-related cataract in AREDS. Ophthalmol 113:1264-0, 2006.
   
3. Major GC, et al. Multivitamin and dietary supplements, body weight and appetite: results from a cross-sectional and a randomized double-blind placebo-controlled study. Br J of Nutrition, Epub, 2007.
   
4. Gariballa S and Forster S. Effects of dietary supplements on depressive symptoms in older patients: A randomized double-blind placebo-controlled trial. Clinical Nutrition 26(5):545-51, 2007.
   
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Spicing it Up with Healthful Turmeric
Turmeric - In India it's the 'Spice of Life'
Many herbs and spices are thought to have healthful properties in addition to adding zing and flavor to foods. Ginger helps settle upset stomachs for instance, while rosemary and thyme contain anti-oxidants. Though less commonly found on American menus, one spice that has garnered attention in the scientific arena is turmeric.
The source of turmeric is a leafy plant in the ginger family called Curcuma longa. Ground turmeric is made from the brightly colored flesh of finger-like rhizomes which extend from the root. The bright yellow color of turmeric comes mainly from pigments known as curcuminoids. Curcumin is the principal and most active curcuminoid.
Turmeric is grown and consumed in China and Indonesia, but the world's primary producer of turmeric is India where it's been used as a spice and for medicinal purposes for centuries. More recently, evidence that curcumin may have anti-inflammatory and anti-cancer activities has prompted scientific interest in its potential to prevent and treat disease.
Curcumin and Colon Health
The incidence rate of most digestive tract cancers, including colon cancer, is lower in India than in developed countries (1). Observational studies also suggest that the presence of natural antioxidants such as curcumin in Indian cooking may contribute to these low rates.
To date, five phase I or preliminary clinical trials have been completed showing the safety of curcumin in colorectal cancer patients (2). The success of these trials has led to the development of phase II trials that are currently underway to test whether high dose curcumin has a role in helping to treat the disease. Extremely high doses are required because the bio- availability of curcumin is low (3).
How Might Curcumin Act?
Experimental work has shown that curcumin posses potent antioxidant and anti-inflammatory activity. It may intervene in cancer development from a number of different angles. Studies in cultured cancer cells or in animals suggest that it may help eliminate potential carcinogens, for example, or block the growth of new blood vessels needed by cancer cells to fuel their rapid growth. Curcumin may also stimulate colon cancer cell death through cell signaling pathways.
While there is no conclusive proof that curcumin helps maintain colon health, it makes sense to include this spice in your diet along with minimizing intake of red and processed meat and getting adequate calcium and vitamin D - factors that reduce colon cancer risk (4).
Spice Up Your Diet
Turmeric has a warm and bitter flavor, with a mild fragrance reminiscent of orange and ginger. While it is best known as one of the ingredients used to make curry, it also gives mustard its bright yellow color. You'll find turmeric in many Southeast Asian and Indian foods, including lentil and meat dishes, mustard blends and chutneys. In addition to traditional curries, rice and chicken dishes, try some new ways to include turmeric:
• Sprinkle the spice on steamed or sautéed green beans and onions;
• Sauté chopped cauliflower florets with a spoonful of turmeric, then toss with olive oil, salt and pepper
• Mix turmeric and dried onion with a little mayo, salt and pepper, and serve with raw veggies for a low-calorie dip;
• Use turmeric to complement lentil dishes;
• Add turmeric to egg salad for a bolder yellow color;
• Combine brown rice with raisins and cashews and season with turmeric, cumin and coriander.
In general, choose turmeric rather than prepared curry blends, which contain less curcumin.
References

1. Mohandas KM, et al. Epidemiology of digestive tract cancers in India: Large and small bowel.18:118-21, 1999.
   
2. Johnson JJ and Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett 255:170-81, 2007.
   
3. Hsu CH and Cheng AL. Review. Clinical studies with curcumin. Adv Exp Med Biol 595:471-80, 2007.
   
4. Ryan-Harshman M, et al. Diet and colorectal cancer: Review of the evidence. Can Fam Physician 53: 1913-1920 2007.
   
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Vitamin D: Higher Levels Needed for Better Health
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 health.
What Does the Research Tell Us?
Many studies have linked higher intakes or blood levels of 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 received 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 of 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 assessment of 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.
Although 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.
Note: In response to emerging research on vitamin D, ScienceBased Health has increased the level of vitamin D to 900 IU in its primary, comprehensive multinutrient products (except OcularEssentials, which has been increased to 800 IU), taking into account the average dietary intake and that many "multi" users also take a separate calcium supplement which usually contains an additional 100-400 IU vitamin D. (The SBH product BoneProtect provides 300 IU vitamin D along with calcium, making it ideal to pair with any SBH multinutrient). OcularProtect (from 400 IU to 900 IU) MacularProtect Complete and MacularProtect Complete-S (from 400 IU to 900 IU) OcularEssentials (from 400 IU to 800 IU)
References

1. Autier P, et al. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 167:1730-7, 2007.
   
2. Lappe JM, et al. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. AJCN 85:1586-91, 2007.
   
3. Bischoff-Ferrari HA, et al. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. AJCN 84:18-28, 2006.
   
4. Hathcock JN, et al. Risk assessment for vitamin D. AJCN 85:6-18, 2007.
   
5. Veith R, et al. The urgent need to recommend an intake of vitamin D that is effective. AJCN 85:649-50, 2007.
   
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Growing Health Importance of Dietary Flavonoids
Enter the Diverse World of Flavonoids
Flavonoids, or 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:
• Flavonols. Good sources of flavonols in the diet are onion, kale, broccoli, lettuce (the greener the leaf, the higher the content), tomato, apple, grape, berries, tea and red wine. Examples include quercetin, myricetin and kaempferol.
• Flavones like luteolin and apigenin are found in foods like celery and parsley.
• Flavonones. Abundant in citrus fruits and juices - members include hesperetin & naringenin.
• Anthocyanins are the red to purple pigments that color fruits and veggies such as red cabbage, plum, cranberry, bilberry and blueberry. Cyanidin, delphinidin and malvidin are examples.
• Catechins (proanthocyanides). Best known as green tea components, they are also found in red wine, chocolate, apples and berries. Members include epicatechin, gallocatechin and EGCG.
• Isoflavones are a special sub-class that includes lignans from flaxseeds, legumes, whole grains, fruits and vegetables, and isoflavones (genistein, daidzein) from soy foods. These compounds can mimic some of the effects of estrogens.
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 nutrients.
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.
References

1. Fink BN, et al. Dietary Flavonoid Intake and Breast Cancer Risk among women on Long Island. Am J of Epi 165:514-23, 2007.
2. Hanneken A, et al. Flavonoids protect human retinal pigment epithelial cells from oxidative stress-induced death. Inv Ophthalmol Vis Sci. 47:3164-77, 2006.
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Lutein and AMD: Results from CAREDS
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 beneficial.
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) (http://www.cfsan.fda.gov/list.html).
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.
Reference

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.

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Nutrition News Bites: Green Tea, Calcium, and Shingles-Fighting Foods
Green Tea: Brain Beverage of Choice?
Drinking more than 2 cups of green tea daily could cut the risk of dementia by half, according to a new population-health study of elderly subjects (1). Researchers analyzed the consumption of beverages and foods for 1000 Japanese men and women with an average age of 74, and tested their cognitive function using a validated examination. Compared to people who drank less than 3 cups weekly, those drinking more than 2 cups daily had a 50% lower chance of having poor mental function.
The researchers believe that compounds in green tea called polyphenols, especially the polyphenol EGCG, could explain their observation. EGCG, which is able to enter brain tissue, is a strong antioxidant and may help prolong nerve cell survival. EGCG may also work by stimulating the growth of neurites, the hair-like projections on neurons that allow nerve cells to communicate with each other.
Big Problems with the WHI Calcium Findings
In addition to examining the health effects of a reduced fat diet (see March Staying Healthy), the Women's Health Initiative also studied the effects of calcium and vitamin D in healthy post-menopausal women. The WHI researchers just reported that "calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, but did not significantly reduce hip fractures" (2). Many public health experts are worried that these headlines could cause women to give up on calcium supplements, thus undermining their bone strength.
An editorial that appeared along with the WHI publication in the New England Journal of Medicine points out that several aspects of the study may well have interfered with its ability to show a benefit in fracture rate. Two of the study's major stumbling blocks include:
• Compliance among the women was poor, with only 59% of the women adhering well to the supplement program. In fact, among those who actually took their calcium and D supplements regularly enough, the number of fractures was 29% lower than in the placebo group.
  
  
• The amount of vitamin D was very likely too low. The women received 1,000 mg of calcium daily along with 400 IU vitamin D. However, in recent years - and long after the WHI trial began - studies pointed to the need for a higher level of vitamin D. A comprehensive review of these studies found that 700-800 IU vitamin D daily is necessary to reduce the risk of hip fracture in older individuals, and concluded that an oral dose of 400 IU/day is not sufficient for fracture prevention in older people (3).
Vitamin D and calcium aren't the only things that can reduce fracture risk: regularly weight-bearing exercise, smoking cessation and adequate protein intake are also risk-reducing. But sufficient D and calcium are still important for women before and after menopause.
Fruits, Veggies Cut the Risk for Shingles
British researchers examined the relationship between vitamin and mineral intake, as well as fruit and veggie consumption and the risk of getting shingles. The virus that causes shingles (herpes zoster) is found in everyone who has had chicken pox, a disease that has affected more than 90% of most populations. If the immune system is weakened, the dormant virus can reactivate. Older people are more at risk for shingles.
The investigators compared the intake of 7 nutrients that are necessary for immune function in 243 people who had shingles with intake of the nutrients in healthy aged-matched controls (4). They found that people with limited intake of these nutrients - vitamins A, B6, C, E, folic acid, iron and zinc - had a 5-fold increased risk of shingles. Eating less than a piece of fruit daily was also linked to a 3-fold increase in risk. Many of these 'immune' nutrients are plentiful in fruits and vegetables.
References
1. Kuriyama S et al. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. .Am J Clinical Nutrition 83:355-61, 2006.
2. Jackson RD et al. Calcium plus vitamin D supplementation and the risk of fractures. N Eng J Med 354:669-83, 2006.
3. Heike A. Fracture prevention with vitamin D Supplementation:. a meta-analysis of randomized controlled trials. JAMA 293:2257- 2264, 2005.
4. Thomas SL et al. Micronutrient intake and the risk of Herpes zoster: a case control study. Inter J of Epidemiology (Epub online, 2005)
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News Briefs: Crucifers, Lung & Stomach Health; Magnesium & Bone Strength; Selenium & Joint Vitality
Crucifers May Help Lower Lung Cancer Risk
Studies have consistently linked consumption of green cruciferous vegetables - broccoli, cabbage and Brussels sprouts - with reduced rates of lung cancer. Crucifers contain protective compounds called isothiocyanates (eye-so-thigh-o-SIGH-en-ates). Newly published research confirms the importance of these compounds (1). The findings also suggest that many of us would benefit from eating more crucifers, though their protective effect appears to be stronger for some individuals.
Protective isothiocyanates are normally eliminated from the body by enzymes produced by two genes named GSTM1 and GSTT1. People with inactive forms of these genes have higher levels of the protective compounds. Researchers wanted to know whether people with the inactive genes might be more shielded from lung cancer risk since they retain more of these protective compounds in the body.
The study found that regular crucifer consumers (weekly vs. infrequently) who had the inactive form of "M1" or "T1"lowered their risk of lung cancer by 33% and 37% respectively. For those with both genes inactive, risk was cut by 72%. While people with the active form of both genes received no added protection, it's important to note that the non-active gene forms are fairly common. They occur in 50% (GSTMI) and 20% (GSTT1) of the population.
Broccoli Sprouts May Also Calm Gastritis
At a cancer conference in October (2), Japanese investigators reported that eating broccoli sprouts daily improves chronic bacterial gastritis (inflamed stomach lining) by fighting H. pylori - the bacteria responsible for many cases of bacterial gastritis and stomach ulcers. These sprouts contain sulfuraphane (sul-FOR-a-fain), an isothiocyanate that may protect cells from injury and slow H. pylori.
Subjects infected with H. pylori consumed about 1½ cups of broccoli sprouts daily or the same amount of alfalfa sprouts, which contain no sulfuraphane. Only the broccoli group had lower markers of H. pylori and gastritis after 2 months, which returned to their initial levels several months after the study ended.
More Magnesium for Stronger Bones
Though less well studied than calcium, magnesium is also believed to play a role in bone strength. The Health ABC Study was conducted in over 2000 older men and women to examine whether magnesium intake is associated with bone mineral density (BMD) (3). People with higher BMD are less likely to experience bone fractures.
BMD was reported to be significantly greater in men and women getting the most magnesium (394 mg on average) compared to those getting the least (about 248 mg). Magnesium supplements appeared to be an important contributor to overall intake. Nearly 58% of those in the highest magnesium group took supplements compared to less than 2% in the lowest group. The magnesium-BMD association was not observed among Afro-Americans who tend to have higher bone mineral densities.
Low Selenium May Increase Arthritis Risk
Older people may also benefit from a more adequate intake of the trace mineral selenium. At the American College of Rheumatology Annual Meeting in San Diego last month, investigators from University of North Carolina reported that low levels of selenium is strongly linked to arthritis of the knee. Selenium content was measured in toenails, an indicator of body stores.
The risk for knee osteoarthritis was 40% lower in those with the highest selenium stores compared to the lowest. In addition, the chance of having severe disease was nearly halved in this group. And in this study, some of the benefits of having adequate selenium stores were even stronger for Afro-Americans. These researchers will now try to learn whether selenium affects knee cartilage or whether the benefits are from selenium's antioxidant role.
References

1. Brennan P, et al. Effect of cruciferous vegetables on lung cancer in patients stratified by genetic status. Lancet 366:1558-60, 2005.
2. Yanaka A, et al. American Association for Cancer Res 4th International Conference Oct 31, 2005, Baltimore, MD.
3. Ryder KM, et al. Magnesium intake from food and supplements is associated with bone mineral density in healthy older white subjects. J Am Geriatr Soc 53:1875-80, 2005.
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News You Can Use: Vitamin C aids Lutein, Calcium Fights Polyps, Higher Vitamin D Needs
Vitamin C Helps Lutein Absorption
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 vitamin C.
Calcium Works Against Polyps
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 (2,3).
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 (5).
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.
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Protecting our Cells with Broccoli, Green Tea, Tomatoes and Berries
Cellular Protection
Find that dietary advice is sometimes contradictory or confusing? Well there's one message that experts from the American Heart Association to the National Cancer Institute consistently agree upon: eating 5 or more fruits and veggies daily is the way to go for better health. Getting the "produce habit" lowers our risk for many diseases, particularly cancer, which is now the leading cause of death in the US. While eating a wide variety of fruits and veggies is paramount, certain plant-based foods and beverages get especially high marks for their cell-protecting actions.
The Crucial Crucifers
Consuming cruciferous veggies such as broccoli, cabbage, cauliflower, radishes and turnips has been associated with a reduced risk of cancer of the lung, stomach and colon (1). Most recently, a Mayo Clinic study reports that people eating 1 cup daily of greens like spinach and ½ cup of crucifers like broccoli, got "particularly strong" cancer protection (2). Crucifers are chock-full of cancer-fighting compounds. One of them, sulforaphane, seems to trigger the body's own enzymes that detoxify many carcinogens. In the lab, sulforaphane has been shown to block the growth of many cancer cell lines (3), and even to protect the eye's retinal cells (4). Young broccoli sprouts have much more sulforaphane than mature broccoli, so include some sprouts among your crucifers.
A Tomato A Day
Back in 1995, a study reported that men eating 10 or more servings of tomato-based foods a week were 45% less likely to develop prostate cancer. Even lower amounts (4-7 weekly servings) reduced the risk by 20%. But prostate protection is not the tomato's only claim to fame. A recent study also suggests that a diet rich in tomatoes and tomato-based products with high lycopene content might help reduce the risk for pancreatic cancer (5). Tomatoes contain many active components, and the antioxidant lycopene is believed to be one of them. lycopene may help neutralize cell-damaging free radicals as well as inhibit abnormal cell growth (6). Remember the old adage an apple a day keeps the doctor away? Well, think tomatoes daily too.
Powerful Polyphenols in Green Tea
This beverage has been used traditionally in Asian countries for its health preserving effects. Modern science has shown that the polyphenols it contains operate in a variety of ways: halting the damage to cellular DNA, neutralizing enzymes needed for tumor growth, and deactivating cancer promoters. While much of this evidence comes from animal research (7) human studies suggest that frequent daily consumption of this beverage may lower the risk for several cancers, including prostate cancer (1). Even if coffee is your beverage of choice, consider brewing some green tea daily too. In addition, the absorption and antioxidant activity of tea polyphenols is enhanced when taken in capsules compared to drinking green tea (8)
Incredible Edible Berries
Findings from lab and animal research over the past decade have led nutritionists to hail the cell-protecting properties of compounds like the anthocyanins found in berries. Animal studies, for example, have found that blueberries have anti-aging effects (Staying Healthy, Feb, 2002) and that raspberries can reduce tumors in experimental cancer (9). Research also shows that certain blends of berries can increase antioxidant capacity and block blood vessel growth, a key event in tumor formation (10). Together, the evidence says that berries belong on our daily menus. Keep in mind that taking supplements of protective food components can enhance our overall intake. However they can't replace whole foods that contain other healthful compounds.
References

1. Heber D. Review: Vegetables, fruits and phytoestrogens in the prevention of disease. J of Postgrad Med 50:145-49, 2004.
2. Kelemen L, et al. Consuming fruits and vegetables lowers risk of non-Hodgkin lymphoma. American Association for Cancer Research, Seattle, Oct. 18, 2004.
3. Frydoonfar HR. Sulforaphane inhibits growth of a colon cancer cell line. Colorectal Dis 6:28-31, 2004.
4. Gao X and Talalay P. Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage. PNAS 101:10446-51, 2004.
   
5. Nkondjock, A et al. Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr 135:592-97, 2005.
6. Canene-Adams K et al. Review: The tomato as a functional food. J Nutr 134:1226-30, 2005.
7. Crespy V. A review of the health effects of green te catechins in in vivo animal models. J Nutr 134:3431-40, 2004.
8. Henning SM, et al. Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea or a green tea extract supplement. Am J Clin Nutr 80:1558-64, 2004.
9. Williamson G. Bioavailability and bioefficacy of polyphenols in humans. Review Am J Clin Nutr.81:243S-55S, 2005.
10. Bagchi D, et al, Anti-Angiogenic, Antioxidant and Anti-Carcinogenic Properties of a Novel Anthocyanin-Rich Berry Extract Formula, Biochemistry (Moscow), 69:75-80, 2004.
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Spotlight on vitamin B12
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?
A 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 absorption.
B12, Brain Function and Bone Health
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 impairment.
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.
References

1. Hutto BR. Folate and cobalamin in psychiatric illness. Comp Psychiatry 38:305-14, 1997.
2. Tucker K, et al. Low plasma vitamin B12 is associated with lower BMD: The Framingham Osteoporosis Study. J of Bone and Min Res 20:152-8, 2005.
3. Dhonukshe-Rutten RA, et al. Vitamin B-12 status is associated with bone mineral content and bone mineral density in frail elderly women but not in men. J Nutr 133:801-807, 2003.
4. Stone KL, et al. Low serum vitamin B12
5. levels are associated with increased hip bone loss in older women: A prospective study. J Clin Endocrinol Metab 89:1217-21, 2004.
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Spotlight on Taurine
Taurine: A Unique Amino Acid
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 the Eye
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 speculative.
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.
Bibliography

1. Kingston R et al. The therapeutic role of taurine in ischemia-reperfusion injury. Curr Pharm Des 10:2401-10, 2004
2. Lourenco R and Camilo ME. Taurine: a conditionally essential amino acid in humans? An overview in health and disease. 17:262-70, 2002.
3. Militante J and Lombardini JB. (Review) Age-related retinal degeneration in animal models of aging: possible involvement of taurine deficiency and oxidative stress. Neurochem Res 29:151-60, 2004.
4. Militante JD and Lombardini JB. Taurine: evidence of physiologic function in the retina. Nutr Neurosci 5:75-90, 2002.
5. Renteria RC et al. Need rods? Get glycine receptors and taurine. Neuron 41:839-41, 2004.
6. Schuller-Lewis G. and Park E. (Review) Taurine: new implications for an old amino acid. FEMS Microbiol Letters 226:195-202, 2003.
7. Young TL and Cepko CL. A role for ligand-gated ion channels in rod photoreceptor development. Neuron 41:839-41, 2004.
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Vitamin E Shown to Fight Colds in the Elderly
Immunity and Nutrition in Older Individuals
Infections, particularly 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 B6, C, D and E.
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 vitamin E.
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.
References

1. Blumberg J and Heber D, eds. Multivitamins and Public Health: Exploring the Evidence. Oct. 1st, 2003 Washington DC New York, NY: BioScience Communications, 2004.
2. Meydani SN et al. Vitamin E supplementation in vivo immune response in healthy elderly subjects: A randomized controlled trial. JAMA 277:1380-6, 1997
3. Meydani SN et al. Vitamin E and respiratory tract infections in elderly nursing home residents. A randomized controlled trial. JAMA 292:828-836, 2004.
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"Benchmark" Findings from New Lutein, Vitamin C Studies
New Study Shows Lutein Improves Eyesight for AMD Patients
The 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 March & April, 2004).
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 ( vitamin C, vitamin E and alpha lipoic acid). Plasma levels of CRP in the volunteers were measured before and at the end of the two month trial.
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 finding of vitamin C's ability to lower CRP is confirmed, vitamin C could become an important public health intervention."
References

1. Richer S, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 75:216-30, 2004.
2. Block G, et al. Plasma C-reactive protein concentrations in active and passive smokers: influence of antioxidant supplementation. J Am Coll Nutr 23:141-47, 2004.
3. Devaraj S, et al. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Rad Biol Med 29:790-92, 2000.
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Tips for Choosing a Good Multi Supplement
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 formulation:


1. Is the product formulated by scientific experts?
   Some companies rely solely on marketing trends and marketers to create products, rather than medical and nutritional experts with the expertise to evaluate safe and effective ingredient combinations. It is also important that qualified experts continually review the scientific literature, so that formulations can be revised to reflect new research findings.
   
   
2. Does it contain meaningful and safe amounts of nutrients?
   Many popular products include ingredients in miniscule quantities, just so a much-publicized ingredient can be listed on the label. Consider lutein. While studies equate milligram amounts of this important nutrient with eye health, some products include insignificant microgram amounts (A microgram is 1/1000 of a milligram). Another example is potassium. Regulations restrict the amount of this mineral in supplements to 100 milligrams - a quantity that takes up valuable capsule space without making a real contribution towards the 3,000-5,000 milligrams of potassium needed daily.
   
   Safety is even more important. Recent studies, for example, suggest that very high levels of vitamin A may not support optimal bone health. Yet some formulas include high potency vitamin A, or unbalanced levels of minerals that can compete for absorption - zinc and copper for instance.
   
   
3. Does it provide a variety of nutrients along with the familiar essential vitamins and minerals?
   Everyone recognizes the importance of essential vitamins like vitamin C. But there are also a variety of key, health-promoting compounds such as bioflavonoids from fruits and vegetables, or other complementary antioxidants that have emerged as important in recent years. Some products give these nutrients short shrift or exclude them altogether.
   
   
4. Does the product take bioavailability into account?
   There's more to a formula than having a scientifically sound combination of Ingredients. Nutrients also need to be "bioavailable", which means that they are in a form the body can absorb and utilize. Look for natural sources of vitamin E, such as "mixed tocopherols" or alpha tocopherol. These forms are better absorbed and retained in the body than their synthetic vitamin E counterpart. What about the delivery form: tablets or capsules? While some tablets are formulated to break apart quickly enough to allow proper absorption, others fall far short. Capsules, on the other hand, offer the reliability of efficient disintegration and are often more easily swallowed.
   
   
5. Quality: Is it a product you can trust?
   Since the quality of nutritional supplements can vary widely, one strategy is to choose an established brand name, or one that's recommended by a health professional. Not every product uses high quality raw materials, or is manufactured according to accepted good manufacturing practices. Take the time to ask what steps a company takes to ensure that the amounts of nutrients in the actual tablet or capsule are the same as those stated on the label.
   
References

1. Consumer Confidence Survey 2000. Angus Reid Group, Omnibus Survey, presented at the Council for Responsible Nutrition, October, 2000.
2. Holquist C et al. Multivitamin Supplements are inversely associated with risk of myocardial infarction in men and women - Stockholm Heart Epidemiology Program (SHEEP). Journal of Nutrition 133:2650-54, 2003.
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EUREYE Study: Blue Light Exposure & Low Antioxidants Increase AMD Risk
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.
Study Design and Methods
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.
Results
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.
Comments
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.
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Anthocyanins from Bilberry & Black Currant Dampen Inflammation
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.
Study Design and Methods
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.
Results
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.
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CTNS Trial: 'Multi' Use Prevents or Delays Certain Cataracts
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.
Study Design and Methods
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.
Results
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).
Comments
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.
Reference
CTNS Study Group. A randomized, double-masked, placebo-controlled clinical trial of multivitamin supplementation for age-related lens opacities. Ophthalmol 115:599-607, 2008.
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CAREDS Trial: Lutein and Zeaxanthin Linked to Lower Cataract Risk
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).
Study Design and Methods
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.
Results
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.

Comments
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.
References
1. Moeller SM et al. Age-Related Macular Degeneration and Lutein and Zeaxanthin in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Arch of Ophthalmology 124:1151-1162, 2006.
2. Moeller SM et al. Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study (CAREDS), an ancillary study of the WHI. Arch Ophthalmol 126:354-364, 2008.
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Zinc & Lutein Protect Against AMD in Blue Mountains Eye Study
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).
Study Design and Methods
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.
Results
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).
Comments
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.
References
1. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 119:1417-36, 2001.
2. van Leeuwen R, et al. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 294:3101-7, 2005.
3. Tan JSL, et al. Dietary antioxidants and the long-term incidence of age-related macular degeneration: The Blue Mountains Eye Study. Ophthalmol 115:334-42, 2008.
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Lutein, Zeaxanthin and Vitamin E "Eyed" for Cataract
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.
Study Design and Methods
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.
Results
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.
Comments
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).
References
1. Christen WG et al Dietary carotenoids, vitamins C and E, and risk of cataract in women: A prospective study. Arch of Ophthalmol 126:102-109, 2008.
2. Christen WG et al. Vitamin E and age-related cataract in a randomized trial of women. Ophthalmology Epub Dec, 2007.
3. AREDS Research Group. Centrum use and progression of age-related cataract in AREDS. Ophthalmol 113:1264-70, 2006.
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AREDS: 'Multi' Use Slows Cataracts
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).
Study Design and Methods
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).
Results
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.
Comments
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
1. Seddon JM, et al. The use of vitamin supplements and the risk of cataract among US male physicians. Am J Public Health 84:788-92, 1994.
2. Leske MC, et al. Antioxidant vitamins and nuclear opacities: the Longitudinal Study of Cataract. Ophthalmology 105:831-6, 1998.
3. Mares-Perlman JA, et al. Vitamin supplement use and incident cataracts in a population-based study. Arch Ophthalmol 118:1556-63, 2000.
4. Hankinson SE, et al. Nutrient intake and cataract in women: a prospective study. BMJ 305:335-9, 1992.
5. AREDS Research Group. Centrum use and progression of age-related cataract in AREDS. Ophthalmol 113:1264-70, 2006.
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Vitamin B Trio Effective Against AMD
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.
Study Design and Methods
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.
Results
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.
Commentary
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.
References
1. Christen WG, et al. Folic acid plus B-vitamins and age-related macular degeneration in a randomized trial in women. Invest Ophthalmol Vis Sci 48:E-abstract 1152, ARVO, 2007.
2. Wald DS, et al. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch of Internal Med 161:695-700, 2001.
3. Homocysteine Lowering Trialists' Collaborative. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. BMJ 316:894-8, 1998.
4. Mason JB, et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: A hypothesis. Cancer Epidemiol Biomarkers Prev 16:1325-9, 2007.
5. Cole BF, et al. Folic acid for the prevention of colorectal adenomas. JAMA 297:2351-9, 2007.
6. Cook NR, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: Results from the WAC Study. Arch of Int Med 167:1610-18, 2007.
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Vitamin D Linked to Lower Risk of AMD
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.
Study Design and Methods
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.

Reference
1. Reference: Parekh N, et al. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey. Arch of Ophthalmol 125:661-69, 2007.
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Zinc and Immunity, Lutein and Skin Health
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.
References
1. AREDS Research Group. Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study. AREDS Report No. 13. Arch Ophthalmol. 122:716-726, 2004.
2. Prasad AS, et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr 85:837-44, 2007.
3. Richer S, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 75:216-30, 2004.
4. Palombo P, et al. Beneficial long-term effects of combined oral/topical antioxidant treatment with the carotenoids lutein and zeaxanthin on human skin. Skin Pharmacol and Physiol 20:199-210, 2007.
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Antioxidants Substantially Lower the Risk of Developing AMD
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).
Study Design
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.
Results
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.
Commentary
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.
References
1. van Leeuwen R, et al. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 2034:3101-7, 2005.
2. Crabb JW, et al. Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci USA. 99:14682-7, Epub Oct 21st, 2002.
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The Scottish Heart Health Study: A Study of Dietary Antioxidant Vitamins and Cardiovascular Disease
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.
Methods:
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.
Results:
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.
References

• Todd S, Woodward M, Tunstell-Pedoe H, Bolton-Smith C. Dietary antioxidant vitamins and fiber in the etiology of cardiovascular disease and all-causes mortality: results from the Scottish Heart Health Study. Am J Epidemiol 150: 1073-1080, 1999.
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Multivitamin Supplements and Birth Defects: Results of a Recent Case-Control Study
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.
Methods:
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.
Results:
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.
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More Results from the Nurses' Health Study: Vitamin Supplement Intake and Cataract Extraction
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.
Methods:
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).
Results:
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.
References

• Chasan-Taber L, Willett WC, Seddon JM, et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in U.S. women. Am J Clin Nutr 1999;70:509-516
• Chasan-Taber L, Willett WC, Seddon JM et. al. A Prospective Study of Vitamin Supplement Intake and Cataract Extraction among U.S. Women. Epidemiology 1999;10:670-684.
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Plasma Vitamin E and Age Related Macular Degeneration: Results from the POLA Study
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.
Methods:
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.
ScienceBased Health's MacularProtect^® Complete is a powerful formulation for macular and whole body health, based on the AREDS clinical trial, and also includes a complete multinutrient component.
References

• Delcourt, C, Cristol JP, Tessier F et al. Age Related Macular Degeneration and Antioxidant Status in the POLA Study. Arch Ophthalmol 1999;117:1384-1390.
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High Concentrations of Antioxidant Enzymes as a Marker for Oxidative Stress: A Report from the POLA Study
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).
Methods:
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.
Results:
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*
Cortical Cataract	6.3	P<0.001	1.8	NS
Nuclear Cataract	2.3	P=0.004	2.2	P=0.02
Mixed	2.5	P=0.003	1.4	NS
Late AMD	10.0	P=0.04**	0.9	NS
*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.
ScienceBased Health's MacularProtect^® Complete is a powerful formulation for macular and whole body health, based on the AREDS clinical trial, and also includes a complete multinutrient component.
References

• Delcourt C, Cristol JP, Leger CL et. al. Associations of antioxidant enzymes with cataract and age-related macular degeneration: the POLA study. Ophthalmology 1999;106:215-222.
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NHANES III: Diabetes Mellitus and Serum Carotenoids
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 levels (1).
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.
Methods:
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.
Results:
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.
References

• Ford ES, Will JC, Bowman BA, and Venkat Narayan KM. Diabetes Mellitus and Serum Carotenoids: Findings from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 1999;149:168-176.
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