Dr. EJ Johnson of the USDA Human Research Center on Aging offers an intriguing evaluation of the mechanisms by which obesity increases the risk of Age-related Macular Degeneration (AMD) (1). The number of Americans with AMD is expected to triple within the next 30-40 years. Obesity is also on the rise. Currently, more than 44 million are obese, a figure that has grown by 74% since 1991. Interestingly, a number of studies have reported a higher risk for AMD in people with a greater body mass index or BMI (see table 2). Obesity is defined as having a BMI greater than 30.

According to Dr. Johnson, the connection between obesity and AMD may be due to changes in lutein metabolism. The pigment lutein functions as an antioxidant and blue-light filter, and is believed to protect the macula and retinal structures from light-initiated oxidative damage. Population and case-control studies suggest that AMD risk is inversely related to dietary intake of lutein, and recent studies also report that supplemental lutein improves visual function in AMD patients (2,3).

Obesity, Oxidative Stress & Inflammation

Obesity increases oxidative stress when the activity of "free radicals" exceeds the ability of antioxidants to neutralize them. Antioxidant defense mechanisms have also been reported to be lower in obesity. Oxidative stress is believed to be involved in the etiology of AMD, just as systemic oxidative stress contributes to atherosclerosis in the obese.

Obesity and inflammation also go hand in hand. C-reactive protein, a marker of inflammation, has been found to be higher in people with a greater body mass index (BMI) and to drop when weight is lost. Analysis of the National Health and Nutrition Examination Survey suggests that chronic inflammation elevates levels of C-reactive protein and - importantly - reduces serum carotenoids such as lutein and zeaxanthin.

How Does Obesity Affect Lutein Metabolism?

The changes that occur in obesity - more oxidative stress, inflammation and changes in lipid profiles - could also increase destruction of lutein and decrease the amount being delivered to the macula. Four mechanisms may be involved:

• Increased body fat, a major storage tissue for carotenoids could act as a "sink" for lutein, resulting in less lutein being available to the macula. Some researchers have noted an association between more body fat and lower serum and macular lutein
• Greater obesity-related oxidative potential could promote oxidative destruction of lutein and zeaxanthin
• Because inflammation and oxidative stress are tightly linked, higher levels of inflammation in the overweight could also result in more oxidative damage to lutein
• Finally, the increased LDL to HDL ratio often noted with obesity may decrease the transport of lutein and zeaxanthin to the eye. Lutein and zeaxanthin are transported within the blood primarily on the surface of HDL (about 53%) and to a lesser extent on LDL (about 31%) and VLDL (about 16%).

The author concludes that efforts to prevent obesity and to improve lutein/ zeaxanthin status may be important in AMD prevention.

References

1. Johnson EJ. Obesity, lutein metabolism, and age-related macular degeneration: a web of connections. [Special Article] Nutrition Reviews 63:9-15, 2005.
2. Falsini B, et al. Influence of short-term antioxidant supplementation on macular function in age-related maculopathy. Ophthalmology 110:51-60, 2003.
3. Richer S, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular generation (LAST). Optometry 75:216-30, 2004.