AREDs2 - public funds for the public good
Saturday, April 03, 2004
The second National Eye Institute Age Related Eye Disease (ARED) long-term study is currently being designed. The multi million dollar (8 figure) AREDs2 study will be funded with our tax dollars; therefore the study subjects need to equally represent both genders. The study micronutrient formulation design also needs to represent the most current science available in 2004, which strongly supports the inclusion of a number of biochemically balanced vitamins, minerals, carotenoids, and phytochemical antioxidants that were not included in the first ARED study formulation.
The recently published LAST study (Lutein Antioxidant Supplementation Trial), as well as other studies that show similar results, strongly point out the need for supplementation with a broader based therapeutic range of micronutrients than the few micronutrients included in the first ARED study formulation.
1) Depressed contrast sensitivity (CSF)
2) Abnormal photo-stress glare recovery (GR)
3) Deficits of the Amsler grid (i.e., intermittent/permanent visual spots (scotomas)
4) Distortions of lines (metamorphopsia)
The placebo group in the LAST study did show disease progression in the four markers above.
The prevalence of ARMD is highest in older women - who were not adequately represented in the LAST government funded VA hospital study on 86 males and only 4 females.
Post-menopausal hormonal shifts particularly affect the absorption of the macula specific carotenoids, lutein and zeaxanthin (new Z studies coming on strong). These carotenoids are transported to both ocular tissue and adipose tissue on lipoprotein molecules, which most likely include estrogen. Unfortunately, adipose tissue (fat) levels naturally increase during menopause and adipose tissue competes with ocular tissues for macula pigment-specific lutein and zeaxanthin, which may explain the lower rates of serum and ocular tissue lutein and zeaxanthin, and the higher rates of ARMD in post-menopausal females and the obese.
Additional AREDs2 concerns are that excessive supplementation with beta carotene, as a source of pro-formed Vitamin A, most likely competes for lipoprotein transport space with the zanthophyll carotenoids (lutein and zeaxanthin) in both females and males. The protein/antioxidant formulation used in the LAST study contained a better balance of dietary carotenoids, which may also explain some of the improvements in visual outcomes compared with the AREDs.
The LAST study, together with previous other studies showing similar results in both males and females, raises the strong possibility that degenerative eye disease prevention and control requires daily intake of a large number of biochemically balanced micronutrients at higher GRAS levels than the currently recommended daily amounts‚ particularly for post-menopausal women.
The LAST study (Lutein Antioxidant Supplementation Trial) Richer, S, Stiles S, et al. Optometry, Volume 75/Number 4/April 2004 [ full study PDF]
Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxahtnin. Brockmans, WM, Berendschot TT, et al. Am J Clin Nutr. 2002 Sept;76(3):595-603 [ abstract]
Zeaxanthin in combination with ascorbic acid or alpha tocopherol protects ARPE-10 cells against photosenstized peroxidation of lipids. Wrona M, Rozanowska M, Sarna T. Free Radic Biol Med. 2004 May 1;36(9):1094-101 [ abstract]
Relationships of body fat level and distribution to age-related maculopathy in the Carotenoids in Age-Related Eye Diseases Study (CAREDS), an ancillary study of the Women's Health Initative. LaRow, TL, Mares JA, et al. CAREDS Group of Investigators, Univ of Wisconsin, Madison. Poster #2244 to be presented Tuesday April 27th at ARVO 2004. [ ARVO 2004 posters]
Improvement of fundus alterations in early AMD treated with a combination of n-3 fatty acids, CoQ10 and acetyl-L-carnitine. FeherJ, Kovacs B, Schvoller M, Ophthalmic Neuroscience Program, Dept of Ophthalmology, University of Rome La Sapeinza, Rome, Italy. Poster # 3093 to be presented Tuesday April 27th at ARVO 2004. [ ARVO 2004 Posters]