AREDS Analysis: Antioxidants, Omega-3 and the AMD-CVD Connection

CVD & AMD Share Common Risks, Processes

A Harvard research team led by Dr. Johanna Seddon notes that age-related macular degeneration (AMD) and cardiovascular disease (CVD) share common risk factors, such as smoking and higher body mass index (BMI). They propose that mechanisms involved in developing AMD could be better understood by evaluating biomarkers of CVD. A number of analyses, in fact, have shown that systemic biomarkers for inflammation and artery damage, including C-reactive protein (CRP) and homocysteine (HCY), are related to AMD. Basic research also demonstrates that inflammatory, immune and atherosclerotic processes are related to AMD development.

To further explore mechanisms related to AMD pathogenesis, these researchers evaluated the relationships between CRP, HCY and other known risk or protective factors for AMD in subjects from the original AREDS trial (1). According to Dr. Seddon, the findings indicate that "sick eyes may occur in sick bodies related to smoking, overweight, inadequate nutrient intake, and other unhealthy behaviors".

Study Design

After randomization for AREDS, 934 subjects from two clinical sites underwent blood draws, measurements, photographs of the macula and answered questionnaires. Dietary, behavioral and medical risk, and protective factors for AMD were evaluated for their associations with blood values of CRP and HCY. This original data provided information on intake of fish as well as antioxidants such as vitamins C and E, alpha- and beta-carotene and lutein/zeaxanthin. In addition, serum nutrient values obtained from participants at one of the sites were also evaluated for their association with CRP and HCY. Multivariable regression analyses were performed after adjusting for age, gender and AREDS treatment.

Results

Higher levels of serum antioxidants vitamin C and lutein/zeaxanthin and higher fish intake (a source of omega-3 fats) were associated with lower serum CRP levels. CRP levels decreased 2 milligrams per litre for every 1000 microgram per decilitre increase in blood levels of lutein/zeaxanthin. A 0.2 milligram per litre decrease in CRP was also associated with more than 2 servings of fish weekly.

Increased BMI and smoking were associated with increased CRP, while serum alpha-carotene, dietary intake of antioxidants and vitamin B6 were associated with lower levels of plasma HCY. Levels of HCY were observed to be higher in those with hypertension. While serum vitamin E was linked to lower concentrations of HCY, it was unexpectedly linked to higher levels of CRP.

Comments

Factors reported to be related to AMD, namely antioxidants, smoking, BMI, HCY (2) and fish intake, are also associated with inflammatory, immune, or other CVD mechanisms. These results are consistent with previous findings associating smoking, BMI, and the biomarkers CRP and interleukin-6 with AMD in a different study cohort of AMD patients (3).

The relationship between fish intake, BMI, and levels of inflammatory markers have been previously reported in other "non-ocular" study populations. These data support and expand on these associations. The positive link between higher vitamin E and CRP deserves further study, according to the authors. This finding disagrees with the recent Rotterdam study, which found that vitamin E significantly lowered AMD risk [EduFacts Vol.6 No.1].

Overall, the Harvard study adds to a growing body of data showing a protective effect of antioxidants such as lutein/zeaxanthin, and omega-3 fats against AMD.

References

  1. Seddon JM et al. C-reactive protein and homocysteine are associated with dietary and behavioral risk factors for age-related macular degeneration. Nutrition 22:441-43, 2006.
  2. Seddon JM et al. Evaluation of homocysteine and risk of age-related macular degeneration. Am J Ophthalmol 141:201-3, 2006.
  3. Seddon JM et al. Progression of age-related macular
    degeneration: prospective assessment of C-reactive protein, interleukin-6, and other cardiovascular biomarkers. Arch Ophthalmol 123:774-82, 2005.