Why do SBH Macular products contain 80 mg of zinc?
In AREDS2, comparing formulas modified with low dose zinc (25 mg) vs. the original zinc dose (80 mg) showed no statistical difference for risk of progression. However a trend favoring greater protection was observed for the higher dose of zinc. Thus the NEI continues to recommend the higher dose, and MacularProtect Complete reflects the official recommendations of the NEI.
Why doesn’t SBH offer a zinc-free AREDS formula?
Two published studies (Awh et al) (1,2) have looked at genotype and the response to AREDS supplements, and concluded that zinc treatment in patients with CFH risk genotypes is associated with increased risk of AMD progression. SBH reviewed these and other relevant studies, which were also independently assessed by Elizabeth Johnson, PhD of the Jean Mayer USDA Human Nutrition Research Center on Aging, and Professor, Friedman School of Nutrition and Science Policy at Tufts University.
After careful and independent review, SBH concludes that current data is insufficient to make personalized supplement recommendations based on individual genotype—a conclusion consistent with that of the American Academy of Ophthalmology Task Force on Genetic Testing (3).
Importantly, the results of the 2 studies reporting a detrimental effect of zinc in those with CFH risk genotypes are in direct conflict with the results of two other studies evaluating this topic:
What are the limitations and concerns related to the 2nd Awh et al study?
Several approaches used in the most recent, 2014 Awh et al study raise concerns about the validity of the findings. Notable examples include:
What is the NEI saying about the controversy?
According to Emily Chew, MD, a principal investigator of the AREDS and AREDS2 studies, the major problem in the second Awh paper relates to how the genotypic subgroups were selected. Finding statistically significant differences is almost a certainty when there are multiple groups (hence multiple comparisons) and when subgroup selection is based on outcome, she and her co-authors wrote in a short report published online November, 2014 (6).
In that publication, Chew et al explain that Awh’s 2nd study was based on a subset of AREDS participants with available genetic information. However Chew et al. had access to the genetic information of an additional 526 participants referred to as the "residual cohort". Chew used the residual cohort to test the validity of Awh’s findings. If the results of the residual cohort analysis were found to be in the same direction (either beneficial or harmful), and generally of the same magnitude as those published by Awh et al, this would validate Awh and his colleague’s analysis.
Chew et al’s analysis did not validate Awh’s findings. Quite the contrary. For all four of Awh’s genotypic groups, the combination of antioxidants and zinc was found to be beneficial and the treatment of choice in the residual cohort.
The Chew et al paper also likened Awh’s subgroup selection based on outcome (progression to late AMD) to an analogy of dividing the population into subgroups based on their astrological sign. One can easily demonstrate “statistical significance” by selecting those with the most beneficial treatment effects and those with the least beneficial effects, then comparing the two groups without accounting for multiple testing or for the lack of a pre-specified comparison.
Using Awh’s cohort of patients, those born under the sign of Aries or Cancer were “harmed” by treatment with zinc, while the residual cohort that was not subjected to selection bias prior to analyses in the Chew et al study (5), showed no harmful effect of zinc for these astrological signs.
Graph Courtesy of: Ophthalmology
Dr. Chew cautioned against using genetic testing to decide whether patients should use an AREDS formula with or without zinc based on a statistically flawed, non-replicated retrospective analysis of existing data. That would deprive patients of a therapy proven to have significant public health impact, she and her fellow authors concluded.
The authors of an accompanying editorial (7) in the same publication echo Chew et al's conclusion, emphasizing that Awh et al defined their genotype subgroups in a post hoc and improper manner.
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