Eye Vitamins - Beneficial to Most, But Harmful to 1 in 6?

By Gerry Belgraver Chief Operating Officer, ArcticDX

Is it time to utilize pharmacogenetics to guide protocol for your AMD patients? We believe so, and here is why. Sometimes AREDS Vitamins can cause harm.

Thousands of Canadians with macular degeneration, or a family history of the disease, are taking an AREDS eye vitamin with zinc. These vitamins have reduced the risk of vision loss in many patients. However, many eye doctors are unaware of recent independent research showing that these supplements are harmful to about 15% of patients, speeding up vision loss.

Since the AREDS2 study showed that the biological effect of AREDS & AREDS2 supplements is identical in reducing the risk of progression, this article will use these terms interchangeably.

These newer studies show that many people with specific macular degeneration risk genes benefit greatly from AREDS vitamins. Their risk of wet AMD is reduced not by a meagre 25% but in the range of 50-60%. However, another 15% of AMD patients have other risk genes. For these patients, taking AREDS supplements increases their risk five-fold for developing “wet AMD,” resulting in vision loss and requiring eye injections. This effect was first validated by Harvard Medical School ophthalmologist Demetrios Vavvas, MD and his team when analyzing the original AREDS study. They showed that some patients with specific macular degeneration risk genes benefited from AREDS supplements, but it harmed others. This observation was consistent in both a discovery and validation set of patients. Vavvas’ research convinced many that genetic testing is a valuable guide before AREDS/AREDS2 supplement use. Even so, it has remained controversial among eye care physicians, primarily due to strident opposition from one of the patent holders – the US National Eye Institute. Recently a team of independent retina specialists led by Dr. Stephen Kaufman, MD, sought to resolve the issue using a case-only approach. They looked at patients who already had wet AMD and then retrospectively looked at the genetics of those who did and those who did not take an AREDS/ AREDS2 supplement prior to developing wet AMD. They confirmed a strong interaction between genetics and AREDS supplement use in the development of wet AMD. Their findings supported those of Vavvas and his team.

How was this done? Patients with a reliable history of at least five years of AREDS use (AREDS users) or less than one month of AREDS use (AREDS nonusers) were genotyped. Those assessing the

AREDS use history were masked to the patient’s genotype, and those doing genetic testing were masked to AREDS use.

If AREDS use increased the risk of wet AMD among ‘zinc-sensitive’ patients, one would expect a disproportionately increased number of AREDS-F users to be ‘zinc sensitive.’ Similarly, if AREDS decreased the risk of wet AMD among ‘zinc-tolerant’ patients, one would expect a disproportionately smaller number of AREDS users to be ‘zinc-tolerant’ because AREDS use would have decreased their risk of wet AMD.

So, what is the American Academy of Ophthalmology (AAO) recommendation regarding its ‘Age-Related Macular Degeneration Preferred Practice Pattern’? Surprisingly, they continue to conclude that the “routine use of genetic testing for AMD patients is not supported by the existing literature and is not recommended at this time.” However, given the new, strong evidence for the utility of genetic testing to guide AREDS use and the low threshold to avoid potential harm, it appears time for the AAO to revisit this.

The Preferred Practice Pattern also asserts, “One or more prospective clinical trials will need to demonstrate the value of genetic testing in AMD” before clinicians recommend utilization. The Kaufman study was prospective, utilizing a caseonly approach. While a true randomized, placebo controlled study would be scientifically desirable, it might not be ethically possible. Given the evidence for increased risk of wet AMD for ‘zinc-sensitive’ patients, institutional review boards might not approve such a study. Both investigators and patients may be challenging to recruit because ‘zinc sensitive’ patients do not benefit from AREDS/AREDS2 and may risk disease progression.

The Hippocratic Oath “primum non nocere” - “first, do no harm” supports genotype-guided treatment until there is compelling evidence that AREDS is safe for all patients.

These tests are readily available in Canada and are simple cheek swabs sent to the lab via Canada Post. Although not covered by provincial health insurance and the cost ($299-$399) may at first glance seem expensive, they are a worthy healthcare investment - especially if you are the one out of the six patients harmed by zinc. For more information, we recommend watching Dr. Kaufman’s 6-minute video at www.youtube.com/watch?v=DOLHbUL4_xE or feel free to contact him directly with questions at stkaufman@mindspring.com.