Vitamin C and zinc controversy: COVID A to Z researchers undeterred by CRN’s dismissal

19 Feb 2021 --- The researchers behind a controversial US study, which found zinc and vitamin C did not help patients with COVID-19, are standing behind their findings despite backlash from The Council for Responsible Nutrition (CRN). NutritionInsight speaks with experts from both sides of the debate.

The COVID A to Z Study concludes that high doses of zinc gluconate, ascorbic acid or a combination of both nutrients did not significantly shorten the duration of symptoms associated with SARS-CoV-2 compared to usual care.

Now published in JAMA, the study included 214 patients with confirmed SARS-CoV-2 infection receiving outpatient care. Patients were randomized in a 1:1:1:1 allocation ratio to receive either ten days of zinc gluconate (50 mg), ascorbic acid (8,000 mg), both agents or standard of care.

However, Steve Mister, CRN’s president and CEO, dismisses the study as “doing nothing to advance our understanding of the role of nutrients in reducing the risk of COVID-19.”

He argues that the investigation could deter future research that may “demonstrate the valuable role nutrients play in supporting immune function over time and preventing COVID-19 in particular.”The CRN recognizes the important role vitamin C and zinc can play in filling nutrient gaps, maintaining good health and supporting immune function.

Methodology flaws?
The CRN maintains that the study is plagued by a poor, open-label design, insufficient number of participants, substantial differences in the health status of participants by group and the expectation that essential nutrients should behave like high-powered pharmaceuticals.

“Health care practitioners and consumers should view this study with appropriate skepticism. The study used an open-label design with no placebo arm and had major differences in the health status of participants by group, along with other significant problems,” says Mister.

For example, over 29 percent of subjects in the vitamin C and zinc group had a history of diabetes compared to in 6 percent the standard of care group. People with diabetes are at increased risk of severe illness from COVID-19.

However, a study author, Dr. Milind Desai of the Heart and Vascular Institute, Cleveland Clinic, stands by the results. 

He explains that the most likely reason for these baseline differences is that the trial was stopped prematurely because of futility.

“We are fairly confident that had the study gone to full recruitment, such random differences would have been nullified. Having said that, this was not a mortality- or outcomes-driven trial where diabetes could potentially influence outcomes,” he explains. The researchers emphasize their manuscript underwent peer review and statistical review by the journal.

Withholding judgment 
The COVID A to Z Study was also lauded by invited commentary published in JAMA. The writers “applaud the investigators for adding rigorous science by testing [zinc’s and ascorbic acid’s] efficacy and challenging popular beliefs. Unfortunately, these two supplements failed to live up to their hype.”

Nonetheless, the CRN is urging healthcare practitioners and consumers alike to reserve judgment on the effects of nutrients like vitamin C and zinc until “more credible science” is published.

Luke Huber, vice president of scientific and regulatory affairs at CRN notes that there are numerous ongoing studies of COVID-19 that use vitamin C or zinc as interventions. 

“A recent search on clinicaltrials.gov using the search terms COVID-19 and vitamin C provides a list of 54 studies globally. Additionally, a search for COVID-19 and zinc yields 49 results globally, illustrating the research interest in these nutrients. CRN will continue to evaluate research as it is published.”

However, Dr. Desai is unaware of any other randomized controlled trial that has demonstrated any significant benefit of supplements. 

“Having said that, it is always a good idea to test a hypothesis that makes plausible biological sense,” he explains.

“Because we have determined, on multiple occasions in the past, that sometimes things that make biological sense do not necessarily pan out in real life clinical practice. We just wanted to test the hypothesis.”

Last March, Northwell Health, New York state’s largest healthcare provider, experimented with administering large doses of vitamin C to some COVID-19 patients in its hospitals.

The vitamin C industry also reported a significant increase in demand for the vitamin early in the pandemic last year. 

By Katherine Durrell