Vitamin C, Zinc Don't Help COVID-19? CRN Dismisses "Weak" JAMA Study

Washington, D.C.—Weak study design, haphazard approach, unclear results...Steve Mister, President & CEO of the Council for Responsible Nutrition (CRN), had strong words in response to a study and accompanying commentary published February 12, 2021 online in JAMA Open Network.

In the study,Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection, researchers from the Cleveland Clinic set out to answer this question:Do high-dose zinc, high-dose ascorbic acid, and/or a combination of the two, reduce the duration of symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)?

The researchers concluded:In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care.

An accompanying commentary,Supplements for the Treatment of Mild COVID-19—Challenging Health Beliefs With Science From A to Z, further called the benefits of supplements into question.

The publication led to headlines in the media like CNN's "Vitamin C and zinc don't help Covid-19 patients, study finds."

CRN responded with a statement by Mister: “Publication of this study and the accompanying commentary does nothing to advance our understanding of the role of nutrients in reducing the risk of COVID-19 and provides little insight for treating the disease. 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.

It's not surprising that the "weak study design and haphazard approach would lead to unclear results," Mister continued. "What’s more disappointing is that JAMA published it at all and accompanied it with a commentary that recklessly makes broad generalizations about the role of dietary supplements in the prevention and treatment of COVID-19. The sleight of hand potentially deters future research that may demonstrate the valuable role nutrients play in supporting immune function over time and preventing COVID-19 in particular."

Offering an overview of why healthcare practitioners and consumers should view the study with "appropriate skeptism," Mister points out several "significant problems."

The study used an open-label design with no placebo arm.
There were major differences in the health status of participants by group; for example, over 29% of subjects in the vitamin C and zinc group had a history of diabetes compared to 6% in the standard of care group. "People with diabetes are at increased risk of severe illness from COVID-19," Mister explained. "The vitamin C and zinc group also had higher rates of hypertension, dyslipidemia, and smoking compared to the standard of care group, any of which may lead to worse outcomes in individuals with COVID-19.
The study did not stratify participants by age, sex, race, or duration of symptoms prior to testing, which Mister noted would have allowed the researchers to analyze the results on a more comparable basis.

“Despite these challenges, patients who received vitamin C or vitamin C and zinc achieved a 50% reduction in their symptoms 1.2 days sooner than the standard of care group, however this finding did not achieve statistical significance by the time the study was prematurely terminated for ‘futility’—having enrolled less than half the intended number," Mister said. "If the study had fully enrolled, the differences in outcomes between groups may have reached statistical significance."

Another important point to consider: No serious adverse events were associated with any of the study interventions and there was no prevention component to this study.

"The dosages administered [50 mg zinc and 8,000 mg vitamin C] exceed the recommended Upper Levels (UL) of those nutrients [UL for zinc = 40 mg; UL for vitamin C = 2,000 mg]," Mister explained. "The adverse events that were reported (nausea, diarrhea, stomach cramps) were predictable and consistent with the doses of the nutrients that were given. Rather than examining moderate doses of zinc and vitamin C for prevention and generally supporting immune health, this was a treatment study with a short duration of intervention (10 days), using high doses of zinc and vitamin C, and only examining patients already positive for COVID-19. It’s a positive outcome when long-recognized nutrients also perform as powerful pharmaceuticals; but when they don’t, it’s hardly a reason to dismiss their long-term benefits."

Mister also pointed to a factor that he considers "even more disturbing:" The commentary, written byErin D. Michos, M.D., MHS, and Miguel Cainzos-Achirica, M.D., MPH, Ph.D., "cites the study as evidence that ‘rigorous science’ challenges ‘popular beliefs’ and demonstrates how these supplements fail to ‘live up to their hype.’ Their editorial reads like a conclusion in search of a premise: that dietary supplements should be viewed as a waste of time just waiting for science to disprove their presumed benefits. This kind of misapplication of a poorly conducted study has the potential effect of dissuading other serious researchers from investigating the potential of a wide range of supplements, such as vitamin C, vitamin D, zinc, melatonin and others, for their ability to support immune function and resistance to respiratory infections, including COVID-19."

That said, Mister concluded, research into the potential of a variety of supplements is already underway in a range of clinical trials examining the relationship between nutrients and resistance to disease. "CRN looks forward to the publication of more research and urges healthcare practitioners and consumers alike to reserve judgment on the effects of nutrients like vitamin C and zinc until more credible science is published.”