CRN Dismisses New JAMA Study on Effects of Vitamin C and Zinc on COVID-19 — Study plagued by weak trial design provides little insights into understanding the appropriate role of these nutrients

FEBRUARY 17, 2021

WASHINGTON – In response to a new study published February 12th online in JAMA Open Network, entitled “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,” and an accompanying commentary “Supplements for the Treatment of Mild COVID-19—Challenging Health Beliefs With Science From A to Z,” The Council for Responsible Nutrition (CRN), the leading trade association for the dietary supplement and functional food industry, issued the following statement: 

Statement by Steve Mister, President & CEO, CRN: 

“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 this weak study design and haphazard approach would lead to unclear results. 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. 

“Healthcare 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. 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. 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, and the study failed to stratify participants by age, sex, race, or duration of symptoms prior to testing, which 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. If the study had fully enrolled, the differences in outcomes between groups may have reached statistical significance.  

“It is important to note 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]. 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.

“Even more disturbing is the commentary by Michos and Cainzos-Achiria that 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.   

“Fortunately, much of that research 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.”

The Council for Responsible Nutrition (CRN), founded in 1973, is a Washington, D.C.-based trade association representing 180+ dietary supplement and functional food manufacturers, ingredient suppliers, and companies providing services to those manufacturers and suppliers. In addition to complying with a host of federal and state regulations governing dietary supplements and food in the areas of manufacturing, marketing, quality control and safety, our manufacturer and supplier members also agree to adhere to additional voluntary guidelines as well as to CRN’s Code of Ethics. Visit Follow us on Twitter @CRN_Supplements and LinkedIn.