Study finds vitamin C, zinc don’t cut COVID-19 duration but was too short, flawed in design, CRN claims

By Hank Schultz

- Last updated on GMT

©Getty Images - nitto100
©Getty Images - nitto100

Related tags coronavirus Vitamin c Zinc

A recent study that found no benefit for vitamin C and zinc in shortening COVID-19 symptoms suffers from weak study design and a possible premature cessation, CRN says.

The Council for Responsible Nutrition was reacting to a study published late last week in JAMA Network Open​. The research, dubbed the COVID A to Z Study, was conducted at the Cleveland Clinic.

The goal of the research was to see if high doses of vitamin C (8,000 mg) and zinc gluconate (50 mg) could lessen the length of symptoms experienced by patients diagnosed with COVID-19 infections who had not been hospitalized.  The patients were recruited at and treated at the Cleveland Clinic. The goal of the study was to recruit aboutGet subjects.

The patents were divided into four groups: a vitamin C group, a zinc group, one group that received both supplements and a control group that got no supplement intervention. 

 The main outcome was the self reported duration and severity of  symptoms in the intervention groups as compared to the controls.  The original plan called for assessment of 4 symptoms: fever/chills, shortness of breath, cough, and fatigue.  In July 2020 after an advisory from the Centers of Disease Control the researchers added additional symptoms to the list, including loss of taste and smell, headache and others, to make a total of 12 symptoms. The subjects were followed for 28 days.

Study halted early because of lack of observed effects

The study was one of more than 30 trials that on the effect of vitamin C in relation to COVID-19 that have been underway since late 2020.  However, the Cleveland Clinic study was halted after 214 subjects were recruited and observed because the authors concluded no statistically significant symptom duration outcomes were being observed and continuing the research would be futile.

“[B]ased on the current study, these supplements cannot be recommended to reduce symptom morbidity in such patients. High-dose zinc gluconate, ascorbic acid, or both supplements did not reduce SARS-CoV-2 symptoms. Most consumers of ascorbic acid and zinc are taking significantly lower doses of these supplements, so demonstrating that even high-dose ascorbic acid and zinc had no benefit suggests clear lack of efficacy,”​ the authors concluded.

In addition to the research, the journal also published a commentary on the study.

“Given the widespread public use of supplements, such as zinc and ascorbic acid, for the prevention and treatment of viral infections, we applaud the COVID A to Z Study5 investigators for adding rigorous science by testing their efficacy and challenging popular beliefs. Unfortunately, these 2 supplements failed to live up to their hype,”​ the commentary concluded.

CRN: Flawed study might nevertheless have yielded positive results if allowed to run course

Steve Mister, president and CEO of CRN, said the study had many shortcomings, not least of which was to assume that a very short term, high dose application would perform like a drug would.

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,​” he said.

Mister said his organization believes the researchers may have pulled the plug too soon.  He noted that the data gathered from less than half of the target subject pool showed a trend toward benefit in the groups that received the vitamin C alone or that took vitamin C along with zinc.  The study might have shown a statistically more robust result if allowed to run its full course.

“[P]atients 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,”​ he said.

Commentary adds insult to injury

In addition, Mister said it was unfortunate that JAMA sought to pile on with the attendant commentary.

“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,”​ Mister said.

“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,​” he concluded. 

Source: JAMA Network Open
2021;4(2):e210369. doi:10.1001/jamanetworkopen.2021.0369
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; The COVID A to Z Randomized Clinical Trial
Authors: Thomas S et al.

Source: JAMA Netork Open
2021;4(2):e210431. doi:10.1001/jamanetworkopen.2021.0431
Supplements for the Treatment of Mild COVID-19—Challenging Health Beliefs With Science From A to Z
Authors: Michos ED, Cainzos-Achirica M

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