You may have heard the news that a small trial carried out at the Cleveland Clinic in the US showed that vitamin C and zinc are useless against covid-19.  

The results of the trial, called the ‘COVID A to Z’ trial, now published in JAMA Network is one of several studies being undertaken by the Cleveland Clinic on covid-19, and the only one involving the oral use of nutritional supplements.


  • A new trial concluded that vitamin C and zinc are not an effective treatment for covid-19
  • The trial did not attempt to evaluate how effective vitamin C and zinc were for prevention, which would have been more appropriate
  • The treatment was started after people became ill, many of whom were also extremely vulnerable to becoming severely ill. Had it been started it may have demonstrated more positive results
  • The vitamin C and zinc supplements were stopped 10 days in – yet the primary outcomes were determined after 28 days (2 weeks after the supplements were stopped)
  • A growing body of evidence shows that vitamin C, zinc and vitamin D help to prime the immune system so it can modulate (not over or under respond) following infection by pathogens
  • Our downloadable flyer shows you how to upgrade your immunity to help reduce your risk of serious illness.

Trial design: looking the business

The single-centre, prospective, randomised trial involved around 200 subjects and compared symptom severity, duration and hospitalisation in 4 different groups of patients with COVID-19 visiting the Clinic as outpatients.

The 4 groups of around 50 each received standard care, vitamin C (8 grams in 3 divided doses with meals) alone, zinc (50 milligrams as zinc gluconate at bedtime) alone, or both vitamin C and zinc (doses as previous). Treatments were initiated on confirmation of disease with a positive PCR test and continued for 10 days. Symptoms were reported electronically or on paper using a scale for severity over 28 days. The primary study objective was to find out how long it took to get to 50% of the symptom severity score after the peak symptom score was reached.

Sounds fine and dandy, yes? But let’s look at a few other factors we know about the trial design.

  • Patients in all groups were, on average, either very overweight (lowest average BMI was 28.3 for the vitamin C only group) or obese (average BMI was highest at 31.0 in the vitamin C and zinc group)
  • Nearly half of the vitamin C and zinc group had hypertension, a major risk factor for severe covid-19, against only 28% in the standard of care group
  • The vitamin D status of the subjects was not known, nor any other aspect of their nutritional status, and most importantly,
  • The treatment with nutrients wasn’t initiated until after disease had taken hold. Yes, it was a treatment, not a prevention, trial.

Plausible but failed, right?

While the study didn’t provide statistical evidence that the vitamin C, zinc or combined regime was better than standard of care, despite the investigators recognising the scientific plausibility of an effect, it did provide two sets of positive results that should not be ignored:

  1. On the 4-symptom scale, the number of days for patients on average to go from peak symptom severity to 50% severity was over a day shorter on the vitamin C treatments with and without zinc (5.5 days with vitamin C compared with 6.7 days for standard of care). But the small numbers and high variance between individuals meant these differences were not statistically significant.
  2. This same relationship of a vitamin C effect (albeit non-significant statistically) was reflected in the Kaplan-Meier curves that show the change in numbers at risk (see below).


Figure: Ascorbic acid treated group show less than half the number at risk 8 out of 10 days into the treatment, this benefit being maintained throughout the trial (day 28) despite supplement treatment being stopped at day 10. Source: Thomas et al. JAMA Network Open. 2021;4(2):e210369.

OK – so these are trends in the right direction, but they weren’t significant statistically. Yes, the small study numbers are perhaps one reason why significance wasn’t achieved but we must agree that the results were disappointing. Especially for those of us who have held sway that humble nutrients like vitamin C and zinc might come to the rescue.

Why did the trial fail?

We hate to have to say: the trial was destined to failure. It may not be one that was designed to fail, but its failure was predictable in our view. Why? Mainly because the nutritional treatments started too late – only after symptoms of disease were being expressed, which may have been between 4 and 12 days after the study participants became infected.

The treatments were also inadequate because the vitamin C dose was too low, and they failed to include another key nutrient, pro-hormone and immune system modulator, vitamin D. We also have no knowledge of the nutritional background of the patients, but their metabolic state would suggest many immune modulating nutrients, including phytonutrients, may have been in poor supply.

Nutritional status prior to infection is key to disease progression for respiratory (and most other) pathogens. How our innate immune system, comprised of physical, chemical barriers and an arsenal of fast-acting immune cells like neutrophils, natural killer cells, macrophages and dendritic cells, determines how effectively a virus can overcome its hosts defences. Think of the innate immune system like a trapdoor: the narrower you can make it, the less you let in. If it’s wide open because your nutritional status is sub-optimal, the loading on your immune system is much greater and the virus can more readily start replicating after hijacking the transcription machinery of the cells in your airways.

The subjects were also highly vulnerable – all being at least heavily overweight if not obese, with a significant proportion having other vulnerabilities including hypertension, high triglycerides, diabetes, as well as suffering anxiety and depression. These vulnerable patients would therefore have a lower ability to get their adaptive immune systems running to effectively bring in the big guns in the form of B cells and T cells.

Not only that, the nutrient supplements were stopped after 10 days following symptoms. In other words, just as the adaptive system was getting itself into gear, it lost invaluable resources in the form of vitamin C and zinc, both of which are not stored by the body.      

What can we learn from this trial?

Oral nutritional supplements like vitamin C and zinc, as well as vitamin D, are all about prevention. They prime the immune system so it’s ready for assaults by pathogens. A healthy innate immune system is just what you need if you want to narrow your trapdoor to the outside world and effectively minimise the load of potentially dangerous pathogens that breach the mucosal barriers in our airways.

So if the trial was really to look at prevention, much more meaningful results would have been gained if the subjects in the supplement arms were already taking vitamin C and zinc for at least 2 weeks prior to symptoms being tracked. In the case of vitamin D, it would be around 3 months – given most adults who are deficient require around 3 months on about 10,000 IU (250 mcg) per day before achieving optimum circulating levels of 25-hydroxyvitamin D. Intake of all three of these nutrients also shouldn’t be stopped after 10 days, especially for those who’ve been infected.

What’s more, once a patient has been infected and moderate to severe symptoms have manifested, the existing evidence suggests intravenous vitamin C is considerably more effective than oral intake.

Find out more in the recommended protocols below.

Trials that show vitamin C and zinc are useful

Prevention protocols

A strong and resilient immune system is one of our best defences against becoming seriously ill from a range of respiratory infections, including covid-19. Use of supplements, eating well, sleeping properly, managing stress and moving regularly are all key to maintaining a healthy immune system. We’ve brought all these areas together into one downloadable flyer that can be shared with friends and family.

Download our flyer here or by clicking on the image below:


Download the ANH-Intl and British Society for Ecologial Medicine's nutritional protocols for healthy immune systems

Download ANH-Intl's Immune support eRecipe book

The I-MASK+ Prophylaxis & Early Outpatient Treatment Protocol for COVID-19 developed by the Front Line COVID-19 Critical Care Alliance is designed for prophylaxis (prevention) and early outpatient treatment.

Download the I-MASK protocol in multiple languages

Webinar: Transform your Immune System for 2021 from the What Doctors Don’t Tell You team, featuring Dr Robert Rountree, Rob Verkerk PhD and Dr Sarah Myhill. (Please note the £3 fee to access.)

Treatment protocols

The C4Covid campaign has created a one-page flyer with recommendations for the use of nutrients for prevention, early treatment, severe covid and those in critical care to support recovery.

Download C4Covid flyer

Dr Brownstein developed a protocol to treat patients with mild covid symptoms early on in the pandemic. He was silenced and forced to remove the protocol from his website. He then published the protocol as a study. His protocol used oral vitamins A, C, and D plus a dilute solution of hydrogen peroxide and saline with Lugol’s iodine which was nebulised. Some patients were also treated with IV hydrogen peroxide and vitamin C.

The MATH+ protocol from the Front Line COVID-19 Critical Care Alliance contains detailed guidance for healthcare professionals treating patients hospitalised with covid-19.

Download the MATH+ protocol

Find out more

>>> Vitamin D campaign

>>> Vitamin C campaign

>>> Zinc campaign

>>> Covid - Adapt Don’t Fight campaign

>>> Food4Health campaign