NEWS and social media platforms have implicated dietary supplements in the treatment and prevention of Covid-19 (SARS-CoV-2). During this pandemic when information quickly evolves in the presence of contradicting messages and misinformation, the reference to evidence-based guidelines should guide treatment decisions.
The role of the immune system is to protect the individual against pathogenic organisms. Nutrition is one of multiple factors that determine the immune response and good nutrition is important in supporting this response.
Immunity can be impaired in older people, particularly those who are frail, have obesity; also in those who are malnourished and in those with low intake of necessary micronutrients. The immune impairments associated with nutritional inadequacy increase susceptibility to infection and permit infections to become more severe, even fatal.
The adverse impact of poor nutrition on the immune system, including its inflammatory component, may be one of the explanations for the higher risk of more severe outcomes from infection with SARS-CoV-2 seen in older people and obesity.
Studies of individual micronutrients, including vitamin D and zinc, suggest roles in reducing severity of infection with SARS-CoV-2. Good nutrition is also important in promoting a diverse gut microbiota, which in turn supports the immune system.
The importance of nutrition in supporting the immune response also applies to assuring robust responses to vaccination. There are many lessons from the study of nutrition and immunity that are relevant for the battle with SARS-CoV-2.
The role of micronutrients in supporting the immune response
Nutrition plays multiple roles in supporting the immune system. The diet provides:
- Fuel for the immune system to function.
- Building blocks for the generation of RNA and DNA and for the production of proteins (antibodies, cytokines, receptors, acute phase proteins etc.) and new cells.
- Specific substrates for the production of immune-active metabolites (e.g. arginine as a substrate for nitric oxide).
- Regulators of immune cell metabolism (e.g. vitamin A, zinc).
- Nutrients with specific antibacterial or anti-viral functions (e.g. vitamin D, zinc).
- Regulators that protect the host from oxidative and inflammatory stress (e.g. vitamin C, vitamin E, zinc, selenium, long-chain omega-3 fatty acids and many plant polyphenols).
- Substrates for the intestinal microbiota which in turn modulates the immune system.
Poor nutrition may not provide sufficient amounts of the nutrients needed by the immune system to function well. This would be associated with increased susceptibility to infection and inability to control the effects of being infected. In this regard the role of micronutrients in supporting the immune system has been widely studied.
Multiple micronutrients play vital roles in supporting the immune response. The roles of vitamins A, C and D and zinc, copper and iron are well explored, but B vitamins, vitamin E, vitamin K, selenium, magnesium and others all have roles.
Deficiencies of several of these micronutrients impair many aspects of both innate and acquired immunity and increase susceptibility to infections.
The immune impairments can be reversed by repletion and this reduces susceptibility to infection. There has been discussion around many micronutrients and anti-viral immunity in the context of infection with SARS-CoV-2 and Covid-19 and there have been numerous publications on this topic since the start of the pandemic.
The appeal of safe, natural treatments is undeniable. It’s true for age-old conditions such as the common cold and for new diseases, especially if they have no known cure. So it makes sense that there would be a lot of interest in supplements for Covid-19, whether as prevention or treatment.
Indeed, zinc, vitamin C, vitamin D, and other supplements have been commonly prescribed from the earliest days of the pandemic.
But do they work? While research can show whether a drug is effective, we may not always know why. When antibiotics were first discovered in the 1920s, there was limited understanding of the biology involved. But lacking an explanation for their benefit did not discourage doctors from recommending these highly effective treatments.
So, what suggests that vitamin C, vitamin D, zinc and vitamin D might help work against any virus?
- Vitamin C is an antioxidant that has long been promoted as a key player in healthy immune function.
- Zinc may have antiviral activity, whether by improving immune cell function that counters viral infections or by reducing the ability of viruses to multiply.
- Some evidence suggests that combining vitamin C and zinc may limit the duration and severity of cold symptoms.
The cases for vitamin D differ. While there is also evidence that vitamin D may have positive effects on immune function, a specific antiviral effect remains unproven.
What is the evidence that supplements are helpful for Covid-19?
Though Covid-19 is a new illness, a few clinical trials have explored the possibility that supplements may be effective. And, unfortunately, most of the evidence is unconvincing.
For example, a few observational studies link lower blood vitamin levels with a higher risk of testing positive for the virus that causes Covid-19. But studies like these cannot prove that vitamin D protects people against infection. Further, a randomised controlled study of people with moderate to severe Covid-19 who received a high dose of vitamin D showed no benefit.
A 2021 study of zinc and vitamin C demonstrated no benefit for people with mild Covid-19. In this study, people whose symptoms did not require hospital admission were randomly assigned to receive:
- only vitamin C, 8,000 mg/day (the recommended daily amount is 75 mg/day for women and 90 mg/day for men)
- only zinc, 50 mg/day (the recommended daily amount is 8 mg/day for women, 11 mg/day for men)
- both supplements at the doses above
- neither supplement.
The researchers found that people receiving the supplements, whether individually or combined, had no improvement in symptoms or a faster recovery when compared with otherwise similar patients receiving neither supplement.
The researchers say that public health officials should issue a clear set of nutritional recommendations to complement messages about the role of hand washing and vaccinations in preventing infection.
Gombart, professor of biochemistry and biophysics in the OSU (Oklahoma State University) College of Science and a principal investigator at the Linus Pauling Institute, said: “Around the world, acute respiratory tract infections kill more than 2.5 million people every year.
“Meanwhile, there’s a wealth of data that shows the role that good nutrition plays in supporting the immune system. As a society we need to be doing a better job of getting that message across along with the other important, more common messages.
“The roles that vitamins C and D play in immunity are particularly well known. Vitamin C has roles in several aspects of immunity, including the growth and function of immune cells and antibody production. Vitamin D receptors on immune cells also affect their function. This means that vitamin D profoundly influences your response to infections.
“The problem is that people simply aren’t eating enough of these nutrients. This could destroy your resistance to infections. Consequently, we will see an increase in disease and all of the extra burdens that go along with that increase.”
The researchers are urging people to take a daily multivitamin as well as doses of 200 milligrams or more of vitamin C and 2,000 international units of vitamin D, rather than the 400 to 800 recommended, depending on age.
Gombart said: “A number of standard public health practices have been developed to help limit the spread and impact of respiratory viruses: regular hand washing, avoiding those showing symptoms of infection, and covering coughs, and for certain viruses like influenza, there are annual vaccination campaigns.”
He notes that there is no doubt that vaccines, when available, can be effective, but they’re not foolproof, and emphasises that current public health practices – stressing social distancing, hygiene and vaccinations – are important and effective, but in need of complementary strategies.
The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system.
Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden.
Against this background the following conclusions are made:
- supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function;
- supplementation above the Recommended Dietary Allowance (RDA), but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and
- public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.
Using supplements to prevent or treat Covid-19 (Research from the US's NIH)
Currently, research is insufficient to support recommendations for or against the use of any vitamin, mineral, herb or other botanical, fish oils or other dietary supplement ingredient to prevent or treat Covid-19.
And by law, dietary supplements are not allowed to be marketed as a treatment, prevention, or cure for any disease; only drugs can legally make such claims.
Nevertheless, sales of dietary supplements marketed for immune health increased after the emergence of Covid-19 because many people hoped that these products might provide some protection from SARS-CoV-2 infection and, for those who develop Covid-19, help reduce disease severity.
People require several vitamins and minerals – including vitamin C, vitamin D, and zinc – for proper immune function, and clinical deficiencies of these nutrients can increase susceptibility to infections.
Other dietary supplement ingredients, such as botanicals and probiotics, do not have essential roles in the body, but they might affect immune function.
However, measuring the impact on the immune system of vitamins, minerals, and other dietary supplement ingredients is difficult because the immune system is a complex network of organs, tissues, and cells; no single, straightforward measure of immune system function and resistance to disease exists.
Currently, data are insufficient to support a recommendation either for or against the use of vitamin C supplements to prevent or treat Covid-19.
However, many researchers recommend studying vitamin C as an adjuvant therapy for Covid-19, including its possible ability to reduce inflammation and vascular injury in these patients [78,105,106,138,139,144-147].
Vitamin C in foods and dietary supplements is safe at intakes up to 400 to 1,800 mg/day for children (depending on age) and up to 2,000 mg/day for adults [137]. These values, however, do not apply to individuals receiving vitamin C treatment under the care of a physician. Higher intakes can cause diarrhea, nausea, and abdominal cramps.
High vitamin C doses might also cause falsely high or low readings on some blood glucose meters that are used to monitor glucose levels in people with diabetes [159-161]. The FNB recommends that these individuals be cautious about consuming vitamin C doses above the RDA/RNI [137].
In an open letter, more than 200 scientists and doctors recommended that adults increase vitamin D intakes from all sources to achieve serum 25(OH)D levels above 75 nmol/L (30 ng/mL) to prevent Covid-19 or reduce its symptoms [210].
They also recommended that adults whose 25(OH)D levels are not tested achieve a daily vitamin D intake of 50 to 100 mcg daily (2,000–4,000 IU); individuals at increased risk of vitamin D deficiency (e.g., those who have obesity, have dark skin, or live in care facilities) might need even larger amounts.
These scientists and doctors also recommended that hospitals measure the serum 25(OH)D levels of all patients hospitalized for Covid-19 and that patients with levels below 75 nmol/L (30 ng/mL) receive vitamin D supplementation.
This open letter is not an official guidance document, however. The NIH Covid-19 Treatment Guidelines Panel states that data are currently insufficient to support a recommendation for or against the use of vitamin D to prevent or treat Covid-19 [165].
Daily intakes of up to 25–100 mcg (1,000 IU–4,000 IU) vitamin D in foods and dietary supplements are safe for children (depending on their age) and up to 100 mcg (4,000 IU) are safe for adults [162].
These values, however, do not apply to individuals receiving vitamin D treatment under the care of a physician. Higher intakes (usually from supplements) can lead to nausea, vomiting, muscle weakness, confusion, pain, loss of appetite, dehydration, excessive urination and thirst, and kidney stones.
In extreme cases, vitamin D toxicity causes kidney failure, calcification of soft tissues throughout the body (including in coronary vessels and heart valves), cardiac arrhythmias, and even death [216-218].
There seems to be nothing to lose and potentially much to gain by recommending vitamin D supplementation for all, e.g. at 800–1000 IU/day, making it clear that this is to help ensure immune health and not solely for bone and muscle health.
People admitted to hospital with Covid-19 should have their vitamin D status checked and/or supplemented.
According to NIH treatment guidelines, data are insufficient to recommend for or against the use of zinc supplements to treat Covid-19 [240]. In addition, the guidelines recommend against doses of zinc supplements above the Reference Daily Intake/Reference Nutrient Intake to prevent Covid-19, except in a clinical trial.
Intakes up to 4–34 mg/day zinc in foods and dietary supplements for children (depending on age) and up to 40 mg/day for adults are safe [219].
These values, however, do not apply to individuals receiving zinc treatment under the care of a physician. Higher intakes can cause nausea, vomiting, loss of appetite, abdominal cramps, diarrhea, and headaches [219].
Chronic consumption of 150–450 mg/day can cause low copper status, reduced immune function, and reduced levels of high-density lipoproteins [243]. In clinical trials among children, zinc supplementation to treat diarrhea increased the risk of vomiting more than placebo [244,245].
Even without convincing evidence, why not take them anyway?
Despite questions about the overall benefit of these supplements, many doctors began prescribing them routinely in the early days of the Covid-19 pandemic. The logic may have been that with so little known about how to best treat this new infection and a long track record of safety for these supplements, why not?
But there are significant hazards to consider. These include side effects, allergic reactions, interactions with other drugs, the cost of unnecessary supplements, and the dangers of taking too much. For example:
- High doses of vitamin C may cause diarrhea or stomach upset. There have also been concerns that high-dose vitamin C supplementation may interfere with blood thinners or cholesterol-lowering medications.
- High doses of vitamin D can cause severe symptoms, such as stomach upsets, kidney injury, and pancreatitis, and may even be life-threatening.
That said, people with nutritional deficiencies should receive supplements. Zinc or vitamin D deficiencies are not rare, and may contribute to poor immune function.
Therefore, even without specific evidence linking supplement use with improvement among people with Covid-19, these supplements may be appropriate for people in whom deficiency is suspected or confirmed.
For example, a person with little sun exposure and a diet low in dairy products may be likely to have vitamin D deficiency. A simple blood test can confirm or rule out vitamin D or zinc deficiency.
If you do take supplements, it is safest to follow the specific daily recommended amounts for your age group and gender unless your doctor/dietitian advises otherwise.
The bottom line
Based on the science, there is reason to be hopeful that supplements such as vitamin C or D, zinc, or others might help in the fight against Covid-19. While there is no proof yet that they do, additional research could show a benefit in certain situations, or with a different dose or formulation of the supplement. So it is worth keeping an open mind.
In the meantime, we should not dismiss the findings of negative studies just because the results were not what we had hoped.
Check with your doctor or dietitian before starting a supplement. Ask about dosage, other medications you are taking and other health conditions you have. The last thing you want to do is to take a supplement that causes more harm than good. – The Vibes, August 2, 2021
Rozanna M Rosly is the Head of Dietetic Services Department (Clinical Dietician) at the UM Specialist Centre
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