Hear me out on this one. A week ago I was adamant that most supplements were useless for COVID-19 prevention or treatment. If you saw my post or page on Coronavirus – I mentioned how no supplement or diet will prevent you from infection. This is still the case. I also previously wrote that Vitamin C will not prevent infection with SARS-CoV2 or treat COVID-19 prophylactically. Zinc on the other hand, I now have a very different opinion on. After digging through the research, I decided to start taking zinc prophylactically.
Last updated: 28 March 2020 19:00EST by Frank Cusimano
Summary
Zinc supplementation may be beneficial to take prophylactically during the SARS-CoV2 pandemic. Zinc plays an important role in modulating the cellular stress response and the immune response. Both Cochrane and independent meta-analyses, recommend zinc supplementation for the prevention and treatment of the common cold and for the reduction in incidence and severity of pneumonia in adults and children, respectively. For patients who develop sepsis, septic shock, and acute respiratory distress syndrome (ARDS) in the ICU, zinc deficiency is a defining feature. In a critical scenario, Zinc plays a role in an immune-mediated response and through a ventilator-induced mechanical stress adaptive response.
Background
The logical assumption is that all viruses or respiratory illnesses are the same. Sadly, this is not the case. The pathophysiology of asthma, COPD, pneumonia, or interstitial lung disease are all different .
Because the pathology is different, so too are the symptoms, the disease progression, and the treatments. When thinking about potential therapies, there are a number of experimental drugs that clinicians are testing on those infected with SARS-CoV2 . These medications affect viral replication, viral cell entry, or inhibit an immune cell-mediated cytokine storm .
In looking at nutritional supplements I take several things into consideration. First, what is it’s role in the body normally, does it effect the virus at all, what is proposed about it’s mechanism of action in a similar disease process, is it clinically used for any purpose, are there clinical trials for its use in a similar disease process, has it ever been recommended or evaluated in a meta-analysis, in high doses does it have toxic effects?
Clinical Data:
Before diving into the science, I asked the question: is there a precedent for zinc use with COVID-19? Has it been used in clinical trials?
First off, Cochrane, a global independent group interested in evidence for better heath outcomes, has published that zinc supplementation may prevent and treat the common cold in adults and that supplementation in children is associated with reduced incidence and prevalence of pneumonia . Other meta-analyses of randomized, double-blind and placebo-controlled trials have confirmed that Zinc supplementation is effective in reducing the mortality of severe pneumonia in both adults and children . In the elderly, an observational study found that those who were deficient in Zinc had an increased incidence and duration of pneumonia . For those over 55, zinc supplementation was found to be anti-inflammatory and an antioxidant that reduced oxidative stress and decrease the incidence of infections . In another randomized controlled-trial, zinc supplementation decreased plasma CRP, Il-6, and lipid peroxidation .
Knowing that COVID-19 results in sepsis and septic shock, I looked into zinc’s role in stress and sepsis. Low zinc concentrations are associated with oxidative damage and inflammation during sepsis . Research has shown that during sepsis, there is a redistribution of zinc from serum into the liver and a correlation between zinc and sepsis outcomes .
Is there precedent to use Zinc in acute respiratory distress syndrome? Human research shows that patients who go on to develop acute respiratory distress syndrome (ARDS) in the ICU have significantly reduced Zinc levels . For ARDS, make sure to check below for a more detailed explanation.
The Science:
In the body, zinc plays an important role in cell regeneration, immunity and growth . It plays a key role in more than 300 enzymes . In modulating the pro-inflammatory response, zinc targets the nuclear factor kappa B (NF-kB), an important transcription factor that is the master regulator of the inflammatory response . Specifically, it is essential for normal cell division, cellular growth, wound healing, carbohydrate metabolism, and is fundamental in smell and taste . While zinc is not stored in the body, it’s deficiency can occur quickly. It is not uncommon for those with bouts of diarrhea to exhibit temporary deficiencies in zinc levels in their body. Zinc deficiency has been shown to decrease T-lymphocytes and T-helper cells and to impair macrophage function and reduce killer cells . It also is involved in controlling oxidative stress and regulating inflammatory cytokines . Deficiency negatively affects the innate immunity because of it’s role in the production of interferon gamma (INFg), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-a) . Previous research has shown when deficient, it elevates the inflammatory response damaging host tissue . Zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation and the induction of cell-mediated immunity over humoral immunity by regulating differentiation . Deficiency of zinc leads to a worse outcome in the response towards bacterial infection and sepsis .
On the virus side, Zinc also been shown to inhibit the RNA polymerase activity of SARS-CoV1 inhibiting replication of the virus in vitro . Although we do not know if this inhibition will occur for SARS-CoV2 in vivo, it is important to note that this inhibition would occur in the cytosol where viral replication occurs and where zinc’s concentration is regulated under times of stress by metallothionein zinc fingers .
ARDS
I think most intriguingly is a paper that was published in 2017 that included both clinical, patient, data and in vitro, cell culture data. In Boudreault et al, they found that mechanical ventilation exacerbates injury through mechanical stress-activated signaling pathways . This stretch occurs from physical positive pressure against the Type I pneumocytes. They found that stress induced by stretching the cells increased the same metalliothionein protein discussed above. In mouse models, modulating this gene, allowed them to limit lung injury. Stretch induction of this protein, metallothionein required zinc and the zinc-binding transcription factor MTF1. In their human data, they found that patients who go on to develop acute respiratory distress syndrome in the intensive care unit have significantly reduced plasma zinc levels. Their data alludes to a novel role for zinc in defining the lung’s tolerance for mechanical ventilation. Failure of stretch-adaptive responses plays an important role in exacerbating mechanical ventilator-induced lung injury .
Discussion
In looking at the above science, several things come to light. One, a common initial symptom in COVID-19 is diarrhea . Diarrhea is a common cause of transient zinc deficiency, something we should all be aware of and something that may weaken the immune system at the onset of the disease.
Seeing as zinc deficiency plays a role in the immune system, the progression of the inflammatory response and the development of sepsis and ARDS, I think supplemental zinc is important during this coronavirus pandemic. The USA recommends daily intake of zinc of 11mg/day for men and 8mg/day for women .
In most of the clinical trials, children were given between 10-20mg and most adult trials were around 42-70mg. Zinc is unique in that, while it isn’t toxic, it does deplete our bodies copper stores at high levels. Previous research has shown that zinc supplementation in adults at 150mg a day is enough to decrease copper levels (a prophylactic treatment for some patients with Wilson disease). Taking it at 150mg/day for only six-weeks, however, may not affect plasma copper levels .
Personally, I think 150mg is excessive. While supplementation is up to the individual, and something everyone should consider with their doctor, the literature points to a 50-100mg dose for most adults in this scenario. While there are different types of zinc supplements, the literature mentions that zinc found in lozenges may not be as affective.
Other Trials
There are also countless of other clinical trials. Since most of these were included in a few meta-analyses mentioned above, here are additional studies for your own edification.
Adjuvant treatment with 20 mg zinc per day accelerates recovery from severe pneumonia in children.
Zinc weekly reduces pneumonia and mortality in young children .
Adjunct treatment with zinc reduced the time to cessation of severe pneumonia and the risk of treatment failure only marginally, if at all, in hospitalized children .
Zinc supplementation in these children significantly decreased case fatality.
The results suggest that adjuvant treatment with zinc accelerates recovery from severe pneumonia in young children and significantly reduces the duration of hospital stay .
Zinc supplementation substantially reduced the incidence of pneumonia .
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Disclaimer: Opinions on this site or on social media do not reflect that of my institutions. I do not provide medical advice. If you have a medical question please see your doctor or if you have a medical emergency, please go to the nearest emergency room.. I have a PhD in Nutrition and Metabolic Biology and three masters degrees including two master’s in nutrition & metabolism. I am a personal trainer & have researched nutrition for 12 years. The info I post is my interpretation of the medical and scientific literature.
