NAC, Melatonin, B Vitamins and Probiotics Supplements: Can They help Against Coronavirus?
COVID-19 kills some people and spares others. How do you ensure that you are on the right side of the statistics? There are just too many self-proclaimed medical experts recommending all kinds of supplements for COVID-19 out there. On one side are experts telling you that supplements don't work and you should avoid them and just rely on wholesome foods. On the other, are experts telling you to take all kinds of supplements that will help protect you against COVID-19. Do they actually work? Some supplements do have evidence and some don't. This guide is based on various references to scientific literature and hopefully, can help you make sense of the options and to separate the facts from fiction.
Update: The FLCCC protocol has been updated (April 26, 2021 version).
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| Image credit: ClevelandClinic |
The medical community themselves are battling over supplements on whether they should be used to treat and prevent COVID-19. On one side are experts telling you that supplements don't work and you should avoid them and just rely on wholesome foods. On the other, are experts telling you to take all kinds of supplements that will help protect you against COVID-19. Do they actually work?
How do you deal with different expert groups dishing out conflicting guides? A common issue is that certain groups have pre-defined narrative that they would like to support. Therefore, only studies that support that pre-defined narrative are picked and cited as references. This is what we call as 'cherry-picking'. Cherry picking will naturally lead to a 'biased' decision. In order to avoid that, scientific information needs to be analysed in a comprehensive, updated and non-biased manner in order to come up with the best 'evidence-based' decision.
As of June 2021, there are more than 70 types of supplements that are being tested for COVID-19. You can review the details of these trials on clinicaltrials.gov. There are more than 120 trials testing the various nutrients and dietary supplements including vitamin D, vitamin C, zinc and melatonin. Vitamin D remains the most tested vitamin with the most evidence followed by zinc and vitamin C, for COVID-19.
We have covered quercetin, vitamin D, C and zinc for COVID-19, but what about B vitamins, melatonin, probiotics and NAC supplements?
Note: This is a highly dynamic topic; therefore, we will be updating this article as new information emerges.
Melatonin and COVID-19
The potential utility of melatonin in treating COVID patients has not gone unnoticed, with a PubMed search combining melatonin and COVID producing more than 50 citations.
You may know about melatonin as a supplement that can support your healthy sleep cycle. Melatonin is released by the brain’s pineal gland in response to nighttime darkness and is a key regulator of circadian synchrony.
Assisting sleep and rest is already an immune system-supporting benefit, but melatonin has more to offer. It is a powerful antioxidant that supports your immune health, brain, eyes, digestion, and more. It may even be helpful when it comes to COVID-19.
Production of melatonin diminishes with age, contributing to immune dysfunction and increasing oxidative stress, inflammation, and infection susceptibility (Ref). In addition, infectious viruses can suppress melatonin production, disrupting circadian controls and impairing immune function (Ref).
As discussed in a review (Cardinali et al. 2020), melatonin might counteract the consequences of COVID-19 via salutary effects on the sleep/wake cycle and more generally on chronobiology, as well as through its antioxidant and anti-inflammatory effects.
Based on melatonin’s therapeutic potential and well-established safety profile, it has been suggested those at higher risk for severe illness and complications from viral respiratory infection, including the elderly and those with chronic medical conditions, may benefit most from regular use of 3–10 mg melatonin at bedtime (Ref).
Fluvoxamine (Selective Serotonin Reuptake Inhibitor) might also exert beneficial effects in COVID patients through its well-characterized ability to substantially increase (~ 2–3-fold) nighttime plasma levels of melatonin. This increase appears to result from fluvoxamine’s inhibition of the melatonin-metabolizing liver enzymes (von Bahr et al. 2000).
"Patients who used melatonin as a supplement had, on average, a 28% lower risk of testing positive for SARS-CoV-2. Blacks who used melatonin were 52% less likely to test positive for the virus."
Some researchers have suggested high doses of melatonin, ranging from 50 to 200 mg twice daily, might help treat patients hospitalized for severe acute respiratory illness (Ref).
In a small Philippine case series study of 10 hospitalised COVID-19 patients, high dose melatonin (hdM) was given in addition (adjuvant) to standard therapy. According to the authors:
"High dose melatonin may have a beneficial role in patients treated for COVID19 pneumonia, in terms of shorter time to clinical improvement, less need for MV, shorter hospital stay, and possibly lower mortality."
Another study of patients tested for COVID-19 found that those who reported taking melatonin were less likely to test positive, but this does not prove that taking melatonin supplements can prevent COVID-19 (Jehi, Chest 2020).
In an observational study that followed 11,672 individuals, melatonin use was associated with a reduced risk of testing positive for a common, highly infectious respiratory virus (Ref).
Another study looked at data from 791 patients intubated for respiratory support during an outbreak of a severe acute viral respiratory illness and 2,981 patients needing the same level of respiratory support for other reasons. The use of melatonin, most often for sleep issues, during the intubation period was associated with significantly improved outcomes in both groups and increased the likelihood of survival in virus-infected patients who required mechanical ventilation (Ref).
As of May 2021, 8 studies are currently underway to investigate the benefits of melatonin against COVID-19. Ultimately, the results of the above trials will offer more definitive evidence.
If you take a melatonin supplement, be careful: Too much can cause daytime sleepiness. There is no federal RDA nor any formal advice on supplement dose ranges. Based on an on-going Spanish study, a 2 mg daily dose protocol is being investigated for prevention of COVID-19. Do take note that the dosage for 'prevention' and 'treatment' is different, For prevention or maintenance, a lower dosage is normally recommended whereas a 'treatment' or 'therapeutic' dosage is normally higher.
For prevention, the Front Line COVID-19 Critical Care Working Group, FLCCC recommends (updated Apr 26, 2021):
- Melatonin: 6 mg before bedtime (causes drowsiness).
Related: Nature's Bounty Melatonin 5 mg > One tablet before bedtime (Amazon)
B Vitamins
B vitamins may constitute a long list, but each one is important for different reasons. B vitamins are especially effective in boosting your immunity when you combine the foods containing them so they can all work together for maximum effect. These include vitamin B1 (thiamin), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid) and B7 (biotin).
B12, also known as cobalamin, is a powerful cold- and flu-fighting nutrient in your system, as is vitamin B6, another important, germ-combating vitamin that naturally benefits and strengthens your immune system and even protects against the damaging effects of air pollution.
Vitamin B9 and folic acid help repair tissues and aid in cell metabolism and immune support. They’re found in dark leafy greens, wild-caught, cold water fish like herring, mackerel, sardines, anchovies and wild-caught Alaskan salmon, and pastured, organic chicken.
B12, also known as cobalamin, is a powerful cold- and flu-fighting nutrient in your system, as is vitamin B6, another important, germ-combating vitamin that naturally benefits and strengthens your immune system and even protects against the damaging effects of air pollution.
Vitamin B9 and folic acid help repair tissues and aid in cell metabolism and immune support. They’re found in dark leafy greens, wild-caught, cold water fish like herring, mackerel, sardines, anchovies and wild-caught Alaskan salmon, and pastured, organic chicken.
Niacin or vitamin B3 is another precursor to nicotinamide adenine dinucleotide (NAD+). There are three main forms of niacin, which are dietary precursors to nicotinamide adenine dinucleotide (NAD). These are nicotinamide riboside, nicotinic acid and nicotinamide.
Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor in all living cells that is involved in fundamental biological processes. Emerging evidence implicates that elevation of NAD+ levels may slow or even reverse the aspects of aging and also delay the progression of age-related diseases.
NMN (Nicotinamide MonoNucleotide), is also another precursor to NAD. A case series (published in September 2020) of 9 elderly COVID-19 patients treated with a combination of NMN, zinc, betaine and sodium chloride resulted in rapid improvement.
To improve your glutathione, you need zinc, and zinc in combination with hydroxychloroquine (a zinc ionophore or zinc transporter) has been shown effective in the treatment of COVID-19.
N-acetyl cysteine (NAC), meanwhile, is a precursor of glutathione, and may protect against coagulation problems associated with COVID-19, as it counteracts hypercoagulation and breaks down blood clots.
Selenium is also important, as some of the enzymes involved in glutathione production are selenium-dependent.
N-acetyl cysteine (NAC), meanwhile, is a precursor of glutathione, and may protect against coagulation problems associated with COVID-19, as it counteracts hypercoagulation and breaks down blood clots.
Selenium is also important, as some of the enzymes involved in glutathione production are selenium-dependent.
NAC (N-Acetyl Cysteine), Glutathione and COVID-19
Studies published in ACS Infectious Disease (ACS Infect Dis. 2020) and Antioxidants proposed that glutathione plays a crucial role in the body's fight against the severe inflammatory response triggered by the SARS-CoV-2 virus. The research group in the ACS Infectious Disease study called it the “most likely cause of serious manifestations and deaths in COVID-19 patients.”
Another study, "Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients" was led by Dr Alexey Polonikov from Russia (ACS Infect Dis. 2020).
What he found was that the reactive-oxygen-species-to-glutathione ratio was able to predict the severity of COVID-19 and the patient’s outcome. When the patient had a low ROS-to-glutathione ratio, the patient had a very mild case. The fever disappeared on the fourth day without any treatment whatsoever.
When the ROS-to-glutathione ratio was high, the patient developed air hunger on the fourth day, experienced significant fever, hoarseness, myalgia and fatigue persisting for 13 days. A patient with even higher ROS and lower reduced glutathione had critical disease requiring hospitalization for COVID-19-related pneumonia.
Foods that have a positive impact on glutathione production include cruciferous vegetables such as broccoli, green tea, curcumin, rosemary and milk thistle. Getting quality sleep may also help.
Different types of exercise can influence your levels as well. In one study, researchers enrolled 80 healthy but sedentary volunteers to measure the type of exercise that may have the greatest effect. They found that aerobic training in combination with circuit weight training showed the greatest benefit.
When the ROS-to-glutathione ratio was high, the patient developed air hunger on the fourth day, experienced significant fever, hoarseness, myalgia and fatigue persisting for 13 days. A patient with even higher ROS and lower reduced glutathione had critical disease requiring hospitalization for COVID-19-related pneumonia.
In another publication on Respiratory Medicine Case Reports:
Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms.
Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms.
Different types of exercise can influence your levels as well. In one study, researchers enrolled 80 healthy but sedentary volunteers to measure the type of exercise that may have the greatest effect. They found that aerobic training in combination with circuit weight training showed the greatest benefit.
What Is the Primary Cause of Severe COVID-19 Illness: Glutathione or Vitamin D Deficiency?
The hypothesis that vitamin D (VD) deficiency is responsible for severe manifestations and death in COVID-19 patients has been proposed and is actively being discussed by the scientific community.
Several studies reported that glutathione levels positively correlate with active vitamin D. (PubMed, PubMed)
Interestingly, a recent experimental study (PubMed) showed that Glutathione deficiency and the associated increased oxidative stress epigenetically alters vitamin D regulatory genes and, as a result, the suppressed gene expression decreases Vitamin D production, ultimately leading to a secondary deficiency of vitamin D. This study provides important information that glutathione is essential for the control of endogenous vitamin D production and demonstrates potential benefits of Glutathione treatment in reducing the deficiency of vitamin D. Taken together, these findings suggest that glutathione deficiency rather than vitamin D deficiency is a primary cause underlying biochemical abnormalities, including the decreased biosynthesis of vitamin D, and is responsible for serious manifestations and death in COVID-19 patients.
NAC (N-Acetyl Cysteine)
N-acetyl L-cysteine (NAC) is a precursor of glutathione, helps to replenish intracellular glutathione, a vital cellular antioxidant. NAC has a low molecular weight and is well absorbed via oral administration. NAC may protect against coagulation problems associated with COVID-19, as it counteracts hypercoagulation and breaks down blood clots.
NAC inhibits cellular entry and replication of some respiratory viruses, assists in clearing thickened mucous from the airways, suppresses inflammatory signaling, and may help mitigate viral infection-induced cytokine storm (Ref).
N-acetylcysteine (NAC) is a precursor to glutathione. In a paper on NAC for COVID-19, published in the October 2020 issue of Clinical Immunology titled “Therapeutic Blockade of Inflammation in Severe COVID-19 Infection With Intravenous N-acetylcysteine”, which is a case series report of 10 patients (including one with G6PD deficiency) given intravenous NAC. NAC elicited clinical improvement and markedly reduced inflammatory marker, CRP in all patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm.
N-acetylcysteine (NAC) is a precursor to glutathione. In a paper on NAC for COVID-19, published in the October 2020 issue of Clinical Immunology titled “Therapeutic Blockade of Inflammation in Severe COVID-19 Infection With Intravenous N-acetylcysteine”, which is a case series report of 10 patients (including one with G6PD deficiency) given intravenous NAC. NAC elicited clinical improvement and markedly reduced inflammatory marker, CRP in all patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm.
As of June 2021, more than 10 clinical trials are underway to assess the efficacy of NAC in the context of highly infectious respiratory viral infections.
Glutathione and Zinc
To improve your glutathione, you need zinc, and zinc in combination with hydroxychloroquine (a zinc ionophore or zinc transporter) has been shown effective in the treatment of COVID-19.
Glutathione and Molecular Hydrogen
One of the best ways to increase glutathione, though, is molecular hydrogen. Molecular hydrogen does so selectively and will not increase glutathione unnecessarily if you don’t need it. You can view Tyler LeBaron’s lecture on the details of how it does this in “How Molecular Hydrogen Can Help Your Immune System.”
Glutathione and Selenium
Selenium is also important, as some of the enzymes involved in glutathione production are selenium-dependent.
Probiotics
Probiotics are living non-pathogenic microorganisms that, when administered in adequate amounts, can have a positive impact on health. Bacteria in theLactobacillus and Bifidobacterium genera, as well as Streptococcus thermophiles and Saccharomyces boulardii, are examples of common probiotics (Ref).
Through the mesenteric lymphatic system, intact bacteria and their metabolites enter the circulation and influence the lung immune response (gut/lung axis). Through this way intestinal metabolites, mainly produced by bacterial fermentation of dietary fiber, such as short-chain fatty acids (SCFAs), significantly influence local gut immunity but also distant organs. SCFAs derived from gut are able to suppress lung inflammation (Ref). Dendritic cells (DCs), the antigen-presenting cells of the immune system, stimulate T-cells subpopulations in mesenteric lymph nodes and gut lymphatic tissue to produce regulatory cytokines. After airways immune-stimulation, these T-cells move from the gut to the respiratory system, providing protection and stimulating an anti-inflammatory response. In fact, gut microbiota rebalancing has been shown to reduce ventilator-associated enteritis and pneumonia (Ref).
Altered bacterial balance (dysbiosis) causes the translocation of cytokines, endotoxins and microbial metabolites in the general circulation to other organs, such as the lung. Conversely, respiratory inflammation (due to many causes, e.g., respiratory viral infections due to COVID-19 virus), causes local dysbiosis and, in turn, the translocation of microbial metabolites and toxins to other organs, such as the gut (below).
Physiological changes in the human microbiota with age leads to a “physiological dysbiosis”, with less diversification in microbial composition, aggravated in case of comorbidity (hypertension, diabetes, chronic inflammatory bowel diseases, etc.) (Ref). Therefore, to establish the condition of eubiosis (healthy condition), “good” bacteria are required. The concept of probiotics as a food with positive effects was firstly used by Parker RB in 1974 and then recognized by the Food and Agriculture Organization (FAO), and more recently by the Word Health Organization (WHO) (Ref).
Multiple randomized controlled trials and several meta-analyses have shown probiotics reduce the risk of acute respiratory tract infections (eg, colds and flu) (Ref).
Another study showed a better prognosis in 28 of 70 symptomatic patients taking probiotics (L. acidophilus DSM 32241, L. helveticus DSM 32242, L. paracasei DSM 32243, L. plantarum DSM 32244, L. brevis DSM 27961, B. lactis DSM 32246, B. lactis DSM 32247, 2400 billion bacteria per day), reducing the risk of admission in ICU. All these actions would be useful in reducing SARS-CoV-2 dissemination in the respiratory tract and gut, reinforcing both anti-inflammatory responses and immune defenses (Ref).
Several peer-reviewed reports of clinical experiences, preclinical studies, small, open clinical trials, case series, and clinical hypotheses have suggested that certain immune-modulating probiotic strains, such as L. rhamnosus CRL-1505 (Ref), Streptococcus salivarius K12 (Ref), L. plantarum LP01 (Ref), and B. lactis BS01 (Ref) may confer protection against respiratory viral infections and/or subsequent inflammatory sequela.
Numerous clinical trials to investigate the usefulness of probiotics in treating severe acute viral respiratory infections have been registered since early 2020, and many are currently underway.
Conclusion
Do take note that the dosages for micronutrients or vitamins are higher for treatment as opposed to maintenance or preventive. This is probably due to higher demand of the body or the deficiency of the micronutrients are worse during a complicated viral infection. However, for prevention or maintenance, the dosages for most of the micronutrients are much lower.Viral infections like the COVID-19 also put added stress on your body, which can affect your blood pressure, heart rate, and overall heart function. That can raise your probability of having a heart attack or stroke. Therefore, make sure your blood pressure is well controlled during this pandemic.
Aside from supplements, there are other ways that may help improve immune response and to prevent you from catching the coronavirus.
- Wear protective face mask. This is to protect not only yourself but others.
- Abundant evidence suggests that eating whole in fruits, vegetables and whole grains—all rich in networks of naturally occurring antioxidants and their helper molecules—provides protection against free radicals.
- Getting Enough Sleep
- Avoid Sugar, red meat and processed foods.
- Don't smoke.
- Take steps to avoid infection, such as washing your hands frequently, using hand sanitizer and cooking meats thoroughly.
- Try to minimize stress.
- Drink enough water to keep your body hydrated.
- Avoid excess alcohol.
- Avoid crowded areas.
- Regular physical activity (outdoor activities may not be allowed in countries with 'lock-down'). Those with active lifestyle has lower risk if hospitalised as compared to those with sedentary lifestyle (Infectious Diseases and Therapy, 2021)
- Consult your nearest local healthcare provider if you have any doubt.
More COVID-19 related topics > COVID-19
Be aware that most of the supplement dosages are above the recommended dietary allowance (RDA) and therefore such dosages should not be maintained on a long term basis.
Disclaimer: The information on this website is not intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice. It is intended as a sharing of knowledge and information from the research and experience of third party sites. If you are pregnant, nursing, taking medication, or have a medical condition, consult your health care professional before using products based on this content.
Supplements you can purchase from Amazon for COVID-19 prevention. Inspired by the FLCCC prevention protocol >
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