The One Amino Acid That Could Cure COVID

Disclaimer: I am not a medical doctor and this is not medical advice. I have a PhD in Nutritional Sciences and this information is educational in nature.

An Italian clinical trial peer-reviewed and published this past month in EClinical Medicine, one of the journals published by The Lancet, is nothing short of incredible.

It provides rigorous evidence that 3.2 grams per day of the amino acid L-arginine dramatically hastens the improvement in respiratory function in patients that already have confirmed pneumonia and are already suffering from hypoxemic respiratory distress. It may turn out to be lifesaving.

One of the things that is so remarkable about this study is that usually nutritional treatments have to be started early in the course of illness to work. For example, as I covered in my comprehensive review of the vitamin D literature, maintaining high vitamin D status is the single best thing you can do for prevention, and if administered early in the course of illness it is extremely powerful in preventing the illness from getting bad enough to put someone in the ICU. By contrast, if vitamin D is given to people who already have severe respiratory distress — at least in the standard form of vitamin D you would buy in the store — it does nothing at all.

In this case, however, the L-arginine works when things have already gotten very bad.

Background

The protein in the food we eat — especially rich in meats, fish, shellfish, dairy products, and legumes such as lentils, peas, and beans — is made of building blocks called amino acids. One of those building blocks is L-arginine, or just “arginine.”

Arginine is the raw material from which we make nitric oxide.

Nitric oxide plays three critical roles that are likely to be extremely important for COVID protection:

  • Since nitric oxide is antimicrobial, the immune system always makes massive amounts of nitric oxide to kill pathogens.
  • Nitric oxide is the main vasodilator. This means it dilates your blood vessels, making them wider, and allowing blood to flow more freely. This would protect against clotting.
  • In the lungs, nitric oxide combines with another molecule we make from the protein we eat, glutathione, to make nitrosoglutathione. Nitrosoglutathione is our own natural bronchodilator. This means it opens up the airways, just like nitric oxide opens up the blood vessels. This allows us to breathe more freely.

In addition, arginine itself is needed for lymphocytes to proliferate. Lymphocytes are a type of white blood cell, and a key player in our immune system. If your doctor orders a complete blood count (CBC), a panel of tests that is also used to diagnose anemia, it will have the number of lymphocytes found in your blood on it. If lymphocytes can't reproduce, or “proliferate,” their numbers will be low. Low lymphocyte counts are a major predictor of whether a COVID patient will die.

Adults and children hospitalized with COVID-19 have low blood levels of arginine. Arginine levels are even lower in those with severe cases than in those hospitalized for more moderate cases. This appears to be at least partly driven by a type of cell that suppresses the immune response, commonly found in obesity and cancer. These immunosuppressive cells make an enzyme known as arginase that destroys arginine. This depletes the arginine available for lymphocyte proliferation, causing low lymphocytes. The low lymphocytes become the major predictor of death.

Lymphocytes taken from severe patients have trouble reproducing. Dumping a little arginine on top of them helps them start multiplying again.

The short of it is this: patients hospitalized with COVID have increased levels of immunosuppressive cells that make the enzyme arginase. This depletes arginine. Arginine depletion causes low lymphocytes and low nitric oxide. Low lymphocytes are known to drive the risk of death, and low nitric oxide probably plays a role as well by making blood vessels and airways more constricted. This makes blood vessels more vulnerable to clotting risk and airways less able to oxygenate the blood.

The Italian Trial

The Italian trial was double-blind, randomized, and placebo-controlled. This means that neither the medical researchers nor the patients had any idea whether they were getting arginine or a placebo that looked, tasted, smelled, and felt just like it. This is the gold standard.

The placebo and arginine were provided by the manufacturer of the arginine supplement, but there does not appear to be any other external funding. The manufacturer played no role in the design, implementation, or analysis of the study. The trial was conducted in a hospital in Naples, and the authors were affiliated with either the COVID-19 division of a nearby hospital, medical colleges in the area, or Albert Einstein College of Medicine in New York. None of the authors reported any conflicts of interest.

In order to be included, patients had to have all of the following: pneumonia confirmed by chest imaging, low blood levels of oxygen, and low lymphocytes.

They excluded anyone who had a known intolerance to arginine, who was pregnant or breastfeeding, who had various blood disorders, who was on certain immunosuppressive drugs or types of chemotherapy, or who had been having COVID symptoms for more than 15 days.

These patients were, on average, eight days into their illness, but some were as far as two weeks into their illness, and they all had severe cases with serious risk of death.

The patients were randomly allocated to the arginine or placebo group. Both patients received a vial twice a day of a liquid that was sweetened with sucrose and soured with citric acid. These were minor components that served to fully disguise the taste of the arginine. The liquid was the same in the two groups except the arginine group had 1.6 grams of arginine added to each vial.

The treatment being tested, then, was 1.6 grams of L-arginine taken twice a day to yield 3.2 grams per day.

The patients took the arginine or placebo until they were discharged from the hospital or died.

The trial is ongoing and will eventually recruit 290 patients. The findings were so remarkable that they published their interim findings in the September issue of The Lancet's EClinicalMedicine after having put the first 101 subjects through the trial. The arginine group had 48 people while the placebo group had 53 people, although some people died before they were treated, and 45 people received treatment in each group.

It is important to note that the small number of patients involved in the interim results actually makes the results more compelling. While we always want research confirmed with bigger and bigger studies done in different populations to make us confident the effect generalizes across populations, the reason they are recruiting 290 people is because they planned on observing a more moderate effect that would require a larger sample size to generate rigorous statistics. Instead, the results were so big and so consistent that they obtained rigorous statistical evidence with only a third of the people they intended to recruit.

Arginine Hastens Respiratory Improvement

The main endpoint was an improvement in the degree of respiratory support needed. This could be moving from more invasive oxygen support to less invasive forms, or it could mean going off oxygen support entirely. When adjusting for demographics and comorbidities, arginine led to 6.6 times greater odds of improving respiratory support by day 10.

This was statistically significant at a P value of 0.01. That means that, if there were no real effect of arginine, we would only have a 1% chance of observing an effect this big.

By day 20, the placebo group started to catch up. That means that the effect of the arginine was to hasten the improvement in respiratory function, making it far more likely to occur by day 10 rather than by day 20.

Did Arginine Abolish the Risk of Death?

While 6.7% of people in the placebo group died, no one in the arginine group died.

With a larger study, we will probably find that the arginine group experiences some death. For example, if the death rate were brought down to 0.5%, we would need 200 people per group to reliably see one person die. Still, that would represent a 93% reduction in the relative risk of death.

However, the difference does not achieve statistical significance. 3 people in the placebo group died, and none in the arginine group. This has a P value of 0.19 or 0.24, depending on the statistical test used, which means that if arginine does not reduce the risk of death, there would be a 19-24 percent chance of observing a difference this large or larger.

In the context of the interim results of this trial, the arginine appeared to abolish the risk of death, but we will need to see the final publication after all 290 patients have been recruited to get more rigorous statistics.

Either way, arginine is extremely powerful at hastening the recovery of respiratory function and appears so far to be lifesaving.

What Was the Mechanism?

Interestingly, this study did not show any improvement in lymphocyte levels.

That makes me think the improvement in nitric oxide function was the primary mechanism involved, but they didn't test that directly.

Implementing These Findings

In the most recent edition of The Food and Supplement Guide for the Coronavirus, my protocol calls for starting 1.6 grams of L-arginine twice per day on an empty stomach with a full glass of water or prior to a meal, beginning with a positive COVID-19 test or upon experiencing any signs of respiratory distress.

This is not medical advice and this is not a substitute for seeking medical care. Importantly, the patients in the trial were hospitalized, and everyone was receiving the standard of care in addition to either the arginine or placebo.

My rationale is that respiratory distress signals the demand for arginine seen in the patients who were studied, while a positive COVID-19 test combined with any other COVID-19 symptoms increases the probability of having respiratory distress in the future. Since L-arginine is quite harmless in most contexts, and since early treatment is probably always better, it is best to start whenever there are decent signs it might become important, rather than waiting till things get bad.

Often people aiming to increase their arginine levels will use a different amino acid known as L-citrulline. While citrulline is usually easily converted to arginine, the disruptions that occur to amino acid metabolism in COVID are not completely and clearly defined. I would worry that the conversion of citrulline to arginine could be hurt, which would make that strategy less effective. I, therefore, think L-arginine should be used.

Some people with herpes infections experience flareups when supplementing with arginine. While anyone would obviously prefer to have a cold sore than die, if you know you get herpes flareups in response to L-arginine, you may wish to be more conservative about when you decide to initiate its use.

There are also some claims that a different amino acid, lysine, protects against COVID. However, these claims are based entirely off of reporting improvement in people who took lysine without comparing them to anyone else. The authors believed the lysine was antagonizing arginine, and this Italian trial clearly refutes that using the gold standard: the double-blind, randomized, placebo-controlled, clinical trial.

Arginine, the Unsung Hero

These results show, using the gold standard of evidence, that 1.6 grams of L-arginine taken twice a day to yield a total of 3.2 grams per day, may have abolished the risk of death in a group of 48 people with severe COVID-19, confirmed pneumonia, and respiratory distress who were hospitalized and receiving the standard of care. More clearly, it led to an almost 7-fold increase in achieving an improvement of respiratory function within ten days. I believe is likely from improving nitric oxide function, opening up the airways and blood vessels and diminishing the harmful effects of blood clots. While we need the final results from this trial to get rigorous statistics on death, so far we know that arginine is a powerful tool to recovery respiratory function and appears to be lifesaving.

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Updates and Corrections to This Article

Several hours after publication this article was revised as follows. This article was originally titled “The One Amino Acid That Cured COVID” and “Cured” was changed to “Could Cure” after statements about the apparent mortality benefit were revised. The statistical significance for the mortality benefit is only seen when several subjects who died before treatment were included. Without them, there were 3 deaths in the placebo group and 0 in the arginine group, which gives a P value of 0.19-0.24. The article was revised to say that death might be abolished by arginine but we need to see the full trial with 290 participants in order to get the potential for statistical significance. The conclusions were revised to emphasize that the 6.6-fold greater odds of achieving respiratory improvement by day 10 are the primary finding and the arginine appears so far to be lifesaving.

October 2 — The article was revised to clarify that the trial was published in EClinicalMedicine, a journal published by The Lancet, but not in the journal The Lancet itself.

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28 Comments

  1. Thanks for directing me to post here from the YouTube live chat. My posit/comment/question on this is a little longer than a comment space. Can I send you an email directly?

  2. Thank you for clarifying towards the end about the Lysine (against arginine) study. I had received that one in a newsletter and wondered how they could be so contradictory. Thank you for digging in and analyzing the research!

  3. I’m confused, other studies say that the amino acid that helps cure covid is L-Lysine, not Arginine. Those studies even mention to avoid foods containing high amounts of Arginine. So which is it then, L-lysine or Arginine?

  4. Thanks for this encouraging article. It prompted me to recall a couple of studies or articles that indicated that arginine was COUNTER-indicated for COVID. I did a search and found these:
    https://www.mdpi.com/1999-4915/13/7/1301/htm
    https://wholefoodsmagazine.com/columns/vitamin-connection/lysine-reported-to-halt-coronaviruses-an-interviw-with-bill-sardi/

    There might be more. I’m wondering if these studies/articles indicating arginine was COUNTER-indicated are plainly wrong; probably wrong; or, whether the proposition is more complicated. They were advocating for lysine and minimizing arginine. Moreover, they were advocating against coffee (particularly disturbing.) Any comments would be appreciated.

  5. Thanks, Chris for the information. It is encouraging to have further supporting facts relating to ‘additional benefits’ from the consistent use of various natural supplementation such as L-Arginine. Thanks for the input!

  6. Ugh, that is a misleading clickbait title. The EClinical Medicine paper describes a treatment that _reduces symptoms_, nobody who is serious about medicine or science would use the word “cure” for this. What’s going on in your life that you think this is OK?

  7. Sir- this is a very ill considered report of a serious unconvincing paper that denies the most basic facts about the Lysine Arginine balance in covid and other viral replication studies such as EBV- I pointed this out to you on your facebook page to no avail.. Quite simply Arginine is DAFT – it will kill people and encourage massive EBV flare ups which are already bad enough with covid- having followed you for a couple of years now I do appreciate your work- but that you do appear to know this fills me with horror hat you should be so blind to basic amino acid / viral interactions and uncritical of this garbage study. RETRACT YOU MUST – see this https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310019/

    1. I took this advice and took Arginine and had a massive EBV flare after my vaccine. Now I am taking lysine, which I previously took for EBV flares and starting to feel better.
      It is puzzling that some studies seem to indicate Arginine helps, and others that it hurts. If the important thing is the ratio, and the ratio is not something people can measure, then it seems irresponsible to suggest using one or the other.

  8. IMO, “could cure” is nearly as bad as “cured.”

    That it significantly reduces the chance of death in those who are already severly ill is great news, of course, but not a “cure.” Numerous folks, including those who were asymptomatic, have long covid.

    Personally, given that I was disabled for over a decade before I reversed my diabetes, long covid scares me much worse than outright death.

    I’d like to see this tried with some of those folks.

  9. 1st The results are laughable….. people still hospitalized 20 days later. Awful.

    2nd, DO NOT GIVE ADVICE of taking arginine in EARLY treatment since this study obviously is for LATE and severe covid which probably indicates is post viral phase of illness. This advice without proof can get people killed. Arginine like you said gives people cold sores. Guess what, arginine in the viral replication phase, would stimulate inducible nitric oxide (the bad NO) inflammation and stimulate viral replication.

    Lastly, if you gave me a covid ward, that has been full for months, and I discharged 80% of subjects in 3 or 4 days, would you consider that a success? Lysine does that, arginine doesn’t. Longest person with covid hospitalized I know was 6 days.

    1. You are totally correct Sir- I appreciate you saying this so clearly – btw – Juliette C speaks very highly of you- fyi I have been advising to take 5g Lysine daily for covid prophylaxis since feb 2020 – I myself have taken that dose since many years for my EBV control – all power to you. SEE THIS. ARGININE IS DAFT AT BEST _ A LYSINE SPOILER AT WORST https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310019/

      1. Bo Kar / BB, you okay, buddy?

        You do realize you’re comparing two different mechanisms of action? Secondly, human clinical trials supersede in vitro studies.

        Just like “theoretically” high-dose Vitamin D3 will make a Covid infection more likely and more severe, yet human clinical trials show the exact *opposite* to be true. This is, once again, because human clinical trials trump in vitro / theoretical studies.

        Your posts (which you seem to be copying + pasting incessantly) come off as agenda-driven and sanctimonious. You don’t seem genuinely concerned of others nor of the pursuit of science and improving the outcomes of infected people.

        1. Sir, because I have experimented with nuts and orange juice when I had covid, while completely suppressing symptoms with lysine. I IMPLORE people that this is dangerous due to the fact this study is now being touted as for early and prophylaxis. You have covid, you want to feel awful in just 30 mins, a half cup of OJ will do it. You better have a 2000mg of lysine, cheese, papaya, yogurt handy to counter that awful effect arginine has on it.

          Look up nitric oxide inflammation. 2 or 3 really good papers on that. Arginine will raise viral replication plus the iNos it produces will make you feel awful. I don’t sell books or guides nor lysine. Just trying to save peoples lives.

    2. Actually, results of using quality forms of L-Arginine, especially in combination with L-Citrulline (which makes the L-Arginine substantially more effective) are amazingly good. In my practice, I have been using a combination of L-Arginine and L-Citrulline with some additional ingredients to help the cardiovascular system and have had amazing results. In addition, L-Arginine does not “cause” cold sores but will exacerbate any traces of herpes (cold sores) already in the system BUT, there is a way to rectify that: Use of Golden Seal for a couple of days at the rate of about 600mg 3 times per day or so should help reverse that ‘cold sore’ scenario quickly.

  10. It would be interesting to see what the results would be with l-citrulline or a combination of l-citrulline and l-arginine:

    “The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure” – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683098/

    “In summary, the evidence presented above suggests that Cit is more suited for long-term elevations of Arg levels compared to the Arg on a gram-to-gram basis. Furthermore, the simultaneous administration of both compounds might be advantageous in situations where acute increases in plasma Arg are desired.”

    1. L-Arginine in combination with L-Citrulline is excellent … I have been using a formulation with these two and other ingredients for a long time very successfully for the ‘prevention’ of cardiovascular problems or for the ‘shoring-up’ of cardiovascular health. It has been said by several ND’s/MD’s/PhD’s that in combination, the L-Citrulline makes the L-Arginine exponentially more effective.

  11. Do you think other supplements that increase nitric oxide production such as Beet Juice or CocoaVia will have a similar effect?

  12. This is interesting because other studies reveal L lysine do the same. Now the problem I have is with arginine and those carrying the herpes virus. The last thing you want is a bad break out of herpes when trying to recover from covid, no? So maybe you would do lysine along side. Thanks

    1. L-Arginine does not “cause” cold soresor herpes but will exacerbate any traces of herpes (cold sores) already in the system BUT, there is a way to rectify that: Use of Golden Seal for a couple of days at the rate of about 600mg 3 times per day or so should help reverse that ‘cold sore’ scenario quickly according to my clientele.

  13. For some of us with chronic epstein barr and susceptibility, arginine supplementation seems to bring on relapse of those diseases.
    Do you have any ideas around that? Maybe large doses of lysine pulsed away from arginine?

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