Arginine + Vitamin C for Long Covid

Very Promising Results in a Study Involving 1390 Long Haulers

A new study from Italy reports excellent improvement across multiple categories of symptoms using a daily supplement of the amino acid L-Arginine and Vitamin C:

“Combining L-Arginine with Vitamin C Improves Long-COVID Symptoms: The Nationwide Multicenter LINCOLN Study.” Pharmacological Research, 19 Jul 2022, PMID 35868478, Full Study.

The study involved two daily doses of 1.66 grams arginine and 500 mg Vitamin C. The hypothesis going into the study was that much of the disability related to Long Covid is caused by issues with the endothelium - the lining of blood vessels. Arginine is a precursor or building block for the body to make nitric oxide (NO), and NO opens up the endothelium and stimulates it in a number of ways. Vitamin C is well known as an anti-oxidant, and it is also involved in recycling nitric oxide … having higher levels of Vitamin C can make a given dose of arginine more effective in boosting the NO levels in the body. Vitamin C might also be helping by supporting the neutralization of caustic, pro-oxidative chemicals. Vitamin C can also be a limiting factor in the production of the collagen-like materials that line the blood vessels, which may have been damaged in the acute phase of covid, or afterward due to continued immune activity and inflammation.

To provide statistical control in this study, approximately half of the patients got a multivitamin pill instead of the arginine/C treatment. At the end of 30 days of treatment, the health of the two groups was evaluated. Each symptom was scored as being ‘severe,’ ‘mild,’ or ‘absent.’ In all categories of symptoms, the patients on arginine+C scored much better. Here is a list of the symptom areas investigated:

• Asthenia (Weakness)

• Dyspnea (Difficulty Breathing)

• Chest Tightness

• Dizziness

• Gastrointestinal Disorders

• Anosmia (Loss of Smell)

• Concentration Difficulty

• Sleeplessness

In the asthenia (weakness) component, the results were nothing short of amazing. After 30 days of a multivitamin, 94.4% of those patients reported severe symptoms. In the group that took the amino acid/vitamin mix, a mere 1.1% of the patients reported severe symptoms.

For the “concentration difficulty” measurement (corresponding to brain fog), the multivitamin group reported 20.4% had severe symptoms, and 46.8% reported moderate impairment. Only 1.5% of the arginine+C group reported severe problems concentrating, and only 19.4% had moderate impairment. Nearly 80% of the arginine+C group reported the absence of concentration problems!

In all 8 categories of symptoms that were studied, the researchers calculated a “p<0.0001,” which translates to the idea that it is very, very unlikely that the differences between the 2 groups were due to random variation… less than one chance in 10,000. In other words, they are pretty dang sure that the improvements in the arginine+C group were due to the treatment and were not some fluke.

Safety

Both Arginine and Vitamin C are generally considered safe at the doses used in the study.

Arginine is found to various degrees in proteins we eat on a daily basis, although the amount is somewhat small compared to all the other amino acids. Foods rich in arginine include watermelon and nuts like almonds and walnuts.

Arginine is taken as a supplement for bodybuilding, and to reduce erectile dysfunction. It is common for these groups to take higher doses - 5 grams (5,000 mg) or more per day. One study gave 142 overweight people up to 30 grams (30,000 mg) of Arginine per day for 90 days and found no adverse effects. They concluded that (at least in the short term), arginine is safe. (PMID 29858688)

Various forms of herpes viruses (including cold sores and shingles) might be made worse by high levels of arginine consumption - one common nutritional strategy for dealing with those infections is to limit arginine and increase the amino acid lysine.

Vitamin C is safe in reasonable doses. Although Vitamin C can become pro-oxidative at high doses, this effect has not been noted in adults at 500 mg twice per day. Vitamin C also has the ability to be metabolized into oxalate (which can impact the kidneys and form stones) - but that typically happens at much higher doses.

Cost

Both of the ingredients in the Italian study are quite inexpensive. The liposomal form of Vitamin C retails for about 12 to 20 cents per daily dose of 1000 milligrams in the United States. And the liposomal form is a bit more expensive than generic Vitamin C. While the liposomal forms of many vitamins might be better absorbed, ordinary Vitamin C is water soluble and usually is very bio-available.

Arginine can be bought in capsules, or as a bulk powder. Capsules for a daily dose of ~3 grams run about 30 to 50 cents depending on brand. If a person buys a pound of the amino acid, the price comes to around 15 cents per day. The ‘free form’ of the amino acid is rather bland, and can be incorporated into coffee or a smoothie. The Arginine HCL form has a bit of a sour bite, and might not be the best for coffee. One other form of this amino acid is Arginine AKG (alpha-ketoglutarate).

The original study was carried out using free arginine, and the dose of other forms would have to be adjusted to maintain the same dose used in the Italian experiment… more is needed because the hydrochloride or alpha-ketogluturate make up a significant amount of the weight of those supplements; they contain less arginine in an ounce.

If a person goes for generic vitamin C and bulk arginine powder, the cost of this program is around 40 cents per day - $12 per month. Excellent.

Comparison to the Oxford Amino Acid Study

I wrote in another post about a study being done at Oxford University using amino acids. It hasn’t released any results yet. The Oxford study also uses arginine - 7.2 grams per day, almost twice as much as the Italian study. But the Oxford study involves a total of 48 grams of amino acids per day (which is equivalent to 48 grams of protein per day). That could raise issues in some susceptible people.

An adult with an average body weight might be advised to eat at least 55 or 60 grams of protein, and if they eat meat, they might get more. Adding another 48 grams of amino acid/protein to someone’s diet (as the Oxford study does) is going to make the liver and kidneys work harder, and with long covid, stressing the liver and kidneys might not be wise. All other things being equal, it is preferable to take the 3.2 grams of arginine in this Italian protocol and eat an otherwise normal diet… unless we get good data showing that the Oxford protocol is clearly superior and safer.

Bottom Line

This study is really promising for long haulers. Assuming that it was well done and can be replicated (ie, “is true), then this might be a safe, effective, low-cost way to help people with Long Covid get their life back.

I will be following the news on this protocol in future posts. You can sign up (for free) for a Friday email that summarizes all my posts for the week.