Friday Hope: L-Arginine: Protecting the Endothelium in Acute and Long COVID

An amino acid with many potential benefits and multiple functions in the body that must be used with great care.

Cartoon representing the main results of the LINCOLN survey.

As we discover therapeutics to prevent and treat damage and disease from SARS-CoV-2 and its Spike Protein, we notice that there are essentially three classes of therapeutics; those that are used prophylactically, those that are used in the acute phase of COVID, and those that are used in treating those suffering from Spike Protein injuries/Long COVID. Some therapeutics overlap and are applicable in multiple settings.

Today I would like to discuss a supplement that is fascinating, yet at the same time gives one pause. It is the amino acid L-Arginine – and it must be used with great care as it can be quite double-edged.

First, let’s discuss what L-Arginine is.

l-arginine is an essential amino acid that plays a crucial role in various physiological processes in the human body [2,3]. It is a precursor for the synthesis of nitric oxide (NO), a potent vasodilator and neurotransmitter [2], and it also participates in protein synthesis, immune function, and wound healing [4]. l-arginine is primarily obtained from dietary sources, including meat, poultry, fish, dairy products, and nuts [2]. It can also be synthesized in the body from other amino acids, such as glutamate and glutamine.

Exploring the medicinal significance of l-Arginine mediated nitric oxide in preventing health disorders
https://www.sciencedirect.com/science/article/pii/S2772417424000475

This sounds wonderful. And, when used correctly, it can be a marvelous therapeutic. However, as I stated earlier, it must be used with caution. Before you go out and buy a bottle of L-Arginine supplements (ALWAYS talk to your primary care provider before using any medication or supplement), let’s look at under what circumstances L-Arginine may NOT benefit you.

In some inflammatory conditions and diseases, introducing excess Arginine may actually, indirectly CAUSE inflammatory damage to tissue.

NO plays an important role in macrophages response to inflammatory processes, but there is a fine line between the non-toxic NO concentrations for host cells and the toxicity required for its antimicrobial action. It can be beneficial or potentially toxic depending on the concentration and tissue in which it acts. Some authors refer to NO as a “double-edged sword,” and arginine, as a precursor of NO, may have both a positive effect against the inflammatory process and also a negative one, potentially damaging tissues indirectly [42].

Also, Arginine is quite useful for some viruses and can reactivate Herpes Simplex Virus at high concentrations.

In vitro studies have demonstrated the necessity of arginine for the replication and reactivation of herpes simplex virus (HSV). The absence of this amino acid did not reduce viral DNA synthesis, but it prevented the formation of complete viroids. However, high concentrations of the amino acid stimulated rapid viral reactivation and resumption of protein synthesis. It is important to note that these findings showcase the significance of amino acids in viral reactivation and protein synthesis [91, 93].

Furthermore, reducing L-Arginine can ameliorate lesions in Human Herpes Virus.

Pedrazini et al. also followed patients with recurrent cold sores for 8 years using the L-lysine 500 mg fasting + dietary arginine suppression protocol, and in the first year of treatment there was an average 49% reduction in lesion healing time and an average 63% reduction in the number of annual lesions [115, 116]. In theory, the consumption of arginine-rich foods such as peanuts, cashews, almonds, granola, and chocolate should be avoided [35, 95].

L-arginine: its role in human physiology, in some diseases and mainly in viral multiplication as a narrative literature review
https://fjps.springeropen.com/articles/10.1186/s43094-024-00673-7

Please also be aware that L-Arginine supplementation in the elderly is probably not a best practice, especially for prolonged periods.

We therefore investigated effects of chronic dietary L-arginine supplementation on kidney aging. In both young (4 months) and old (18–24 months) mice, animals either receive standard chow containing 0.65% L-arginine or diet supplemented with L-arginine to 2.46% for 16 weeks. Inflammation and fibrosis markers and albuminuria are then analyzed. Age-associated increases in tnf-α, il-1β, and il-6, vcam-1, icam-1, mcp1, inos, and macrophage infiltration, collagen expression, and S6K1 activation are observed, which is not favorably affected, but rather further enhanced, by L-arginine supplementation. Importantly, L-arginine supplementation further enhances age-associated albuminuria and mortality particularly in females, accompanied by elevated renal arginase-II (Arg-II) levels. The enhanced albuminuria by L-arginine supplementation in aging is not protected in Arg-II−/− mice. In contrast, L-arginine supplementation increases ROS and decreases nitric oxide production in old mouse aortas, which is reduced in Arg-II−/− mice. The results do not support benefits of long-term L-arginine supplementation. It rather accelerates functional decline of kidney and vasculature in aging. Thus, the long-term dietary L-arginine supplementation should be avoided particularly in elderly population.

Detrimental Effects of Chronic L-Arginine Rich Food on Aging Kidney
https://pmc.ncbi.nlm.nih.gov/articles/PMC7851093/

Given the caveats discussed above, we can now talk about the many ways L-Argenine is beneficial for us in supplementation.

Much evidence shows that oral administration of Arg within the physiological range can confer health benefits to both men and women by increasing NO synthesis and thus blood flow in tissues (e.g., skeletal muscle and the corpora cavernosa of the penis). NO is a vasodilator, a neurotransmitter, a regulator of nutrient metabolism, and a killer of bacteria, fungi, parasites, and viruses [including coronaviruses, such as SARS-CoV and SARS-CoV-2 (the virus causing COVID-19). Thus, Arg supplementation can enhance immunity, anti-infectious, and anti-oxidative responses, fertility, wound healing, ammonia detoxification, nutrient digestion and absorption, lean tissue mass, and brown adipose tissue development; ameliorate metabolic syndromes (including dyslipidemia, obesity, diabetes, and hypertension); and treat individuals with erectile dysfunction, sickle cell disease, muscular dystrophy, and pre-eclampsia.

Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans
https://link.springer.com/chapter/10.1007/978-3-030-74180-8_10

Now we arrive at how L-Arginine may be very beneficial, when used correctly, in treating COVID/Spike Protein disease and injury. A study from 2022 showed that combining L-Arginine with Vitamin C was effective in treating the endothelial dysfunction we have all come to know as the hallmark of COVID and Spike Protein disease/injury.

This survey is the first to show the beneficial effects of the combination of L-Arginine and Vitamin C in Long-COVID. Our investigation was based on a robust rationale, i.e. targeting endothelial dysfunction in Long-COVID. Indeed, endothelial cell infection with consecutive inflammatory cell recruitment and endothelial dysfunction could explain the impaired microcirculation observed across vascular beds in COVID-19, triggering vasoconstriction, ischemia, and a pro-coagulant state [92], [93], [94], [95]. Consistent with our view, several investigators had proposed that endotheliitis could be a critical mechanism underlying systemic impaired microcirculatory function observed in different vascular beds in patients experiencing Long-COVID symptoms [92], [96].

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey
https://pmc.ncbi.nlm.nih.gov/articles/PMC9295384/

As with so much we have discovered, simply eating a well-balance diet of REAL food goes a long way in preventing/treating COVID/Spike Protein injury and disease. Nature has generously provided us many therapeutics to assist us. I continue to be astounded. Please remember, this is a work of medical research and not medical advice. As I mentioned earlier, always consult your Primary Care Provider before using any medicine or supplement.

Thank you, as always, for your readership, dialogue and support. I hope everyone has kept warm during this very frigid week. A good Irish Stew comes to mind to keep the body and soul satisfied – while gaining some L-Arginine.