L-Arginine saves the day

[thegiantess]

Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis

In this interim analysis, adding oral L-arginine to standard therapy in patients with severe COVID-19 significantly decreases the length of hospitalization and reduces the respiratory support at 10 but not at 20 days after starting the treatment.

www.thelancet.com

 

[David PS]

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

chrismasterjohnphd.com

 

[Peater Piper]

If it's the increased nitric oxide that's protective, then that could be another mechanism through which sunlight is protective (besides vitamin D).

 

[Amazoniac]

- Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine

Spoiler

"Arginine is a conditionally essential amino acid involved in multiple pathways in health and disease.[7,8] Arginine becomes essential under conditions of stress and catabolic states when capacity of endogenous arginine synthesis is surpassed, including hemolytic anemias,[8–12] asthma,[13–15] pregnancy, and critical illness such as sepsis, burns, and trauma.[16,17] Arginine also plays a key role in the metabolic, immune, and reparative response to trauma.[18] Serving as a substrate for protein synthesis, L-arginine is the precursor for nitric oxide (NO), polyamines, proline, glutamate, creatine, and agmatine[19,20] (Figure 1). Arginine metabolism is highly compartmentalized because its enzymes are expressed to different extents in varying tissues and cell types. Since it is involved in multiple metabolic processes, an arginine deficiency has the potential to disrupt many cellular and organ functions.[21]"

"Arginine is derived from dietary protein intake, body protein breakdown (approximately 80%), or endogenous de novo arginine production in the kidneys (10%–15% of the total arginine production). Arginine is absorbed in the intestine, with the jejunum as the major absorption site, and exhibits a significant liver uptake and metabolism by arginase. Most whole-body arginine synthesis in adults is performed in a metabolic collaboration by the small intestines and kidneys in what has been termed the intestinal-renal axis.[22] Dietary glutamine plays an important role in this process, as 90% of circulating citrulline arises from glutamine.[23–25] Intestine-derived citrulline is released into the circulation and taken up primarily by the kidneys for arginine synthesis.[26] Therefore, damage or dysfunction of either organ system can compromise arginine bioavailability when requirements exceed production capacity: small intestinal inflammation, malabsorption, maldigestion, protein-losing enteropathy, or any condition where intestinal metabolic functions are impaired will affect availability and delivery of protein and amino acids to circulation, while renal dysfunction will affect de novo synthesis of arginine from citrulline in the kidney directly. Ultimately, global arginine bioavailability depends on the flux of other amino acids in the body, including glutamine and citrulline but also glutamate, ornithine, and lysine.[27]"

"While the affinity (Km) of L-arginine for arginase is in the low micromolar range compared with the low millimolar range for NOS, substrate competition does occur between arginase and NOS because the speed of the reaction (Vmax) for arginase is 1000-fold faster than NOS.[22] By competing for a common substrate, arginase reduces the bioavailability of L-arginine for NOS, therefore limiting NO production in a path toward endothelial dysfunction."

"[..]adequate arginine bioavailability plays an important role in normal immunologic function and host defense. Arginase I is constitutively expressed in granulocyte subsets (collagenase granules) and is released locally and/or systemically upon immune activation. In addition, immune activation during certain illnesses, through the release of mediators (eg, prostaglandin E1 and E2; interleukins 4, 10, and 13; catecholamines; and certain growth factors), induces the accumulation of a heterogeneous group of mostly immature myeloid cells that express arginase I. In immune organs, immature myeloid cells expressing arginase effectively deplete arginine from the surrounding environment. Arginine metabolism is involved in macrophage class transition from M1 (inflammatory; macrophages expressing NOS) to M2 (resolution of inflammation and healing macrophage; macrophages expressing arginase).[36] Arginine is an essential amino acid for normal proliferation and maturation of human T cells,[33,37–39] while arginine depletion will induce T-cell dysfunction and increase susceptibility to infection. This latter phenomenon has important implications for trauma and critical illness."

"T cells are exquisitely sensitive to nutrition status, particularly to levels of key amino acids.[45] These include arginine, which is essential for naive T-cell activation, as well as glutamine and branched-chain amino acids, which are required for anabolic processes (eg, induced expression of relevant cytokines and receptors) needed for activated T cells to undergo polarization and properly implement their function.[33,38,39,46] T-cell proliferation is significantly blunted, production of interferon-γ and interleukin 2 is inhibited, and T-lymphocyte–mediated cytotoxicity and memory responses are nearly completely abolished when arginine is depleted.[47–49] The provision of arginine to culture media has been shown to restore T-lymphocyte function.[50] Plasma arginine levels drop acutely after trauma within minutes to hours,[16,51] while arginase activity is increased.[17,33,52–55] Plasma arginine levels may remain low for up to a week or longer in severe injury.[17,48]"

"L-citrulline supplementation dose-dependently increases plasma L-arginine levels in healthy human volunteers more effectively than equivalent doses of arginine itself.[152] In fact, data suggest that oral supplementation of citrulline may be more efficient than oral arginine supplementation during inflammatory conditions.[153]"

"Interestingly, in a pharmacokinetics study, we found that 10 g of oral glutamine significantly increased both glutamine and arginine bioavailability in patients with SCD at risk for pulmonary hypertension within 4 hours,[150] while glutamine-enriched enteral nutrition (EN) improved arginine bioavailability in patients with multiple trauma.[156] Combination amino acid therapy also warrants consideration. In an animal model, coadministration of arginine and citrulline resulted in a more rapid increase in plasma arginine levels and marked enhancement of NO bioavailability than supplementation of the single amino acids alone.[157]"

⚠

- Role of Nitric Oxide in Pathogenesis of Herpes Simplex Virus Encephalitis in Rats

"As in bacterial and parasitic infections, iNOS expression, which brings about overproduction of NO, has been documented in various viral infections in vivo (Akaike et al., 1998). Although the suppressive effect of NO on virus replication was reported for some viruses including coxsackievirus (Zaragoza et al., 1997, 1998), Epstein-Barr virus (Mannick et al., 1994), and herpes simplex virus type 1 (HSV-1) (Croen, 1993; Karupiah et al., 1993; Nathan, 1997; MacLean et al., 1998), it seems that excessive NO production is not necessarily beneficial for hosts experimentally infected with a number of viruses (Akaike et al., 1996, 1998; Kreil and Eibl, 1996; Adler et al., 1997). For example, use of NOS inhibitor to treat mice infected with influenza virus resulted in amelioration of virus-induced pneumonia, suggesting that NO produced during the infection is involved in viral pathogenesis. In addition, Adler et al. (1997) reported that suppression of NO biosynthesis led to improvement of HSV-1-induced pneumonia in mice despite moderate impairment of antiviral defense in the mice."​

- Arginine depletion as a therapeutic approach for patients with COVID-19


- Guanidinoacetate Is More Effective than Creatine at Enhancing Tissue Creatine Stores while Consequently Limiting Methionine Availability in Yucatan Miniature Pigs (sometimes solded as guanidinoacetic acid or glycocyamine)