Immunity

Peng Li, Guoyao Wu. Important roles of amino acids in immune responses. Br J Nutr. 2022 Feb 14;127(3):398-402.
Peng Li et al. Amino acids and immune function. Br J Nutr. 2007 Aug;98(2):237-52.

A deficiency of dietary protein or amino acids has long been known to impair immune function and increase the susceptibility of animals and humans to infectious disease.

Findings from recent studies indicate an important role for amino acids in immune responses by regulating: (1) the activation of T lymphocytes, B lymphocytes, natural killer cells and macrophages; (2) cellular redox state, gene expression and lymphocyte proliferation; and (3) the production of antibodies, cytokines and other cytotoxic substances.

Increasing evidence shows that dietary supplementation of specific amino acids to animals and humans with malnutrition and infectious disease enhances the immune status, thereby reducing morbidity and mortality.

Beth Kelly et al. Amino Assets: How Amino Acids Support Immunity. Cell Metab. 2020 Aug 4;32(2):154-175.

Amino acid metabolism plays a key role in this metabolic rewiring, and it supports various immune cell functions beyond increased protein synthesis.

Guoyao Wu. Amino acids: metabolism, functions, and nutrition. Amino Acids. 2009 May;37(1):1-17.
Michio Miyajima. Amino acids: key sources for immunometabolites and immunotransmitters. Int Immunol. 2020 Jun 26;32(7):435-446.

Many amino acids and their derivatives have been classified as neurotransmitters and their functions are clear as transmitters between nerve cells, or between nerve cells and immune cells, functioning as immunotransmitters. Thus, this review will describe the intracellular and external functions of amino acid from the perspective of immunometabolism and immunotransmission.

Maya C Poffenberger et al. Amino acids fuel T cell-mediated inflammation. Immunity. 2014 May 15;40(5):635-7.

Reprogramming cellular metabolism helps support T cell growth and effector function upon activation. In this issue of Immunity, Nakaya et al. (2014) report that the glutamine transporter ASCT2 regulates T cell metabolism and mTOR kinase signaling to shape inflammatory T helper cell responses.

Michio Miyajima. Amino acids: key sources for immunometabolites and immunotransmitters. Int Immunol. 2020 Jun 26;32(7):435-446.

Roth E. Immune and cell modulation by amino acids. Clin Nutr. 2007 Oct;26(5):535-44.

Evasio Pasini et al. Hypercatabolic syndrome: molecular basis and effects of nutritional supplements with amino acids. Am J Cardiol. 2008 Jun 2;101(11A):11E-15E.

Ning Ma et al. Dietary Amino Acids and the Gut-Microbiome-Immune Axis: Physiological Metabolism and Therapeutic Prospects. Compr Rev Food Sci Food Saf. 2019 Jan;18(1):221-242.

These findings have shed light on the clinical applications of dietary AAs in improving gut microbiota and mucosal immunity, therefore benefiting the gut as well as local and systemic health.

Rebecca L Gould et al. Impact of Supplementary Amino Acids, Micronutrients, and Overall Diet on Glutathione Homeostasis. Nutrients. 2019 May 11;11(5):1056.

Oral GSH supplementation is not the most efficient option due to the enzymatic degradation of ingested GSH within the intestine by γ-glutamyltransferase, but supplementation of its component amino acids-cysteine, glycine, and glutamate-enhances tissue GSH synthesis.

Shigekazu Kurihara et al. Cystine and theanine: amino acids as oral immunomodulative nutrients. Springerplus. 2013 Nov 26;2:635.

Sekhar RV et al. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care. 2011 Jan;34(1):162-7.

Dietary supplementation with GSH precursor amino acids can restore GSH synthesis and lower oxidative stress and oxidant damage in the face of persistent hyperglycemia.

Koichi Miyagawa et al. Co-administration of l-cystine and l-theanine enhances efficacy of influenza vaccination in elderly persons: nutritional status-dependent immunogenicity. Geriatr Gerontol Int. 2008 Dec;8(4):243-50.

Co-administration of L-cystine and L-theanine before vaccination may enhance the immune response to influenza vaccine in elderly subjects with low serum total protein or hemoglobin.

Akira Mitsui et al. Elucidation of the antiviral mechanism of cystine and theanine through transcriptome analysis of mice and comparison with COVID-19 gene set data. Preprint.2021

In conclusion, the unique gene signatures observed in response to orally administered CT in IAV-infected mouse spleen tissues suggested that CT may attenuate viral infection, replication and associated symptoms such as cytokine storm.

Shigeo Kawada et al. Cystine and theanine supplementation restores high-intensity resistance exercise-induced attenuation of natural killer cell activity in well-trained men. J Strength Cond Res. 2010 Mar;24(3):846-51.

Therefore, in practical application, CT supplementation would be useful for athletes to restore the attenuation of NK cell activity during high-intensity and high-frequency training

Shigeki Murakami et al. Suppression of exercise-induced neutrophilia and lymphopenia in athletes by cystine/theanine intake: a randomized, double-blind, placebo-controlled trial. J Int Soc Sports Nutr. 2010; 7: 23.

CT supplementation significantly attenuated the increase in neutrophil count and the reduction in lymphocyte count induced by intense endurance exercise. These results suggest that CT supplementation may suppress the exercise-induced fluctuation of the blood immunocompetent cells and may help to reduce the alteration of the immune state.

C Jones et al. Improving rehabilitation after critical illness through outpatient physiotherapy classes and essential amino acid supplement: A randomized controlled trial. J Crit Care. 2015 Oct;30(5):901-7.

During severe illness and immobility, skeletal muscle declines by 2% to 4% per day. Enhanced rehabilitation combined with GEAA (glutamine and essential amino acid mixture) supplement may enhance physical recovery and reduce anxiety and depression.

Evasio Pasini et al. Protein-Amino Acid Metabolism Disarrangements: The Hidden Enemy of Chronic Age-Related Conditions. Nutrients. 2018 Mar 22;10(4):391.

Clinicians should consider protein homeostasis as essential to maintaining metabolic competence in patients with chronic diseases. This is fundamental for any further therapeutic approaches.

Francesco Bifari et al. Amino acid supplements and metabolic health: a potential interplay between intestinal microbiota and systems control. Genes Nutr. 2017 Oct 4; 12:27.

We hypothesize that specific amino acid mixtures are likely to be of benefit to people who follow a typical Western-style diet, in addition to dietary fiber and prebiotics. A deeper understanding of the efficacy of such dietary supplements to maintain gut microbiota has the potential to contribute important therapeutic tools in human metabolic health and weight control.

Martin Beaumont et al. Amino Acids in Intestinal Physiology and Health. Adv Exp Med Biol. 2020; 1265:1-20.

Thus, adequate dietary supply of amino acids represents a key determinant of gut health and functions.

Vinicius Fernandes Cruzat et al. Amino acid supplementation and impact on immune function in the context of exercise. J Int Soc Sports Nutr. 2014 Dec 14;11(1):61.

Griffith RS. Success of L-lysine therapy in frequently recurrent Herpes simplex infection. Treatment and prophylaxis. Dermatologica. 1987;175:183-190.

A double-blind, placebo-controlled, multicenter trial of oral L-lysine monohydrochloride for the prevention and treatment of recurrent herpes simplex (HSV) infection was conducted. L-Lysine appears to be an effective agent for reduction of occurrence, severity and healing time for recurrent HSV infection.

Milman N. Lysine prophylaxis in recurrent Herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol. 1980;60:85-87.

Calder PC. Branched-chain amino acids and immunity. J Nutr. 2006;136(1 Suppl):288S-93S

De Bandt JP. Therapeutic use of branched-chain amino acids in burn, trauma, and sepsis. J Nutr. 2006;136(1 Suppl):308S-13S

Wilmore DW. Role of glutamine in immunologic responses. Nutrition. 1998;14(7-8):618-26.

Vinicius Cruzat et al. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018 Nov; 10(11): 1564.

Ziegler TR. Glutamine: from basic science to clinical applications. Nutrition. 1996;12(11-12 Suppl):S68-70.

Song QH. Glutamine supplementation and immune function during heavy load training. Int J Clin Pharmacol Ther. 2015 May;53(5):372-6.

Aquilani R. Effects of oral amino acid supplementation on long‐term‐care‐acquired infections in elderly patients. Arch Gerontol Geriatr. 2011;52:e123‐128