• Laura Bonfili et al. Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation.  FEBS J. 2017 Jun;284(11):1726-1737.

    In this study, two AA mixtures, one exclusively consisting of EAAs and the other consisting of 85% EAAs and15% NEAAs, were tested to explore their effects on the viability of both normal and cancer cell lines and to clarify the molecular mechanisms involved. Both mixtures exerted a cell-dependent anti-proliferative, cytotoxic effect involving the inhibition of proteasome activity and the consequent activation of autophagy and apoptosis.

        • Maurizio Ragni et al.    Amino Acids in Cancer and Cachexia: An Integrated View.  Cancers (Basel). 2022 Nov 19;14(22):5691.

            •  Mylène Tajan et al. Dietary Approaches to Cancer Therapy.  Cancer Cell. 2020 Jun 8;37(6):767-785.

            Oral supplementation with branched amino acid appears to reduce the length of hospital stay, decrease morbidity and improve the quality of life, without any changes in mortality. Perioperative supplementation with arginine has shown a reduced incidence of complications and a significant increase in long-term survival.

                • Campos-Ferraz PL.  An overview of amines as nutritional supplements to counteract cancer cachexia.  J Cachexia Sarcopenia Muscle. 2014 Jun;5(2):105-10.

                  • Engelen MP. High anabolic potential of essential amino acid mixtures in advanced nonsmall cell lung cancer. Ann Oncol. 2015 Sep;26(9):1960-6.

                There is no anabolic resistance or attenuated anabolic potential to intake of 14 g of EAA/leucine or balanced amino acid mixture in advanced (mainly stage III) NSCLC. The high anabolic potential of dietary EAA in cancer patients is independent of their nutritional status, systemic inflammatory response or disease trajectory, suggesting a key role of EAA in new nutritional approaches to prevent muscle loss, thereby improving outcome of patients with advanced cancer.

                    • Deutz NE. Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food. Clin Nutr. 2011 Dec;30(6):759-68.

                  In cancer patients, conventional nutritional supplementation is ineffective in stimulating muscle protein synthesis. This anabolic resistance can be overcome with a specially formulated nutritional supplement.

                      • Jéssika D P Soares et al.  Dietary Amino Acids and Immunonutrition Supplementation in Cancer-Induced Skeletal Muscle Mass Depletion: A Mini-Review.  Curr Pharm Des. 2020;26(9):970-978.

                      In addition to being substrates, some amino acids, for example leucine, act as intracellular signals to promote protein synthesis. Recent acute studies demonstrated that provision of amino acids, sufficient to considerably elevate circulating leucine concentrations concurrent with other amino acid and nutrient availability, resulted in significant protein anabolism in cancer patients. This occurred even during weight loss and inflammation

                          • Larsson SC. Methionine and vitamin B6 intake and risk of pancreatic cancer: a prospective study of Swedish women and men. Gastroenterology. 2007;132(1):113-118.

                        These findings suggest that higher methionine intake may reduce the risk of pancreatic cancer.

                            • Ling Chen et al. Efficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysis. Nutr J. 2015 Jul 9;14:67.
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                            • Pasini E. Amino acids: chemistry and metabolism in normal and hypercatabolic states. Am J Cardiol. 2004 Apr 22;93(8A):3A-5A.

                              Amino acids are the “alphabet” of protein structure, determining many of the properties of proteins. Amino acids are rapidly absorbed and readily available in the blood. In the cell, amino acids maintain protein stores and counteract hormone-mediated catabolic stimuli. Thus, amino acid supplementation may be effective in counteracting the metabolic and morphologic consequences of the hypercatabolic state of chronic diseases such as heart failure, diabetes mellitus, or liver cirrhosis.

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                            • Guoyao Wu . Amino acids: metabolism, functions, and nutrition. Amino Acids. 2009 May;37(1):1-17.

                              In contrast to protein, crystalline AA in the diet do not undergo digestion and are directly available for absorption by the small intestine. Therefore, they are absorbed into enterocytes and appear in the portal vein more rapidly than protein-bound AA.

                            • Paddon-Jones D. Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol Endocrinol Metab. 2004 Mar;286(3):E321-8.   

                              Esansiyel Amino acid supplementation acutely stimulated muscle protein synthesis in both young and elderly individuals.

                            • Robert R Wolfe. The 2017 Sir David P Cuthbertson lecture. Amino acids and muscle protein metabolism in critical care.  Clin Nutr. 2018 Aug;37(4):1093-1100.

                              Use of single amino acids (e.g., leucine), or groups of amino acids (e.g., branched chain amino acids) is ineffective, as all EAAs must be consumed to support a clinically significant increase in protein synthesis.

                              Regardless of the approach, ensuring an adequate availability of dietary essential amino acids is necessary for pharmacologic therapy to result in an increased rate of protein synthesis.

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