Proposals for Upper Limits of Safe Intake for Methionine, Histidine, and Lysine in Healthy Humans.

Based on research presented during the 10th Amino Acid Assessment Workshop, no observed adverse effect levels (NOAELs) for supplemental methionine at 46 mg/(kg·d) (∼3.2 g/d), for supplemental histidine at 8.0 g/d, and for supplemental lysine at 6.0 g/d have been proposed. These NOAELs are relevant to healthy adults and are applicable only to high-purity amino acids administered in fortified foods or dietary supplements. Because individuals are exposed to the above supplemental amino acids in the context of complex combinations of essential amino acids or individually in dietary supplements for various physiologic benefits, such as body fat reduction, skin conditioning, mental energy increase, or herpes simplex treatments, the above safety recommendations will make an important contribution to regulatory and nutritional practices.

[1]  N. Deutz,et al.  Metabolic Consequences of Supplemented Methionine in a Clinical Context. , 2020, The Journal of nutrition.

[2]  N. Gibbs l-Histidine Supplementation in Adults and Young Children with Atopic Dermatitis (Eczema). , 2020, The Journal of nutrition.

[3]  A. Thalacker-Mercer,et al.  Benefits and Adverse Effects of Histidine Supplementation. , 2020, The Journal of nutrition.

[4]  K. Hayamizu,et al.  Comprehensive Safety Assessment of l-Lysine Supplementation from Clinical Studies: A Systematic Review. , 2020, The Journal of nutrition.

[5]  R. Elango Methionine Nutrition and Metabolism: Insights from Animal Studies to Inform Human Nutrition. , 2020, The Journal of nutrition.

[6]  V. Kožich,et al.  Lessons Learned from Inherited Metabolic Disorders of Sulfur-Containing Amino Acids Metabolism. , 2020, The Journal of nutrition.

[7]  Boryana Petrova,et al.  Potential Benefits and Pitfalls of Histidine Supplementation for Cancer Therapy Enhancement. , 2020, The Journal of nutrition.

[8]  K. Hayamizu,et al.  Safety assessment of l-lysine oral intake: a systematic review , 2019, Amino Acids.

[9]  R. Weller,et al.  Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis , 2017, Clinical, cosmetic and investigational dermatology.

[10]  N. Deutz,et al.  Tolerance to increased supplemented dietary intakes of methionine in healthy older adults. , 2017, The American journal of clinical nutrition.

[11]  R. Elango,et al.  Safety and Tolerability of Leucine Supplementation in Elderly Men. , 2016, The Journal of nutrition.

[12]  R. Elango,et al.  Proposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly. , 2016, The Journal of nutrition.

[13]  T. Key,et al.  Plasma concentrations and intakes of amino acids in male meat-eaters, fish-eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort , 2015, European Journal of Clinical Nutrition.

[14]  Y. Furuhata,et al.  The effect of histidine on mental fatigue and cognitive performance in subjects with high fatigue and sleep disruption scores , 2015, Physiology & Behavior.

[15]  Y. Kawamata,et al.  A 4-Week Toxicity Study of Methionine in Male Rats , 2015, International journal of toxicology.

[16]  l-Methionine supplementation maintains the integrity and barrier function of the small-intestinal mucosa in post-weaning piglets , 2014, Amino Acids.

[17]  R. Ball,et al.  Determination of the tolerable upper intake level of leucine in adult men. , 2012, The Journal of nutrition.

[18]  B. Stoll,et al.  Intestinal metabolism of sulfur amino acids , 2009, Nutrition Research Reviews.

[19]  K. Miwa,et al.  Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans. , 2007, Biomedical research.

[20]  C. Der-Martirosian,et al.  Safety and effectiveness of an L-lysine, zinc, and herbal-based product on the treatment of facial and circumoral herpes. , 2005, Alternative medicine review : a journal of clinical therapeutic.

[21]  N. Scrimshaw,et al.  Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Shibani A. Ghosh,et al.  Lysine Fortification: Past, Present, and Future , 2004, Food and nutrition bulletin.

[23]  K. Allen,et al.  Dietary L-histidine-induced hypercholesterolemia and hypocupremia in the rat. , 1981, The Journal of nutrition.