Safety assessment of l-lysine oral intake: a systematic review

• Published in: Amino acids Vol. 51; no. 4; pp. 647 - 659
• Main Authors: Hayamizu, Kohsuke, Oshima, Ikuyo, Fukuda, Zesoku, Kuramochi, Yui, Nagai, Yuki, Izumo, Nobuo, Nakano, Makoto
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.04.2019; Springer Nature B.V
• Subjects: Administration, Oral; Amino acids; Analytical Chemistry; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; clinical trials; Diarrhea; diet; Dietary Supplements; Dosage; Eating; food safety; functional foods; Functional foods & nutraceuticals; Gastrointestinal symptoms; Gastrointestinal system; Gastrointestinal tract; Gastrointestinal Tract - metabolism; guidelines; Humans; Ingestion; Life Sciences; Lysine; Lysine - administration & dosage; Lysine - analysis; Nausea; Neurobiology; no observed adverse effect level; Organic chemistry; Original Article; Proteomics; relative risk; Risk analysis; Risk Assessment - methods; Safety; safety assessment; Systematic review; Gastrointestinal symptom; Systematic review; Safety; Lysine; NOAEL; L-Lysine
• ISSN: 0939-4451; 1438-2199; 1438-2199
• DOI: 10.1007/s00726-019-02697-3

Currently, the use of amino acids in supplements and functional foods is increasing globally. However, there are no guidelines for the upper limit of ingestion for the safe use of these amino acids. Safety evaluation of chemical substances is generally performed through non-clinical and clinical studies. However, amino acids that have these safety data are limited. Therefore, we used a systematic review approach for evaluating the safety of amino acids. In the present study, we evaluated the safety of l -lysine added to an ordinary diet in humans. Using PubMed, Cochrane Library, Ichushi Web, and EBSCO host as search databases, we comprehensively searched human studies on oral ingestion of l -lysine. Ultimately, 71 studies were selected for evaluation. Of these, 12 studies were of relatively high quality with Jadad scores ≥ 3. The dose range of l -lysine in the selected studies was 16.8–17,500 mg/day, and the range of dosing period was 1–1095 days. The observed adverse events were mainly subjective symptoms related to the gastrointestinal tract such as nausea, stomachache, and diarrhea. The provisional no-observed-adverse-effect level obtained based on these gastrointestinal symptoms was 6000 mg/person/day. Integrated analysis of the risk for developing gastrointestinal symptoms revealed that the risk ratio was 1.02 (95% CI, 0.96–1.07; p  = 0.49); thus, no significant increase was observed. (UMIN000028914)