Comprehensive Safety Assessment of l-Lysine Supplementation from Clinical Studies: A Systematic Review.

Background Despite the widespread use of l-lysine in dietary supplements, the safety information pertinent to excessive l-lysine ingestion is limited and, to the best of our knowledge, there is no published systematic review of safety. Objective The objective of this study was to assess the clinical safety of l-lysine supplementation of a regular diet. Methods We searched PubMed, Cochrane Library, Ichushi Web, and EBSCOhost using the relevant keywords, "l-lysine" and "clinical trial." To investigate all adverse events observed during intervention trials, we included all intervention studies with orally ingested l-lysine without restricting background factors, environment, study designs, and sample sizes. Results We identified 71 articles, which included 3357 study subjects. The l-lysine doses ranged from 16.8 to 17.5 g/d, and the dosing period ranged from 1 to 1095 d. The observed adverse events were mainly subjective gastrointestinal tract symptoms; however, the risk analysis for incidence of gastrointestinal symptoms was not statistically significant (risk ratio of 1.02). Conclusion The provisional no-observed-adverse-effect level in healthy human subjects was based on gastrointestinal symptoms and identified at 6.0 g/d. The review protocol was registered at umin.ac.jp as UMIN000028914 before the beginning of the study.