Comprehensive safety assessment of l-lysine supplementation from clinical studies: A systematic review

Abstract

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.