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.