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Amino Acids

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

  • Kohsuke HayamizuEmail author
  • Ikuyo Oshima
  • Zesoku Fukuda
  • Yui Kuramochi
  • Yuki Nagai
  • Nobuo Izumo
  • Makoto Nakano
Original Article
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Abstract

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 EBSCOhost 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)

Keywords

l-Lysine Systematic review Safety NOAEL Gastrointestinal symptom 
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Notes

Acknowledgements

This study was conducted with research funds provided by the International Council on Amino Acid Science (Grant no. ICAAS_4-4-19) (Brussels, Belgium).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with humans or animals. Authors make sure that the manuscript complies with the ethical rules applicable for this journal.

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© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Food ChemistryYokohama University of PharmacyYokohamaJapan
  2. 2.General Health Medical CenterYokohama University of PharmacyYokohamaJapan

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