Potential Benefits and Pitfalls of Histidine Supplementation for Cancer Therapy Enhancement

J Nutr. 2020 Oct 1;150(Suppl 1):2580S-2587S. doi: 10.1093/jn/nxaa132.


Dietary supplementation of the amino acid histidine has demonstrable benefits in various clinical conditions. Recent work in a pediatric leukemia mouse model exposed a surprising potential application of histidine supplementation for cancer therapy enhancement. These findings demand a deeper reassessment of the physiological effects and potential drawbacks of histidine supplementation. As pertinent to this question, we discuss the safety of high doses of histidine and its relevant metabolic fates in the human body. We refrain from recommendations or final conclusions because comprehensive preclinical evidence for safety and efficacy of histidine supplementation is still lacking. However, we emphasize the incentive to study the safety of histidine supplementation and its potential to improve the clinical outcome of pediatric blood cancers through a simple dietary supplementation. The need for comprehensive preclinical testing of histidine supplementation in healthy and tumor-bearing mice is fundamental, and we hope that this review will facilitate such studies.

Keywords: amino acid; antifolate; cancer therapy; dietary supplement; folate; histidine; leukemia; methotrexate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dietary Supplements*
  • Folic Acid / metabolism
  • Formiminoglutamic Acid / metabolism
  • Histidine / adverse effects
  • Histidine / metabolism*
  • Histidine / pharmacology*
  • Histidine / therapeutic use
  • Humans
  • Leukemia / drug therapy
  • Methotrexate / therapeutic use
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*


  • Histidine
  • Formiminoglutamic Acid
  • Folic Acid
  • Methotrexate