Tolerance to graded dosages of histidine supplementation in healthy human adults. Issue 5 (7th August 2020)

• Record Type: Journal Article
• Authors: Gheller, Mary E; Vermeylen, Francoise; Handzlik, Michal K; Gheller, Brandon J; Bender, Erica; Metallo, Christian; Aydemir, Tolunay B; Smriga, Miro; Thalacker-Mercer, Anna E
• Is Part Of: American journal of clinical nutrition. Volume 112:Issue 5(2020)
• Page Start: 1358
• Page End: 1367
• Publication Date: 2020-08-07
• Subjects: tolerance -- histidine -- adverse effect -- upper level -- human NOAEL; Diet therapy -- Periodicals; Nutrition -- Periodicals; Dietetics -- Periodicals; 613.205
• DOI: 10.1093/ajcn/nqaa210
• Languages: English
• ISSNs: 0002-9165

Abstract

ABSTRACT: Background: Histidine is an essential amino acid with health benefits that may warrant histidine supplementation; however, the clinical safety of histidine intake above the average dietary intake (1.52–5.20 g/d) needs to be vetted. Objectives: We aimed to determine the tolerance to graded dosages of histidine in a healthy adult population. Methods: Healthy adults aged 21–50 y completed graded dosages of histidine supplement (4, 8, and 12 g/d, Study 1) ( n = 20 men and n = 20 women) and/or a 16-g/d dosage of histidine (Study 2, n = 21 men and n = 19 women); 27 participants ( n = 12 men and n = 15 women) completed both studies. After study enrollment and baseline measures, participants consumed encapsulated histidine for 4 wk followed by a 3-wk recovery period. Primary outcomes included vitals, select biochemical analytes, anthropometry, serum zinc, and body composition (via DXA). Results: No changes in vitals or body composition occurred with histidine supplementation in either study. Plasma histidine (measured in subjects who completed all dosages for Studies 1 and 2) was elevated at the 12- and 16-g/d dosages (compared with 0–8 g/d, P < 0.05) and blood urea nitrogen increased with dosage ( P = 0.013) and time ( P < 0.001) in Study 1 and with time in Study 2 ( P < 0.001). In Study 1, mean ferritin concentrations were lower in 12 g/d (46.0 ng/mL; 95% CI: 34.8, 60.9 ng/mL) than in 4 g/d (51.6 ng/mL; 95% CI: 39.0, 68.4 ng/mL; P = 0.038). In Study 2, 16 g/d increased mean aspartate aminotransferase from baseline (19 U/L; 95% CI: 17, 22 U/L) to week 4 (24 U/L; 95% CI: 21, 27 U/L; P < 0.001) and mean serum zinc decreased from baseline (0.75 μg/dL; 95% CI: 0.71, 0.80 μg/dL) to week 4 (0.70 μg/dL; 95% CI: 0.66, 0.74 μg/dL; P = 0.011). Conclusions: Although values remained within the normal reference ranges for all analytes measured, in all dosages tested, the human no-observed adverse effect level was determined to be 8 g/d owing to changes in blood parameters at the 12-g/d dosage. This trial was registered at clinicaltrials.gov as NCT04142294.