Safety of Graded-Dose of Histidine in Humans

NCT04142294 | Completed

• 1 other identifier: 83676/A001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Histidine is an essential amino acid with health benefits that include anti-inflammatory, anti-oxidant, glucoregulatory, and weight management. The current expert opinion for histidine intake is 8 and 12 mg/(kg body weight per day), an estimate that was extrapolated from the infant requirement for histidine. Further, the clinical safety of histidine supplementation above the average dietary intake has not been determined.The overarching objectives are to 1) measure the safety of histidine supplementation and 2) measure the potential benefits of histidine at doses above the average intake and current recommendation in a healthy adult population.

Conditions

Healthy

Outcome Measures

Primary Outcomes (9)

• Change in concentration of zinc in mg/ml

  The safety of histidine supplementation at each dose is monitored through blood markers of zinc

  at week 0 and 4 of each dose

• Change in concentration of liver enzymes (ALT, ALP, and AST) in Units per Liter

  The safety of histidine supplementation at each dose is monitored through circulating liver enzymes

  at weeks 0 (washout), 2 and 4 of each dose

• Change in body weight in kilograms

  The safety of histidine supplementation at each dose is monitored through changes in weight

  at weeks 0 (washout), 2 and 4 of each dose

• Change in concentration of total protein and albumin in g/dl

  The safety of histidine supplementation at each dose is monitored through circulating total protein and albumin

  at weeks 2 and 4 of each dose

• Change in concentration of blood urea nitrogen, Creatinine, bilirubin and glucose each in mg/gL

  The safety of histidine supplementation at each dose is monitored through circulating blood urea nitrogen, Creatinine, bilirubin and glucose

  at weeks 0 (washout), 2 and 4 of each dose

• Change in concentration of C-reactive protein mg/L

  The safety of histidine supplementation at each dose is monitored through circulating CRP

  at weeks 0 (washout), 2 and 4 of each dose

• HgbA1c in %

  The safety of histidine supplementation at each dose is monitored through circulating HgbA1c

  at week 4 of each dose

• Change in heart rate in beats per minute

  The safety of histidine supplementation at each dose is monitored through heart rate

  weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose

• Change in systolic and diastolic blood pressures in mmHG

  The safety of histidine supplementation at each dose is monitored through blood pressure

  weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose

Secondary Outcomes (5)

• Change in hours of sleep

  week 0 to 4 of each dose

• Change in dietary intake of energy, macronutrients, and amino acids measured in kcals and g/day with 4 day food record

  week 0 to 4 of each dose

• Change in physical activity measured in steps per day

  week 0 to 4 of each dose

• Change in subjective mood measured in arbitrary units

  week 0 to 4 of each dose

• Change in subjective desire to eat measured in arbitrary units

  week 0 to 4 of each dose

Study Arms (4)

4 g / day histidine

EXPERIMENTAL

subjects ingest encapsulated high quality histidine for four continuous weeks at 4 g/day.

Dietary Supplement: Histidine

8 g / day histidine

EXPERIMENTAL

subjects ingest encapsulated high quality histidine for four continuous weeks at 8 g/day

Dietary Supplement: Histidine

12 g /day histidine

EXPERIMENTAL

subjects ingest encapsulated high quality histidine for four continuous weeks at 12 g/day

Dietary Supplement: Histidine

16 g /day histidine

EXPERIMENTAL

subjects ingest encapsulated high quality histidine for four continuous weeks at 16 g/day. The 16 g /day dose will be administered if no adverse effects are observed for doses 4-12 g/day

Dietary Supplement: Histidine

Interventions

Histidine DIETARY_SUPPLEMENT

ingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks

12 g /day histidine; 16 g /day histidine; 4 g / day histidine; 8 g / day histidine

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy young males and females aged 21-50 y.

You may not qualify if:

• A body-mass index (BMI) \<19.9 kg/m2 or \> 29.9 kg/m2
• taking/on immunosuppressive medications or prescription anti-coagulation therapy
• pregnancy
• breastfeeding
• musculoskeletal disorder
• diabetes
• alcoholism (\>11 drinks per week for women, \>14 drinks per week for men) or other drug addiction
• acute illness
• inability to travel to Cornell University campus
• A blood pressure at or above 140/90

Sponsors & Collaborators

• Cornell University: lead

Study Sites (1)

Human Metabolic Research Unit

Ithaca, New York, 14853, United States

Location

Related Publications (1)

• Gheller ME, Vermeylen F, Handzlik MK, Gheller BJ, Bender E, Metallo C, Aydemir TB, Smriga M, Thalacker-Mercer AE. Tolerance to graded dosages of histidine supplementation in healthy human adults. Am J Clin Nutr. 2020 Nov 11;112(5):1358-1367. doi: 10.1093/ajcn/nqaa210.

  PMID: 32766885 DERIVED

MeSH Terms

Interventions

Histidine

Intervention Hierarchy (Ancestors)

Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Histidine supplementation trial, non-randomized, sequential delivery of graded doses of the amino acid histidine. All participants serve as their own controls. Following baseline measurements, subjects ingest encapsulated high quality histidine for four continuous weeks at graded doses of 4, 8 and 12 g/day. A forth dose at 16 g/day is assessed if no adverse outcomes are observed for the three graded doses. Histidine doses are suggested based on experience with other amino acids (relative difference of average intake and metabolic limits). Each dose is followed by a 3-week minimum recovery period. During the recovery period, subjects will continue to be monitored (vitals and weight) but no supplementation is consumed. At the conclusion of each washout period, before the start of the next dose, subjects provide a blood sample, vitals (blood pressure and heart rate), weight, 4-day diet record, sleep log, hunger and satiety VAS, mood VAS, and physical activity monitoring.

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: October 29, 2019
• Study Start: September 21, 2017
• Primary Completion: August 31, 2019
• Study Completion: August 31, 2019
• Last Updated: February 7, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)