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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.
Histidine is an essential amino acid with health benefits that include anti-inflammatory, anti-oxidant, glucoregulatory, and weight management. Because of the extended period of time (>35 days) that is required to deplete body histidine pools in adults, it has not been possible to fully determine histidine requirements. 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. The average intake of histidine from a normal adult diet in the U.S., Europe, and Japan was reported between 2.12 and 2.40 g/day with the 99th percentile intake in men at 50-70 years of age consuming 5.20 g/day. The clinical safety of histidine supplementation above the average dietary intake has not been determined. Therefore, this study will utilize graded doses of histidine that are at are moderately above the average intake to identify safety and benefits of histidine in a healthy human population. 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. Following the completion and review of a health history questionnaire, vitals, and a biochemical panel, participants will be deemed healthy by a nurse practitioner and able to participate. After baseline measures are obtained, supplements (encapsulated histidine) will be provided at three graded doses (4 g/day, 8 g/day and 12 g/day) a forth dose (16 g/day) will be consumed if no adverse effects are observed at the three graded doses. Each dose will be for 28 days followed by a three week recovery period. At baseline, weeks 2 and 4 of supplement, and recovery a basic biochemical panel, anthropometric, urinary and serum zinc, will be conducted. Additionally, body composition will be conducted at baseline and week 4 of each dose. Changes in dietary intake and physical activity will be measured with 4-day food records and Actigraph activity monitors, respectively. Changes in sleep patterns will be measured with the Pittsburgh sleep questionnaire.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 4 g / day histidine | Experimental | subjects ingest encapsulated high quality histidine for four continuous weeks at 4 g/day. |
|
| 8 g / day histidine | Experimental | subjects ingest encapsulated high quality histidine for four continuous weeks at 8 g/day |
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| 12 g /day histidine | Experimental | subjects ingest encapsulated high quality histidine for four continuous weeks at 12 g/day |
|
| 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Histidine | Dietary Supplement | ingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 % |
| Measure | Description | Time Frame |
|---|---|---|
| Change in hours of sleep | The effects of histidine will be assessed with changes in sleep pattern as determined using a subjective measurement tool | 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 |
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Inclusion Criteria:
• healthy young males and females aged 21-50 y.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Human Metabolic Research Unit | Ithaca | New York | 14853 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32766885 | Derived | 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. |
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| ID | Term |
|---|---|
| D006639 | Histidine |
| ID | Term |
|---|---|
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000601 | Amino Acids, Essential |
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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.
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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 |
The effects of histidine will be assessed with changes dietary intake as determined with 4 day food records |
| week 0 to 4 of each dose |
| Change in physical activity measured in steps per day | The effects of histidine will be assessed with changes in physical activity patterns using an Actigraph | week 0 to 4 of each dose |
| Change in subjective mood measured in arbitrary units | The effects of histidine will be assessed with changes in mood as determined using a subjective visual analog scale. 100 mm line is anchored by two opposing statements. The higher number the greater the mood. | week 0 to 4 of each dose |
| Change in subjective desire to eat measured in arbitrary units | The effects of histidine will be assessed with changes in desire to eat will be determined using a visual analog scale. 100 mm line is anchored by two opposing statements. The greater the number the stronger the desire. | week 0 to 4 of each dose |