Safety of Graded-Dose of Histidine in Humans
- Conditions
- Healthy
- Interventions
- Dietary Supplement: Histidine
- Registration Number
- NCT04142294
- Lead Sponsor
- Cornell University
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
• healthy young males and females aged 21-50 y.
- 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
- For individuals desiring to participate in the optional biopsy, a history of a negative or allergic reaction to local anesthetic is an exclusion criteria
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 12 g /day histidine Histidine subjects ingest encapsulated high quality histidine for four continuous weeks at 12 g/day 4 g / day histidine Histidine subjects ingest encapsulated high quality histidine for four continuous weeks at 4 g/day. 16 g /day histidine Histidine 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 8 g / day histidine Histidine subjects ingest encapsulated high quality histidine for four continuous weeks at 8 g/day
- Primary Outcome Measures
Name Time Method HgbA1c in % at week 4 of each dose The safety of histidine supplementation at each dose is monitored through circulating HgbA1c
Change in heart rate in beats per minute weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose The safety of histidine supplementation at each dose is monitored through heart rate
Change in concentration of zinc in mg/ml at week 0 and 4 of each dose The safety of histidine supplementation at each dose is monitored through blood markers of zinc
Change in concentration of C-reactive protein mg/L at weeks 0 (washout), 2 and 4 of each dose The safety of histidine supplementation at each dose is monitored through circulating CRP
Change in concentration of liver enzymes (ALT, ALP, and AST) in Units per Liter at weeks 0 (washout), 2 and 4 of each dose The safety of histidine supplementation at each dose is monitored through circulating liver enzymes
Change in concentration of total protein and albumin in g/dl at weeks 2 and 4 of each dose The safety of histidine supplementation at each dose is monitored through circulating total protein and albumin
Change in body weight in kilograms at weeks 0 (washout), 2 and 4 of each dose The safety of histidine supplementation at each dose is monitored through changes in weight
Change in concentration of blood urea nitrogen, Creatinine, bilirubin and glucose each in mg/gL at weeks 0 (washout), 2 and 4 of each dose The safety of histidine supplementation at each dose is monitored through circulating blood urea nitrogen, Creatinine, bilirubin and glucose
Change in systolic and diastolic blood pressures in mmHG weeks 0 (baseline and washout), 1, 2, 3, and 4 of each dose The safety of histidine supplementation at each dose is monitored through blood pressure
- Secondary Outcome Measures
Name Time Method 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 The effects of histidine will be assessed with changes dietary intake as determined with 4 day food records
Change in subjective mood measured in arbitrary units week 0 to 4 of each dose 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.
Change in subjective desire to eat measured in arbitrary units week 0 to 4 of each dose 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.
Change in hours of sleep week 0 to 4 of each dose The effects of histidine will be assessed with changes in sleep pattern as determined using a subjective measurement tool
Change in physical activity measured in steps per day week 0 to 4 of each dose The effects of histidine will be assessed with changes in physical activity patterns using an Actigraph
Trial Locations
- Locations (1)
Human Metabolic Research Unit
🇺🇸Ithaca, New York, United States