Safety of Graded-Dose of Histidine in Humans
Condition: Healthy
Study type: Interventional

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.
    

Intervention name(s): Histidine
Intervention type(s): Dietary Supplement
Intervention description(s): ingestion of encapsulated high quality histidine for four continuous weeks followed by a washout period of 3 weeks
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: 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.
Masking: None (Open Label)
Primary purpose: Other