L-Histidine
Also known as: histidine, L-histidine
Two randomised controlled trials in humans used oral L-histidine 4 g/day for ~12 weeks in obese women with metabolic syndrome and reported improvements in insulin resistance, body composition and inflammatory markers, and systemic changes in serum and urine metabolomics. A small older trial in chronically uraemic and dialysis patients found no benefit for anaemia. A systematic review summarises metabolism and potential effects but also notes possible adverse effects with excess intake.
Last reviewed: 2026-10-14 · 3 indexed studies
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Overview
L-histidine is an essential amino acid used in trials at gram doses to alter amino acid and metabolic profiles. Human randomised trials have tested 4 g/day for 12 weeks in obese women with metabolic syndrome and older dialysis/uraemic patients but results differ by outcome and population.
Mechanism & Function
Mechanism of Action
Histidine is a proteinogenic amino acid and precursor to histamine and carnosine; it can alter amino acid pools and influence inflammatory and oxidative pathways, adipokine secretion and lipid/glucose metabolism as suggested by human metabolomic and cellular data.
Physiological Role
Essential amino acid involved in protein synthesis, precursor to histamine and components such as carnosine, and a regulator of acid–base balance and metal ion binding in physiology.
Primary Pathways
Performance / Health Relevance
Direct evidence for ergogenic benefit is lacking; metabolic and inflammatory changes seen in obese participants could indirectly affect exercise tolerance or recovery but this was not tested.
Evidence Review
No meta-analyses or systematic reviews indexed for this ingredient yet.
Dimensions marked N/A have no indexed evidence of that class. They are shown as unavailable rather than scored.
Practical Use & Dosage
- Minimum Effective Dose
- 4 g/day (used in RCTs)
- Optimal Range
- 4 g/day (evidence-based range from human trials)
- Upper / Caution Level
- Not established
- Timing
- Not specified in trials; once-daily dosing was used
- Best Format
- Oral powder or capsules (free amino acid form used in studies)
- Bioavailability
- Free L-histidine is well absorbed orally and raises plasma histidine concentrations.
- Absorption Considerations
- Competes with other large neutral amino acids for intestinal and blood–brain transport; co-ingestion with protein or other AAs may affect uptake.
Safety & Interactions
Side Effects
- •Potential GI upset (not reported in abstracts)
- •Excess intake associated with eating and memory disorders in review data
Contraindications
- Not established in trials; caution in patients with inborn errors of histidine metabolism
Drug Interactions
- •None reported in the provided abstracts; theoretical interactions via histamine metabolism with drugs affecting histamine pathways
Who Should Avoid
- •People with histidine metabolism disorders
- •Those advised to avoid increased histamine levels (use caution)
Monitoring
Monitor metabolic markers and clinical response in patients with metabolic disease; monitor for neuropsychiatric symptoms with prolonged high intake per review notes.
Frequently Asked Questions
Auto-generated from indexed evidence — dosage, safety, interactions, and more.
When is L-Histidine typically used or indicated?
L-Histidine is most commonly used for: Metabolic syndrome / insulin resistance support, Adjunct to improve serum amino acid profile, Research on anaemia of uraemia (historical). Essential amino acid involved in protein synthesis, precursor to histamine and components such as carnosine, and a regulator of acid–base balance and metal ion binding in physiology.
How does L-Histidine work?
Histidine is a proteinogenic amino acid and precursor to histamine and carnosine; it can alter amino acid pools and influence inflammatory and oxidative pathways, adipokine secretion and lipid/glucose metabolism as suggested by human metabolomic and cellular data.
What is the recommended dose of L-Histidine?
The optimal range is 4 g/day (evidence-based range from human trials). with a minimum effective dose of 4 g/day (used in RCTs). Best taken: Not specified in trials; once-daily dosing was used. Upper / caution level: Not established.
What are the side effects of L-Histidine?
Reported side effects include: Potential GI upset (not reported in abstracts); and Excess intake associated with eating and memory disorders in review data. Monitoring: Monitor metabolic markers and clinical response in patients with metabolic disease; monitor for neuropsychiatric symptoms with prolonged high intake per review notes.
Does L-Histidine interact with medications?
Known or theoretical interactions: None reported in the provided abstracts; theoretical interactions via histamine metabolism with drugs affecting histamine pathways. Always check with a clinician before combining with prescription medication.
Who should avoid L-Histidine?
L-Histidine is generally not recommended for: People with histidine metabolism disorders; Those advised to avoid increased histamine levels (use caution); and Not established in trials; caution in patients with inborn errors of histidine metabolism.
How strong is the evidence for L-Histidine?
Evidence level: Limited (overall score 50/100), based on 3 indexed studies on SuppIndex.
Research & References (3)
Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.
Randomised, double-blind, placebo-controlled trial in 100 obese women with metabolic syndrome; 4 g/day histidine vs placebo for 12 weeks.
Effects of Histidine Supplementation on Global Serum and Urine 1H NMR-based Metabolomics and Serum Amino Acid Profiles in Obese Women from a Randomized Controlled Study.
Randomised controlled study examining serum and urine 1H NMR metabolomics and serum amino acid profiles in obese women with metabolic syndrome given histidine or placebo for 12 weeks.
Histidine supplementation for treatment of anaemia of uraemia.
Randomised double-blind controlled study in 42 chronically uraemic or dialysis patients given 4 g/day L-histidine or placebo for a mean of ~17.5 weeks to assess anaemia outcomes.
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Beta-Alanine
78/100A rate-limiting precursor to carnosine (β-alanyl-L-histidine) synthesis, enhancing intramuscular pH buffering capacity during high-intensity anaerobic exercise.
EAA Blend
78/100Free-form blend of 9 EAAs (Leu, Ile, Val, Lys, Met, Phe, Thr, Trp, His) at evidence-based ratios; bypasses gastric digestion for rapid plasma aminoacidaemia.
Research Overview
Limited EvidenceCite this ingredient
One-click citation export in APA, MLA, Chicago, BibTeX, or HTML. The URL below is stable and safe to link.
Stable URL
https://thesuppindex.com/ingredients/l-histidine
SuppIndex. (2026). L-Histidine: Evidence summary, dosage and clinical studies. Retrieved October 16, 2026, from https://thesuppindex.com/ingredients/l-histidine
Based on 3 indexed studies · Evidence level: Limited.
Goal Ratings
Stack Compatibility
May interact at absorption level with other large neutral amino acids; co-supplementation with other EAAs should consider competitive transport.