L-Histidine
Summary
Histidine is an essential amino acid; adults need about 14 mg per kg of body weight daily. Single small trials reported lower insulin resistance in obese women (4 g/day), less fatigue (1.65 g/day) and milder eczema (4 g/day), all grade D. A dose-ranging study set 8 g/day as the highest dose without blood changes.
Key facts
- Estimated average requirement 11 mg/kg/day; RDA 14 mg/kg/day (18 mg/kg/day in pregnancy)[1]
- 8 g/day for 4 weeks in healthy adults; 12–16 g/day lowered ferritin or zinc and raised AST[5]
- About 1.5–5.2 g/day from food, according to the dose-ranging study[5]
- High-dose histidine caused zinc loss with taste, smell and neurological symptoms in a 1975 patient study[6]
- 3 graded human outcomes on this page
- October 13, 2026
How it works
ProposedHistidine is built into proteins and is the precursor of histamine, a brain signalling molecule linked to wakefulness, and of carnosine in muscle. In skin it is incorporated into filaggrin, a barrier protein whose breakdown releases natural moisturising factors. Histidine binds zinc, and large doses increased urinary zinc loss in people.[3][4][6]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Insulin resistance | Grade D | Improved | RCT · n = 92 · 2013 | 1 row |
| Skin | Grade D | Improved | Crossover RCT · n = 24 · 2017 | 1 row |
| Fatigue | Grade D | Improved | Crossover RCT · n = 20 · 2015 | 1 row |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Insulin resistance (HOMA-IR), body fat and inflammatory markers | Improved | Grade D | RCT · n = 92 · 2013 Obese women aged 33–51 with the metabolic syndrome Form: L-histidine tablets · Dose: 4 g/day · Duration: 12 weeks Compared with placebo, histidine lowered HOMA-IR, BMI (−0.86 kg/m²), waist (−2.9 cm), fat mass (−2.7 kg), free fatty acids, TNF-α and IL-6, and raised adiponectin. No side effects were reported. | 23361591 (opens PubMed)Source [2] |
| Atopic dermatitis severity (SCORAD and patient-rated POEM) | Improved | Grade D | Crossover RCT · n = 24 · 2017 Adults with atopic dermatitis Form: L-histidine dissolved in a morning drink · Dose: 4 g/day (placebo: 4 g erythritol) · Duration: 4 weeks per period Disease severity fell by 34% on physician scoring and 39% on patient scoring after 4 weeks of histidine; no change with placebo. | 29042806 (opens PubMed)Source [4] |
| Feelings of fatigue, clear thinking and working-memory reaction time | Improved | Grade D | Crossover RCT · n = 20 · 2015 Adults with high fatigue and sleep-disruption scores Form: L-histidine capsules · Dose: 1.65 g/day (dose reported in the full text and a 2020 review) · Duration: 2 weeks per period Profile of Mood States fatigue scores fell, reaction time on a working-memory task shortened, and ratings of clear thinking and attentiveness rose versus placebo. | 25921948 (opens PubMed)Source [3] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| Free-form L-histidine (powder, tablets or capsules) | Varies[8] | Plasma histidine rose at 12 and 16 g/day but not clearly at 4–8 g/day in healthy adults.[5] | No changes in vitals or body composition at 4–16 g/day for 4 weeks; blood urea nitrogen rose with dose, and 12–16 g/day lowered ferritin or zinc.[5] | Insulin resistance, fatigue, atopic dermatitis |
| Histidine-containing dipeptides (carnosine, anserine) | Varies[7] | No head-to-head human data versus free histidine.[7] | Not assessed in the histidine studies cited here.[7] | See the carnosine page |
Studied doses
Doses studied in human trials ranged from 1.65 g/day for 2 weeks (fatigue) and 4 g/day for 4–12 weeks (eczema, insulin resistance) to 16 g/day for 4 weeks in a tolerance study.[2][3][4][5][7]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
Who should be careful
- High doses
- Doses of 12 g/day and above changed blood markers (ferritin, zinc, AST) in healthy adults; 8 g/day was the highest dose without changes.[5]
- Low zinc status
- Large histidine doses caused zinc loss with taste, smell and coordination problems in a small patient study, which reversed with zinc.[6]
- Pregnancy and breastfeeding
- Requirements are higher (RDA 18 mg/kg/day in pregnancy, 19 mg/kg/day in lactation), but no trial has tested histidine supplements in these groups.[1]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
How to read the label
- Label dose vs studied doseA 500 mg powder serving is less than a third of the 1.65 g/day fatigue dose and an eighth of the 4 g/day used in the eczema and insulin-resistance trials.[8][3][2][4]
- Label dose vs requirementA 70 kg adult's RDA is about 1 g of histidine a day, and normal diets already supply roughly 1.5–5 g.[1][5]
- Upper bound from tolerance dataChanges in blood markers appeared at 12 g/day; 8 g/day was the highest dose without changes over 4 weeks.[5]
Cost per studied dose, without the sales pitch
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Cost per studied dose
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Frequently asked questions
How much histidine do adults need?
The Institute of Medicine RDA is 14 mg per kg of body weight per day for adults, about 1 g for a 70 kg person. Typical diets supply more than that.[1][5]
Does histidine help with insulin resistance?
One 12-week trial in 92 obese women with the metabolic syndrome found 4 g/day lowered insulin resistance, waist size and inflammatory markers versus placebo. It has not been repeated.[2]
Does histidine reduce fatigue?
A 2-week crossover trial in 20 adults with high fatigue found 1.65 g/day lowered fatigue scores and improved working-memory speed versus placebo.[3][7]
Does histidine help eczema?
A pilot crossover trial in 24 adults found 4 g/day reduced atopic dermatitis severity by about a third after 4 weeks. Larger trials are needed.[4]
How much histidine is too much?
In healthy adults, 8 g/day for 4 weeks caused no blood changes, while 12–16 g/day lowered ferritin or zinc and raised a liver enzyme within normal ranges.[5]
Sources
- [1]Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Appendix E: DRI values for indispensable amino acids by life stage and gender group. Institute of Medicine, National Academies Press, 2006. guideline
- [2]Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.. Diabetologia, 2013. RCT
- [3]The effect of histidine on mental fatigue and cognitive performance in subjects with high fatigue and sleep disruption scores.. Physiol Behav, 2015. crossover-RCT
- [4]Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis.. Clin Cosmet Investig Dermatol, 2017. crossover-RCT
- [5]Tolerance to graded dosages of histidine supplementation in healthy human adults.. Am J Clin Nutr, 2020. open-label
- [6]A syndrome of acute zinc loss. Cerebellar dysfunction, mental changes, anorexia, and taste and smell dysfunction.. Arch Neurol, 1975. open-label
- [7]Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement (Table: Sasahara 2015, 1.65 g/day histidine for 2 weeks). Nutrients (PMC7146355), 2020. review
- [8]L-Histidine Base (BulkSupplements.com), DSLD label 312158: 500 mg L-histidine per serving (about 1/5 teaspoon), once daily. NIH Office of Dietary Supplements, Dietary Supplement Label Database, 2024. label
What changed
- Strict adversarial pass: PMIDs re-checked; doses confirmed (4 g/day eczema from PMC full text; 1.65 g/day fatigue from trial full text via a 2020 PMC review). Grades held at D (single small trials). Removed an unsupported note about the fatigue-trial supplier; zinc-loss interaction kept with case-report evidence type.
- First draft rebuilt from scratch after the earlier draft files were lost. Every PMID checked against NCBI esummary and abstracts read for each row; the eczema dose (4 g/day) taken from the PMC full text, and the fatigue dose (1.65 g/day) from the trial full text as tabulated in a 2020 PMC review. Requirement values from the Institute of Medicine DRI Essential Guide, Appendix E. Label amount read from the DSLD API as 500 mg per serving.