Table of ContentsView AllTable of ContentsUsesDeficiencySide EffectsDosageToxicityStorageSources
Table of ContentsView All
View All
Table of Contents
Uses
Deficiency
Side Effects
Dosage
Toxicity
Storage
Sources
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Histidine, also called L-histidine, is an essential amino acid with several functions in the body, such as making proteins, protecting nerve cells, and assisting in the formation of brain and muscle tissue.
Because L-histidine is an essential amino acid, the body doesn’t make it naturally. Therefore, it must be consumed in food.Some people also take supplements to increase their levels of L-histidine, believing that the boost can prevent heart disease or improve several conditions, such as rheumatoid arthritis. However, there is very little evidence to support the efficacy of histidine supplementation.
In the United States, the Food and Drug Administration (FDA) does not regulate supplements the way it regulates prescription drugs. That means some supplement products may not contain what the label says. Whenchoosing a supplement, look for independently tested products and consult a healthcare provider, registered dietitian nutritionist (RD or RDN), or pharmacist
Purported Uses of L-Histidine
L-histidine has several functions in the body, including:
In supplement form, histidine has been researched for the possible benefits it may provide in treating various health conditions.
Supplement FactsActive ingredient(s): HistidineAlternate name(s):L-histidineSuggested dose:Recommended Dietary Allowance (RDA) is 8 to 12 milligrams/kilogram of body weight, which most get through diet; insufficient data for proper dosage as a supplementSafety considerations: Generally safe in appropriate amounts; see precautions below
Supplement Facts
Active ingredient(s): HistidineAlternate name(s):L-histidineSuggested dose:Recommended Dietary Allowance (RDA) is 8 to 12 milligrams/kilogram of body weight, which most get through diet; insufficient data for proper dosage as a supplementSafety considerations: Generally safe in appropriate amounts; see precautions below
Obesity and Metabolic Syndrome
Most research showing some promising results of L-histidine has been for those withobesityandmetabolic syndrome, which is a cluster of conditions that can lead to heart disease, diabetes, and stroke.
A study looked at L-histidine supplementation in 100 women with obesity and metabolic syndrome and assessed insulin resistance, inflammation, oxidative stress, and metabolic disorders. After 12 weeks, those who took L-histidine supplements demonstrated:
A separate systematic review of 30 different studies found that people with obesity who took histidine-containing dipeptides vs. a placebo had lower waist circumferences and decreased fasting glucose andhemoglobin A1c levels.Hemoglobin A1C measures glucose control over the previous three months.
There may be a role for L-histidine supplementation in people with obesity and metabolic syndrome, but further research is needed. If you are considering supplementation to help with these conditions, it’s best to speak to a healthcare provider beforehand to learn about whether it’s appropriate for your specific circumstances.
Rheumatoid Arthritis
There is not enough high-quality research and evidence to suggest that L-histidine supplementation improves outcomes in people with rheumatoid arthritis (RA). An older study found no benefit overall from L-histidine supplementation. It did suggest some benefit in individuals with “more active and prolonged disease,” but the authors did not advocate for histidine as a treatment for people with RA.
Since then, there has been no further research on L-histidine in this population, and it has not become a standard therapy for this condition.
Heart Disease Prevention
There is not enough evidence that L-histidine supplementation alone will prevent heart disease. L-histidine is one amino acid that makes up the dipeptide carnosine.Carnosinesupplementation has been studied in heart disease prevention.
One systematic review found that carnosine lowered hemoglobin A1C levels but did not affect lipid profiles.But just because carnosine lowered hemoglobin A1C levels does not mean that L-histidine would lead to the same result.
L-Histidine Deficiency
An L-histidine deficiency is possible but rare. An L-histidine-deficient diet doesn’t result in a negative nitrogen balance for at least a month (longer than it takes for other essential amino acids). A negative nitrogen balance represents net protein breakdown in the body.
L-histidine-deficient individuals have low plasma levels of histidine and may experience atopic dermatitis. They may also have low hemoglobin levels andanemia.
If you have a low protein intake in your diet for a month or more, discuss your diet and supplement concerns with your healthcare provider. Amino acid profiles in the blood can be measured, but this is rarely done. Any suspected single amino acid deficiencies can be corrected with adequate protein intake.
What Are the Side Effects of L-Histidine?
L-histidine is well tolerated and safe when taken at low supplement doses (less than 4.5 grams or 4,500 milligrams per day) in healthy people for a short period (four weeks), according to the 2005 U.S. Dietary Reference Intake Report.
If consumed in excess, more side effects may occur. Some have reported lower levels offolic acid, anorexia or reduced appetite, and a greater loss of zinc.
Taken in proper doses, L-histidine is considered safe for most people. However, you should be cautious about L-histidine supplementation and consult your healthcare provider if the following apply to you:
Dosage: How Much L-Histidine Should I Take?
The Food and Agricultural Organization (FAO) of the UN suggests that histidine requirements for dietary intake are 8 to 12 milligrams (mg) per kilogram (kg) of body weight. The recommended dietary allowance (RDA) for histidine is also 8 to 12 milligrams per kilogram of body weight for adults.
The average adult consumes much more than this requirement through diet alone (30 to 35 milligrams per kilogram).
For supplementation, there is not enough information to recommend a specific dose. In one study, 4 grams of histidine daily for 12 weeks appeared to be safe and without side effects.
Most people consume more histidine than required through diet alone.
What Happens if I Take Too Much L-Histidine?
There are no reports of L-histidine toxicity. Also, there is no tolerable upper limit (TUL) established. Yet some healthcare institutions warn against single amino acid supplementation for the following reasons:
Single amino acid supplements are not recommended for those with an adequate protein intake in their diet.
People with liver failure could experience complications with histidine supplementation, including liver enlargement and further progression of liver disease.
Taking 8 grams of L-histidine daily or more has resulted in anorexia and weight loss.Taking higher amounts of histidine (24 to 65 grams daily) may cause:
There are no known medication interactions with histidine.
How to Store L-Histidine
It is best to follow manufacturer directions for proper storage of supplements. As always, store medications and supplements out of the reach of children and pets to prevent accidental consumption.
Sources of Histidine and What to Look For
Amino acid supplements are available as single amino acids, combination amino acids (e.g., branched-chain amino acids), or protein supplements.
Since amino acids combine to form proteins, any protein supplement or powder will also provide L-histidine. Be sure to read supplement fact labels to know how much L-histidine you are taking from all sources.
L-histidine is found mostly in high-protein foods, including:
Plant-based sources of L-histidine include:
Single amino acid supplements are available, but histidine can also be found in protein supplements and powders.
When looking for supplements, look for ones that have been independently tested. This ensures the quality of the supplement, meaning that it contains what the label claims and is free of contaminants. Supplements with seals from USP, ConsumerLabs, and NSF have been independently tested.
Summary
L-histidine is an essential amino acid. Assuming adequate protein intake, deficiency is rare, and single amino acid supplementation is usually not needed. You will get enough L-histidine if you consume the right amount of protein.
L-histidine supplementation has been marketed for several conditions, but not enough research supports its use. Preliminary research suggests histidine may be helpful for people with metabolic syndrome and obesity, but more research is needed. Therefore, using L-histidine supplements to self-treat any health condition is not recommended. Always consult your healthcare provider before starting a new supplement.
9 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Holeček M.Histidine in health and disease: metabolism, physiological importance, and use as a supplement.Nutrients. 2020;12(3):848. doi:10.3390/nu12030848Kessler AT, Raja A.Biochemistry, histidine. In: StatPearls. Treasure Island (FL): StatPearls Publishing.Moro J, Tomé D, Schmidely P, Demersay TC, Azzout-Marniche D.Histidine: a systematic review on metabolism and physiological effects in human and different animal species.Nutrients. 2020;12(5):1414. doi:10.3390/nu12051414Feng RN, Niu YC, Sun XW, et al.Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.Diabetologia. 2013;56(5):985-994. doi:10.1007/s00125-013-2839-7Menon K, Marquina C, Liew D, Mousa A, de Courten B.Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: a systematic review and meta-analysis of randomized controlled trials.Obes Rev. 2020;21(3):e12975. doi:10.1111/obr.12975Pinals RS, Harris ED, Burnett JB, et al.Treatment of rheumatoid arthritis with L-histidine: a randomized, placebo-controlled, double-blind trial.J Rheumatol. 1977;4:414–419.Peng W, Mao P, Liu L, et al.Effect of carnosine supplementation on lipid profile, fasting blood glucose, HbA1C and insulin resistance: A systematic review and meta-analysis of long-term randomized controlled trials.Complement Ther Med. 2020;48:102241. doi:10.1016/j.ctim.2019.102241Thalacker-Mercer AE, Gheller ME.Benefits and adverse effects of histidine supplementation.J Nutr. 20201;150(Suppl 1):2588S-2592S. doi:10.1093/jn/nxaa229National Library of Medicine.Protein and Amino Acids.In: Recommended Dietary Allowances. https://www.ncbi.nlm.nih.gov/books/NBK234922/.
9 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Holeček M.Histidine in health and disease: metabolism, physiological importance, and use as a supplement.Nutrients. 2020;12(3):848. doi:10.3390/nu12030848Kessler AT, Raja A.Biochemistry, histidine. In: StatPearls. Treasure Island (FL): StatPearls Publishing.Moro J, Tomé D, Schmidely P, Demersay TC, Azzout-Marniche D.Histidine: a systematic review on metabolism and physiological effects in human and different animal species.Nutrients. 2020;12(5):1414. doi:10.3390/nu12051414Feng RN, Niu YC, Sun XW, et al.Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.Diabetologia. 2013;56(5):985-994. doi:10.1007/s00125-013-2839-7Menon K, Marquina C, Liew D, Mousa A, de Courten B.Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: a systematic review and meta-analysis of randomized controlled trials.Obes Rev. 2020;21(3):e12975. doi:10.1111/obr.12975Pinals RS, Harris ED, Burnett JB, et al.Treatment of rheumatoid arthritis with L-histidine: a randomized, placebo-controlled, double-blind trial.J Rheumatol. 1977;4:414–419.Peng W, Mao P, Liu L, et al.Effect of carnosine supplementation on lipid profile, fasting blood glucose, HbA1C and insulin resistance: A systematic review and meta-analysis of long-term randomized controlled trials.Complement Ther Med. 2020;48:102241. doi:10.1016/j.ctim.2019.102241Thalacker-Mercer AE, Gheller ME.Benefits and adverse effects of histidine supplementation.J Nutr. 20201;150(Suppl 1):2588S-2592S. doi:10.1093/jn/nxaa229National Library of Medicine.Protein and Amino Acids.In: Recommended Dietary Allowances. https://www.ncbi.nlm.nih.gov/books/NBK234922/.
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Holeček M.Histidine in health and disease: metabolism, physiological importance, and use as a supplement.Nutrients. 2020;12(3):848. doi:10.3390/nu12030848Kessler AT, Raja A.Biochemistry, histidine. In: StatPearls. Treasure Island (FL): StatPearls Publishing.Moro J, Tomé D, Schmidely P, Demersay TC, Azzout-Marniche D.Histidine: a systematic review on metabolism and physiological effects in human and different animal species.Nutrients. 2020;12(5):1414. doi:10.3390/nu12051414Feng RN, Niu YC, Sun XW, et al.Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.Diabetologia. 2013;56(5):985-994. doi:10.1007/s00125-013-2839-7Menon K, Marquina C, Liew D, Mousa A, de Courten B.Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: a systematic review and meta-analysis of randomized controlled trials.Obes Rev. 2020;21(3):e12975. doi:10.1111/obr.12975Pinals RS, Harris ED, Burnett JB, et al.Treatment of rheumatoid arthritis with L-histidine: a randomized, placebo-controlled, double-blind trial.J Rheumatol. 1977;4:414–419.Peng W, Mao P, Liu L, et al.Effect of carnosine supplementation on lipid profile, fasting blood glucose, HbA1C and insulin resistance: A systematic review and meta-analysis of long-term randomized controlled trials.Complement Ther Med. 2020;48:102241. doi:10.1016/j.ctim.2019.102241Thalacker-Mercer AE, Gheller ME.Benefits and adverse effects of histidine supplementation.J Nutr. 20201;150(Suppl 1):2588S-2592S. doi:10.1093/jn/nxaa229National Library of Medicine.Protein and Amino Acids.In: Recommended Dietary Allowances. https://www.ncbi.nlm.nih.gov/books/NBK234922/.
Holeček M.Histidine in health and disease: metabolism, physiological importance, and use as a supplement.Nutrients. 2020;12(3):848. doi:10.3390/nu12030848
Kessler AT, Raja A.Biochemistry, histidine. In: StatPearls. Treasure Island (FL): StatPearls Publishing.
Moro J, Tomé D, Schmidely P, Demersay TC, Azzout-Marniche D.Histidine: a systematic review on metabolism and physiological effects in human and different animal species.Nutrients. 2020;12(5):1414. doi:10.3390/nu12051414
Feng RN, Niu YC, Sun XW, et al.Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial.Diabetologia. 2013;56(5):985-994. doi:10.1007/s00125-013-2839-7
Menon K, Marquina C, Liew D, Mousa A, de Courten B.Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: a systematic review and meta-analysis of randomized controlled trials.Obes Rev. 2020;21(3):e12975. doi:10.1111/obr.12975
Pinals RS, Harris ED, Burnett JB, et al.Treatment of rheumatoid arthritis with L-histidine: a randomized, placebo-controlled, double-blind trial.J Rheumatol. 1977;4:414–419.
Peng W, Mao P, Liu L, et al.Effect of carnosine supplementation on lipid profile, fasting blood glucose, HbA1C and insulin resistance: A systematic review and meta-analysis of long-term randomized controlled trials.Complement Ther Med. 2020;48:102241. doi:10.1016/j.ctim.2019.102241
Thalacker-Mercer AE, Gheller ME.Benefits and adverse effects of histidine supplementation.J Nutr. 20201;150(Suppl 1):2588S-2592S. doi:10.1093/jn/nxaa229
National Library of Medicine.Protein and Amino Acids.In: Recommended Dietary Allowances. https://www.ncbi.nlm.nih.gov/books/NBK234922/.
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