Histidine is one of the nine essential amino acids that humans need to acquire from their diet.
This important amino acid has many vital functions within the body, and it plays a crucial role in the immune system.
In this article, we take a look at what histidine is, the dietary intake requirements, and the functions, benefits, and best food sources.
What Is Histidine?
Histidine is an amino acid that plays an essential role in the growth and repair of the body’s cells (1).
The human body cannot synthesize histidine. This means that we need to obtain sufficient amounts from dietary sources to meet our requirements.
Interestingly, histidine was once considered to be a ‘semi-essential amino acid.’ It is not uncommon to still see this outdated definition.
This ‘semi-essential’ terminology was because researchers felt that histidine was essential for infants, but not for adults.
However, further research on histidine demonstrated that this amino acid is just as important for adults (3, 4).
The IUPAC (chemical) name for the amino acid is ‘histidine‘, and the systematic name is ‘2-Amino-3-(1H-imidazol-4-yl)propanoic acid‘.
Structure
The chemical formula of histidine is ‘C6H9N3O2′.
In the below image, you can see the chemical formula and the amino acid’s molecular structure;
Histidine Requirements
The recommended histidine requirements vary depending upon body weight.
For adults over the age of 19, the recommended daily intake of histidine is 14 mg per kilogram of body weight (5, 6).
In the following table, based on this daily intake recommendation, you can see the approximate histidine requirements for various body weights;
| Body Weight | Histidine Requirement per Day |
|---|---|
| 40 kg (88 lbs) | 560 mg |
| 50 kg (110 lbs) | 700 mg |
| 60 kg (132 lbs) | 840 mg |
| 70 kg (154 lbs) | 980 mg |
| 80 kg (176 lbs) | 1120 mg |
| 90 kg (198 lbs) | 1260 mg |
| 100 kg (220 lbs) | 1400 mg |
| 110 kg (242 lbs) | 1540 mg |
| 120 kg (264 lbs) | 1680 mg |
| 130 kg (286 lbs) | 1820 mg |
Key Point: For adults, the daily histidine requirement is 14 mg per kilogram of body weight.
Histidine Functions (and Potential Benefits)
Since it is an essential amino acid, histidine has a variety of critical functions within the human body.
Precursor For Histamine Synthesis
Histidine is a precursor for the synthesis of a compound called histamine. In other words, histamine is produced from histidine in the body (7).
Among its numerous functions, histamine plays an important role in;
- Helping with blood pressure regulation (8).
- Regulating the secretion of hydrochloric acid in the stomach (9).
- Upregulation of nitric oxide. Nitric oxide is a compound that has benefits for blood pressure and exercise performance (10).
- Immune response: histamines play a primary role in eliminating allergens or pathogens (11).
- Histamine is a neurotransmitter, and it has an important role in the sleep cycle and promoting wakefulness (12, 13).
Key Point: Histidine is a precursor for histamine, a compound which plays an important role in immune response.
Potential Mood and Cognitive Function Benefits
Research demonstrates that histidine may offer cognitive benefits and mood-enhancing properties.
For instance, one recent randomized controlled trial found that increased histidine intake improved attentiveness and focus. Additionally, the histidine group had a better mood state and decreased feelings of fatigue compared to the placebo group (14).
In a further study featuring seventeen participants, histidine depletion had a negative impact on response to time-based tasks (15).
Key Point: Histidine levels may be important for mood and cognitive performance.
May Have Anti-Inflammatory Effects
Recent research has demonstrated that some amino acids, including histidine, may have anti-inflammatory properties.
In one study, histidine had an inhibitory effect on the activation of nuclear factor-kappa B (16).
Nuclear factor-kappa B is a type of protein that regulates DNA and cytokine (a protein released by immune cells) production.
Studies suggest that overexpression of nuclear factor-kappa B may be involved in atherosclerosis, which is the development of plaque in coronary arteries (17, 18).
Furthermore, low levels of histidine are associated with inflammation and oxidative stress.
In a study that analyzed blood levels of amino acids in 235 obese women and 217 non-obese controls, histidine levels were significantly lower in obese women. Higher histidine levels were also inversely associated with inflammation and oxidative stress (19).
Based on a randomized controlled trial featuring 100 individuals, histidine supplementation also appears to lower markers of inflammation (20).
Key Point: Histidine appears to have anti-inflammatory properties.
Has a Protective Role In Uremia and Chronic Kidney Disease
Research indicates that histidine has protective properties for kidney health.
For instance, a study investigating histidine deficiency in 325 patients with chronic kidney disease found that (21);
- Low histidine was significantly associated with greater all-cause mortality.
- Higher blood levels of histidine were associated with lower levels of inflammatory markers.
- Patients with lower blood levels of histidine had greater levels of oxidative stress.
Uremia is a condition that can occur when kidney damage prevents the kidneys from doing their job correctly. When the kidneys cannot filter and eliminate waste products from the blood, urea and other compounds can build up (22).
However, some studies show that histidine supplementation can lower blood levels of urea and attenuate symptoms of uremia (23, 24, 25).
Key Point: Histidine has a protective effect against uremia and chronic kidney disease.
Assists With the Growth and Repair of Nerve Cells and Other Tissues
As an essential amino acid, the body requires histidine for the growth and repair of tissues.
Histidine is crucial for its role in protecting the myelin sheath (26).
The myelin sheath is a layer—or outer coating—made of fat and protein that surrounds and protect nerve cells. Here it shields them from damage and helps to transmit electrical impulses quickly (27).
Key Point: Histidine helps to maintain and repair cells.
Important For the Absorption of Zinc
When we consume any mineral, we do not fully absorb the total amount that we eat, and a range of factors can promote or inhibit mineral absorption (28, 29).
In this regard, histidine appears to have a positive impact on the absorption of the mineral zinc.
Histidine, alongside other amino acids such as methionine, helps to promote zinc absorption. For this reason, we can often find histidine as an ingredient in zinc supplements (30, 31, 32).
Key Point: Histidine increases the bioavailability of zinc.
Precursor For Carnosine Synthesis
In addition to being a precursor for histamine, histidine is also a precursor for the synthesis of carnosine (33).
Carnosine is a dipeptide molecule, which is a compound formed by the bonding of two amino acids. In the case of carnosine, the compound is made from the amino acids alanine and histidine (34).
According to a systematic review and meta-analysis of randomized controlled trials, carnosine may have several benefits (35);
- A systematic review and meta-analysis of 49 randomized controlled trials featuring 1709 participants demonstrated that carnosine might have a protective effect against diabetes. In this review, carnosine supplementation led to improvements in fasting glucose, HbA1c, and post-prandial (post-meal) glucose.
- The review also found that carnosine may lower several markers of cardiovascular risk. These markers included inflammatory markers such as C-reactive protein and triglycerides.
Key Point: Histidine (along with alanine) is a precursor for the synthesis of carnosine.
Best Dietary Sources of Histidine
Generally speaking, the best way to get histidine is through eating protein-rich foods like meat, dairy, eggs, and seafood.
However, the table below shows the foods which are most concentrated in histidine per 100 grams (36);
| Food | Histidine Content (g) |
|---|---|
| Beef, round, lean, cooked | 1.41 g |
| Bacon, broiled | 1.39 g |
| Hard parmesan cheese | 1.38 g |
| Pork chops, lean, cooked | 1.27 g |
| Romano cheese | 1.23 g |
| Chicken breast, cooked | 1.20 g |
| Bratwurst | 1.09 g |
| Lamb, lean, cooked | 1.08 g |
| Soybeans, dry-roasted | 1.07 g |
| Hemp seed | 0.97 g |
Key Point: Meat and hard cheese tends to be the best gram-for-gram source of histidine.
Final Thoughts
Like all essential amino acids, histidine plays an important role in a wide range of metabolic processes.
Fortunately, providing we consume sufficient protein, we don’t need to overthink whether or not we are consuming enough.
However, the research does show that histidine supplementation could potentially have benefits in certain circ*mstances.
For those interested in histidine (or carnosine) supplementation, some useful further reading can be found below;
For more on amino acids, see this guide to leucine.
