Getting a good variety of amino acids in your diet — especially essential amino acids that your body can’t make on its own — is crucial for maintaining overall health. That’s because deficiency in any essential amino acid can cause side effects like sluggishness, compromised immune function, loss muscle mass, changes in appetite and more. The human body needs the amino acid called histidine for many metabolic processes. Why? It’s a precursor for a number of important biochemical products.
For example, histidine helps produce adequate red blood cells and the substances called histamine and carnosine, which have effects on immune function, heart health and more.
What Is Histidine? (Function and Role in Body)
Histidine, also known as L-histidine, is a type of essential amino acid. Essential amino acids are often described as the “building blocks of proteins.” Histidine considered an “essential” amino acid because we must get it from our diets, considering our bodies cannot make this amino acid on its own, like it can other “nonessential” amino acids.
Some actually believe that histidine should be classified as “semi-essential” because the adult human body can make some, but it’s essential in the diets of infants and individuals with kidney disorder.
What is the function of histidine?
Some roles it has in the body include:
- Reducing inflammation and oxidative stress
- Producing red blood cells and maintaining normal hemoglobin levels. Hemoglobin is a protein that delivers oxygen from the lungs to the rest of the body
- Helping form molecules containing iron, including ferritin, which is needed for energy supply
- Helping regulate feeding behavior and energy metabolism
- Forming myelin sheaths, the layers surrounding nerves that allow for chemical signaling
- Helping regulate levels of elements like iron, copper, molybdenum, zinc and manganese
- Utilizing the antioxidant superoxide dismutase
- Modulating wakefulness, learning, memory and emotions in the brain
- Producing histamine, a neurotransmitter involved in immune responses, including allergic reactions, and other functions like digestion
- Producing carnosine, which reduces plaque buildup in the arteries and may lower the risk for some chronic diseases
- Repairing tissue and wounds
- Regulating the pH value of the blood
- Protecting the skin against UV radiation by producing urocanic acid, an absorber of UV light
What is histidine used for?
Histidine sources include both high-protein foods and supplements. Some of the most common histidine uses include treating:
- Joint pain and rheumatoid arthritis
- High blood pressure
- Cognitive decline
- Stomach ulcers
- Symptoms caused by kidney failure or kidney dialysis
- Poor growth and development in infants
- Health problems like heart disease
Essential amino acids in general, obtained from high-protein foods, may also help promote weight loss, preserve muscle mass, improve exercise performance, promote better sleep and enhance your mood.
What is unique about histidine at physiological pH? Its structure allows it to participate in acid-base catalysis. It’s one of three amino acids that has basic side chains at neutral pH, which means it can bind protons and gain a positive charge in the process. This allows it to react with various enzymes to catalyze chemical reactions in the body.
Does histidine increase histamine?
Histidine is the source and precursor from which histamine is derived in the body. The enzyme histidine decarboxylase produces histamine from histidine. While histamine is most well-known for being tied to allergies, it also has functions in the brain related to attention and arousal. For example, studies have found that patients with schizophrenia are commonly “histapenic.” This means they have low blood histamine and high blood serum copper levels. Additionally, it plays a role in triggering inflammation.
Certain enzymes also convert histidine into ammonia, urocanic acid, 3-methylhistidine, the antioxidant ergothioneine and carnosine. These have important functions, including regulating heart health, skeletal muscle damage and more.
1. May Help Fight Chronic Diseases, Including Heart Disease
Histidine is converted to carnosine, which is a “histidine-containing dipeptide” (HCD) that is found in brain tissue and skeletal and heart muscle. Some studies have found that HCDs may prevent chronic diseases via their anti-inflammatory, antioxidative, antiglycating, anti-ischaemic and chelating properties. According to a systematic review published in the BMJ:
Human randomized controlled trials (RCTs) have shown that supplementation with carnosine or β-alanine (1–6 g) daily for 1 to 6 months improved a range of outcomes related to chronic diseases including: cognition and exercise capacity in young and elderly healthy adults.
2. Reduces Fatigue
A 2015 placebo-controlled, double-blind, crossover trial published in Physiology and Behavior found that histidine decreased fatigue scores in men feeling tired and drowsy, shortened reaction times on a cognitive function test, and increased sensations of clear thinking and of attentiveness. The study was conducted to investigate the effects of histidine intake on the feeling of fatigue, mood states and mental task performance in 20 adult men with high fatigue symptoms and sleep disruption. After two weeks of supplementation, reaction times for working memory tasks were significantly shortened compared to placebo, and mood disturbances also decreased significantly.
Some studies have found that depressed patients show decreased brain histamine receptor binding, and this decrease correlates with the severity of depression symptoms. Animal studies also suggest that low histidine levels can increase symptoms of anxiety. This amino acid has been shown to cross the blood–brain barrier in mammals. This suggests that taking histidine supplements may increase brain histamine levels and reduce symptoms like poor motivation and mental fatigue.
3. Improves Mental Performance and Cognitive Health
Because it helps form myelin sheath and protect cells from oxidative damage, histidine may also defend against cognitive degenerative disorders, such as Alzheimer’s disease and Parkinson’s disease.
4. Helps Reduce Oxidative Stress, Inflammation and Metabolic Syndrome
Histidine supplementation has been shown in certain human and animal studies to reduce oxidative stress, lower inflammation and improve insulin sensitivity in obese adults with metabolic syndrome. A 2013 study found that supplementation with this amino acid could reduce insulin resistance, lower body mass index (BMI) and fat mass, and reduce inflammation through suppressed pro-inflammatory cytokine expression.
In animal studies, supplementation with histidine and carnosine has been shown to defend against diabetic complications in multiple ways, such as reducing triglyceride and cholesterol levels, enhancing catalase activity, and decreasing lipid oxidation in the kidneys and liver. Studies have also found that higher dietary histidine intake is associated with reduced obesity, BMI, waist circumference and blood pressure. Another reason it may have anti-inflammatory effects is because it’s involved in the production of red and white blood cells, which influence immune responses.
5. Can Help Protect and Heal Skin
According to the Environmental Working Group, histamine is used in skin and hair-conditioning products because it can help to reduce dryness and irritation. It’s also sometimes used to treat eczema symptoms.
Because it works to increase antioxidant activity, neutralizes free radicals and reduces inflammation, it may help boost UV protection and also help prevent against certain types of skin infections Research shows that histidine can protect the body, including the skin, from radiation damage by binding to the damaging molecules, as well as heavy metals.
6. Can Help Defend Against Allergies and Infections
When used with zinc, there’s evidence that histidine can help protect against colds and reduce the duration that colds last. Histidine supplementation may also reduce the duration of viral or bacterial infections. Because it plays a role in regulating responses of the immune system and production of histamines, it may help decrease severity of allergic reactions and inflammatory processes as well.
Deficiency Symptoms and Causes
Deficiency in this amino acid can occur when someone eats a diet that lacks histidine over long periods of time. There’s evidence that this may occur because people are eating more processed meats and less quality meat, fish and poultry than in past decades. Other cause of low histidine levels and risk factors for deficiency include older age, folate deficiency (since this causes an increased amount of histidine to be lost through urine), high levels of stress, existing chronic conditions and injuries. These factors increase the daily requirements of histidine.
Some signs and symptoms of histidine deficiency can include:
- Anemia and reduced hemoglobin, which is the protein that carries oxygen in red blood cells
- Joint pain (some research suggests that many people with rheumatoid arthritis have low levels)
- Symptoms of anxiety and depression
- Fatigue and brain fog
- Problems with growth in infants
- Inflammation of the skin and mucous membranes and dry or scaly skin lesions
- Poor kidney and liver function
If someone is deficient in histidine, chances are that person is low in other amino acids and protein in general. Amino acid deficiency symptoms can include:
- Splitting hair, thinning hair and hair loss
- Brittle nails
- Decreased muscle mass
- Impaired growth in children
- Changes in weight and appetite
- Decreased immune function
- Bone loss
- Puffiness and swelling
Risks and Side Effects
While it’s unlikely that you’d consume very high amounts of histidine from foods alone, it’s possible to consume excess amounts from supplements, which can cause certain side effects. Studies have found that when people take very high doses of histidine, around 32 grams/day or more, they can experience side effects like muscle weakness, drowsiness and fatigue, headaches, digestive issues like nausea and loss of appetite, depression, and poor memory. Some of these may be due to negative nitrogen balance.
Other negative effects tied to high histidine levels have also been shown in animal studies, but it’s unknown how these effects carry over to humans. In studies involving rats, complications tied to high histidine levels in the brain and liver have included copper deficiency, reduced liver function, high cholesterol and loss of appetite.
Some of the possible side effects of consuming too much protein in general include weight gain, kidney issues, constipation and bad breath. Anyone with kidney or liver disease should not consume large amounts of amino acids without working with a doctor.
Histidine Foods and Supplements
What foods are high in histidine?
Histidine foods include those that are high in protein, which means they provide amino acids. Some of the top protein-based, histine foods include:
- Poultry like chicken and turkey
- Grass-fed beef and meats
- Protein powders
- Fish and seafood
- Soybean products (like tempeh, organic edamame, etc.)
- Legumes and beans
- Whole grains like quinoa, rice, buckwheat, oats, etc.
Aside from getting histidine from foods in your diet, you can also obtain this amino acid from supplements, including powders, fluids and capsules.
What is the purpose of histidine supplements?
They are used to reverse deficiency and help treat conditions like poor kidney function and anemia. They are also used to support heart health and the immune system, manage arthritis symptoms and treat eczema.
Amino acids are available as single amino acids or in combinations. Sometimes multivitamins and food supplements contain all essential amino acids. Protein powder supplements like whey protein, collagen protein, hemp protein, pea protein or brown rice protein offer many essential amino acids that your body needs, including histidine.
Because protein deficiency is not common in many industrialized nations, it’s believed that most people do not need to supplement with histidine.
How to Use (and Dosage Recommendations)
According to the National Research Council’s 10th Edition of the Recommended Dietary Allowances, the estimated histidine requirement for adults is between eight and 12 milligrams per kilogram of body weight per day.
Histidine seems to be safe for most adults in supplement form when taken in doses up to four grams per day. This dosage should not cause side effects in most people. On the other hand, issues tied to histidine deficiency, such as loss of nitrogen balance, seems to occur when intake is less than 2 mg/kg per day.
The safest and best way to ensure you meet your needs for histidine and all nine essential amino acids is to include a wide array of quality protein foods in your diet. Common examples of proteins like meat, fish, poultry, eggs and dairy products are some of the top essential amino acids sources. For vegetarians, quinoa, buckwheat, and fermented soy foods like tempeh or natto are also considered complete proteins.
Below are healthy recipes containing a good amount of protein — and therefore histidine and other essential amino acids:
- Cajun Blackened Chicken Recipe
- Beef Stroganoff Recipe
- Chicken Tikka Masala Recipe
- Cilantro Salmon Burgers
- Turmeric Eggs
- Protein Shake Recipes
- Histidine is an essential amino acid. That means your body is unable to produce on its own. Thus, it’s required to obtain through food sources.
- This amino acid is one “building blocks of protein molecules.” It has functions including helping with metabolic processes, producing white and red blood cells, producing ferritin and hemoglobin, regulating feeding behavior and energy metabolism, producing histamine and carnosine, and repairing cells and tissues in your body.
- Benefits of histidine include reducing oxidative stress and inflammation, improving metabolic health, supporting cognitive/mental health, defending against colds and infections, reducing allergies, and protecting the skin from UV radiation.
- You can get the histidine that your body needs by eating a well-balanced, healthy diet that includes enough protein foods like meat, fish, poultry, eggs, legumes, nuts and seeds.