Histidine

Histidine is a nutrient belonging to the essential amino acid class.

Histidine is also known as L-Histidine, (2S)-2-Amino-3-(1H-Imidazol-5-yl) Propanoic Acid, (S)-4-(2-Amino-2-Carboxyethyl) Imidazole, Histidina, L-Histidine AKG, L-Histidine-Alpha Ketoglutaric Acid, L-Histidine HCl, Levo-Histidine and (S)-Alpha-Amino-1H-Imidazole-4-Propanoic Acid.

Histidine is vital as it is a precursor to various hormones, including thyrotropin-releasing hormone, and important metabolites that directly affect the immune system, neurotransmission, renal function, and gastric secretion.

A deficiency of the enzyme histidase leads to Histidinemia which is a metabolic disorder. The symptoms of histidinemia may vary, and Symptoms can vary in severity and may include delay in cognitive development, speech difficulties, hyperactivity, seizures and behavioural issues.

Histidine may be found naturally in various meals high in protein from both plant and animal sources. Foods like wheat germ, soybeans, and lentils are examples of plant sources, whereas products like chicken, fish (salmon, tuna), eggs, and dairy (milk, yoghurt, and cheese) are examples of animal sources.

In the small intestine, histidine is absorbed and transported to many organs, including the brain. It serves as a precursor for neurotransmitters like histamine. Decarboxylation occurs throughout metabolism, and excess histidine is eliminated through the urea cycle at the influence of genetics and nutrition.

The common side effects of histidine include GI disturbances, nausea, skin rashes, itching and nasal congestion.

Histidine is available in tablets, capsules and oral powders.

Biochemical action of histidine

Histidine belonging to the essential amino acid class, acts in several biological processes. It works via the histidine degradation pathway.

Histidine plays an essential role in various cellular activities. The critical function of 3-methylhistidine in the ATP binding site of actin is an example of how histidine residues may undergo enzyme-catalyzed methylation (with S-adenosyl methionine as the methyl donor). Histidine residues also play a structural and catalytic role in numerous enzymes. Additionally, histidine residues are essential for maintaining the myelin sheath because they take part in the hydroxylation of the galactosylceramide, which causes the myelin to become compact.

During allergic reactions, histamine, produced by mast cells, binds to histamine receptors (H1) and causes various effects, including itching, prostaglandin production, muscular contraction, increased vascular permeability, and increased heart rate. Histamine has a critical paracrine role in controlling and producing stomach acid. When food is ingested, the hormone gastrin is produced, which causes enterochromaffin-like (ECL) cells to secrete histamine. Histamine then binds to H2 receptors on parietal cells, activating proton pumps and inducing the production of stomach acid.

By stabilising the pH of internal and external muscle tissue, carnosine (beta-alanyl-L-histidine), a histidine metabolite, prevents histidine muscular acidosis. Thus, histidine contributes to numerous physiological processes, demonstrating its importance in maintaining overall health and functionality.

Histidine is available in tablets, capsules and oral powders.

• Tablets: To be swallowed whole with water/liquid, as applicable.
• Capsules: To be swallowed whole with water/liquid, as applicable.
• Powders, oral: Powders must be mixed thoroughly with the appropriate amount of liquid and stirred well to dissolve the powder, as applicable.

Histidine can be used as a supplement when the amount of histidine taken histidine diet is insufficient.

Taking histidine supplements effectively treats histidine deficiency caused by specific genetic diseases or other disorders.

Histidine supplements are commonly used to reduce diarrhoea in people with cholera who receive antibiotics.

Supplemental histidine may be essential in supporting the body's healing processes.

When used as a supplement, histidine helps histidine growth and recovery.

Supplemental histidine might cause the histidine formation of carnosine, which has antioxidant characteristics and promotes muscular function when exercising.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Histidine can help to support as a supplement for the following health benefits:

• Deficiency: Although rare, histidine deficiency is possible. It takes at least a month (more extended than other necessary amino acids) for a diet lacking in histidine to cause histidine nitrogen balance. A negative nitrogen balance indicates net protein breakdown in the body. People with histidine deficiencies may develop atopic dermatitis and have low plasma levels of histidine. They might also be anaemic and have low haemoglobin levels. With sufficient histidine consumption, histidine deficiency can be treated.
• Obesity and Metabolic Syndrome: The potential of L-histidine for those with obesity and metabolic syndrome(conditions associated with heart disease and diabetes) is mainly supported by research. L-histidine supplementation for 12 weeks reduced oxidative stress, inflammation, and insulin resistance in a trial involving 100 women. Histidine-containing dipeptides may help obese individuals with their lower waist circumferences, fasting glucose levels, and haemoglobin A1c levels, according to a comprehensive evaluation of 30 research. Despite these results, additional study is needed to determine histidine's function in effectively treating obesity and metabolic syndrome.
• Rheumatoid Arthritis: Histidine has been investigated for its potential to reduce the pain associated with arthritis since research shows an association between decreased blood histidine levels and the development of rheumatoid arthritis. The antioxidant properties of histidine, which histidine oxidative stress, reduce rheumatoid arthritis. Its ability to control inflammation also helps reduce discomfort. Future investigation into the effects of low histidine levels on arthritic pain and inflammation may be possible.
• Heart disease: Patients with heart disease or those at risk for developing it benefit from histidine's ability to lower blood pressure. The dosage size affects the extent of the effect. Before taking the supplement, it is also advisable to consult with a healthcare professional. Histidine has been found to improve heart health and lower blood pressure. Some studies have shown that patients frequently take it before open heart surgery since it can lessen the need for other medications and increase the recovery process for patients.

• Anemia: Anaemia develops from a lack of red blood cells, restricting the body's organs of oxygen and resulting in fatigue, weakness, disorientation, and dyspnea. Reduced red blood cell numbers can result from a number of issues, including vitamin deficits like folate and B12, among others. Supplemental histidine may help with symptoms of anaemia brought on by a folate deficit. A histidine supplement could be helpful in tiredness, headaches and lack of a healthy diet.

• Allergic Reactions: Histidine is essential for preserving the body's equilibrium with histamine. One of the primary substances involved in allergic responses is histamine. More severe allergic reactions might result from the body having low amounts of histidine. Histihistidined help with allergies. It's frequently used as a therapy for patients who experience severe allergic responses. The intensity of the allergies can be minimised by taking a histidine supplement.

• Skin Health: Atopic dermatitis (AD), an incurable inflammatory skin disorder, is recommended for children by Scottish analysis. This method was developed in response to the efficacy of histidine in treating eczematous skin. Histidine helps synthesise urocanic acid, which protects against UV radiation's damaging effects and skin cancer development. Supplementing with histidine increases UV protection but is not a substitute for sunscreen.

Histidine supplementation may be administered orally.

Orally: Histidine supplements are available as tablets, capsules and powders that can be taken orally. To maximise absorption and reduce the possibility of gastrointestinal discomfort, it is advisable to take histidine supplements with meals.

Taking it before, during or after exercise may boost its impact on growth hormone release for goals associated with exercise.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets: 1000 mg
• Capsules: 450mg, 500mg, 600 mg, 1000 mg
• Powder, oral: 125g

Dosage Adjustment for Adult Patients

Ideally, powdered formulas should be consumed immediately after mixing.

When taken orally: Adults typically consume 4 grams of histidine supplements by mouth daily for up to 12 weeks.

Histidine is available in tablets, capsules and oral powders.

Histidine should be used as a supplement that helps in several biological processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.
• Stay within your daily calorie needs.
• Limit foods and drinks that are high in histamine, such as aged cheeses, fermented foods, processed meats, caffeine, processed foods, saturated fat, and sodium.

The dietary restriction should be individualized as per patient requirements.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of histidine is 10 mg/kg body weight per day.

Upper Tolerable Intake (UTL):

The UTL of histidine is not established.

Histidine supplementation may be contraindicated in the following conditions:

• Hypersensitivity; sensitive to histidine.
• Chronic liver disease
• Chronic kidney disease (CKD)
• Kidney failure
• Hypotension
• Histidine metabolism disorders like histidinemia
• Post-surgery
• Folic acid deficiency

High-dose supplements should be used cautiously in pregnancy, breastfeeding and the elderly.

Before taking histidine, individuals with renal or liver disorders should see a physician since the dosage may need to be adjusted to prevent negative effects.

It is recommended to use histidine supplements cautiously since prolonged usage may result in adverse reactions or allergies.

In case of any underlying health conditions like histidine metabolism disorders or Parkinson's disease, it is recommended to consult a healthcare provider.

To avoid potential interactions, it is recommended to use only one amino acid supplement or dietary supplements.

Caution is advised when consuming alcohol with Histidine.

There is no sufficient scientific evidence traceable regarding the use and safety of histidine for breastfeeding populations.

Limit the consumption of foods and beverages higher in histamine, such as aged cheeses, fermented foods, processed meats, caffeine, processed foods, saturated fat, and sodium.

The adverse reactions related to histidine can be categorised as:

• Common: GI disturbances like bloating, gas, nausea, diarrhoea, vomiting and allergic reactions in histamine-intolerant individuals
• Less Common: Blood pressure fluctuations and headaches.
• Rare: None

The clinically relevant drug interactions of histidine are summarized here:

• Supplemental iron: Histidine and iron can combine to generate complexes that interfere with iron absorption and utilisation. To avoid possible conflicts, avoid using histidine supplements simultaneously with iron supplements.
• Levodopa: Supplements containing histidine may interact with levodopa, a medication used to treat Parkinson's disease, potentially altering its effects.
• Other supplemental amino acids: Combining histidine with other amino acids may disturb the normal functioning of the metabolism and disrupt nutrient absorption.

The common side of histidine include the following:

• Nause
• Diarrhoea
• Dizziness
• Vomiting
• Stomach discomfort
• Headaches (continuing or severe)
• Skin rashes
• Itching
• Swelling
• Nasal congestion.
• Blood Pressure Fluctuations

Histidine should be prudent in the following group of special populations.

• Pregnancy:

There is no sufficient scientific evidence traceable regarding the use and safety of histidine for pregnant populations. Avoid histidine supplements unless advised to do so by a healthcare professional while pregnant.

• Paediatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of histidine for paediatric populations.

Dosage Adjustment for Paediatric Patients

There are no specific dosage adjustments provided.

• Geriatrics:

The elderly population may be drawn to the possible role of histidine in immunity and muscle maintenance. The use of it in geriatrics, however, requires caution. The appropriate amount should be determined according to the patient's health, potential interactions, and desired outcomes.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of histidine for lactating mothers populations. Avoid histidine supplements unless advised to do so by a healthcare professional while lactating.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of histidine. Overconsumption of histidine may lead to symptoms that might include gastrointestinal discomfort like nausea, diarrhoea, vomiting, anorexia, weight loss and allergic reactions.

There is no specific antidote or treatment for excessive intake of supplemental histidine.

Histidine supplements should be terminated immediately when an overdose is suspected or experience any unusual symptoms after histidine supplement use or dietary intake. Fluid intake should be increased along with electrolyte monitoring. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of Histidine

Histidine has an aromatic imidazole ring, stabilising it and making it polar at physiological pH. The imidazole side chain of histidine is distinctive among amino acids, resulting in its aromaticity and amphoteric characteristics at physiological pH. Because of the factors set out by its specific structure, histidine is significant to the human body. The side chain of the molecule is made up of a heterocyclic imidazole ring with nitrogen atoms at positions 1 (pi) and 3 (tau). Histidine's pK is one pH unit below neutrality due to its ionizability and the fact that it exists in both neutral and protonated forms in the body, enabling it to be both an acid and a base at physiological pH levels.

Additionally, histidine is an effective chelator of copper, zinc, manganese, and cobalt metal ions. The imidazole nitrogen atoms, which may function as electron donors or acceptors in different circumstances, are responsible for this characteristic. The significance of this is shown by the analysis of histidine-rich motifs in DNA transcription factors, which take part in the association of proteins and nucleic acids through Zn-fingers.

Kinetic profile:

• Absorption: Histidine is primarily absorbed in the small intestine through active transport pathways after ingestion. Its absorption is not isolated, and it competes for uptake with other amino acids, which may affect the extent to which it is absorbed.
• Distribution: Histidine gets absorbed within the body and distributes to different tissues via circulation. Particularly, histidine can cross the blood-brain barrier, enabling it to enter the central nervous system and contribute to its availability in brain tissues.
• Metabolism: Through the processes of decarboxylation, transamination, and deamination, histidine is metabolised. Histidine is transformed into histamine by the histidine decarboxylase, a neurotransmitter and immune system mediator essential for allergic and inflammatory reactions.
• Elimination: Any excess histidine is catabolized into intermediates that enter the urea cycle, a process to detoxify and eliminate ammonia. In this process, histidine is transformed into urocanic acid, which then goes through further changes to become metabolites that are ultimately excreted in the urine.