What Is Histidine?
Histidine (L-histidine) is one of twenty amino acids that make up proteins in our body. These building blocks are generally classified as either nonessential or essential. Nonessential amino acids are those that the body can produce itself, while essential amino acids must be acquired through diet because the body cannot make its own supply .
It is an essential amino acid. A long-term study demonstrated that adults who consume a diet deficient in histidine over long periods of time may experience negative health effects such as reduced hemoglobin (the protein that carries oxygen in red blood cells) levels [2, 3, 4].
Histidine is produced by the liver in small quantities. Hence, it must be consumed in the diet to maintain necessary histidine levels in the body. Here, it is converted into a number of important substances such as histamine and carnosine [5, 6, 7].
Histidine is required for the growth and repair of tissues, red blood cell production, and protecting tissues from damage from radiation and heavy metals. It is especially necessary for the formation of myelin sheaths, which are layers surrounding nerves which enables faster transmission of signals to the brain [1, 8].
It is also a major component (along with β-alanine) of carnosine, an important antioxidant that slows the progression of multiple degenerative diseases and reduces plaque buildup in the arteries. It may also help improve muscle performance for high-intensity exercise [5, 6].
Health Benefits of Histidine
1) May Protect the Heart
A histidine-containing solution (Bretschneider’s histidine-tryptophan-ketoglutarate solution) is very useful in protecting the heart. In a study involving 30 patients undergoing open-heart surgery, treatment with histidine-tryptophan-ketoglutarate (HTK) solution decreased the incidence of irregular heartbeats, the necessity of drugs, and length-of-stay in the intensive care unit (ICU) .
Another study (retrospective) evaluated the use of histidine-tryptophan-ketoglutarate solution on 101 high-risk (for heart disease) patients. The study concluded that the solution is an effective alternative to another treatment (St. Thomas’ solution) for protecting the heart .
A retrospective study evaluated the use of a histidine-tryptophan-ketoglutarate solution to preserve donor hearts from 67 patients undergoing transplant surgery. When compared to another treatment, this solution was very useful in preserving the hearts .
Damaged (reperfusion injury) rat hearts were treated with histidine to evaluate its protective effects. Rat hearts treated with histidine improved recovery. This is because histidine reduced reactive oxidative species and helped preserve energy (ATP) .
Carnosine (histidine derivative) supplementation in diabetic mice reduced fat levels and plaque build-up in the arteries .
A study on chickens showed that histidine supplementation increases carnosine levels .
2) May Reduce Blood Pressure
Histidine reduced blood pressure, with higher doses being more effective, in a study (observational cohort) involving 92 patients with heart disease .
3) Antioxidant Effects
A 12-week study involved 92 obese women with histidine deficiency which caused oxidative stress. Histidine supplementation over this period reduced oxidative stress .
Additionally, another study involving 235 obese women and 217 non-obese individuals found significantly reduced histidine levels in the obese women. They concluded that increased histidine is strongly associated with reduced oxidative stress, which shows it plays a role in antioxidation .
4) May Reduce Inflammation
Two different studies, one with 92 obese women and another with 235 obese women and 217 non-obese controls, reported reduced histidine levels in obese women. In both studies, histidine supplementation led to reduced inflammation by blocking the production of inflammatory cytokines [21, 20].
5) May Be Beneficial For Diabetes
One study conducted on 92 obese women found that histidine supplementation (4 g/day for 12 weeks) significantly decreased insulin resistance (which is frequently due, in part, to inflammation). An additional study indicated that higher dietary histidine was associated with lower fasting blood glucose levels [20, 21, 22].
In another study, researchers supplemented mice with histidine and carnosine and concluded that this has strong potential for preventing or treating diabetic complications .
6) May Prevent Obesity
A recent Chinese study (cross-sectional) evaluated 88 obese individuals and determined that they consumed significantly less dietary histidine than healthy controls. Higher dietary histidine was associated with a reduced body mass index (BMI), waist circumference and blood pressure in the overall population (2376 total participants) .
Histidine is converted to histamine in the brain, and supplementation of histidine reduced the feeding behavior of rats through the action of histamine. In an additional study, histidine supplementation reduced feeding and fat accumulation in rats. Therefore, it is thought that histidine may suppress appetite in humans to help lose weight [24, 25].
7) May Protect the Skin
Histidine is the precursor for the production of urocanic acid, a substance that accumulates in human skin cells and absorbs UV radiation. By doing so, urocanic acid protects DNA from being damaged by sunlight and thus has been referred to as a “natural sunscreen” [10, 26].
24 patients with skin disease (atopic dermatitis) were supplemented with histidine for 4 weeks. This significantly reduced disease severity by 34% and 39% of patients reported feeling much better .
8) May Improve Brain Function
20 individuals with chronic fatigue and sleep disruption either received histidine or a placebo for 2 weeks. Subjects supplemented with histidine reported much clearer thinking and had improved attention and memory. They also concluded that daily histidine ingestion may reduce fatigue .
Additionally, histidine supplementation in rats improved their short-term memory. Another study on rats concluded that histidine provides remarkable long-term protection on brain function and reduces scarring (glial) after the brain is deprived of oxygen (cerebral ischemia) [31, 32].
9) May Prevent Blood Clots
18 healthy subjects were evaluated because they had increased spontaneous blood clots (platelet aggregation). Participants received 3 g of histidine for a week. Histidine effectively blocked spontaneous blood clots, and these effects are probably mediated by the action of arachidonic acid metabolites .
10) May Possibly Treat Wilson’s Disease
Wilson’s disease is a rare genetic disease that causes copper to build up in the organs of the body, particularly the liver. A study in rats indicated that a diet containing excess histidine caused accumulated copper in the liver to be flushed out in urine [34, 35].
11) May Possibly Suppress Seizures
One study in rats discovered that injections of histidine effectively reduced the severity of seizures. Researchers believe this is due to histidine’s role as a precursor to histamine, which is known to inhibit seizures [36, 37].
12) May Possibly Protect the Eyes
Histidine supplementation prevented the development of eye disease (cataracts) in adult salmon. It is effective when supplemented just before and during the early stages of cataracts .
Limitations and Caveats
More clinical trials need to be conducted on histidine supplementation to treat or monitor specific diseases. Some of the studies were only performed on animal models. Additionally, some of the studies mentioned pair histidine supplementation with another substance, and so effects may vary when histidine is taken alone.
Symptoms of Deficiency
Inflammation and Oxidative Stress
In patients (325) with chronic kidney disease, low blood levels of histidine correlated with more inflammation, oxidative stress, and death .
Two additional studies (one with 235 obese women and the other with 100 obese women) found significantly reduced histidine levels in obese women. In both studies, low histidine levels were also linked to increased inflammation and oxidative stress [20, 21].
Four healthy adults consumed a histidine-free diet for 48 days and their hemoglobin and other protein levels were monitored. An 11% decrease in hemoglobin levels was observed overtime with histidine depletion. A deficiency in hemoglobin causes anemia .
May Reduce Brain Function
A study involving 17 healthy individuals evaluated the outcome of histidine deficiency on brain function (sensory and motor process). The study concluded that this deficiency may play a role in reduced brain function, though the effects need to be confirmed with additional studies .
Patients with wounds (and seven controls) were evaluated for their protein and amino acid levels (pilot study). Out of the 18 with wounds, 16 had significantly lower histidine levels. A deficiency in histidine may weaken the skin leading to larger wounds .
May Possibly Cause Anxiety
High amounts of histidine in the body may result in unwanted side effects. In humans (4), excess consumption of histidine (> 32g/day) caused headaches, weakness, fatigue, nausea, anorexia, depression, and memory failure .
Scientists measured the amino acid levels of 11 patients diagnosed with schizophrenia. These patients had significantly higher than normal histidine levels. Although this is not necessarily a side effect, chronically high histidine levels (leading to high histamine levels) may have certain effects on the brain .
Factors That Decrease Histidine
The main cause of histidine deficiency is not consuming enough histidine in your diet. Our bodies do not naturally produce enough histidine as necessary. Vitamin B9 (folate, folic acid) deficiency also causes the body to lose histidine through urination. Maintaining normal levels of folate in the body is important for preventing histidine deficiency .
Foods and Supplementation
There are a number of foods that contain high amounts of histidine and may help supplement low histidine levels. Some protein-based foods include eggs, beef, chicken, pork, and fish. Additional foods are soybeans, beans, wheat, maize, quinoa, and rice .
There are also histidine supplement powders available online.
The World Health Organization (WHO) estimated that the recommended intake of histidine is 8-12 mg/kg per day in adults .
Irregular Histidine Levels?
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