Health

12 Health Benefits of Histidine + Function, Foods & Side Effects


When it comes to human health, histidine is an essential amino acid that wears many hats. As a protein building block and precursor for important biochemical products, it is involved in protecting the skin against UV radiation and reducing inflammation and oxidative stress. Read on to learn more about the importance of maintaining healthy levels.

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 [R].

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 [R, R, R].

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 [R, R, R].

Function

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 [R, R].

In both human and animal studies, histidine functioned in maintaining normal levels of hemoglobin, the protein responsible for delivering oxygen from the lungs to the tissues of the body [R, R].

Urocanic acid, produced through histidine, is a major absorber of ultraviolet radiation (UVR). This protects skin cells from damage [R, R].

Additionally, it is converted to histamine, a neurotransmitter involved in immunity, digestion, and sexual function [R, R].

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 [R, R].

Health Benefits of Histidine

1) Histidine May Protect the Heart

A histidine-containing solution (Bretschneider’s histidine-tryptophan-ketoglutarate solution) is very useful in protecting the heart. In a study (RCT) 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) [R].

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 [R].

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 [R].

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) [R].  

Carnosine (histidine derivative) supplementation in diabetic mice reduced fat levels and plaque build-up in the arteries [R, R].

A study on chickens showed that histidine supplementation increases carnosine levels [R].

2) Histidine 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 [R].

In a study on rats with elevated blood pressure, oral histidine supplementation significantly reduced their blood pressure. Additionally, carnosine reduced blood pressure in obese rats [R, R].  

3) Antioxidant Effects

A 12-week study (DB-RCT) involved 92 obese women with histidine deficiency which caused oxidative stress. Histidine supplementation over this period reduced oxidative stress [R].

Additionally, another study (RCT) 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 [R].  

4) Histidine May Reduce Inflammation

Two different studies (DB-RCT with 92 obese women and RCT 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 [R, R].

5) Histidine May Be Beneficial For Diabetes

One study (DB-RCT) 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 [R, R, R].

In another study, researchers supplemented mice with histidine and carnosine and concluded that this has strong potential for preventing or treating diabetic complications [R].

6) Histidine 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) [R].

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 [R, R].

7) Histidine 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” [R, R].

24 patients with skin disease (atopic dermatitis) were supplemented with histidine for 4 weeks (DB-RCT). This significantly reduced disease severity by 34% and 39% of patients reported feeling much better [R].

A study on mice also demonstrated that histidine supplementation increases urocanic acid levels on the skin, and in turn provides protection from UV-radiation [R, R].

8) Histidine May Improve Brain Function

20 individuals with chronic fatigue and sleep disruption either received histidine or a placebo for 2 weeks (DB-RCT). Subjects supplemented with histidine reported much clearer thinking and had improved attention and memory. They also concluded that daily histidine ingestion may reduce fatigue [R].  

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) [R, R].

9) Histidine May Prevent Blood Clots

18 healthy subjects (RCT) 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 [R].  

10) Histidine 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 [R, R].

11) Histidine 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 [R, R].

12) Histidine 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 [R].  

Symptoms of Deficiency

Histidine deficiency may have a lot of detrimental effects on the body. Symptoms include dry or scaly skin lesions, anemia, poor hearing, general feelings of unwellness, and more [R, R, R].

Histidine Deficiency Causes Inflammation and Oxidative Stress

In patients (325) with chronic kidney disease, low blood levels of histidine correlated with more inflammation, oxidative stress, and death [R].

Two additional studies (RCT of 235 obese women and DB-RCT of 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 [R, R].

Histidine Deficiency Causes Anemia

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 [R].

Histidine Deficiency May Reduce Brain Function

A study involving 17 healthy individuals (DB-RCT) 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 [R].

Histidine Deficiency And The Skin

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 [R].

Histidine Deficiency May Possibly Cause Anxiety

A deficiency of histidine in the diet of mice caused a deficiency in histamine in their brains, causing anxiety-like behavior [R].

CMP blood test

Are You Deficient in Histidine?

If you are struggling with chronic health issues – the way I used to – you probably have piles of lab tests that can potentially tell you a lot about your health. Histidine may be one of them. However, doctors never had enough time to explain it properly. They will only notice it if the lab flags your test results as outside of normal. But what if all your results are coming back normal, yet you know you are feeling nowhere near healthy? They may even tell you there is nothing wrong with you, and that it’s all in your head – I’ve been there.

Lab Test Analyzer is the tool I wish I had when I was dealing with all of my health issues. Instead of normal, it will tell you the optimal values for many lab tests. And if you are outside the optimal range, it will give you actionable tips and recommendations that will help you get there.

Side Effects

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 [R].  

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 [R].

In rats, consumption of excess histidine was found to lead to a deficiency of copper in the liver, high cholesterol, an enlarged liver, and appetite suppression [R, R].

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 [R].

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 [R].

There are also histidine supplement powders available online.

Dosage

The World Health Organization (WHO) estimated that the recommended intake of histidine is 8-12 mg/day in adults [R].

Studies involving histidine supplementation of up to 4 g/day have been carried out with no adverse side effects reported [R, R, R].

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.

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues, I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on PubMed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
  • SelfDecode – a software tool that will help you analyze your genetic data from companies such as Ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you

SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

Source of this (above) article: https://www.selfhacked.com/blog/histidine/

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