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Histidine, the Amino Acid that Fights Arthritis

Histidine is an amino acid that is abundant in hemoglobin, the iron-rich protein that carries oxygen to every cell in the human body. When the diet is deficient in protein, hemoglobin is one of the first sources of essential amino acids the body uses to make proteins for vital hormones and tissue repair. Breaking down hemoglobin always releases more histidine than the body can use, so histidine accumulates in the urine.

Spill-over of histidine into the urine is one of the best indications of a protein-deficient diet. Excess histidine is released not just from the destruction of hemoglobin, but also from the destruction of muscle. You don’t have to be starving to break down muscle-poorly planned weight loss diets can have the same effect.

Histidine Food Sources

Histidine is an essential amino acid that the body has to obtain from food or supplements. The liver can make tiny amounts of histidine from a combination of carnosine, glutamic acid, and the B vitamin biotin, but it can never make enough histidine to keep up with the body’s needs. Histidine can also be released from hemoglobin and muscle tissue, but since red blood cells and muscle eventually have to be replaced, there is always a need for histidine from outside the body.

The body can absorb either the D- or L-form of histidine, but L-histidine is absorbed more readily. The best food sources of L-histidine are meat and dairy products.

FoodMg Histidine in a 200-Calorie Serving
Game Meats (Deer, Elk, Whale, Wild Boar)1892
Cured Ham (Pork)1794
Pork Loin Roast1586
Turkey (White Meat)1384
Tuna (Canned)1295
Tofu, Extra-Firm931
Sunflower Seeds818
Kidney Beans814

Buckwheat and quinoa also contain histidine. The US National Academy of Sciences estimates that infants up to 6 months of age need 33 mg of histidine every day for every kilogram of body weight, but no recommended daily intakes have been established for older children or adults.

Supplemental L-histidine is available in 500- and 600-mg tablets. Up to 20,000 mg in a single dose is not likely to cause any problems, although using histidine supplements for months at a time may interfere with the menstrual cycle in women of reproductive age, causing the cycle to come too early. Histidine supplements are not recommended for people who have chronic allergies, bipolar disorder, or schizophrenia.

Histidine for Preventing Cataracts

Animals who are given diets deprived of histidine develop cataracts very quickly. The sutures holding the lens to the sclera (white) of the eye widen, and the collagen fibers in the lens deteriorate.

Advocates of L-carnosine eye drops include L-histidine in their products. Grandiose claims are made for these products, but proof is not readily available for objective examination. Still, it seems prudent to avoid L-carnosine deficiency, if not to take expensive amino acid eye drops, to help prevent or forestall the formation of cataracts. This is most important for people who follow vegan or reduced-calorie diets.

Histidine for Rheumatoid Arthritis

Rheumatoid arthritis results from the destruction of the lining of the joint by a complex of immune factors related to IgG, the immune globulin that can also be activated by certain foods. (Different people will have different IgG reactions to different foods.) Scientists have known since the late 1990s that a protein made with histidine called histidine-rich glycoprotein (or HRG) traps the immune complex so that it does not destroy the lining of the joint.

A physician named Donald A. Gerber published 14 papers on the role of histidine in the development and treatment of rheumatoid arthritis in the 1970’s and early 1980’s. Dr. Gerber’s research constitutes a lot of what is known about the use of histidine for arthritic joints. First Dr. Gerber took blood samples from 285 rheumatoid arthritis patients and looked for correlations with various aspects of the disease. The data showed that within statistical significance:

  • The higher the concentration of histidine in the bloodstream, the lower the sedimentation rate (a measure of inflammation) in the blood sample.
  • The higher the concentration of histidine in the bloodstream, the shorter the duration of stiffness in the morning.
  • The higher the concentration of histidine in the bloodstream, the greater the measured grip strength of the patient.
  • The higher the concentration of histidine in the bloodstream, the farther the patient could walk without unbearable pain.
  • The higher the concentration of histidine in the bloodstream, the lower the concentration of rheumatoid factor.
  • The longer the patient had had rheumatoid arthritis, the lower the concentration of histidine in the bloodstream.
  • Taking aspirin lowered histidine levels.
  • Taking drugs based on gold lowered histidine levels.
  • Taking steroids dramatically lowered histidine levels.
  • Patients who had rheumatoid arthritis who gave blood samples between 11 a.m. and 1 p.m. had the lowest bloodstream concentrations of histidine.
  • Both men and women who had rheumatoid arthritis had histidine levels about 30% lower than those of healthy people.

Understandably, Dr. Gerber began to experiment with histidine supplements as a treatment for rheumatoid arthritis. First, he confirmed that histidine deficiency in rheumatoid arthritis could occur even if patients ate high-protein diets and were not deficient in other amino acids. Then, Dr. Gerber found that a mixture of histidine, another amino acid called cystine, and copper prevented the denaturation, or “curdling,” of the protein that protects the lining of the joints.

In 1977, Dr. Gerber reported the results of a randomized, placebo-controlled, double-blind clinical trial of 4,500 mg of histidine daily as a treatment for rheumatoid arthritis. Overall, the results of histidine supplements were not statistically significant. Some patients, however, did a great deal better after receiving the histidine supplement.

This is the point at which Dr. Gerber stopped his work. For 28 years, there was no progress in understanding how histidine might help rheumatoid arthritis until a group of medical researchers at Hacettepe University in Turkey hit on the idea of using histidine-enriched nanoparticles to capture the antibodies that cause tissue destruction in arthritic joints. The Turkish research team found that the histidine on the bead is bound to the immune globulins that cause tissue destruction without interfering with other red or white blood cells.Arthritis

At about the same time, a team of researchers at the Pomeranian Medical University in Szczecin, Poland, found that there is a gene that causes histidine to be incorporated into one of the proteins that regulate the immune system in the joint where another amino acid, alanine, is supposed to go. This both takes histidine out of the bloodstream and leaves the joint unprotected against tissue-destructive antibodies produced by the immune system. Only about 48% of the people who had rheumatoid arthritis who participated in this study had this gene.

And only about 50% of people who have rheumatoid arthritis benefit from histidine supplements.

Taking histidine supplements may help your rheumatoid arthritis a lot, or it may not help at all. The only way to find out is to try the supplement for about three months. The usual dosage is 4,500 mg a day, although up to 20,000 mg a day may be helpful.

There is no way to know ahead of time (unless you had genetic testing that currently is only available in Poland and is not offered to the public) that histidine will help your personal case of rheumatoid arthritis. People who have rheumatoid arthritis and who consume more than 2 alcoholic beverages a day, however, often have histidine depletion and may benefit from histidine supplementation regardless of genetic status.

Histidine for Allergies

The amino acid histidine is converted to the allergy-provoking compound histamine by the actions of enzymes that release carbon dioxide (CO2) from histidine and leave histamine behind. Once histidine has been converted to histamine, the newly formed histamine can:

  • Cause blood vessels to dilate so that they leak fluids into surrounding tissues, causing swelling, and isolating the particles that triggered the allergy.
  • Trigger the release of stomach acid to digest allergy-causing particles in the throat and stomach.
  • Lock onto histamine receptors in the brain that reduce the release of epinephrine (also known as adrenalin) and serotonin.
  • Signal the immune system to send specialized white blood cells to release inflammatory chemicals that destroy the swollen tissues around the trapped allergy-causing particles.

All of these actions, as every allergy sufferer already knows, create very unpleasant symptoms. Histamine causes sneezing, wheezing, tearing, itching, and inflammation, and it also saps energy as it reduces the production of epinephrine and serotonin. It produces sleepiness, and, paradoxically, increases strength of erections in men.

Since the body uses histidine to make histamine, how could histidine supplements possibly reduce allergies? It turns out that the higher the concentration of histidine in the bloodstream, the slower the release of histamine from the mast cells where it is stored. There are many testimonials along the lines of “Histidine gave me my life back” among sufferers of severe allergies who were not able to find relief any other way. A typical daily dosage of histidine is 3,000 mg, taken in three doses of two 500-mg histidine tablets between meals.

If you have allergies and you take histidine, you should also take zinc, since histidine removes zinc from circulation. Take 10 mg of zinc for every 1,000 mg of histidine. Do not take supplemental zinc if you do not take histidine, since zinc in this dosage can increase the activity of the immune system, which in the case of allergies is not a good thing.

Frequently Asked Questions About Histidine

Q. Is histidine aromatic?

A. I really wouldn’t call it that. One of the components of the odor of decaying fish is histidine. If you are referring to the chemistry of histidine, no, it is not aromatic. Histidine consists of an imidazole group joined to propionic acid.

Q. Is histidine safe to give to dogs?

A. Histidine is an essential amino acid in both dogs and people, although the dog’s kidneys can make tiny amounts of it. Histidine deficiency diets in dogs result in weight loss and muscle wasting in just a few days. Giving a dog carnosine or histidine supplements can increase histidine levels, provided zinc is not deficient. But I would simply feed my dog any kind of meat other than horse meat, to which many dogs are allergic.

Q. What is histidine tagging?

A. A polyhistidine tag is a method of separating proteins out of a mix. It’s used to purify recombinant proteins made by bacteria. For instance, almost all insulin used for injection is made by genetically engineered bacteria. The bacteria are broken up, and histidine tagging is used to remove the insulin they make.

Q. Can histidine be used to treat pernicious anemia?

A. The condition now known as megaloblastic anemia (formerly known as pernicious anemia) occurs when the stomach does not produce enough intrinsic factors to digest vitamin B12 from food. The shortage of vitamin B12 interferes with the production of red blood cells. Megaloblastic anemia can never be cured, but taking supplemental B12 restores the production of red blood cells.

Red blood cells contain hemoglobin, which requires large amounts of histidine. Taking histidine without vitamin B12, however, will not enable the production of more red blood cells. Vitamin B12 supplementation has to come first.

Q. Do histidine supplements treat histidinemia?

A. No, they would be harmful. Histidinemia is a condition of excessive histidine levels caused by a deficiency of the enzyme histidase, which is needed to convert it to urocanic acid, which in turn becomes the amino acid glutamic acid. This condition exists from birth and is associated with developmental delays, especially delays in the development of speech. It is a genetic condition, and it is rare outside Japan.

Q. Would histidine treat erectile dysfunction?

A. Probably not. Histamine, not histidine, increases erections in men and sexual satisfaction in women. Taking supplemental histidine, however, has the paradoxical effect of reducing the release of histamine and probably would not be helpful in treating sexual problems.

Q. Does histidine lower blood pressure?

A. No, it is more likely to raise blood pressure.

Q. Does histidine relieve stress?

A. No, but it will help the body restore blood and muscle broken down during stress. Do not take histidine supplements to relieve anxiety, depression, or post-traumatic stress disorder. They are not what you need.