L-Histidine: Benefits, Side Effects, Best Time to Take It & More

L-Histidine

(Histidine)

Evidence: Low
Possible Benefits: Low
Safety: High

What is L-histidine?

Histidine is one of 9 essential amino acids. Our bodies cannot synthesize this amino acid but need it for survival. As a supplement, L-histidine is often used for diarrhea due to cholera infection, eczema, kidney failure, metabolic syndrome, and other conditions. Unfortunately, there is not a lot of scientific data to support these uses. This article is about the main benefits of L-histidine, its potential side effects, the best time to take it, and more.

What does histidine do for the body?

L-histidine is sometimes called a semi-essential amino acid because it is essential for children but may not be essential for adults. This is because the body may develop a way to make histidine.

The main function of histidine in the body is to regulate and metabolize trace minerals, such as copper, zinc, iron, manganese, and more.

This amino acid is used by the body to make specific hormones and metabolites that impact kidney function, the transmission of nerves, stomach secretions, and the immune system.

Histidine also has an impact on the repair and growth of tissue, making blood cells and helping to protect nerve cells. It is also used to make histamine in the body.

Possible benefits

It is important to note that all of the potential benefits mentioned below are dose-dependent. Generally, the higher the dose, the more pronounced the effects are. However, they do reach a plateau at a certain point. We will discuss the best dosing protocol later in this article.

Major benefits

Correcting a histidine deficiency – Since histidine is an essential amino acid, the body needs at least some amount to survive and function properly. Not getting enough histidine can lead to multiple health problems, especially in adults who cannot synthesize it in their bodies. Fortunately, a deficiency in this amino acid is rare and shouldn’t happen unless you consume too low amounts of protein.

Minor benefits

Reduced diarrhea related to cholera – Drinking a solution containing histidine seems to reduce diarrhea in people with cholera who are also receiving antibiotics.
Treatment of arthritis – One study from 1975 shows that 4.5 grams of histidine taken for 30 days has a mild but positive effect on the treatment of rheumatoid arthritis.
Weight loss – Histidine has a very mild but beneficial effect on weight loss in obese women with metabolic syndrome. It is somewhat effective at lowering insulin resistance and fat mass.

Possible side effects

These side effects are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.

FIGLU – If you are deficient in vitamin B9 (folate), too much histidine can cause an unwanted chemical called formiminoglutamic acid (FIGLU) to build up in the body. People with a vitamin B9 deficiency should avoid the supplement.
L-Histidine toxicity – While acute toxicity has never been documented, taking high amounts of L-Histidine could lead to chronic toxicity over time. That is why it is best to stay below 5 grams a day unless you have a great reason to take more.
Contamination – Contaminated supplements are uncommon in the USA and other well-regulated countries. However, if you wish to buy products from China, India, or other countries without strict regulations, beware that the supplements may be contaminated. Either way, you need to choose the brand you order from wisely. It is highly recommended to check the certificates or read through some reviews for the specific product before you buy it. The FDA (Food and Drug Administration) has the power to regulate dietary supplements but can only do so after they have been on the market for a while. That’s because supplement companies are not obligated to announce to the FDA when releasing a new product on the market. The FDA has to discover the product and test it for potential impurities, which can take a lot of time. During that time, the supplement can be sold on the market even if it’s impure. Also, supplement companies can change their manufacturers without announcing it to the FDA.

Who should not take L-histidine?

You should probably avoid taking the supplement if you:

eat high amounts of protein from food (most whole foods contain at least some amount of each essential amino acid)
experience a severe adverse reaction after taking the amino acid
are deficient in folate (vitamin B9)
are on a tight supplement budget (since there are more cost-effective supplements on the market for most people)

Who will benefit the most?

You should consider taking the supplement if you:

experience diarrhea due to cholera infection
consume too low amounts of protein (less than 0.3 grams/pound of body weight)
suffer from chronic kidney failure (this condition can lead to low levels of histidine)
have a high budget for supplements (assuming the supplement doesn’t contain impurities, it is safe for most people when taken at regular doses and shouldn’t do more harm than good)

How much L-Histidine should you take?

The RDA (recommended daily allowance) for this amino acid is 14 mg/kg/day for all adult men and most adult women. This is enough for the majority of people to prevent any symptoms of deficiency.

The RDA increases to 18 and 19 mg/kg/day for pregnant and lactating women, respectively.

Since this amino acid is in almost every food, you probably already get sufficient amounts from food alone. About 0.36 grams of protein/pound of body weight should be enough to prevent a deficiency.

If you plan to take L-histidine as a supplement, 500 mg/d appears to be the best daily target. This amount should provide most of the benefits without meaningful side effects.

Some people may benefit from doses higher than 500 mg/d. These include bodybuilders, overweight people, and people experiencing diarrhea due to cholera infection.

The upper safety limit for this amino acid is not well-established. To stay on the safe side, don’t take more than 5 g/d unless you have a great reason to do so. Higher amounts may cause problems if you take the supplement for a prolonged period.

Food sources of histidine

Like every other essential amino acid, histidine is found in all foods that contain dietary protein. The amount of histidine per gram of protein varies from food to food but a general rule of thumb is that the more protein you eat, the more histidine you are getting from food.

The easiest way to find out exactly how much histidine or other amino acids you are getting from food is with Cronometer.com. This free app allows you to track all vitamins, minerals, and more.

Best time to take L-histidine

Like most other amino acids, L-histidine is water-soluble, so you don’t have to take it with food to absorb it well. Taking the supplement with food is better if it causes stomach upset when you take it on an empty stomach.

To maximize the benefits, take L-histidine and other amino acids before or after a workout.

Whether you take the supplement in the morning or the evening doesn’t matter. It should not interrupt your sleep in any way.

If you practice time-restricted eating, take this amino acid during your eating window to guarantee it doesn’t break your fast.

Interactions

Other amino acids
All essential and non-essential amino acids need to be kept in balance as they act synergistically in many ways. Too much of one amino acid can sometimes cause side effects without enough of another amino acid. That is most notably the case for glycine and methionine, but the principle applies to other amino acids, such as lysine and arginine, and the BCAA trio. Using a single amino acid supplement may lead to a negative nitrogen balance, which can lessen how well your metabolism works. A protein powder is usually a better choice for getting enough amino acids unless you have a specific goal in mind targeted by a specific amino acid/s.
Vitamin B9
If you are deficient in vitamin B9 (folate), too much histidine can cause an unwanted chemical called formiminoglutamic acid (FIGLU) to build up in the body. People with a vitamin B9 deficiency should avoid the supplement.

Where to buy L-histidine

Amazon is the best option for ordering L-histidine supplements in most countries. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the internet.

Beware some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.

FAQ

You can take the supplement daily and do not need to cycle it. However, it is certainly not a problem if you don’t take it daily. Not taking the supplement every once in a while could lead to better absorption. That is yet to be proven or disproven.

All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, you may need a highly accurate scale to dose them correctly (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes some time that can add up over months or years. The disadvantage of capsules is that they often contain bovine gelatin, which rarely comes from an ethical source.

Yes. Most amino acids, including L-histidine, absorb and digest well if you take them before falling asleep. The supplement should not impact sleep quality in any significant way.

This amino acid should not become harmful once it exceeds the expiration date but can lose potency over time.

Keep the supplement in a cold, dark, and dry place, and it should remain just as potent for many months or even years.

While toxicity is rare, too much histidine in the system can cause some health problems, often related to causing an imbalance in other amino acids. It is best to stay below 5 grams a day to prevent these side effects.

You may need more of this amino acid if you:
– experience diarrhea due to cholera infection
– suffer from chronic kidney failure (this condition can lead to low levels of histidine)
– don’t eat enough protein (less than 0.3 grams/pound of body weight)

The half-life of histidine in the body is about 12.2 hours. This amino acid stays in your system for about 66 hours after you ingest it.

In the long term, you need to take the supplement for about 2-4 weeks to begin noticing the benefits.

Amino acid supplements often come from animal products, but they do not have to be since all whole plant foods contain all essential amino acids. You can easily find vegan-friendly L-histidine powders but always check the label to be sure. If you buy the amino acid in a capsulated form, beware that the capsules often contain animal-based gelatin. Instead, find a brand that puts its products into cellulose capsules.

Like most other amino acids, L-histidine is water-soluble, so you don’t have to take it with food to absorb it well.

While low doses may not break a fast, higher doses certainly can. If you practice time-restricted eating, take this amino acid during your eating window so it doesn’t break your fast.

References

Most of the information provided in this guide is supported by scientific research that can be found and verified in the PubMed medical library. We highly encourage you to use the library to verify anything said in this article. We excluded from consideration studies that are either confounded or have a high conflict of interest.

TABLE OF CONTENTS