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

L-Isoleucine

(Isoleucine)

Evidence: Reasonable
Possible Benefits: Low
Safety: Reasonable

What is L-isoleucine?

Isoleucine is one of 9 essential amino acids. Our bodies cannot synthesize this amino acid but need it to survive. Isoleucine is also one of the 3 branched-chain amino acids (BCAAs), along with valine and leucine. As a supplement, L-isoleucine is often used to reduce catabolism and preserve muscle mass. This article is about the main benefits of L-isoleucine, its potential side effects, the best time to take it, and more.

What does L-isoleucine do for the body?

Isoleucine is an essential amino acid, which means the body needs it to survive and cannot synthesize it. It is also one of the three branched-chain amino acids (BCAAs).

In the body, isoleucine helps activate protein synthesis but to a much smaller extent than leucine.

Isoleucine has anti-catabolic effects, which means it slows down the breakdown of muscle mass, amongst other things in the body.

Despite the increase in muscle protein synthesis and the reduction in muscle catabolism, long-term supplementation of this amino acid does not lead to increases in muscle mass in most cases.

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 an isoleucine deficiency – Since isoleucine is an essential amino acid, the body needs at least some amount to survive and function properly. Not getting enough L-isoleucine can lead to the weakening and wasting of muscles, and tremors. Fortunately, a deficiency in this amino acid is rare and shouldn’t happen unless you consume very low amounts of protein.
Improved carbohydrate absorption – Isoleucine promotes insulin secretion from the pancreas and helps the body utilize carbohydrates. Taking this amino acid before a carbohydrate-rich meal lowers the blood glucose spike from it. This effect is more notable for isoleucine than for either valine or leucine.

Minor benefits

Reduced muscle catabolism – Isoleucine reduces muscle breakdown to a higher degree than leucine but to a lesser degree than HMB, a metabolite of leucine.

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.

Amino acid imbalance – 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 particular amino acid/s.
Toxicity – While acute toxicity has never been reported, taking high amounts of L-isoleucine could lead to chronic toxicity and cause some health problems. To prevent chronic toxicity, 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-isoleucine?

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 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:

consume very little protein (less than 0.3 grams/pound of body weight)
are muscular and work out a lot
are an older person (older people need up to 2 times more isoleucine than young adults to reduce the rate of muscle catabolism)

How much isoleucine should you take?

The RDA (recommended daily allowance) for this amino acid is 19 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 25 and 30 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-isoleucine as a supplement, 1-2 grams appears to be the best daily target for most people. This amount should provide most of the benefits without meaningful side effects.

Some people may benefit from doses higher than 4 grams. These include older people, bodybuilders, very physically active individuals, and those on a low-protein diet.

The upper safety limit for isoleucine is not well-established. To stay on the safe side, don’t take more than 5 grams daily unless you have a great reason to do so.

Food sources of isoleucine

L-isoleucine is found in all whole foods that contain dietary protein.

The amount of isoleucine per gram of protein varies from food to food but a general rule of thumb is that the more protein you eat, the more isoleucine you are getting from food.

The easiest way to find out exactly how much isoleucine 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 isoleucine

Like most other amino acids, isoleucine 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-isoleucine 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 won’t break your fast.

Unless it feels too impractical, spread the daily dose into 2+ smaller doses throughout the day.

Interactions

Carbohydrates
Isoleucine promotes insulin secretion from the pancreas and helps the body utilize glucose. Taking this amino acid before a carbohydrate-rich meal lowers the blood glucose spike from it and increases muscle protein synthesis.
Leucine
These two amino acids act synergistically with each other and have to be kept in balance.
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 particular amino acid/s.

Where to buy L-isoleucine

Amazon is the best option for ordering L-isoleucine 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-isoleucine, 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 L-isoleucine 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:
– eat very little protein (less than 0.3 grams/pound of body weight)
– are muscular and work out a lot
– are an older person (older people need up to 2 times more isoleucine than young adults to lower the rate of muscle catabolism)

The half-life of isoleucine in the body is 3-5 hours. This amino acid stays in your system for at least 20 hours after you consume it.

In the long term, you need to take the supplement for many months 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 isoleucine pills and 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, isoleucine 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.

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