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

L-Leucine

(Leucine)

Evidence: High
Possible Benefits: Low
Safety: Reasonable

What is L-leucine?

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

What does L-leucine do for the body?

Leucine 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, leucine is the main activator of protein synthesis.

Cells turn on protein synthesis through the mammalian target of rapamycin (mTOR) based on leucine levels. The higher the leucine levels in the body, the more this enzyme gets activated.

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

Leucine also helps activate the SIRT1 gene. This effect may be associated with slowing down aging but more research is needed to prove this.

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 leucine deficiency – Since leucine is an essential amino acid, the body needs at least some amount to survive and function properly. Not getting enough L-leucine can lead to multiple health problems, such as decreased appetite, lethargy, poor growth, weight loss, skin rashes, and hair loss. Fortunately, a deficiency in this amino acid is rare and shouldn’t happen unless you consume too low amounts of protein.

Minor benefits

Improved carbohydrate absorption – Leucine 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.

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-leucine could lead to chronic toxicity and cause some health problems. For example, doses over 500 mg/kg/d have caused increases in serum ammonia. To prevent chronic toxicity, it is best to stay below 10 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-leucine?

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 leucine than young adults for similar activations of muscle protein synthesis)

How much leucine should you take?

The RDA (recommended daily allowance) for this amino acid is 42 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 56 and 62 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-leucine as a supplement, 2-4 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 leucine is established at 500 mg/kg/d. However, even lower amounts can cause some health problems if you take the supplement for a prolonged period.

To stay on the safe side, don’t take more than 10 grams daily unless you have a great reason to do so.

Food sources of leucine

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

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

The easiest way to find out exactly how much leucine 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 leucine

Like most other amino acids, leucine 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-leucine 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
Leucine 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.
Isoleucine
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.
Resveratrol
Both resveratrol and leucine can activate the SIRT1 gene and act synergistically in doing so when taken together. Whether or not this effect is of practical significance is not yet clear.

Where to buy L-leucine

Amazon is the best option for ordering L-leucine 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-leucine, 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-leucine in the system can cause some health problems, often related to causing an imbalance in other amino acids. It is best to stay below 10 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 leucine than young adults for similar activations of muscle protein synthesis)

The half-life of leucine in the body is about 45 minutes. This amino acid stays in your system for a few hours after you consume it.

If you take the supplement before a workout, you may notice a mild increase in power output. 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 leucine 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, leucine 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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