Leucine

What it is

Together with isoleucine and valine, leucine belongs to the branched-chain amino acids, BCAA for short. The body cannot produce it itself; it has to come from food. The WHO sets the requirement for adults at 39 mg per kilogram of body weight per day. In fact, most people eat considerably more: in the US, the mean intake is 6.1 g of leucine per day, in the UK the median is 108 mg per kilogram. Leucine is found in all protein-containing foods, in meat, fish, dairy products and legumes. Whey protein is particularly rich in it; 25 g of whey provide 3.0 g of leucine.

As a preparation, leucine is available as a single powder, in BCAA blends, in blends of essential amino acids and in fortified oral nutritional supplements for older people. A close relative is HMB, a metabolite of leucine that the body forms itself and that is also sold as a supplement. How leucine fits into the overall picture of amino acids is described in more detail in the entry on amino acids.

How it is supposed to work

Leucine is not only a building block but also a signal. When its level rises after a meal, it activates mTORC1 in the muscle cell, a central switch for growth. This releases protein production. The BfR describes leucine as a strong stimulator of mTOR, and among the three branched-chain amino acids it is considered the most important for metabolism. For the actual building, however, the muscle then needs all the essential amino acids. Leucine is, so to speak, the ignition key; the building material has to come from the rest of the protein.

With age, muscle responds more weakly to the same amount of protein; experts speak of anabolic resistance. The idea behind leucine supplements is to amplify this signal so that even a smaller meal starts muscle building. HMB is additionally supposed to slow muscle breakdown.

What users are looking for

Strength athletes take leucine to upgrade a meal or a shake anabolically, especially with plant-based food with a lower leucine density. Older people and their relatives are looking for a simple remedy against age-related muscle loss. How you feel after training is a poor yardstick here. Anyone testing it is best off judging it by strength values and muscle mass over months, not by how they feel after a week.

What the studies show

Meta-analysis of 17 studies in older adults

The analysis comprised 17 randomized studies with 1,418 older people. Isolated leucine changed neither fat-free mass nor grip strength nor leg press strength. Combinations with vitamin D and other nutrients, by contrast, improved grip strength by 2.17 kg and walking speed by 0.03 m per second.

Three months of leucine in healthy older men

30 men aged around 71 took 2.5 g of leucine or placebo with each main meal, 7.5 g per day in total, for 3 months. Muscle mass by CT and DXA, strength, insulin sensitivity and blood lipids did not change in either group. The study is considered the most important evidence that the acute synthesis effect does not automatically lead to more muscle.

PROVIDE: oral nutritional supplement in sarcopenia

380 older people with sarcopenia drank a preparation of whey protein, leucine and vitamin D or a control product with the same number of calories twice daily for 13 weeks. The primary outcomes, grip strength and a performance test, improved equally in both groups. On the secondary outcomes, the active group was ahead: 0.17 kg more muscle mass in arms and legs and a chair-stand test that was 1.01 seconds faster. What share is attributable to leucine cannot be separated out.

Where the data stop

The most important catch: with isolated leucine, the short-term rise in the synthesis rate does not translate into more muscle. The same meta-analysis that shows the synthesis effect in older adults found no difference in fat-free mass and leg muscle mass. It did not help during immobilization either: 24 young and 24 older adults wore a leg cast for 3 days and took 5 g of leucine 3 times daily or placebo; synthesis rate and muscle cross-sectional area fell equally in both groups. A meta-analysis specifically in sarcopenia did find advantages, but rates the evidence as low and considers the benefit of leucine alone to be limited.

The picture is similar for its relative HMB. In young people doing resistance training, it brought no additional fat-free mass and no strength in a meta-analysis of 11 studies. In sarcopenia, only grip strength improved, by 1.26 kg. Long-term data on isolated leucine intake are lacking, and whether a permanently high leucine intake influences aging via mTOR has not been studied in humans.

Status, approval and legal

Leucine is a nutrient and is sold in Germany as an ingredient of dietary supplements and sports nutrition. In 2013, the BVL permitted, by general administrative order, capsules with L-leucine, L-valine and L-isoleucine from other EU states at 600 mg each per day. There is no statutory maximum amount. In 2019 the BfR derived guidance values for additional isolated intake: 4.0 g of leucine per day, 8.2 g for all three BCAA together. Because sufficient human data were lacking, these values are based on animal studies. Leucine and HMB are not on the WADA Prohibited List 2026.

Safety

In usual amounts, leucine is a normal component of food; 7.5 g per day over 3 months changed neither insulin sensitivity nor blood lipids in older men. With very high single amounts, the ammonia level in the blood rises: in acute studies it was above normal values in young men from over 500 mg per kilogram per day, and in older adults from 550 mg per kilogram. The BfR advises children, adolescents, pregnant and breastfeeding women to avoid relevant amounts of isolated BCAA, and people with impaired kidney function or on a low-protein diet to consult a physician. It also recommends taking the branched-chain amino acids combined rather than individually. In the rare maple syrup urine disease, the breakdown of leucine is impaired; additional leucine there belongs only in a physician’s hands.

Sources

• Guo et al., Front Nutr 2022 – leucine and sarcopenia measures in older adults, meta-analysis of 17 RCTs
• Xu et al., Br J Nutr 2015 – leucine, muscle protein synthesis and muscle mass in older adults, meta-analysis
• Verhoeven et al., Am J Clin Nutr 2009 – leucine over 3 months in healthy older men
• Wilkinson et al., J Physiol 2013 – leucine and HMB in human muscle protein metabolism
• Churchward-Venne et al., Am J Clin Nutr 2014 – leucine in a low-protein drink
• Katsanos et al., Am J Physiol Endocrinol Metab 2006 – high proportion of leucine in older adults
• Bauer et al., J Am Med Dir Assoc 2015 – PROVIDE study
• Jakubowski et al., Nutrients 2020 – HMB in resistance training, meta-analysis
• BfR opinion 052/2019 – isolated branched-chain amino acids
• Elango et al., Am J Clin Nutr 2012 – upper limit for leucine in acute studies