Leucine Is Crucial to Prevent Muscle Depletion

Muscle mass decreases with age, a phenomenon known as sarcopenia. After the age of 30, most people experience muscle mass decreases of about 3% to 8% per decade, with the rate of decline increasing further after age 60.1 This isn’t set in stone, however, and you can influence muscle loss, slowing down its progress significantly, via lifestyle factors like diet and exercise.
Luc van Loon, a professor of exercise physiology and nutrition at Maastricht University in The Netherlands, has been studying muscle loss for years, revealing the importance of diet to your muscle health. Every day, 1% to 2% of your muscle is broken down and rebuilt, according to van Loon, which means that your muscle is rebuilt every two to three months.2
Amino acids from protein are particularly important in this process, acting as the raw material or “building blocks” of your muscle while also playing a role in new muscle growth. Leucine, in particular, has been established as an amino acid with greater anabolic properties.3
The richest source of leucine, which helps regulate the turnover of protein in your muscle, is whey protein. Older people not only have accelerated muscle loss, but also require greater protein intake to stimulate maximum muscle protein synthesis compared to younger people.4
For instance, while the muscle protein synthesis rate of healthy young adults increases by about 75% following intake of 20 grams of protein, older adults require about 40 grams of protein to experience a similar increase.5
Without whey, it can be difficult to achieve enough leucine to maintain body protein from diet alone. Fortunately, whey, in combination with exercise, represents a simple option for older adults looking to maintain their muscle mass.
‘You Are What You Just Ate’

In 2015, van Loon and colleagues published a comprehensive overview of how the body handles protein after a meal, including details such as protein digestion, amino acid absorption and muscle protein synthesis rates.6 The study’s title, “You Are What You Just Ate,” hints at the findings, which revealed that when 12 young men ingested 20 grams (g) of protein, 55.3% of it was released into their circulation within five hours.
After consuming the protein, muscle protein synthesis rates also increased significantly and a rise in plasma essential amino acid also occurred, translating into improved leg muscle protein balance. According to the study:7

“Ingestion of a single meal-like amount of protein allows ~55% of the protein derived amino acids to become available in the circulation, thereby improving whole-body and leg protein balance.

About 20% of the dietary protein derived amino acids released in the circulation are taken up in skeletal muscle tissue following protein ingestion, thereby stimulating muscle protein synthesis rates and providing precursors for de novo muscle protein synthesis.”

The influence of protein on your muscle may be even more important post-exercise, especially in the elderly, but van Loon and colleagues found that even those who are frail benefit from protein supplementation after exercise.
In fact, their study involved 62 frail elderly subjects with an average age of 78 years, who engaged in progressive resistance exercise twice a week for 24 weeks. They received either a protein drink or a placebo beverage during the exercise.
Those in the protein group gained significant benefits, including an increase in lean body mass from 47.2 kilograms (104 pounds) to 48.5 kilograms (106.9 pounds), an effect that wasn’t seen in the placebo group. According to the researchers, “Dietary protein supplementation is required to allow muscle mass gain during exercise training in frail elderly people.”8
Protect Your Muscles During ‘Catabolic Crises’

While muscle mass does decline gradually over time, it’s also possible that a single event can trigger a catabolic crisis that acts as a tipping point, breaking down muscle to a point that’s difficult to recover from.
Even a brief period of bed rest, such as recovering from a surgery or illness, can initiate significant declines in muscle strength and it’s also known that muscle loss is accelerated during periods of bed rest while muscle protein synthesis declines.9
During typical daily life, consuming a moderate amount of high-quality protein with each meal, and exercising close to protein-containing meals, can help to limit losses of muscle mass and function in older adults.10 Protecting muscles during periods of inactivity, however, is crucial for older adults.
This can be achieved by consuming targeted nutritional support, including protein and amino acid supplementation, along with physical therapy. Van Loon also suggests that making small changes during bed rest can make a big difference. As Outside Online reported:11

“Van Loon advocates some simple fixes — like never, ever feed someone in a hospital bed unless it’s absolutely necessary. Make them get up, and ideally make them shuffle down the hallway to get food. Same for watching TV.

Even this tiny amount of muscle contraction, he says, will enhance muscle synthesis when the patient eats. Similarly, since you don’t eat as much when you’re in bed, the proportion of protein in the meal should be higher to ensure sufficient muscle synthesis signals.”

Protein Before Bed Increases Muscle Mass

I generally recommend avoiding food close to bedtime, and past research has linked eating close to night-time sleep to an increased risk of heart disease, obesity and diabetes. However, targeted nutritional therapy prior to sleep may have a different, beneficial effect, acting as an opportunity to support muscle reconditioning in the elderly or athletes, for instance.12
In a review by Van Loon and colleagues, they found that ingesting protein prior to sleep increases muscle protein synthesis rates while you sleep and may be useful following resistance exercise in both young and old adults:

“Protein ingested prior to sleep is effectively digested and absorbed during sleep, thereby increasing plasma amino acid availability and stimulating muscle protein synthesis during overnight sleep in both young and old. When pre-sleep protein intake is combined with exercise performed the same evening, overnight muscle protein synthesis rates will be further increased.13

Protein ingestion prior to sleep can be applied in combination with resistance type exercise training to further augment the gains in muscle mass and strength when compared to no protein supplementation …

Protein ingestion before sleep has been hypothesized to represent an effective nutritional strategy to increase daily protein intake and, as such, to attenuate muscle mass loss in hospitalized older adults.

In more clinically compromised older populations the combination with exercise or exercise mimetics (such as NMES [neuromuscular electrical stimulation]) may further increase the efficacy of pre-sleep protein ingestion to improve overnight muscle protein balance.”

Leucine as a Pharmaconutrient

Van Loon describes leucine as a pharmaconutrient that may be useful for preventing and treating sarcopenia and other conditions like Type 2 diabetes.14 Muscle protein synthesis may become blunted in response to amino acid or protein intake in the elderly, but free leucine ingestion may reverse this blunted response.15
Older adults may also have attenuated postexercise increases in muscle protein synthesis when they consume small amounts of protein compared to younger adults. This can also be improved via leucine, as research suggests that in older adults, consuming leucine along with protein boosts muscle protein synthesis rates after exercise compared to consuming protein alone.16
As far back as 1975, it’s been known that leucine may also “play a pivotal role in the protein-sparing effect of amino acids.”17 As explained in a more recent study, published in 2017, this is what makes whey such an efficient protein source:18

“Protein ingestion produces a strong anabolic stimulus that elevates muscle protein synthesis. The ability of a serving of protein to stimulate muscle protein synthesis (MPS) is dependent on absorption and blood kinetics of amino acids, amount of protein ingested, and the amino acid composition of the protein source.

Only the essential amino acids (EAA), especially leucine, initiate an immediate increase in MPS. Being a rapidly digested protein with a high leucine content, whey has been shown to stimulate MPS more than equal amounts of casein and soy in the first hours after exercise …

At the molecular level the mechanistic target of rapamycin complex 1 (mTORC1) and its substrates … are believed to largely be responsible for the protein synthetic response to resistance exercise and protein intake, with resistance exercise potentiating the effect of protein ingestion.”

How Much Leucine Is Best?
Ori Hofmekler, author of “Unlock Your Muscle Gene: Trigger the Biological Mechanisms That Transform Your Body and Extend Your Life,” is an expert on how to use food to build muscle and improve your health. He believes you need far higher amounts of leucine than the recommended daily allowance, as most leucine is used as a building block rather than an anabolic agent.
The typical requirement for leucine to maintain body protein is 1 to 3 grams daily. However, to optimize its anabolic pathway, Hofmekler believes you need somewhere between 8 and 16 grams of leucine per day, in divided doses.
Siim Land, author of “Metabolic Autophagy: Practice Intermittent Fasting and Resistance Training to Build Muscle and Promote Longevity,” also states that to activate mTOR and boost muscle protein synthesis, you need a significant quantity of leucine, at least 3 grams. In our August 2020 interview, he stated:

“Using leucine or HMB [hydroxy methylbutyrate, a metabolite of leucine] can be really useful for getting more protein synthesis from less protein. You can get away with eating less protein and still getting the benefits of the mTOR stimulation. But I would say that leucine itself could be better than HMB by itself.

HMB has some anticatabolic effects, but most of those effects are mediated by leucine and mTOR itself. You could use both, but if you want to get more benefits from the mTOR and muscle growth, then leucine is probably more important than HMB.”

More Frequent Protein Intake Useful for Muscle Building
Breaking the doses up into multiple meals may be especially beneficial, because if you eat twice, six hours apart, you can activate mTOR twice a day, thus allowing you to get better muscle-building benefits. As explained by Land:

“What determines your muscle growth throughout the 24-hour period is the balance between mTOR stimulation and autophagy. So, if you’re eating only once a day, then the amount of mTOR stimulation is relatively small compared to eating twice a day or three times a day.

That’s why if someone has the goal of increasing their muscle mass, maintaining muscle mass or preventing sarcopenia, then for them it is much wiser to incorporate more frequent meals. For them I would say that a 16-to-8 type of fasting where they eat twice a day is perfectly suitable, and is actually better than the one meal a day.

It becomes increasingly more difficult to maintain muscle mass if you’re already predisposed to sarcopenia and you’re eating once a day, because there’s a threshold of how much mTOR you can stimulate per meal, and how much muscle protein synthesis you can create per meal as well. It doesn’t have to mean that you start eating six times a day. Increasing the eating window is generally a better idea.

For most people, I would say that the 16-to-8 type of fasting, where they fast for 16 hours and eat within eight hours, is a really good balance between getting a daily stimulation in autophagy, while at the same time also stimulating enough mTOR and being able to build muscle.”

Getting large amounts of leucine from your regular diet may be difficult. For example, 4.6 eggs will provide you with 2.5 grams of leucine,19 which means you’d have to eat nearly 15 eggs to reach the 8-gram minimum. High-quality whey, on the other hand, contains about 10% leucine (10 grams of leucine per 100 grams of protein).20
So, 80 grams of whey protein will give you 8 grams of leucine. Whey derived from cheese manufacturing that uses raw grass fed milk is the highest quality whey available and one of the best sources of leucine around.