What’s with HMB Supplements?

HMB has been shown to promote muscle gain in individuals who are working out. However, this muscle-promoting effect is dependent on adequate availability of essential amino acids (EAAs). HMB supplements without the support of EAAs just don’t cut it.

From hydroxymethylbutyrate to beta-hydroxy-beta-methylbutyrate (or β-hydroxy-β-methylbutyrate), HMB—a chemical produced when the body breaks down the amino acid leucine—is known by a variety of names. But what exactly are HMB supplements?

HMB supplements are promoted as nutritional substances that can help speed wound healing and support individuals with muscle-wasting diseases such as cancer and HIV. Proponents also tout HMB supplements (or HMB in combination with creatine monohydrate) as a way to slow the muscle wasting that comes with aging.

To be fair, research does support the presence of some beneficial effects of HMB. For example, it’s been shown to promote muscle growth in individuals who work out. However, it should also be noted that this muscle-promoting effect is dependent on the adequate availability of essential amino acids (EAAs).

In other words, HMB supplements in isolation, without the support of EAAs, have a minimal effect on muscle building.

How Does HMB Work?

HMB and the EAA leucine are closely linked, and it’s necessary to understand the relationship between them to understand how HMB works.

Leucine is the most abundant of the nine EAAs found in muscle protein. It also acts as a nutraceutical aid in turning on the body’s muscle-building switch. In fact, it’s one of the three branched-chain amino acids—the others being isoleucine and valine—that make up about a third of muscle protein. Some experts also propose that leucine turns on the process of protein synthesis (muscle building) via the action of HMB.

HMB is a metabolite of leucine, meaning it’s derived from the breakdown of leucine. In a series of step-by-step reactions, about 15% of the leucine present in blood is also irreversibly broken down to ammonia and carbon dioxide. This sequence of reactions by which leucine is reduced to its basic components is called a metabolic pathway.

But there’s more than one metabolic pathway involved in the breakdown of leucine. And it’s actually via a minor pathway that the leucine metabolite HMB is produced, yet it’s still proposed to be the active component of leucine. However, as leucine is being broken down by the body, only about 5% of it is broken down via the pathway that results in HMB.

Combine this with the fact that only 15% of leucine is broken down at any given time, and it’s clear that the amount of HMB produced by leucine breakdown makes up only a very small percentage of available leucine.

As a result, the concentration of HMB in body fluids is far less than that of leucine. And since results with dietary supplementation aren’t achieved unless the concentration of HMB is increased many times above the normal physiological level, it’s unlikely that leucine’s effects on muscle protein synthesis are, in fact, mediated by HMB.

However, when the availability of HMB is increased using dietary supplements, it seems to work as a nutraceutical in the same way leucine does in that it activates the molecular mechanisms involved in the initiation of protein synthesis.

Specifically, the increase in HMB concentration supplied by supplementation activates a molecule known as mammalian target of rapamycin, or mTOR.

The molecule mTOR plays a key role in controlling the initiation of protein synthesis. When mTOR is activated, a series of additional chemicals involved in the initiation of protein synthesis is activated as well. And when all of these molecules are switched on, the process of protein synthesis begins. Likewise, when mTOR is activated by excess levels of HMB, the process of protein synthesis is also stimulated.

A sustained increase in muscle protein synthesis should ultimately be reflected by an increase in muscle strength, function, and mass over time. However, the use of HMB alone does not result in an increase in protein synthesis.

In fact, any increase in protein synthesis resulting from HMB supplements will last only as long as there’s an adequate supply of EAAs. And once there’s a dip in the EAA supply, the effect of HMB stops as well.

HMB Needs EAAs to Work

If you activate mTOR but your body doesn’t have enough EAAs circulating in the bloodstream, then muscle protein synthesis will only be increased to a limited extent.

As stated earlier, muscle protein contains nine EAAs, each of them unique and each a vital component of newly produced proteins. Unlike the 11 nonessential amino acids, EAAs can’t be produced in the body and have to be obtained through dietary sources.

However, if you aren’t getting enough EAAs through protein-rich foods or EAA supplements, then your only source of EAAs is the protein already present in your body.

In this case, your body begins to break down its protein stores and release the component amino acids, including EAAs, for use by the cells of the body. However, under normal conditions, only about 85% of amino acids released in this manner are reincorporated into protein; the rest are lost to oxidation.

But let’s circle back to HMB.

To be effective on its own, HMB must increase the efficiency of EAA reutilization for protein synthesis. However, as we just indicated, that process is already 85% efficient, which means there’s a definite limit as to how much more efficient the recycling of EAAs back into protein can be.

Therefore, it becomes clear that dietary supplementation with HMB works only when there’s an excess amount of EAAs available. And an excess supply of EAAs can occur via only two mechanisms:

  • EAAs must be consumed at the same time as HMB
  • The rate of protein breakdown must be accelerated

However, an increase in protein breakdown would only undermine the beneficial effect of an increase in protein synthesis, as protein gain is the result of the balance between protein synthesis and breakdown. Thus, supplemental doses of HMB can only result in a sustained increase in the net gain of muscle protein if consumed at the same time as an abundant supply of EAAs.

Benefits of HMB Supplements

All this being said, there are still a few conditions—such as catabolic states involving rapid muscle loss—that may benefit from HMB supplementation. This is because protein breaks down much more rapidly in catabolic states such as critical illness or HIV.

This protein breakdown provides extra EAAs that would, under normal conditions, be oxidized. In these situations of increased EAA availability that occur during catabolic states, the anti-catabolic action of HMB may help maintain muscle mass and function and decrease the rate of muscle protein breakdown.

However, recommendations for catabolic states generally specify that HMB should be included as part of a multifaceted approach for muscle maintenance that also incorporates resistance training and a high-protein diet for EAA maintenance.

Exercise also accelerates muscle breakdown (via muscle damage that occurs as a natural part of muscle use) and EAA oxidation. Consequently, the use of supplemental HMB may result in improved performance by improving the reutilization of EAAs released by protein breakdown for the synthesis of new protein.

Is HMB Better Than EAAs Featuring Leucine?

The body’s response to dietary supplementation with HMB alone is similar to that resulting from supplementation with leucine alone.

Just as HMB requires the presence of elevated levels of all the EAAs, so, too, does leucine require the other EAAs to be effective. In addition, the body’s response is more robust when leucine is included as part of a mixture of all the other EAAs than when it (or HMB) is used alone.

Two studies performed in the same laboratory, using the exact same protocol, demonstrate this most clearly. In one experiment, the effectiveness of HMB was assessed, and in the other experiment, the effectiveness of a mixture of EAAs (containing about 40% leucine) was determined.

Both studies investigated how effective HMB and EAA supplements were, compared with a placebo, at diminishing the loss in muscle mass and function that normally occurs with inactivity.

The subjects tested were over the age of 65, and both lean body mass and performance on various physical function tests were measured before and after 10 days of strict bed rest.

In the first study, following 10 days of bed rest, participants were put through a strength training program for a period of 8 weeks. In addition, beginning 5 days prior to bed rest and lasting until the end of the rehabilitation phase, the control group received a placebo powder and the subjects in the experimental group received 1.5 grams of HMB twice daily in its calcium salt form, for a total of 10 weeks of supplementation.

In the second study, participants in the control group received a placebo, while subjects in the experimental group received 15 grams of EAAs 3 times a day throughout the entire 10 days of bed rest. However, in this study, neither group received any weight training.

When comparing the data collected on all the subjects included in these studies, it becomes clear that the major differences between HMB and EAAs can be seen in terms of the tests of physical function—all of which have been validated as representative of the normal physical requirements for activities of daily living in older adults.

While the placebo group had major impairments in all tests of physical function after 10 days of bed rest, those given EAA supplementation—but not HMB supplementation—had significantly improved outcomes.

For example, the time required for subjects to go from a standing position to the floor and back up again (floor transfer test) increased by approximately 40% in the placebo group. Floor transfer rate was also not significantly affected by HMB supplementation. However, the group given EAA supplementation shortened their floor transfer time by 6%.

In another example, the time required to walk up a flight of stairs increased by 18% in the placebo group. HMB once again had no beneficial effect on this response, but those receiving EAA supplementation showed virtually no increase in the amount of time it took them to perform this task.

Finally, the number of toe raises (test of foot flexibility) that could be completed in 1 minute was reduced by almost 80% in both the control group and the HMB supplementation group, whereas the loss of this function with bed rest was completely prevented with EAA supplementation.

These bed rest studies are the only direct comparison that’s been completed of the muscle-building effects and strength gains provided by dietary supplementation with HMB and a formulation of EAAs. Yet the results clearly demonstrate the beneficial effects of EAAs in preventing declines in physical function and fail to demonstrate any beneficial effect of HMB alone.

These results are also consistent with the fact that stimulation of protein synthesis requires the availability of excess amounts of all component amino acids—especially EAAs.

While HMB’s activation of mTOR and other molecules involved in the initiation of protein synthesis may result in a transient increase in muscle protein synthesis, this increase can’t be sustained at a rate sufficient to result in improvements in physical function.

The HMB Takeaway

HMB is widely promoted as a muscle-building molecule that stimulates protein synthesis. While in some cases HMB supplementation may provide benefits, direct comparison with EAA supplementation highlights the fact that any benefit provided by HMB is minimal.

Whatever molecular signaling occurs as a result of HMB supplementation can instead be achieved by taking an EAA supplement that contains leucine. The availability of all EAAs—which are not present in HMB supplements—in excess amounts is required for a sustained increase in protein synthesis, muscle cell growth, and body composition changes that result in greater lean mass versus fat mass.

Furthermore, combining HMB with EAAs would not be expected to be particularly helpful, as the EAAs would elicit the action of HMB on their own.

HMB Supplements

Key Facts About EAA Supplements and Resistance Exercise

Together, resistance exercise and EAAs can stimulate muscle protein synthesis greater than they can alone. Increasing muscle strength and mass requires a close interaction between exercise, daily diet, and EAA supplementation. Let’s take it step by step.

In a previous blog post, I covered aerobic exercise and how essential amino acid (EAA) supplements can be used to mitigate the effects of muscle breakdown and improve performance. But what about combining EAA supplements and resistance training? Does that lead to any impressive benefits?

If you’ve spent any time in the company of individuals seeking to increase their physical strength and build muscle mass recently, you’ve likely heard them talking about branched-chain amino acid supplements (often referred to as BCAAs). They’ve become about as ubiquitous as whey protein! Proponents believe BCAAs can maximize muscle growth, decrease post-workout muscle soreness, enhance mental focus, and more. But recent studies indicate that when it comes to using amino acid supplements to enhance muscle protein synthesis (the building of muscle protein), there may be a much more effective option.

Before exploring the relationships between resistance exercise, amino acid supplements, and muscle protein turnover, let’s get clear on some of the basic terminology.

Resistance Training, Defined

Resistance training can take many forms. You can lift weights to build muscles, or use the machines at the gym, or even use your own body weight in resistance exercises such as planks and pull-ups. If you’re curious about resistance training but not sure where to begin, I recommend checking out this post.

Research links resistance exercise to a wealth of benefits, including better joint function, increased bone density, and enhanced muscle, tendon, and ligament strength.

To get the best results from any exercise program, including resistance training, it’s vital to provide your body with the fuel it needs to power through workouts and recover in between sessions. Increasing muscle strength and mass requires close interaction between exercise and daily diet.

Protein is, hands down, the most important nutrient for anyone engaged in a regular resistance exercise training program. Protein contains amino acids, which are the building blocks of your muscle tissue. Even if you make sure to prioritize protein intake at every meal, you can still amplify your anabolic response via amino acid ingestion. In the most basic terms, taking amino acid supplements promotes muscle protein synthesis (sometimes abbreviated to MPS response) and can help your body build the most muscle in the shortest amount of time.

Understanding the Role of Amino Acids

In technical terms, amino acids can be defined as simple organic compounds that contain a carboxyl (-COOH) and an amino (-NH2) group. When these compounds link together, they form protein molecules. And it is those protein macromolecules that make up your muscles.

Your body needs 20 different amino acids to produce protein. Scientists categorized nine of these as essential amino acids.

Key Facts About EAA Supplements and Resistance Exercise

Your body absolutely requires these nine amino acids not only to produce protein but also to carry out basic bodily functions that keep you alive. However, it cannot make them. Instead, they must be obtained from the food you eat. Anyone seeking to optimize her physical performance and muscle growth should review this list below outlining some of the important roles the essential amino acids play:

  1. Leucine: Many bodybuilders and athletes sing the praises of leucine supplementation—and for good reasons. One of the three branched-chain amino acids (BCAAs), leucine plays a significant role in muscle anabolism. It also activates mTORC1 (more on what that means later).
  2. Lysine: This amino acid contributes to muscle growth as well as tissue repair and nutrient uptake throughout the body. Lysine is the second most abundant protein found in human muscle tissue.
  3. Valine: Another of the three BCAAs, valine promotes muscle growth and tissue repair. Studies show that valine can have significant anabolic effects.
  4. Isoleucine: The third BCAA, isoleucine makes major contributions to hemoglobin synthesis as well as the regulation of energy and blood sugar levels. Isoleucine also speeds recovery, decreasing the time needed to repair post-exercise muscle damage.
  5. Threonine: Best known for keeping your muscles and connective tissues strong and limber, threonine also contributes to muscle protein synthesis. Plus, it can speed healing and help you bounce back faster from injuries.
  6. Phenylalanine: Adequate levels of phenylalanine are crucial for the structure and function of a vast number of proteins and enzymes. One of this amino acid’s most notable functions is as a precursor to another amino acid, tyrosine, which your body converts into a number of brain chemicals including dopamine, epinephrine, and norepinephrine.
  7. Methionine: Your body needs methionine in order to carry out tissue repairs as well as to generate new tissue. Without methionine, the synthesis of protein cannot begin. Methionine also spurs the formation of collagen and cartilage.
  8. Histidine: Another of the amino acids involved in muscle anabolism, histidine combines with beta-alanine to form the dipeptide carnosine, which improves your performance during high-intensity exercise. Histidine is also involved in the synthesis of hemoglobin as well as tissue repair.
  9. Tryptophan: This amino acid maintains the balance between protein synthesis and breakdown in adults. And like phenylalanine, tryptophan is a precursor for important brain chemicals—in this case, serotonin and melatonin.

Amino Acids Flip the Switch for Muscle Growth

After you’ve considered the list of the ways the essential amino acids contribute to muscle protein turnover, you will hopefully have grasped a key fact: BCAAs are not the only amino acids involved in muscle growth and repair. So when it comes to amino acid supplementation for sports nutrition purposes, taking a BCAA supplement simply doesn’t make sense.

Over the course of the 3 decades I have spent conducting NIH-funded research on muscle metabolism, I have garnered extensive data on how the muscles of the human body maintain themselves. The protein in your muscles continually break themselves down and rebuild themselves. In order to do this, they need a steady supply of all 20 of the amino acids involved in muscle protein turnover.

In order for muscle protein synthesis to begin, you must provide your body with one of the organic compounds that flip the “on switch.” Research indicates that leucine, an EAA and BCAA, may just be the most potent activator of the MPS response.

As I mentioned above, leucine supplementation activates the mTORC1, or the mammalian target of rapamycin complex 1, thereby flipping the switch that turns on muscle protein synthesis. Scientists have found that leucine supplementation on its own requires a protein dose containing between 2.5 and 3 grams of protein in order to activate mTORC1. However, when individuals consume leucine in combination with the other eight essential amino acids, the required dose drops to 1.8 grams of leucine.

The mTORC1 pathway controls both anabolic and catabolic signaling of skeletal muscle mass, meaning it regulates both muscle growth and muscle tissue breakdown. Research has shown that pairing resistance exercise with essential amino acid supplementation has an additive effect when it comes to stimulating muscle protein synthesis via the mTORC1 pathway.

In other words, taking essential amino acids maximizes the hard work you put in during your training sessions and makes it easier for you to gain muscle.

How EAA Supplements Amplify the Benefits of Resistance Exercise

Resistance exercise stimulates muscle protein turnover. Muscle protein turnover is the balance between how much muscle protein is broken down and how much muscle protein is built back up. This is how muscle fiber function improves. Newer, better functioning fibers are synthesized to replace older ones that are not functioning as well. Both muscle protein breakdown and muscle protein synthesis are stimulated.

Since resistance exercise increases the efficiency of muscle protein synthesis, the increase in synthesis will be slightly greater than the increase in breakdown. The stimulation of protein synthesis is limited, however, because some of the essential amino acids released by protein breakdown are oxidized and not available to be reused for synthesis. Thus, even though the muscle is able to produce new protein more efficiently during resistance exercise, the balance between muscle protein synthesis and breakdown remains negative (i.e., net loss of muscle protein) in the absence of nutrient intake.

Therefore, performing resistance exercise in a fasted state does not result in a positive muscle protein balance. To tip the balance in favor of muscle building, you must consume essential amino acids to replace those oxidized while exercising.

If you’re simply looking to increase muscle strength, then you only need to consume EAAs. But, if increasing muscle strength and muscle mass is your goal, you need to eat extra calories in addition to EAAs. You can tailor your nutrition to your resistance-exercise goals—mass, strength, or both—by adjusting your EAA and extra calorie intake.

Together They Are Stronger

As I mentioned briefly earlier, there is an interactive effect between resistance exercise and EAAs. Both stimulate muscle protein synthesis, and the combined effect is greater than either of their individual effects.

Essentially, resistance exercise primes the muscle to produce protein at an accelerated rate, but muscle protein synthesis is limited by the availability of essential amino acids in the fasted state. With targeted supplement support, you can go from fasted to full of free essential amino acids ready and waiting to be put to use. The ingested EAAs are rapidly consumed by the muscle, in part because blood flow to muscle is increased by resistance exercise, and in part because the molecular mechanisms in the muscle cells that regulate the rate of synthesis are turned on. The net result is that the major gain in muscle mass that occurs after resistance exercise is due to the combined effects of exercise and the increased availability of EAAs.

In my research, I have found that when EAAs were given before resistance exercise, muscle protein synthesis was stimulated more than when given after exercise, but the EAAs given after exercise still caused a significant stimulation.

Together, resistance exercise and EAAs can stimulate muscle protein synthesis greater than they can alone.

When Do I Take My EAA Supplements?

Unlike EAA supplementation for aerobic training, EAA supplementation during resistance training necessitates a before, during, and after approach that is customized according to your muscle and strength-building aims.

If an EAA supplement is ingested 30 minutes before resistance exercise, the muscle is put into a very anabolic state (where it is building up). If EAAs are consumed immediately after exercise there is also a stimulation of net muscle protein synthesis, but less so than if given before the workout.

So, you’ll want to take EAAs before a resistance workout to prevent the net breakdown of muscle protein during the workout. During resistance exercise, there’s an increase in blood flow to the muscle, and this increase can help deliver the ingested amino acids directly to the muscle for absorption. By increasing the blood concentrations of EAAs, the concentration gradients force EAAs into the muscle cells instead of out. Without EAA supplementation, the EAAs are forced out of the muscle.

Consuming EAAs after the workout will further stimulate protein synthesis and prolong the muscle-building response. The optimal approach is to take EAAs before and after resistance workouts, and throughout if possible.

Together, resistance exercise and EAAs can stimulate muscle protein synthesis greater than they can alone.

The Importance of Muscle Protein Synthesis

What is muscle protein synthesis and why is it so important? In this article, we’re going to explore this topic and uncover everything you need to know about this vital function.

Whether you’re a young athlete engaged in high-intensity physical activity or an older adult who thinks of exercise training as a weekend tangle with the weed wacker, your body relies on muscle protein synthesis. But what is muscle protein synthesis, and why is it so important? In this article, we’re going to explore this topic and uncover everything you need to know about this vital function.

What Is Muscle Protein Synthesis?

Muscle protein synthesis is the process whereby human skeletal muscle is built (protein anabolism). This so-called mixed muscle protein synthesis can be further broken down into myofibrillar protein synthesis, which refers to protein synthesis involving muscle fibers, and mitochondrial protein synthesis, which involves the synthesis of proteins necessary for energy production in muscle cells.

The muscle-building of protein synthesis is balanced by muscle breakdown (protein catabolism) in an ongoing process called protein metabolism. And the muscle protein turnover that results from the interaction between protein synthesis and breakdown is controlled by amino acids.

The Practical Handbook of Biochemistry and Molecular Biology lists more than 300 common amino acids, but only 20 of these are incorporated into the body’s proteins. These 20 amino acids—the building blocks of life—build human muscle by combining in long chains to create thousands of different proteins.

But because the entire body needs proteins to function, these same proteins—even those used in skeletal muscle protein synthesis—will eventually be broken down as they’re used by the cells.

Moreover, 11 of these 20 different amino acids are considered nonessential because they can be created by the body, but 9 are considered essential because they must be obtained from dietary sources.

The 11 nonessential amino acids are:

  • Alanine
  • Arginine
  • Asparagine
  • Aspartic acid
  • Cysteine
  • Glutamic acid
  • Glutamine
  • Glycine
  • Proline
  • Serine
  • Tyrosine

And the nine essential amino acids are:

  • Histidine
  • Isoleucine
  • Leucine
  • Lysine
  • Methionine
  • Phenylalanine
  • Threonine
  • Tryptophan
  • Valine

Amino acids are vital for helping to maintain the body’s protein balance as it moves through the never-ending process of breaking down and synthesizing new proteins. But muscle protein synthesis rates must remain in balance with rates of breakdown or more muscle will be lost than created.

This feat is accomplished by ensuring a steady supply of all 20 amino acids. And because the nonessential amino acids can be created by the body—and also make up at least 50% to 60% of most dietary proteins—we generally consume more than enough of these amino acids via the foods we eat.

However, because we must obtain essential amino acids from food, diets lacking in high-quality protein sources can limit the supply of necessary amino acids.

To avoid a situation in which our bodies don’t have enough essential amino acids to keep protein synthesis and breakdown in balance, we must be sure we’re getting plenty of high-quality protein sources in our diet.

12 Top Sources of Essential Amino Acids

Amino Acids and Muscles

The body’s main reservoir of protein is muscle tissue, so if we’re not giving our bodies the fuel they need—and if we’re not engaging in regular resistance exercise, which has been shown to increase the response of muscle protein synthesis—one of the first areas we may notice the imbalance is in our muscles.

In other words, without the amino acids the body needs for muscle tissue growth, maintenance, and repair, both muscle mass and muscle strength will be lost and exercise performance—and even basic functioning—will suffer.

Let’s break this down and see why amino acids are so important for muscle health.

As we stated earlier, if the balance between protein synthesis and breakdown is tilted in favor of protein breakdown, the amount of protein in the body will decrease.

For muscles, less protein being synthesized means less muscle growth (muscle hypertrophy) and more muscle breakdown. And because muscles are the body’s main reservoir of amino acids, if the daily intake of amino acids can’t keep up with the demands of protein synthesis, the muscles will actually release some of their amino acids for use by other parts of the body.

Over time, this emphasis on protein degradation instead of protein synthesis can have implications that go far beyond simple losses in exercise performance.

In fact, excessive muscle wasting can cause a cascade of negative reactions that may first be noticeable as changes in body composition but can eventually affect everything from wound healing to heart function. And in older adults, loss of muscle tissue can lead to a more serious condition called sarcopenia, which can have life-threatening consequences in the face of serious illness, injury, or surgery.

What the Research Has to Say

A number of studies can help us illustrate the various ways muscle protein synthesis may be affected by age, exercise, and nutritional status.

For example, researchers including M. Drummond, B. Pennings, and B. Rasmussen conducted a study in 2008, published in the Journal of Applied Physiology (J Appl Physiol), that compared anabolic signaling in both young and elderly men. And they found that the activation of mammalian target of rapamycin (mTOR)—a key initiator of the MPS response (muscle protein synthesis)—occurs faster in young men after both resistance exercise and ingestion of essential amino acids.

Similarly, the authors (V. Kumar, P. Atherton, K. Smith, and M. Rennie) of another study from 2009, published in the same journal, found that the muscle protein synthetic response decreases even further in older women—a finding also noted in a 2019 study conducted by J. Trommelen, M. Betz, and L. van Loon, published in Sports Medicine (Sports Med).

Both of these studies back up an earlier study from 2005, conducted by researchers including C. Katsanos, M. Sheffield-Moore, A. Aarsland, and R. Wolfe and published in the American Journal of Clinical Nutrition (Am J Clin Nutr), which found that the anabolic response to dietary protein decreases with age.

And a 2013 study conducted by researchers including L. Breen and T. Churchward-Venne, published in the Journal of Clinical Endocrinology and Metabolism (J Clin Endocrinol Metab), found that as little as 14 days of reduced activity can induce a state of anabolic resistance in even healthy elderly adults.

In addition, a 2008 study by researchers that included D. Moore, M. Tarnopolsky, and S. Phillips, also published in the American Journal of Clinical Nutrition, demonstrated that 20 grams of intact protein—the whole protein found in food sources, with its strings of individual amino acids connected to one another—was needed to achieve the maximum protein dose response after resistance exercise.

And a 1997 study by researchers G. Biolo, K. Tipton, S. Klein, and R. Wolfe, published in the American Journal of Physiology (Am J Physiol), found that the effect of amino acids on muscle protein synthesis was enhanced by prior exercise—a finding that was thought to be due in part to increased blood flow.

Finally, a number of studies have found that ingestion of whey protein results in a rapid but short-lived postprandial increase in amino acid concentrations in the blood, while casein protein is more slowly digested and results in a more moderate and prolonged postprandial increase.

Whey protein also tends to stimulate muscle protein synthesis to a greater extent than both casein and its predigested form, casein hydrolysate—a fact that’s been attributed to (among other factors) the higher leucine content in whey protein.

Branched-Chain Amino Acids

To correct imbalances in muscle protein turnover and shift the focus heavily toward muscle protein synthesis, the world of bodybuilders and endurance athletes has long been interested in the benefits of branched-chain amino acids, or BCAAs.

The BCAAs—leucine, isoleucine, and valine—are touted by fitness junkies for their ability to preserve muscle stores of glycogen (the primary fuel used by muscles during exercise), minimize protein breakdown during exercise, and reduce post-exercise muscle soreness and muscle recovery.

On the face of it, this sounds great.

However, as we’ve learned, muscle protein synthesis involves all 20 amino acids working together—linking together—in specific ways to build the protein our bodies need. And if any essential amino acid is in short supply—the so-called limiting amino acid—protein synthesis will stop as soon as its supply has been exhausted.

Because making a complete protein requires sufficient quantities of each of the 20 amino acids, there’s no single best amino acid or group of amino acids for optimal muscle growth and muscle repair, as the body needs a balanced supply of all of them to produce protein.

However, essential amino acid supplements that emphasize specific amino acids to target specific areas—while also supplying a balanced supply of every other essential amino acid—can still be helpful.

Muscle Must-Knows

The Importance of Protein Synthesis for Tissues and Organs

Amino acids are known as the building blocks of life because the proteins they create are involved in almost every biochemical process that occurs inside the body—which means that protein synthesis is important not just for skeletal muscle but for whole-body health as well.

Every organ undergoes protein synthesis. Muscle protein synthesis simply refers specifically to the building of new muscle protein. However, the body’s various tissues and organs depend on the process of muscle protein synthesis as well.

Tissues and organs are able to sustain a balance between protein synthesis and breakdown—even if protein ingestion doesn’t occur in sufficient quantities—because they can draw from amino acids circulating in the blood.

These amino acids are released into the bloodstream during muscle protein breakdown and held at stable levels so the body’s tissues and organs can take them up as needed—whether for fighting infections, repairing wounds, controlling vascular function, balancing metabolic processes, or any number of other tasks.

What’s more, muscle is the only tissue in the body that can lose some of its mass without negatively impacting health. However, in the absence of dietary protein intake, the result of this catabolic response is a net loss of skeletal muscle.

But when you again ingest dietary protein, the situation is reversed, creating an anabolic response in muscle tissue whereby dietary amino acids are absorbed and sufficient skeletal muscle protein is produced to offset the muscle protein lost during the postabsorptive state (when the gastrointestinal tract is empty and energy comes from the breakdown of the body’s reserves).

The importance of muscle as a source of amino acids in the blood, in the absence of dietary intake, can be illustrated by the Irish Republican Army (IRA) hunger strike that took place in 1981, when a number of protestors starved themselves to death while imprisoned in Northern Ireland.

During the strike, the protestors requested that samples of their blood be taken daily so that some medical benefit might also be derived from their sacrifice. All of the protestors were of normal weight at the outset of the strike, and they remained in reasonably good health throughout, with normal blood concentrations of amino acids.

However, when their muscle mass eventually became so depleted that insufficient amino acids were left to sustain normal blood concentrations, it served as a signal that death was imminent. For most of the protestors, this wasting process took an average of 60 days.

By contrast, morbidly obese people generally have both increased fat mass and increased muscle mass (with associated greater stores of amino acids)—so much so that there are documented cases of obese individuals surviving for more than a year on only micronutrients (vitamins and minerals) and water.

While these examples depict extreme circumstances, they clearly highlight the central role of muscle mass in maintaining normal amino acid availability during periods in which nutrients from food are not being absorbed.

They also illustrate the importance of dietary amino acids for maintaining muscle protein and overall health and offer graphic proof that the optimal diet is one that emphasizes both protein and amino acid nutrition, regardless of whether the individual engages in regular resistance training or is a sedentary person and unconcerned about physical function.