BCAAs and Life Extension

The branched-chain amino acids consist of three essential amino acids: leucine, isoleucine and valine. BCAAs are often referred to as the “muscle aminos” because unlike other amino acids they undergo extensive metabolism in muscle tissue. Indeed, 14 to 18 percent of the total muscle content of amino acids is BCAAs.

Of all the essential amino acids, the BCAAs are the most linked to muscle protein synthesis—especially leucine. They’re considered “essential” because they must be supplied in the diet, whereas other, “nonessential” aminos can be synthesized in the body from other substances, including other amino acids. Recent work has shown that the essential amino acids play the primary role in boosting muscle protein synthesis. In fact, a mere six grams of essential aminos taken after a workout are sufficient to stimulate muscle protein synthesis.

The BCAAs are also involved in energy production. When the body’s energy needs increase in the absence of other energy-yielding nutrients, such as carbohydrates and fats, mechanisms come into play that lead to a breakdown of BCAAs in muscle. Then off they go to the liver and are converted to glucose. BCAAs support immune function, reduce fatigue, encourage fat burning and help reduce post-training muscle soreness. Intense exercise hastens BCAA breakdown, which has led some scientists to suggest that those who regularly engage in intense exercise may need more BCAAs than others.

BCAAs are anabolic in that they stimulate a substance called mTOR, which plays a pivotal role in muscle protein synthesis. When mTOR is stimulated, other so-called “downstream” proteins—such as p70 S6 kinase, 4E-BP1 and ERK 1—are turned on and collectively help generate muscle growth. Some studies suggest that BCAAs may be involved in the release of growth hormone as well as testosterone, creating more anabolic impact on muscle. When bodybuilders take a dose of five grams of BCAAs before a workout, they show elevated testosterone compared to those who get a placebo and use the same training routine.

No doubt those factors figure into research findings that BCAAs help prevent muscle breakdown following exercise, an effect that can last five days. BCAAs also boost exercise endurance by helping reduce lactate produced during intense exercise.

A very recent study of BCAAs’ health effects has uncovered still another possible benefit.¹ Middle-aged mice were given a BCAA supplement. Researchers wanted to know whether getting BCAAs would affect the rodents’ longevity. Back in 2008 researchers had found that adding a BCAA mixture to yeast significantly extended its longevity. So the newer study was designed to see whether they would do the same for mammals. After three months researchers observed several beneficial changes in the mice consistent with life extension.

To understand how that occurred, you need to know a bit about negative changes that happen in cells with passing years. An emerging theory holds that a major cause of aging is deterioration of mitochondria, cigar-shaped organelles that are the power plants of cells and the site of energy production. Mitochondria are also the site of fat burning, and one effect of exercise, particularly aerobic exercise, is to increase their number in cells. That permits not only more efficient use of oxygen in cells but also a higher degree of fat burning. In short, the more mitochondria you have, the more fat you burn. Obese people who don’t exercise show defects in mitochondrial function, which is one reason exercise is so vital for efficient bodyfat reduction.

Since oxygen is so heavily involved in mitochondrial energy, however, there is a price to pay. The high oxygen use in mitochondria also produces by-products called reactive oxygen species, a.k.a. free radicals, which can damage cell membranes, eventually compromising cellular integrity and leading to cell death. That’s another theory of aging—that free radicals increase with age and result in cell death. The body deals with them by way of a built-in antioxidant defense system consisting of a number of enzymes that is buttressed when you eat foods high in antioxidant nutrients. With age your natural antioxidant network diminishes, resulting in out-of-control free-radical production that damages cells in general and mitochondria in particular. Result: You age.

When mitochondria die, it’s as if the power to the cell has been turned off, and when enough mitochondria disappear, the cell undergoes a process called apoptosis, or cell suicide. The mitochondrial theory of aging states that if you can preserve mitochondria with age, you will live longer and be healthier. One way to do that is to reduce your calories by about 30 percent. That increases the production of PGC-1A, a substance that regulates and increases the number of cellular mitochondria as well as free-radical activity. Calorie restriction boosts another protein called SIRT-1, which is linked to extended longevity through upregulation of certain genes. A lesser-known effect of calorie restriction is that it helps the body maintain production of nitric oxide, which provides a number of benefits, among them controlling blood pressure and hormone release.

While calorie restriction probably does increase longevity, it’s too hard for most people to swallow—literally—for very long. Besides, one by-product of calorie restriction is the significant reduction of all anabolic hormones—not exactly great news if you’re interested in increasing muscle size and strength. So scientists have searched for substances that may mimic the health benefits of calorie restriction. According to the mouse study, BCAAs may be one answer.

The middle-aged mice that got BCAA supplements experienced increased production of mitochondria as well as elevated SIRT-1. The supplement also increased the expression of genes involved in antioxidant defense, which resulted in marked reduction of free radicals in the heart and skeletal muscles of the mice. There was upregulation of nitric oxide production and an increase in PGC-1a, which controls mitochondrial synthesis. Recent studies have suggested that taking antioxidants after exercise prevents some of the benefits of exercise, such as increased insulin sensitivity, from kicking in. That was traced to an antioxidant-induced blunting of the production of PGC-1a and SIRT-1. The mouse study, however, showed that taking BCAAs boosts both substances and thus may be an antidote to the antioxidant conundrum. It also helps explain why bodybuilders, known to get large amounts of BCAAs from both supplements and whey protein, which is 26 percent BCAAs, show no negative effects from taking antioxidants.

The primary way that BCAAs support muscle protein synthesis is by activating mTOR, which is associated with increased cellular oxidative capacity. The authors suggest that the stimulation of mTOR by BCAAs also boosts the nitric oxide system, which plays a role in increasing mitochondria in cells. What’s confusing about that is that other studies suggest that decreased mTOR activity is linked to decreased aging in the body. That’s based on the finding that a drug called rapamycin, which inhibits mTOR (“TOR” stands for “target of rapamycin”) extended the life span of middle-aged mice. Well, so do BCAAs—which support mTOR! Besides, rapamycin is a potent inhibitor of immune response, which opens the door to cancer and other diseases. That would hardly be conducive to human survival.

Since BCAAs also support the activity of SIRT-1, however, it’s a good bet that they’re good for longevity. Other substances known to activate SIRT-1, such as resveratrol, appear to support bodily changes associated with longevity in animal studies, although no human studies have yet shown that effect. Moreover, the resveratrol animal studies show that it helps increase life span in mice that are on a diet containing 60 percent fat. Human studies have found that BCAAs, when combined with weight training, may effectively block sarcopenia, which is the excessive loss of muscle with age that occurs as the body heads for its final decline. BCAAs also reduce inflammatory markers in humans who have heart failure. Increased inflammation is a cornerstone of most degenerative disease linked to aging, including heart failure and Alzheimer’s disease. Meanwhile, the major cause of muscle aging linked to loss of muscle size, endurance and strength with age is the loss of mitochondria in muscle. The implication: that BCAAs, by working with nitric oxide to increase mitochondria in muscle, may help preserve muscle as you age.

—Jerry Brainum

 

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¹ D’Antona, G., et al. (2010). Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metabol. 12:362-372.