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By Robert M. Hackman, Ph.D.
Research unravels an amino acid's intricate link to physical fitness
A proliferation of new studies about the amino acid glutamine is making its way into scientific journals, and for good reason. Our understanding of glutamine is turning topsy-turvy as scientists uncover its many unique and powerful roles--from enhancing muscle growth and neutralizing excess body acid to losing weight and combating the effects of aging
Amino acids are the building blocks that form body and dietary proteins. Twenty-two different amino acids occur in nature and have traditionally been grouped into two categories--nonessential and essential. Nonessential amino acids are made by the liver from general dietary protein intake and don't have to be consumed directly. In contrast, essential amino acids cannot be made "from scratch" by the liver and therefore must come from diet or supplements to meet the body's daily demands.
Glutamine has traditionally been considered a "nonessential" amino acid, but current research suggests that it may be "conditionally essential" under certain metabolic conditions such as exercise.
Exercise And Muscle Mass During strenuous exercise the need for glutamine appears to increase beyond the level ordinarily made in the liver. Recent research findings illustrate the dramatic effect exertion has on the body's glutamine reserves. Seven healthy athletes doing intensive anaerobic exercise (a single short-distance sprint) showed a 45 percent drop in plasma glutamine compared to their pre-exercise levels. When the same athletes did intensive aerobic exercise (10 days of long-distance running), their plasma glutamine dropped 50 percent.1 Some runners still had depressed glutamine levels even six days after recovering from the aerobic program, suggesting that they needed more glutamine than their diets provided.
These findings are especially important to athletes, as glutamine is essential to muscle growth. It may help reduce the rate of muscle breakdown (anticatabolic) relative to the rate of muscle growth (anabolic)2 and increase concentrations of plasma arginine and glutamate, two amino acids linked to muscle-strengthening growth hormone.
In another study, nine healthy volunteers ages 32 to 64 were given either a beverage containing 2 g of glutamine or a placebo drink. During the next 90 minutes, blood samples were collected and measured for bicarbonate and plasma growth hormone--two substances stimulated by glutamine. Subjects who consumed supplemental glutamine showed significant increases in glutamine (12 percent to 19 percent above presupplement values), bicarbonate (12 percent) and growth hormone (up to 430 percent), whereas those drinking the placebo beverage showed no changes.3
Bicarbonate is one of the body's primary base buffers and helps to deactivate excess blood acids such as ammonia or urea that are generated during heavy anaerobic exercises like weight training or sprinting. In addition to stimulating the production of bicarbonate, glutamine itself acts as a buffer--its negative charge negates the net positive charge of an acid. Without this neutralization, blood acids and muscle acid (e.g., lactic acid) might accumulate, leading to fatigue and muscle soreness.
During strenuous exercise, however, the liver may not be able to produce enough glutamine to keep up with the amount of acid being generated by the body. New research suggests that glutamine supplements may provide additional buffering power when the acid/base balance becomes more acidic--enabling longer, harder workouts with less muscle soreness the next day.4
This study also showed that subjects taking a glutamine supplement had accelerated fat burning compared to those taking the placebo. No one exercised during the study period. Inducing the body to burn more fat while preserving muscle with growth hormone is one of the most effective, healthy ways to lose weight and keep it off. Of course, nothing replaces a well-balanced diet and regular exercise for weight management, but supplemental glutamine may direct the body's metabolism in a helpful direction. In addition, if a person exercises, even gently, glutamine may maximize the benefits and minimize the discomfort.
Considering all of these effects together, glutamine may have the potential to retard some of the effects of aging by preserving muscle mass and reducing fat accumulation. Its ability to boost growth hormone levels (up to 430 percent) is a case in point. Growth hormone helps build and strengthen muscles and clear acid from body fluids, but starting at age 30, its production declines. This decline is associated with muscle loss (muscle breakdown is accelerated under acid conditions), increased body fat and accelerated aging.5 Glutamine supplements may help stall such developments.
Insulin Resistance Supplemental glutamine was recently shown to reduce body weight and prevent high blood sugar and high insulin levels in mice fed a high-fat diet.6 The mice were genetically predisposed to become overweight and develop high blood-sugar levels when consuming a high-fat diet, but these unhealthy outcomes were essentially neutralized for the mice that had glutamine added to their food.
Increases in body fat and body weight and high blood sugar are thought to result from persistently high levels of insulin in the blood, a condition known as insulin resistance (see NSN, March 1996, for an article on insulin resistance). Insulin levels skyrocketed in the mice fed a high-fat diet without supplemental glutamine, while those fed the glutamine-supplemented diet showed normal insulin patterns.
Although this is only an animal trial, the potential ability of glutamine supplements to reduce insulin resistance is exciting. Insulin resistance is now estimated to occur in half of all obese people and is considered a major risk factor for heart disease, high blood pressure and diabetes. While it is premature to jump from animal studies to conclusions about humans, the research so far may suggest a safe, nutritional way to adjust metabolism and look and feel healthy.
Mental Energy Glutamine and other amino acids such as choline, tyrosine and phenylalanine are used by the brain and central nervous system (CNS) to make neurotransmitters--biochemical mediators that stimulate or reduce the brain's electrical impulses that translate into thoughts, sensations and emotions. Different neurotransmitters can also influence perceptions of energy or fatigue. Neurotransmitters appear to get metabolized, or "used up," as a normal part of body function. Heavy mental or physical stress may cause the CNS to metabolize more neurotransmitters, so whether depletion is caused by intensive concentration, a demanding job or exercise, full replenishment of these essential biochemicals is vital to keep the brain "tuned up."
Neurotransmitter production is thought to increase when the amino acids they are formed from are supplemented in the diet. If this is true for glutamine, nutritional strategies that replenish it may also boost perception of energy or help prevent mental fatigue.
Two final points are important for the glutamine story. First, too much glutamine may be counterproductive. In humans, more than two grams is likely to result in less growth hormone production, less bicarbonate buffer, and probably no further energy benefit. In fact, elevated doses may overstimulate brain neurotransmitters and be dangerous. So, while some glutamine may be beneficial, large amounts may be a waste of money and even harmful.
Secondly, most of the glutamine studies appearing in scientific journals are conducted with isolated cells or animals. More human clinical research is needed to fill in missing pieces of the glutamine puzzle. Nonetheless, glutamine's emerging picture is exciting and cause for optimism. It may become an essential supplement for consumers in years to come.
Robert M. Hackman, Ph.D., is executive director of the Center for Complementary and Alternative Medicine Research at the University of California, Davis, and associate professor of Nutrition at the University of Oregon. His research and teaching focus on sports nutrition, weight management and optimal human performance. Hackman is an international consultant to nutrition- and health-oriented companies and professional and Olympic athletes.
1. Keast, D., Arstein, D., et al. "Depression of plasma glutamine concentration after exercise stress and its possible influence on the immune system," Med J Aust, 162: 15-8, 1995.
2. MacLennan, P.A., Smith, K., et al. "Inhibition of protein breakdown by glutamine in perfused rat skeletal muscle," FEBS Lett, 257: 133-36, 1988.
3. Welbourne, T.C. "Increased plasma bicarbonate and growth hormone after an oral glutamine load," Am J Clin Nutr, 61: 1058-61, 1995.
4. Welbourne, T.C., & Joshi, S. "Interorgan glutamine metabolism during acidosis," Jnl Parent Ent Nutr, 14: 775-855, 1990.
5. Rudman, D., Kutner, M.H., et al. "Impaired growth hormone secretion in the adult population: Relation to age and adiposity," J Clin Invest, 67: 1361-69, 1981.
6. Opara, E.C., Petro A., et al. "L-glutamine supplementation of a high fat diet reduces body weight and attenuates hyperglycemia and hyperinsulinemia in C57BL/6J mice," J Nutr, 126: 273-79, 1996.
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