Nutrient activation takes place when one nutrient helps another nutrient perform its job more efficiently. More exactly, nutrient activation is a process by which the biological effects of a certain nutrient are influenced through direct or indirect interaction with one or more other nutrients. This is a key concept in the Nutrient Timing System.
As you’ve learned, muscle recovery and growth occur fastest when the right nutrients are consumed at the right times in relation to training. That’s simple enough, but it’s also important to understand how these various nutrients interact to promote muscle growth. This chapter discusses the key nutrient activators and their potential benefits to the body when taken at the right time. It also alerts you to the questionable activators—supplements you might be taking to enhance your performance that just might not work the way they are purported to.
NUTRIENT ACTIVATORS
Most strength athletes think of nutrients in terms of their direct effects not in terms of their indirect effects. For example, they think of protein as the constituent that muscles are made of, but they don’t think of protein as a nutrient that can enhance muscle glycogen storage by stimulating insulin (protein as activator). Let’s take a look at the important nutrient activators that can cooperate to maximize the rate at which proteins become biologically active components of your growing muscles.
Carbohydrate
The most important nutrient activator in relation to protein is carbohydrate. This connection is mediated through insulin, which is strongly stimulated by the consumption of carbohydrate. Insulin not only stimulates the transport of amino acids into the muscle, but also activates key elements of the protein synthetic machinery. The manner in which amino acids activate protein synthesis is different from the manner in which insulin does, so their effects on protein synthesis become additive. Insulin also helps decrease protein degradation, which is important for tipping the protein turnover balance toward net protein accretion (an increase in the protein concentration within the muscle). So, in order to get greater protein synthesis, you need to consume carbohydrate along with your protein drink during the Anabolic and Growth phases. For example, researchers have shown that a combined protein/carbohydrate supplement taken after exercise results in a 38 percent faster rate of protein synthesis as a protein supplement without carbohydrate. It is therefore fair to say that the path to greater protein synthesis and ultimately to muscle development is traveled quicker when carbohydrate is consumed with protein.
Protein
Just as carbohydrate activates protein, protein is able to work with carbohydrate to activate certain metabolic processes, which include muscle glucose uptake and glycogen storage. As mentioned, one effect of combined carbohydrate/protein supplementation is a greater insulin response. Protein alone has only a small effect on blood insulin levels. However, when protein is combined with carbohydrate, the insulin response is greater than that produced by either carbohydrate or protein alone.
Insulin is, as we’ve seen, a strong activator of muscle glucose uptake and glycogen synthesis. However, the nutrient activation caused by protein is not due solely to a greater insulin response. Certain amino acids such as leucine and isoleucine can activate muscle glucose uptake and glycogen storage through insulin-independent pathways. Thus, the addition of protein to a carbohydrate supplement can greatly increase the rate of muscle glycogen synthesis. In research studies, the addition of protein to a carbohydrate supplement has been shown to increase glycogen storage by 40 to 100 percent during the early hours of postworkout recovery.
Amino Acids
Amino acids are a broad class of structurally similar biochemical compounds that serve as the building blocks of protein. As parts of a protein molecule, they are linked together by peptide bonds. Thousands of amino acids can be linked to form proteins involved in cell structure (membranes), cell function (actin and myosin), or energy production (myosin ATPase). In addition, amino acids can function as biochemical messengers and as intermediates in metabolism. Three amino acids in particular are important nutrient activators in NTS: arginine, glutamine, and leucine.
ARGININE
Arginine is important in helping the muscles to manufacture other amino acids. In addition, arginine is an excellent stimulator of insulin and therefore has the ability to enhance carbohydrate metabolism.
Another beneficial characteristic of arginine is its ability to increase blood flow. When blood vessels are expanded (or dilated), greater blood flow is possible. This is particularly important during exercise and recovery from exercise, because at these times muscles need greater amounts of oxygen and nutrients and there is also a greater need to remove metabolic byproducts such as carbon dioxide and lactic acid. An essential regulator of vasodilation is nitric oxide (NO). The production of NO requires arginine, which serves as a precursor for NO formation. Arginine supplementation has been shown to stimulate the NO system. A number of arginine supplements are now sold as circulation boosters. There is, however, a downside to supplementing with this amino acid: consuming arginine in large amounts (greater than 10 grams) can cause gastrointestinal distress.
GLUTAMINE
Glutamine is the most abundant amino acid in the blood and muscle cells. It comprises more than 60 percent of the free amino acid pool in muscle tissue. Glutamine is also the most nitrogen-rich amino acid, supplying 35 percent of the nitrogen that muscle cells use to synthesize proteins.
Glutamine is considered to be a “conditionally essential” amino acid because, although the body can synthesize it, there are times when the body’s high demand for glutamine exceeds its glutamine stores and manufacturing efforts. Several kinds of stress can dramatically increase the body’s glutamine needs. Strenuous exercise, injuries, and illnesses are the main ones.
In addition to promoting protein synthesis, glutamine, by helping to maintain a positive nitrogen balance in muscle tissue, also prevents protein breakdown, which is equally important when it comes to building muscle.
At one time it was believed that carbohydrate provided all of the necessary nutrition to support immune system function. It is now well documented that glutamine is also an important nutrient for cells of the immune system. During prolonged exercise, glutamine levels are depleted. Within twenty-four hours, glutamine levels usually return to normal, assuming the athlete is consuming a healthy diet. However, in athletes who train intensively, glutamine levels may be chronically low. Because of the relationship between glutamine and immune system function, these athletes may be more susceptible to upper respiratory tract infections. One study reported that 73 percent of athletes with infection had glutamine levels below normal. This suggests that athletes who train intensively would benefit from glutamine supplementation. Researchers have demonstrated that supplementation could increase baseline levels of glutamine. It has also been demonstrated that when protein is taken following exercise, the normal drop in glutamine can be prevented.
Recent research suggests that glutamine may also promote protein synthesis by activating metabolic pathways through cell volumization (hydration of cells). Protein synthesis proceeds more quickly when muscle fibers are enlarged or swollen. Glutamine draws water and salt into muscle cells, thereby expediting protein synthesis.
Finally, glutamine can also promote the storage of glycogen. In a study by Bowtell and colleagues from the University of Dundee, Scotland, groups of six subjects each cycled until exhausted and were then given either a carbohydrate supplement, a glutamine supplement, or a carbohydrate/glutamine supplement. Although the carbohydrate/glutamine supplement did not promote more muscle glycogen storage than the carbohydrate supplement, it was more effective in increasing the liver glycogen stores.
Studies have shown that a minimum of 2 grams of glutamine is needed to increase plasma growth hormone levels. An 8-gram dose has been demonstrated to be effective in promoting glycogen resynthesis. Because of glutamine’s role in supporting the immune system and postexercise muscle recovery, it should be a standard part of a postexercise meal.
Studies have shown that short- and long-term glutamine supplementation is safe in humans. Oral doses of glutamine as high as 0.3 grams per kilogram of body weight have been administered with no evidence of toxicity.
BRANCHED-CHAIN AMINO ACIDS (BCAAS)
Leucine, isoleucine, and valine are three special amino acids known as the branched-chain amino acids (BCAAs). They serve as precursors for the synthesis of glutamine and alanine, two amino acids that are used up rapidly and in large quantities during intense exercise. Isoleucine and valine are used as a direct source of energy during exercise. Ingestion of BCAAs during exercise not only provides needed energy but may also prevent muscle protein breakdown, resulting in faster postworkout recovery.
In one study, Coombes and McNaughton had two groups of subjects exercise for two hours on a stationary bicycle. One group had taken a daily BCAA supplement for the preceding fourteen days, while the second group had received a placebo. In both groups, biomarkers of muscle damage were elevated from four hours to five days after cycling. However, this indication of muscle damage was substantially lower in the BCAA group.
Leucine in particular is one of the most potent nutrient activators in relation to muscle growth. Leucine is not just used as a building block for muscle proteins, but it can also help amplify muscle protein synthesis. First, it can increase blood insulin levels by stimulating the release of insulin from the pancreas. Second, it can work cooperatively with insulin to initiate protein synthesis. Insulin serves to activate the signal pathway, while leucine enhances the signal for protein synthesis at the level of peptide initiation (translation). This effect is particularly pronounced after exercise, when the muscle cells exhibit increased insulin sensitivity. Some research also suggests that leucine is able to stimulate both muscle protein synthesis and glucose uptake through another insulin-independent mechanism.
Creatine
Creatine is the most popular muscle-building nutritional supplement. In the early 1990s, creatine exploded in popularity among athletes in strength and speed sports when research demonstrated that creatine supplementation could increase the strength and muscle mass gains associated with resistance training.
Creatine is necessary for the production of creatine phosphate (CP), the high-energy phosphate compound stored in the muscles and responsible for the rapid resynthesis of ATP. Creatine can be manufactured from its constituent amino acids in the liver and through dietary consumption of creatine, which is found in animal foods such as beef. Creatine supplementation can significantly increase the amount of creatine that is stored in the muscles and thereby increase CP stores.
Many studies have demonstrated that creatine supplementation will enhance training-induced gains in muscle strength and mass. For example, in a study conducted by Vandenberghe and colleagues, subjects were placed on creatine or placebo throughout a ten-week strength- training program. Compared with placebo, maximal strength was increased by 20 to 25 percent and muscle mass by 60 percent with creatine supplementation. Also, Kreider and colleagues reported that college football players who supplemented with creatine and glucose during twenty-eight days of conditioning had greater gains in body weight, muscle mass, and strength compared with players who received a placebo.
Three different mechanisms have been hypothesized to explain how creatine increases muscle mass and strength. The first is that an increase in CP directly stimulates protein synthesis. The second is that an increase in total muscle creatine draws water into the muscle fiber, causing it to swell, and the swelling then stimulates protein synthesis. The third is that high levels of intramuscular creatine slow the use of ATP during exercise and speeds the recovery of CP. This allows for a harder workout and thus a greater stimulus for protein synthesis.
Most of the studies have utilized a brief loading phase, which is 20 grams per day (4 doses of 5 grams each consumed over the day) for five to seven days. This should increase your skeletal muscles’ creatine and CP levels. A maintenance dose of 2.5-5 grams per day should be enough to maintain skeletal muscle creatine and CP levels. Stout and colleagues have shown that the addition of carbohydrate can augment intramuscular creatine, CP, and total creatine levels. A serving of 36 grams of carbohydrate with 5 grams of creatine will improve performance more than creatine alone. However, many athletes often use lower levels of carbohydrate mixed with creatine with good results.
Caffeine
For decades, athletes of all kinds have used the stimulant caffeine—sometimes referred to as the world’s most popular drug—to enhance performance. The popularity of caffeine as a performance aid started to rise more than twenty-five years ago when Dr. David Costill of Ball State University reported that caffeine could improve endurance performance. The improvement was thought to be due to caffeine’s ability to increase fat oxidation and spare the use of muscle glycogen. While this is still a possible explanation, recent research suggests that caffeine may also delay fatigue by reducing the athlete’s perception of effort. Laurent and colleagues found that caffeine increased the concentration of hormone-like substances in the brain called ß-endorphins during exercise. The endorphins affect mood state, reduce perception of pain, and create a sense of well-being.
Caffeine has also been found to delay fatigue during exercise by blocking adenosine receptors. Adenosine is produced during exercise and inhibits the release of the brain neurotransmitter dopamine. Decreases in dopamine, along with increases in serotonin, another brain neurotransmitter have been linked to central nervous system fatigue during exercise. A decrease in the dopamine-serotonin ratio has been shown to reduce arousal, induce sleep, and suppress spontaneous activity of animals.
Caffeine has also been popular among strength athletes because of its metabolic and central nervous system effects. Because caffeine increases fat breakdown and oxidation during exercise, strength athletes have used caffeine to lower body-fat content. In addition, they have used caffeine to increase workout intensity because of its ability to increase arousal and reduce perception of effort. However, caffeine is a weak stimulant and has not been found to acutely increase muscle strength or to have a significant effect on body-fat content.
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