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Muscle-Science Roundup

Here we are moving into 2008. Wow. It seems like only yesterday that we were stocking our garages with protein powder in preparation for the Y2K apocalypse, which didn’t happen. Good thing, too, because it freed up our scientists to research building muscle and burning fat instead of how to destroy the computers that are bent on taking over planet Earth. The past year’s research is a good example, having produced a number of studies that can directly affect your results in those areas. Jerry Brainum, IM’s number-one science scribe, is responsible for digging up most of the important info you’re about to read, so get ready to make bigger and better gains in ’08. Let’s hit the lab.

1) Lighter Weight and More Tension Bring New Muscle Dimension

Twenty-four untrained young men were divided into three groups, each using a different style of training:

1) Low intensity (50 percent of one-rep max with slow movement and tonic force generation), taking three seconds each to raise and lower the weight, a one-second pause and no relaxing phase. This style involved lighter weights, with a high level of muscular tension.

2) High intensity (80 percent of one-rep max), taking one second to raise the weight and one second to lower it, with one second of rest between reps. It’s a conventional style of training for building muscle.

3) Low intensity with normal speed (same as 2).

The workout consisted of three sets, done three times a week for 12 weeks. The first two groups experienced significant muscle gains, with no gains in group 3. Group 1, using the sustained-tension technique, showed the greatest muscle oxygen deficit, suggesting that the localized drop in oxygen levels caused by greater sustained tension, even during lighter exercise, results in gains similar to what you get when you use heavier weights in the conventional training style.

The authors suggest that the gains in size and strength are due to a localized increase in hormonal signaling factors, such as lactate and protons, which encourage the release of growth hormone and insulinlike growth factor 1.

In addition, the lack of oxygen in the trained muscles leads to a heightened presence of free radicals. One of them is none other than nitric oxide, which stimulates the activity of muscle satellite cells—the basis of muscle growth.

Restricting blood flow to the muscle, known as occlusion, releases more NO because NO acts to dilate blood vessels in an effort to overcome the decreased blood flow.

While the training intensity was the same in groups 1 and 3, the muscle force generation was three times higher in group 1. The authors note, “Maintaining slow movement speed in both lifting and lowering actions may be necessary in order to achieve constant tension.”

Application: This study verifies the heavy/light training system that was popular in the presteroid era. At one workout go heavy, using lower reps and a controlled explosiveness; follow a few days later with a light “feel” workout, performing sets of 12 to 15 reps, each one lasting about five seconds. [For more on heavy/light training see Train, Eat, Grow, page 62.]

Tanimoto, M., et al. (2006). Effects of low-intensity resistance exercise with slow movement and tonic force generation on muscular function in young men. J App Physiol. 100:1150-1157.

2) Got Glutamine?

Recent research shows previously unrecognized effects of glutamine. For example, glutamine aides the activity of genes that produce heat shock proteins—special cell-protecting proteins that kick in under stressful conditions. They preserve cell function and prevent cell destruction due to uncontrolled stress. Without heat shock proteins, cells would die. Among substances known to interact with heat shock proteins in muscle are anabolic steroids.

Glutamine helps catabolic hospital patients by encouraging the synthesis of heat shock proteins, which enables them to survive and recover.1 A recent study showed that giving glutamine to isolated joint cells prevented their degeneration. The effect was traced to glutamine’s induction of heat shock proteins.2 The joint cells were exposed to heat stress, which is linked to joint inflammation and breakdown. A secondary joint-protecting effect involves the production of glucosamine and glutathione.

Another way glutamine helps both hospital patients and athletes is by blunting the catabolic effects of cortisol on muscle. Cortisol is released under high-stress conditions. It stimulates the activity of cellular enzymes and proteins that degrade protein.

Why cortisol prevents muscle growth wasn’t known until researchers found that it aids in the synthesis of myostatin, a protein that interferes with muscle protein synthesis and repair. A new study shows that glutamine blocks that action, thereby blocking the anti-anabolic effect of cortisol in muscle.3

That finding casts glutamine in a new light, indicating that it has enormous potential for stimulating anabolic effects in muscle. Once again, however, the effects are likely to become apparent only with high-intensity exercise. So glutamine is most beneficial to serious bodybuilders.

Application: Liberal use of a glutamine supplement can give you an edge, providinig both anabolic and anticatabolic effects—and perhaps joint fortification and protection as well.

1 Wischmeyer, P.E. (2006). Glutamine: The first clinically relevant pharmacological regulator of heat shock protein? Curr Opin Clin Nutr Metab Care. 9:201-206.

2 Tonomura, H., et al. (2006). Glutamine protects articular chondrocytes from heat stress and NO-induced apoptosis with HSP70 expression. OsteoArth and Cartil. 14:545-63.

3 Salehian, B., et al. (2006). The effect of glutamine on prevention of glucocorticoid-induced skeletal muscle atrophy is associated with myostatin expression. Metabolism. 55:1239-47.

3) Creatine Plus Beta-Alanine

A recent study compared the effects of taking either creatine alone or creatine combined with beta-alanine. It lasted four weeks and involved 45 men divided into four groups:

1) Placebo
2) Creatine alone
3) Beta-alanine alone
4) Creatine and beta-alanine

The exercise portion of the study included various tests done on a stationary cycle. Creatine alone increased aerobic power, which was expected, since that involves higher exercise intensity. When creatine was combined with beta-alanine, however, five out of eight tests of cardiorespiratory endurance showed significant improvement. The tests most affected were those related to breathing capacity and lactate thresholds.

Those results indicate that a combination of creatine and beta-alanine may increase the efficiency of incremental aerobic training. They would be most relevant for those engaged in interval-type aerobic training, which features alternate periods of high and low intensity. Interval training is now considered the most efficient form of aerobic work because it leads to improvements in both cardiovascular endurance and body composition; for example, lowered bodyfat.

Application: Beta-alanine has been shown to increase carnosine stores in muscle tissue. Carnosine provides a buffering effect, postponing muscle burn so you can get more growth reps at the end of a set. Carnosine is synergistic with creatine in that they promote increased power production in muscles. Now the combo of creatine and beta-alanine is proving beneficial in aerobic training as well. Be sure your muscles are loaded with carnosine. Take three to four grams each of creatine and beta-alanine a day.

Zoeller, R.F., et al. (2006). Effects of 28 days of beta-alanine and creatine monohydrate supplementation on aerobic power, ventilatory and lactate thresholds and time to exhaustion. Amino Acids. In press.

4) Stretch Overload for Faster Growth

Researchers found that college students who did leg extensions were able to add muscle to their front thighs in as little as two to four weeks, far faster than was previously believed. The authors cite the rapid response of anabolic hormones induced by the training.

A new study expands and confirms those findings and suggests that exercise intensity is the major factor responsible for rapid initial muscle gains (but don’t discount muscle tension and occlusion, as discussed in item 1). Seven healthy young men trained for 35 days doing leg extensions on a special flywheel-based machine. The design of the machine made it gravity-independent, which maximizes both the raising of the weight (the concentric part of the rep) and the lowering of it (the eccentric part of the rep). Maximum stress was applied to the exercised muscles.

Recent investigations of muscle growth show that satellite cells, which are progenitor muscle stem cells involved in the hypertrophy and repair processes after exercise, begin to proliferate within four days of a single weight workout. Muscle protein synthesis increases 60 percent within 4 1/2 hours after a workout that features both concentric and eccentric muscle contractions—the usual style of bodybuilding training.

The men training on the leg extension–flywheel apparatus showed a rate of front-thigh-muscle growth of 3.5 to 5.2 percent after only 20 days. That translates to a 0.2 percent increase per day. Maximum muscle strength rose by 38 percent by the end of the training period. Since the cross-sectional area of the front thighs (an indicator of muscle increase) increased by 7 percent, the strength gain largely came from neuromuscular changes, confirming long-held findings.

On the other hand, the gains in muscle size surpassed previous expectations of the time required to acquire such growth. The maximum voluntary muscle contraction improved significantly in only 10 days, detectable before any size increase. That points to increased muscle efficiency.

At the molecular level the training rapidly led to the production of intramuscular growth factors, mainly insulinlike growth factor 1 and its cleavage form, mechano-growth factor. The upgraded production of IGF-1 signals a biochemical cascade resulting in increased muscle protein synthesis, which in turn leads to muscle growth. The authors think that the flywheel design of the machine maximized every rep the subjects did, and it was the maximal effort that set off the IGF-1 response.

Another interesting finding was that a muscle’s internal architecture changes when exercise begins. The purpose of the change is to prepare the muscle for growth. Structures in muscle called sarcomeres are lined up in an orderly pattern conducive to muscle growth. As it happened, the flywheel apparatus provided more stretch—which facilitates the lineup of sarcomeres within muscle—than ordinary leg extension machines.

Application: While the authors suggest that some of these changes occurred because of the unusual design of the machine, the principles, such as stretch overload, could be applied to any type of resistance training. You can duplicate the stretch aspect by using a full range of exercise motion and at full-range exhaustion moving to the semistretch point and doing partials, a.k.a. X Reps. You should also include in your program stretch-position exercises, such as stiff-legged deadlifts for hamstrings, overhead extensions for triceps and flyes for pectorals. Again, that lines up the muscle sarcomeres, not only leading to a stronger muscle contraction but also acting as a precursor of the muscle architectural changes that precede actual muscle growth.
Note: For more on stretch overload and X Reps, visit

Seynnes, O.R., et al. (2007). Early skeletal muscle hypertrophy and architectural changes in response to high-intensity resistance training. J Appl Physiol. 102:368-373.

5) Stretching, Strength and Size

Animal studies, done mainly with mice and rabbits, show that stretching specifically increases the release in muscle of insulinlike growth factor 1. IGF-1 is considered the primary anabolic mechanism for releasing growth hormone and is essential for muscular growth and repair following exercise. In addition, stretching is the primary stimulus to the intramuscular production of a variant of IGF-1 called mechano-growth factor, which may be the most anabolic muscle hormone factor of all. MGF helps activate satellite cells, which are required for muscle repair and growth, as shown in the flywheel study discussed in item 4 above. Keep in mind that the stretch overload in that study was accomplished with resistance.

Several recent studies have indicted pretraining stretching as a cause of muscle-strength loss, losses varying from 4.5 to 28 percent when stretching is done before a heavy weight set. The strength loss is most often attributed to a drop in muscle tension. Strength requires a certain amount of tension within muscle, and stretching can deactivate some of that.

Application: Based on the existing research, the common practice of doing freehand-type stretching of the target muscle before a weight-training session or between sets is not a good idea. Bodybuilders who think they’re helping the muscle recover between sets are in fact weakening it and even setting themselves up for injury. The best time to perform a stretch routine would be independent from a weight workout or following a workout. On the other hand, weight-bearing stretch exercises like dumbbell flyes are pro-anabolic, with a link to mechano-growth factor and even hyperplasia, a.k.a. fiber splitting.

Witvrouw, E., et al. (2007). The role of stretching in tendon injuries. Br J Sports Med. 41:224-26.

6) Hot Stuff to Get Buff

According to an article by Jose Antonio, Ph.D., subjecting skeletal muscle to heat can help encourage growth. Yes, you read that right. Scientists tested the hypothesis that intermittent hyperthermia during reloading lessens oxidative damage and augments skeletal muscle regrowth following immobilization.

To clarify, here’s an analogy. Let’s say you break your arm and it’s in a cast. The muscles in the arm will shrink. When you take the cast off, you will subsequently put stress on the muscle (i.e., the reloading phase), causing it to grow back to normal. Put some extra heat on that muscle and—abracadabra—you get even better growth. Here’s the study.

Forty animals were randomly divided into four groups: control, immobilized, reloaded and reloaded and heated. All but the control animals were immobilized for seven days. Animals in the two reloading groups were then reloaded for seven days, with or without the heat (41 to 41.5 degrees C for 30 minutes on alternating days).

What happened? Heating resulted in approximately 30 percent greater soleus regrowth in the group that received it, while oxidant damage was also lower; the scientists believe that “intermittent hyperthermia during reloading attenuates oxidative stress and improves the rate of skeletal muscle regrowth during reloading after immobilization.”

Why does heat have that effect on muscle growth? The research team hypothesized that heat-shock-protein overexpression may increase muscle mass through a decrease in local oxidative stress and damage.

Application: It may be time to spend some serious time in the sauna or hot tub, which may turn on your heat shock proteins. Training in a sweat shirt and sweat pants may help too. The benefits of subjecting muscle to heat may explain why so many pro bodybuilders are moving to Las Vegas or training in the Texas heat—and why so many of us make better muscle gains in the summer months.

Selsby, J.T., et al. (2006). Intermittent hyperthermia enhances skeletal muscle regrowth and attenuates oxidative damage following reloading. J Appl Physiol. In press.

7) L-Carnitine: Anabolic Gasoline

Several studies show that taking two grams of carnitine after a workout prevents excessive muscle soreness and improves exercise recovery. Carnitine enhances the function of the endothelial lining of the blood vessels, thus enhancing blood flow within muscle and providing oxygen to cells. Carnitine appears to act as a vasodilator, opening blood vessels and improving circulation. Experiments have demonstrated that exercisers who take carnitine orally experience only limited damage to muscle fibers caused by eccentric, or negative, muscle contractions.

Now even bigger news: Carnitine may also interact with anabolic hormones, further aiding recovery after intense training. One recent study found that taking carnitine for 21 days increased the number of androgen receptors in muscle, which interact with testosterone.1 Carnitine is involved in the pituitary and testicular production of testosterone, and it works with testosterone in treating male sexual dysfunction.2 In the testes, carnitine is needed to transport fat in order to fuel testosterone synthesis. Rats subjected to the stress of cold-water swimming had lower testosterone levels—except when they were given carnitine.

Application: Try taking three grams of L-carnitine a day, in two divided doses—one upon awakening and the other with lunch—for a possible fat-to-muscle punch.

1 Kraemer, W.J., et al. (2006). Androgenic responses to resistance exercise: Effects of feeding and L-carnitine. Med Sci Sports Exer. 38:1288-1296.

2 Cavallini, G., et al. (2004). Carnitine versus androgen administration in the treatment of sexual dysfunction, depressed mood and fatigue associated with male aging. Urology. 63:641-46.

8) BCAAs Build and Save Muscle

The muscle-sparing action of branched-chain amino acids has been confirmed by a recent study. Eight healthy subjects, four men and four women, average age 26, all of whom were untrained, engaged in three bouts of 20-minute cycling sessions, with five-minute breaks between bouts, using a moderate level of exercise intensity (50 percent of maximal oxygen intake). The subjects were given a drink containing two grams of the BCAAs—leucine, isoleucine and valine—plus 500 milligrams of L-arginine. Other subjects received a placebo containing the same number of calories but no added nutrients.

While previous studies of BCAAs did show protein-sparing actions during exercise, the doses used ranged from 23 to 40 grams—huge compared to what you find in real-world training. Taking two grams of BCAAs enables you to maintain higher blood levels of them for two hours, thus providing the rationale for that particular dose.

To determine protein use from muscle during exercise, the researchers measured the loss of phenylalanine, an amino acid found in muscle. Those in the placebo group lost phenylalanine during the exercise sessions, a sign of muscle breakdown; however, the effect was blocked in those who drank the BCAA-and-arginine cocktail. The arginine was added to the drink because of its suggested effects of aiding growth hormone release and nitric oxide synthesis. Neither effect occurred during the study, leading the researchers to suggest that the 500-milligram arginine dose was insufficient. Previous studies used arginine doses ranging from 12.6 to 30 grams.

This study shows that taking two grams of a BCAA mixture effectively blocks the use of muscle protein as a fuel source during moderate-intensity aerobic exercise.

Application: As anticatabolic insurance, take at least two grams of branched-chain amino acids before your cardio workouts, especially if you do them on an empty stomach. Also take a few BCAA caps before your weight workout to suppress cortisol and preserve muscle.

Matsumoto, K., et al. (2007). Branched-chain amino acids and arginine supplementation attenuates skeletal muscle proteolysis induced by moderate exercise in young individuals. Int J Sports Med. 28:531–538.

9) The Anabolic Egg?

Some studies have come to the surprising conclusion that cholesterol may be an anabolic stimulus to muscle. So far the studies used older adults as subjects. In one, people aged 60 to 69 engaged in a 12-week weight-training routine. All the subjects got moderate amounts of protein, but half also followed a low-cholesterol diet (150 to 250 milligrams daily), while the other half followed a high-cholesterol diet (250 to 450 milligrams daily). Those in the low-cholesterol group gained no muscle mass but did experience a 37 percent strength gain. In contrast, those eating more cholesterol gained an average of five pounds of muscle and experienced an 86 percent strength gain.

The authors suggest that gains in the higher-cholesterol group may be related to the fact that cholesterol is the precursor of testosterone synthesis—older people are often low in testosterone—and because of the stabilizing effect of cholesterol in muscle cell membranes.

Another study found a link between blood cholesterol and muscle growth. Specifically, subjects with cholesterol counts below 178 showed negligible muscle gains, while those with counts of 238 gained about five pounds of muscle.

In the most recent study, presented at the 2007 meeting of the American College of Sports Medicine, healthy men and women, aged 50 to 69, trained with weights for 12 weeks. They were divided into three groups:

1) No eggs
2) 1 egg daily
3) 3 eggs daily

Those in the three-egg group made significantly greater gains in strength and muscle mass than those in the one-egg group. The most interesting aspect of the study was that blood cholesterol increased only in the one-egg group, which goes completely against conventional wisdom about the “dangers” of eating too many eggs.

Application: Don’t throw away the yolks when you eat eggs. Eating only egg whites makes no nutritional sense. The yolk contains half the protein and is more digestible than the white. In addition, yolks contain all the vitamins and minerals found in eggs. The white contains only protein. Eating eggs has a negligible effect on cardiovascular risk in active people.

Reichman, S., et al. (2007). Effect of dietary cholesterol on muscle hypertrophy with resistence training. Med Sci Sports Exer. 39(supp):S291-S292.

10) Failure to Grow

A recent review examined whether training to failure is right for all types of weight training, even that featuring multiple sets. The author noted that training to failure is an ideal way for an advanced bodybuilder to break through a tough plateau, in which muscular gains have ceased for an extended time.

Many believed that training to failure works because you activate the muscle fibers most amenable to gains in size and strength, the type 2B fibers. When muscles work, the fibers are recruited in an orderly pattern, with the smaller type 1, or slow-twitch, muscle fibers activated first. As the exercise intensity increases, the type 1 fibers fatigue and the brunt of the exercise movement is taken up by the type 2As, then the type 2Bs. Training to failure is so intense that the type 2B fibers are guaranteed to come into play unless you use too light a weight. In that case the cause of muscle failure would be metabolic, such as increased muscle acidity or a drop in creatine levels.

It does work, but according to the new review, training to failure should be used in a periodized fashion. In other words, training to failure is an effective method for breaking through a stubborn training plateau, and it can be useful for anyone who lifts weights and is interested in making muscular gains. Just don’t do it all the time or for an extended period.

Application: When it comes to all-out high-intensity training, use a phase-training approach. That means take three steps forward, then a half step back—after six to eight weeks of hard training, back off on the intensity for a week or two or take four to seven days off from the gym. That will let your nervous system heal and your recovery ability regroup so you can ratchet up the intensity again without overtraining. Look at it as taking three more growth steps forward instead of having your feet stuck in no-grow quicksand.

Willardson, J.M. (2007). The application of training to failure in periodized multiple-set resistance exercise programs. J Strength Cond Res. 21:628-31. IM

Instantized Creatine- Gains In Bulk

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