Creatine and HMB: The Power Team!

by Alfredo Franco-Obregón, PhD It is now widely accepted by the sports medicine community that creatine supplementation promotes the production of lean muscle mass and enhances athletic performance in sporting events encompassing explosive bursts of power in the majority of athletes who supplement. Creatine principally acts by increasing the availability of Adenosine TriPhosphate (ATP), the cell’s energy currency, to muscles during exhaustive exercise. The increase in exercise output afforded by the prolonged longevity of muscle’s ATP reserves then serves as a greater training stimulus for subsequent muscle development. In addition, there are also strong indications that the increase in muscle fluid content, a process known as muscle volumizing, that commonly accompanies creatine use, may also stimulate the production of new muscle proteins, or protein synthesis. Finally, there are also some indications that creatine buffers muscle acidity (delaying the onset of muscle fatigue), improves insulin-sensitivity (increasing cellular amino acid and carbohydrate storage) and possesses antioxidants properties (protecting against oxidative stress). Therefore, a large body of scientific evidence overwhelmingly supports a role for creatine in stimulating muscle growth and enhancing athletic performance. Because of its positive effect on muscle development, creatine is classified as an anabolic (tissue building) agent. The mechanisms of action of other nutritional supplements are not as thoroughly studied and understood as that of creatine. Nonetheless, the lack of clear scientific support has not dissuaded many supplement manufactures from flooding the market with utterly bogus nutritional supplements. HMB (beta-Hydroxy-beta-MethylButyrate) is one nutritional supplement that has the promise of being an authentic ergogenic supplement. Although the bulk of the scientific evidence demonstrating an ergogenic effect of HMB, at least for the moment, is not as compelling as for creatine, the future appears bright for this intriguing nutritional supplement. Interestingly, HMB appears to exert its particular ergogenic effect by making the muscle cell membrane more resistant to mechanical damage. HMB’s principal mechanism of action appears to be mediated via its ability to sustain cholesterol synthesis. Although cholesterol is a major structural component of all cellular membranes, it plays an especially important role in stabilizing the membranes of cells undergoing constant mechanical stresses. Of importance to the topic at hand, muscle membranes deficient in cholesterol will inevitably succumb to mechanical stress of exercise by tearing, thereby collapsing the essential barrier that protects the inside of the muscle cell from potentially damaging agents in the extracellular (outside the cell) space. Left unchecked, this leakage pathway could then initiate a proteolytic (protein degrading) enzymatic cascade within the muscle cell that will consume existing proteins and make muscle growth nearly impossible. In fact, under conditions of cholesterol deficiency

surprisingly little mechanical stress is actually necessary to provoke muscle degeneration. For example, reducing the availability of cholesterol to the body augments the production of biochemical markers of muscle cell damage even under normal levels of physical activity. HMB thus strengthens the muscle membrane by making cholesterol readily available for incorporation into the membrane. It is thus no wonder that HMB has been shown to attenuate the degree of muscle cell breakdown in response to intense exercise. This is the reason that HMB is widely considered an anti-catabolic (prevents the degradation of muscle proteins) agent. These attributes of HMB were thoroughly discussed in last month’s Creatine Newsletter.

The Study
In this issue of the Creatine Newsletter we will discuss the results of a recent study that addressed the issue of whether creatine and HMB exert their ergogenic benefits via common or complementary cellular pathways. One of the authors of this study is Steve Nissen of Iowa State University, a very influential person in the field of HMB research. Those of us following the field of HMB research are very familiar with his name.

Experimental Design
The study in question consisted of a double-blind design, meaning that neither the experimenters nor the subjects had any knowledge of what supplementation group they pertained to. Such an experimental design has the advantage that it largely circumvents the possibility of anyone (experimenter or subject) from introducing a personal bias into the results of the study. Briefly, subjects were given one of four different supplement protocols while undergoing resistance training (free weights). The aim of the study was to elucidate interactions between any of the supplement conditions and indices of exercise performance and muscle growth. Forty experimental subjects were randomly assigned to one of four different supplement groups, placebo (rice flour and glucose), creatine (20 grams of creatine per day during a loading phase of 7 days followed by 10 grams of creatine per day for the remainder of the study), HMB (3 grams of HMB a day for the duration of the entire study), or creatine plus HMB (combining the creatine and HMB protocols).

The subjects concomitantly performed a comprehensive whole-body workout three times a week for the duration of the study (three weeks). The exercises examined included the bench press, power clean, behind the neck military press, bicep curls, tricep extensions, squats and stomach crunches. Importantly, such a rigorous training schedule would place most individuals into the realm of overtraining. That is, creating more damage than the muscle cell can repair and replace. The results of the study pertaining to athletic performance are given as accumulative strength, which simply means that the individual increases in weight lifted for each exercise category were summed together and plotted against the relevant supplement condition.

Results

In all cases body weight and accumulative strength increased to greater degrees in subjects administered creatine and HMB, either alone or in combination, when compared to the placebo group. Generally, creatine supplementation tended to increase body mass and promote cellular fluid retention to a greater degree than HMB (and certainly placebo). This effect of creatine is clearly demonstrated in panel A (top) of the figure below. This result was actually no surprise, since it agrees with previous studies examining the effects of creatine on body composition.

On the other hand, creatine and HMB exhibited roughly similar abilities to improve strength (panel B; middle), although both produced much greater gains in strength than the placebo condition. Greater amounts of weight lifted may be equated to increased amounts of mechanical stress placed upon the muscle cell.

Biochemical markers of muscle damage were then examined with reference to the different supplement conditions. In this respect, HMB greatly attenuated the release of creatine kinase into the blood stream as is predominantly observed in the placebo scenario (panel C; bottom). Since creatine kinase is released into the blood stream in response to tears of the muscle membrane resulting from mechanical stress, this result clearly indicates that HMB protects against muscle damage resulting from an intense exercise regime. Interestingly, creatine had a relatively modest, but nonetheless significant, capacity to diminish the release of creatine kinase.

This result indicates that creatine also exhibits a muscle sparring effect and agrees with previous scientific findings showing that creatine supplementation reduced muscle protein degradation products. HMB also significantly reduced the release of protein degradation products (urea nitrogen) into the blood stream, a further indication that HMB reduces muscle protein break down during strenuous exercise. In summary, the results of this study indicate that creatine promotes muscle growth and strength, while HMB increases muscle cell resilience and strength.

Combining Creatine and HMB
Although both creatine and HMB both merit classification as ergogenic substances, the true rationale for this study was to examine the effects of combining creatine and HMB on muscle growth and athletic ability. In brief, mixing creatine and HMB effectively combined the effects of both separately on body weight (panel A). That is, the effects of combining creatine and HMB on body weight were additive, implying that they exert their influences on body weight through different mechanisms, though complementary. The effect of the combination of creatine and HMB on accumulative strength, on the other hand, did not as effectively summate (panel B), although the effect of combining the two was greater than either separately. Upon first inspection of the data in panel C, it may initially seem that creatine is mitigating the capacity for HMB to protect against muscle damage. In truth, making this assumption might be misinterpreting the results. Firstly, since physical output increased nearly twice as much in subjects combining the two supplements (panel A), it is entirely expected that biochemical markers for muscle damage should likewise double. In other words, the amount of mechanical stress placed upon muscle cells in subjects consuming both creatine and HMB likely exceeds the protection offered by the pair. The liberation of these biochemical markers for muscle damage, however, is still less than that observed in the control (placebo) scenario clearly demonstrating some degree of protection despite the greater mechanical load.

Concluding Remarks

Based on previous studies strong cases can be made for both creatine and HMB acting to increase muscle growth and enhance athletic performance. This study now demonstrates that creatine and HMB can act in cohorts to better increase muscle growth and improve athletic performance. This is an important point since many creatine formulations combine supplements acting through common cellular pathways, which may not render an additional benefit due to their redundancy in mechanism of action. By contrast, this study has demonstrated that creatine accentuates lean muscle growth at the same time HMB reduces muscle breakdown in response to strenuous exercise. The effects of creatine and HMB thus complement each other to provide an overall superior ergogenic effect.

Scientific Reference
Jowko E., Ostaszewski P., Jank M., Sacharuk J., Zieniewicz A., Wilczak J., Nissen S. (2001) Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition Volume 17(7-8), pages 558566

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