Creatine Monohydrate

The biologic effects of nutrients and in product-driven articles commonly seen in popular bodybuilding and fitness magazines. However, it is unclear whether these products can be adequately absorbed by the body. Regardless of nutrient effects, if it is not assimilated into the body, any supposed effect will be negated. This is true especially of chromium and is particularly relevant when discussing chromium’s biologic properties for use in physique augmentation as well as its application in medicine.

Two forms of chromium are found in food, inorganic and organic. They have different absorption rates ranging from 0.4-2% and 10-25%, respectively. Data in humans are sparse, with most of the information on absorption coming from animal studies. 179 In this regard, only organically complexed chromium is active. Inorganic chromium entering the general circulation must be changed into the organic form to be used by the body. Chromium appears to be transported in the body bound to transferrin, albumin, globulins, and lipoproteins. Although data are lacking, the liver is hypothesized to be a major site for the synthesis of organic chromium (active) from the inorganic (inactive) form of the mineral. To date, its precise transport mechanism have yet to be clearly defined. Furthermore, no research studies have established how chromium moves from the digestive tract to sites of synthesis or to various storage depots throughout the body. This void in the literature becomes important when discussing oral dosing.

Three chromium supplements are commercially available: chromium picolinate (organic), chromium nicotinate (organic), and chromium chloride (inorganic). Absorption of these three compounds differ, as do their biologic effects. Chromium chloride is believed to be poorly absorbed and not well used by the body, in supplements available to the public, or in laboratory settings.

Chromium picolinate, the most widely used chromium salt, increases receptor-bound and internalized insulin in cultured cells, whereas nicotinate and chloride salts have different actions on the glucose insulin system. These differences indicate a fertile area of research, and future efforts in the laboratory should look into -

a) Establishing how the different forms of chromium act on insulin tissue responsive

b) Defining the exact mechanism by which chromium is processed and transported within the body.

Another important aspect to consider when discussing chromium usage is the pattern of excretion in athletic populations. Exercise increases chromium loss, but as with other physiological adaptations to stress, the form or type of stress (i.e., the mode of exercise) plays a large role in how the body responds. The effects of stress on urinary chromium loss are correlated directly with cortisol. Most of the data collected to date have been reported on aerobic athletes and have shown an increase in unnary excretion after training. Those interested in the effects of aerobic exercise and chromium loss should read the articles by Anderson et al because this chapter will touch on only those studies associated with resistance training.

Currently, not much research has been done on the effects of weight training and chromium excretion. What has been published indicates that those individuals who are involved in high-intensity resistance training may display altered chromium status owing to increased excretion. Despite this finding it is more than likely that these individuals are easily replacing lost chromium because of the typical high-calorie and nutrient-intake patterns associated with these athletes. Also note that a chromium deficiency is unlikely in strength athletes because the majority of these individuals are ingesting supplements (e.g., meal replacements, protein powders, multivitamins/ minerals, and various thermogenic supplements) that contain 200 µg or more of the mineral.

To fully understand the use of creatine as an ergogenic aid, one must appreciate its role in energy metabolism. In this regard, a primary objective for students to understand is that skeletal muscle performs mechanical work through the hydrolysis of adenosine triphosphate (ATP). Commonly referred to as the energy currency of a cell,the quantity of ATP present in skeletal muscle is approximately 3 to 5 µmol/kg or 6 mmol/kg of fresh muscle. The continuation of physical work is based on the maintenance of ATP at a rate equal to the rate of its use. Energy reserves consist of intramuscular phosphagen stores (ATP, phosphocreatine [PCr]) and muscle and liver glycogen and adipose stores. The rate and the extent to which these energy sources are used depends on the intensity and/or duration of exercise. To this end, high-intensity anaerobic exercise is supplied almost exclusively by ATP, PCr, and intramuscular glycogen stores.

In a classic series demonstrating the shift of energy usage in skeletal muscle, Hirvonen et al. examined the changes in the intramuscular concentrations of muscle ATP, PCr, and blood lactic acid concentration in sprinters running distances of 40 to 400 meters lasting approximately 4.5 to 50 seconds . Blood lactic acid is a reflection of muscle glycogen usage or glycolysis. Even on casual observation it is interesting to note that despite the increase in running distance, ATP stores initially decline but appear to reach a minimal or critical level after which no further decrease is observed. In contrast, PCr continually and rapidly decreases while the appearance of blood lactic acid or muscle glycogen usage increases. At this point, the reader should embrace two key points. One is to recognize the immediate contribution of all energy systems simultaneously and cooperatively to facilitate energy needs. These energy contributions do not occur sequentially (i.e., one after the other), but instead are time and intensity dependent as to which system dominates. This continued energy production has been conceptualized as a metabolic flux or energy currency that transforms stored energy into muscle contraction.

The maximum work attainable from any energy source can be characterized as both ATP capacity (amount of ATP produced per mole of available substrate) and ATP power (the rate of ATP produced per substrate storage depot). Despite the low intramuscular stores of ATP and PCr within skeletal muscle, their energy production capabilities are exceptional . A review by Sahlin provides an excellent consensus of research findings elaborating on the available energy capacity (mol ATP), maximal ATP power produced from each source (per mmol ATP/kg of dry muscle), as well as the exercise intensity supported and duration of activity allowed per endogenous energy source. It should become readily apparent that events of shorter duration and higher intensity necessitate physical training and nutritional support aimed toward the enhancement of ATP, PCr, and muscle glycogen as opposed to alternative energy sources such as liver glycogen and adipose stores. These sources serve as less adequate sources of ATP power.

Research has shown an improvement in endogenous energy stores of glycogen, PCr, and ATP following 5 months of heavy resistance training although this correlation has not been universally shown. Although changes in resting PCr concentrations might enhance performance during anaerobic activities (e.g., sprinting, weightlifting, etc.), increases in skeletal muscle glycogen may not confer a similar advantage in these types of activities. Strong evidence shows that the dietary manipulation of glycogen stores does not improve various anaerobic performance indices. Also, oral ATP administration does not appear to be prudent owing to the presence of phosphatase enzymes in the blood and gut. These enzymes readily cleave the phosphate portions of ATP. Thus, it appears that oral ATP does not present itself as a suitable ergogenic aid. The same point may be argued for PCr as well. Thus, it is plausible that creatine ingestion may be the best way of augmenting athletic performance vis-a-vis changes in the phosphagen energy system.

One study that examined PCr supplementation showed a performance benefit, albeit to a smaller degree than creatine supplementation. However, any effect of orally ingested PCr would be expected to be mediated by creatine alone because gut phosphatase enzymes would readily cleave off the phosphate portion of the molecule, liberating free creatine in a smaller quantity than when taking the monohydrate form. To date, no human studies have evaluated PCr’s oral absorption and intramuscular uptake. Additionally, blood serum also possesses high phosphatase activity, leading to rapid breakdown of intravenously administered PCr to creatine and phosphate. A study by Peeters et al. determined that PCr-supplemented subjects exhibited a performance response that was approximately 50% less than than that of a creatine monohydrate group. Given that the creatine portion of the monohydrate form makes up about 92% of the molecule and only 50% of the PCr molecule, these results are not surprising. Similarly, although glycolysis is initiated at muscle contraction, increasing glycogen stores may be more advantageous to longer, high-intensity work efforts (>400 m) because of its lower ATP power. These same objectives do not appear to apply to the use of creatine supplementation because both early and more recent studies involving creatine show that it is readily found in food, is absorbed intact, appears rapidly in the blood, and increases intramuscular stores of total creatine and PCr.

Creatine is a guanidino compound that is found in meat­containing products and produced endogenously by the liver and pancreas. Creatine is transported into a variety of tissues via a sodium-dependent transporter. The major stores for creatine include brain, heart, and skeletal muscle. Creatine functions as an energy buffer during periods of increased metabolic demand, and as an energy shuttle between mitochondria and cytosol, and may have a role in protein synthesis. Studies in young, healthy males have shown an increase in muscle creatine content by 10-20% following a creatine loading protocol (approximately 20 g/day X 5 days). This has resulted in an increase in high-intensity exercise performance and an increase in fat-free mass after 3 to 7 days of loading. The performance effects are greatest in those who have the lowest intramuscular creatine concentrations. Patients with muscular dystrophy, inflammatory myopathies, and mitochondrial cytopathies have been shown to have low total creatine and phosphocreatine concentrations. Muscle weakness and fatigue are common symptoms in these patients. Studies have shown an increase in high-intensity exercise performance and total body weight in patients who have mitochondrial cytopathy and neuromuscular disorders following creatine loading. Longer-term studies are required to measure the impact of this on functional activities of daily living. Two recent animal studies have provided fascinating insight to the potential for creatine to attenuate neurodegenerative disorder progression. In one study, rats were poisoned with 3-nitro-proprionic (NP) acid (complex 2 inhibitor), which resulted in degeneration of the corpus striatum (Huntington’s disease model). In those rats treated with creatine and 3Np, there was an attenuation of neural drop-out and lesser oxidative stress compared with those receiving only 3NP. This research group later showed a neuroprotective effect and survival benefit from creatine administration to mice with the G93A FALS mutation (a model of amyotrophic lateral sclerosis [ALS]).

The aforementioned study suggests that creatine may be a useful adjunctive treatment in neuromuscular and neurometabolic disorders. However, long-term studies with objective outcome measures and functional measures are required to explore the therapeutic potential of this compound.

Octacosanol is one of many compounds found in wheat germ oil. Interestingly, this supplement may have indirect effects on muscle mass by acting on the central nervous system (CNS). Octacosanol is not known to have any anabolic or anticatabolic effects on muscle tissue itself, but may playa role in muscle and strength development by acting on nerve tissue. One aspect of increasing speed and strength, in addition to muscular hypertrophy, is via neural adaptation. If athletes can increase the efficiency at which the nervous system acts, this may facilitate speed and strength production and influence the growth response in skeletal muscle by activating more muscle fibers during a given lift.

Scientists have theorized octacosanol has various health benefits. It improves neuromuscular function by stabilizing nerve cell membranes and improving oxygen transport. However, there is no solid evidence that supports this notion. Some studies show increases in grip strength, reaction speed, and increased endurance performance with octacosanol supplementation. Others show no changes in performance. Interestingly, Russian scientists believe that the ability of octacosanol to facilitate oxygen transport was overemphasized by their American counterparts and that the real benefit of octacosanol supplementation is its ability to improve reaction time.

Animal Studies

Animal studies involving octacosanol are inconclusive regarding a definite performance-enhancing effect with this supplement. Studies in the literature show equivocal data from swimming time tests in rodents However, the studies are quite old and investigations conducted today on octacosanol would benefit from advances in technology and laboratory techniques available to the modern sport scientist. Theoretically, this supplement may elicit beneficial effects in certain sports. Nonetheless, there is little evidence to establish scientific support for physique, strength, and/or speed athletes to use this compound.

Human Studies

Limited research exists demonstrating octacosanol has performance-enhancing effects in activities requiring a high degree of quickness (i.e., reaction time). Theoretically, specific instances in which reaction time may be aided by octacosanol are the explosive transition from eccentric to concentric phases of power lifting/Olympic weightlifting (i.e. squatting and pressing), getting out of the blocks for a sprint race, getting off the line quickly after the snap in football, and rapid throwing movements in baseball.

In one 8-week, double-blind study, 16 subjects were administered either 1000 µg of octacosanol or placebo per day? Results showed that those receiving octacosanol had improved reaction time to visual stimuli as well as a significant increase in grip strength. There were no differences in either grip strength or endurance time as measured by cycle ergometry.

Safety and Toxicity

This substance has been widely used as a food and nutritional supplement since the 1950s. There are no reports in the literature of toxicity in animals or humans.