Creatine Monohydrate

One of the most controversial concerns involving creatine supplementation is its effect on renal function. Creatine supplementation can cause an increase in urinary creatinine excretion, which is often used as an indicator of kidney function. However, this increase correlates well with the increase in muscle creatine that is observed during supplementation and reflects the increased rate of muscle creatine degradation to creatinine rather than any abnormality of renal function. Pritchard recently reported on adverse effects associated with creatine supplementation in an isolated case involving presence of kidney disease. However, other studies have shown normal kidney function in creatine-supplemented healthy individuals. Normally, creatine does not exit muscle cells until it has degraded to creatinine in an irreversible reaction involving the loss of a water molecule from the creatine molecule itself. Following its formation, creatinine diffuses from skeletal muscle and is excreted by the kidneys.

Poortmans recently reported on five healthy men ingesting either a placebo or 20g of creatine per day for 5 consecutive days. In their study, blood samples and urine collections were analyzed for creatine and creatinine concentrations after each experimental session. Total protein and albumin urine excretion rates were also determined. Oral creatine supplementation had a significant incremental impact on arterial content (3.7 -fold) and urine excretion rate (90-fold) of this compound. In contrast, arterial and urine creatinine values were not affected by creatine ingestion. The glomerular filtration rate (creatinine clearance) and the total protein and albumin excretion rates remained within the normal range.

In one of the most recent studies, Poortmans et al. examined creatinine, urea, and plasma albumin clearances in individuals supplemented with creatine as well as placebo from 10 months to 5 years. During this trial, no statistical differences were found between the control group and the creatine group in plasma concentration and urine excretion rates for creatinine, urea, or albumin. Glomerular filtration rate, tubular reabsorption, and glomerular membrane permeability were normal in both groups. Therefore, it is becoming increasingly apparent that neither short-term, medium-term, nor long-term oral creatine supplementation induces detrimental effects on kidney function in healthy individuals. Whether creatine is safe for patients who suffer from renal dysfunction has yet to be determined, indicating the need for more research in this area.

Harris et al. further demonstrated that oral creatine supplementation improved cumulative repeated running times following 300 m and 1000 m . Individual running times for the final measured repeat run times improved as well. Final 300-m running time decreased by 0.7 second and 1000-m running time decreased by 5.5 seconds. However, one criticism of this study is that all subjects were asked to run at 90-95% of their maximal effort. Each running pace was therefore dictated by the subjective opinion of each runner. Although a threat to the study’s internal validity, these are intriguing findings because traditionally, PCr’s primary contribution to ATP maintenance takes place within approximately the first 10 seconds of intense physical exertion. Because PCr may aid ATP resynthesis for up to 3 minutes (albeit in a decreasing role with time and intensity of work) and may also act as an energy shuttle between the mitochondria and myofibrils, the efficacy of creatine as an ergogenic aid during longer anaerobic work bouts may be warranted.

In an early study, Balsom et al. investigated the effects of creatine supplementation on endurance exercise performance. Performed in a double-blind manner, habitually active to well-trained male subjects were evenly divided into treatment and placebo groups. Following 6 days of creatine supplementation, no significant differences in time to exhaustion, terrain runs, or were noted between groups and it was thus concluded that creatine supplementation clearly had no effect on endurance performance. However, other reports of anaerobic running performance suggest that creatine mayor may not improve exhaustive work bouts that last between 40 and 240 seconds.

A study by Earnest et al sought to determine if creatine supplementation would improve intermediate-length anaerobic treadmill running. In this study male subjects randomly and blindly received a creatine or glucose placebo at 20 g/day X 4 days and 10 g/day X 6 days. Following 2 weeks of rehearsal, subjects performed two exhaustive runs, separated by 8 minutes of recovery, at individually prescribed grades. Time to exhaustion for independent runs, for both runs combined, and blood lactic acid concentration were examined for each run. Significant treatment effects on group estimates of total time to exhaustion were noted. Overall, running times in the creatine group improved more during the second run , were negligible for the first run (0.5 sec), yet were significantly greater for total time to exhaustion .

In a follow-up to this investigation, Smith et al examined the effect of creatine ingestion on -

a) Time to exhaustion during intense exercise bouts used to establish the work rate-time relationship

b) The estimates of anaerobic capacity and critical power in a larger population.

Fifteen (eight male and seven female) recreationally active university students were randomly assigned and completed three phases of cycle ergometer testing, including the following -

1) familiarization-three learning trials to establish subsequent work rates

2) four baseline trials that elicited fatigue within 1 to 10 min

3) four experimental trials (post) after 5 days of either creatine or placebo ingestion given in a double-blind manner.

ANCOVA revealed a significant effect for creatine on anaerobic capacity but not critical power. Within-group time to exhaustion was also significantly different for creatine at the two highest work rates. Effect sizes for W3 and W4 were 0.86 and 0.87, respectively At work bouts of 357 and 268 watts, time to exhaustion increased from 93 seconds to 103 seconds and 236 seconds to 253 seconds , respectively. Furthermore, anaerobic capacity increased from 17.6 to 20.2 kJ .

The results of these last two studies suggest that creatine supplementation will improve shorter bouts of anaerobic work as well as longer exercise bouts lasting up to approximately 4 minutes. Although these results appear to remain consistent on a cycle ergometer, similar results obtained on the treadmill yield a conflict in the results. Creatine’s efficacy during longer anaerobic work tasks is not easily conceded in that, although improvement may be present, standardized laboratory procedures yield different results than those typically seen in practice and application. However, continued justification for this argument is provided by Jacobs et al who demonstrated that creatine ingestion increased maximally accumulated oxygen deficit (MAOD) during treadmill work bouts at 120% of max lasting approximately 120 seconds. Although most studies do show a performance benefit with creatine supplementation, several studies show no response to creatine supplementation. These results should be interpreted judiciously, however, because protocols of some studies deviated from the 5-day loading protocol shown to be effective for increasing performance. Furthermore, performance enhancement appears to be strongly related to the extent of creatine uptake into muscle with supplementation. Therefore, studies that do not measure creatine uptake by the muscle cannot rule out study participants that are nonresponders who, for one reason or another, do not absorb creatine into the muscle.

N, N, dimethylglycine (DMG) was discovered in 1943 and marketed under the name pangamic acid or vitamin B15. This substance was touted as a cure for various ailments such as cancer and glaucoma. Since then, it is the belief that supplementation with DMG could increase performance. Marketers of DMG have made various claims such as an increased use of oxygen and increased mental alertness with the use of DMG. A review of DMG has shown an increase in tissue oxygen uptake and increased exercise performance however, most of these studies were highly criticized.

Animal Studies

In a crossover study by Rose et al., 1.2 mg/kg of DMG or a placebo paste were orally administered to six thorough­bred horses (body weight = 424-492 kg) twice per day for 5 days. The horses exercised at 40-50% for 2 minutes followed by 1 minute of exercise at 60, 70, 80, 90, and 100%. carbon dioxide production, heart rate, arterial blood and plasma lactate concentration, arterial blood gases, and pH were measured during the last 5 seconds of each stage. Also, muscle biopsy specimens were taken from the middle gluteal muscle before and immediately after exercise to determine muscle lactate concentrations. The results showed no significant differences between the groups for any of the parameters measured.

Human Studies

A study by Pipes was conducted using 12 male track athletes (18-21 years of age). The subjects received 5 mg of pangamic acid or a placebo for 1 week. Performance was measured by having the subjects run on a treadmill at a 7.5% grade and 9.0 mph. The speed was increased 1.5 mph every minute until exhaustion. The subjects receiving pangamic acid improved their running times significantly (23.6%) when compared with the placebo group (0.9%). There was also a significant increase in the treatment group (27.5%) when compared with the placebo (3.3%). Pangamic acid also significantly improved performance in a study by Kemp however, neither one of these studies involved subject or investigator blinding.

The effect of pangamic acid on treadmill performance was determined using 16 male track athletes. The athletes ingested six, 50-mg tablets per day of pangamic acid or a placebo for 3 weeks in this double-blind study. Before and after supplementation, the subjects performed a Bruce treadmill protocol to determine maximal heart rate, tread­mill time, recovery heart rate (1 and 3 min), blood glucose levels, and lactate levels. The results showed no significant difference between groups for any of the parameters.

Black and Sucec also showed no improvement with the ingestion of DMG. They had 18 physically active men perform an inclined treadmill test after the ingestion of six 50-mg tablets of calcium pangamate (two per meal) or a placebo for 2 weeks. The results showed no significant improvement or 15-minute running performance time.

A study by Bishop et al. was conducted using trained runners. The results showed no significant improvement in ventilation, oxygen uptake, heart rate, or total run time when compared with a placebo. These results were similar to a study done by Girandola et al.

DMG has been proposed to increase oxygen use by skeletal muscle. This should lead to an increase in endurance performance. Regardless, DMG has not shown much potential as an endurance enhancement.

Safety and Toxicity

Studies have been conducted on the effects of DMG using rabbit models. When testing for the immunomodulating capacity of DMG, no toxic or adverse side effects occurred. Also, when DMG (300-600 mg/day) was administered to patients with epilepsy to control seizure frequency, no toxicity was noted.

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.