Creatine Monohydrate

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.

Several studies have been published indicating that creatine ingestion greater than 20 g/day for 5 to 7 days increases total muscle creatine concentrations and improves performance during short-duration, high-intensity activities such as resistance training. More recent studies also indicate that creatine supplementation in conjunction with resistance exercise training from 4 to 12 weeks enhances the physiological adaptations to weight training in both men and women. Studies examining the influence of creatine supplementation (5-30 g/day) during weight training (4-12 wks) generally indicate enhanced body mass, including an increase in fat­free mass (FFM), an increase in muscular strength, and the ability to train at higher intensities.

Several lines of research suggest that creatine could playa role in augmenting skeletal muscle fiber hypertrophy. Gyrate atrophy patients who consumed 1.5 g creatine per day for 1 year showed significant increases in type II muscle fiber diameter. Creatine supplementation has also been shown to facilitate muscle rehabilitation following disuse atrophy. In fact, our laboratory recently published data showing that muscle fiber hypertrophy was enhanced in men who consumed 25 g of creatine per day for 7 days followed by a daily 5-gram dose for the remainder of a 12-week resistance training program. In addition, creatine-supplemented subjects showed significantly greater improvements in maximal strength, fat-free mass, and creatine accumulation compared with placebo subjects. The percentage increases in cross­sectional area for all fiber types in creatine subjects ranged from 29-35%, more than twice the increase observed in placebo subjects (6-15%). Greater muscle fiber hypertrophy implies enhanced myofibrillar protein synthesis and/or reduced degradation. Creatine may play a direct role in myosin and actin synthesis in vitro, which may be mediated via cell swelling. A more likely scenario to explain the augmented skeletal muscle fiber cross-sectional areas observed with creatine supplementation is that the intensity of individual resistance training sessions is enhanced (Le., heavier loads can be lihed), leading to a greater stimulus for muscle fiber hypertrophy.

The direct or indirect nature of this anabolic effect of creatine has not been elucidated, however, most researchers agree that endocrine mechanisms are most likely not involved. Furthermore, there is still uncertainty regarding the optimal amount of creatine required to maximize the ergogenic potential of creatine. An ideal dose may be dependent on individual differences in diet composition, fiber type distribution, sex, age, and initial total muscle creatine concentrations. Creatine requirements may be altered depending on the specific training regimen and exercise configurations. The ability to exercise more intensely with creatine supplementation and thus augment training adaptations has wide application for a large number of athletes who participate in resistance training as a part of their overall training program.