Human Studies

In a study by Blomstrand et al. BCAAs or a placebo were given to subjects during a 30-km cross-country race or a marathon (42.2 km). The subjects who ran the marathon in 3.05-3.30 hours had a significant improvement in their running time, whereas the faster runners (less than 3.05 hours) showed no improvement in their performance. However, if subjects were grouped together, no significant differences in performance were noted.

Another study by Blomstrand et al. had five male endurance-trained subjects cycle at 75% VO2 max until exhaustion. During exercise, the subjects were randomly given a 6% carbohydrate solution with or without 7 g/L of BCAAs or a flavored water solution (placebo). Performance decreased in four out of the five subjects during the flavored water trial when compared with the two carbohydrate periods. However, no differences in performance were seen between the two carbohydrate groups.

In a similar study by van Hall et al. ten endurance­trained males cycled at 70-75% of their maximum power output and randomly ingested a 6% sucrose solution (control) or a 6% sucrose solution with 3 g/L of tryptophan, 6 g/L of BCAAs, or 18 g/L of BCAAs. Exercise time to exhaustion was not different between the groups.

Moreover, a study by Struder et al. was conducted with ten male subjects. These subjects were required to cycle until exhaustion during four different trials. Subjects ingested a placebo, 20 mg paroxetine, 21 g BCAAs, and 20 g tyrosine separately during the four trials. The results showed that exhaustion was reached earlier during the paroxetine trial, but there were no significant differences among the other trials. When nine well-trained cyclists ingested glucose, glucose plus BCAA, or a placebo, the results were similar. is No differences in performance times were noted in any of the groups after a 100-km cycling test.

Elderly men have also been used as subjects in BCAA studies. Seventeen men, with a mean age of 63 years, were given either BCAA 06, 2, and 2 g of leucine, isoleucine, and valine, respectively) or a placebo The subjects performed cycling at 75% of their maximum heart rate 1 hour per day, 4 days per week. Maximal oxygen uptake significantly increased by about 5%, but the increase also occurred in the placebo group.

However, when BCAAs were given to subjects in the heat, the results were quite different. Six women and seven men rested in the heat (-34°C) before cycling at 40% of their VO2max until exhaustion. The subjects performed this routine twice while ingesting 5 mL/kg of either a placebo or BCAA drink every 30 minutes. The subjects’ times to exhaustion increased significantly during the BCAA trial.

With a decreased concentration of leucine after aerobic exercise, it would seem probable that the ingestion of supplemental BCAA would increase endurance performance. However, the preponderance of studies shows no effect of BCAA supplementation.

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.

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.

Other substances such as sodium bicarbonates and phosphates are considered physiological agents. These substances are naturally occurring in the body and aid in exercise performance by changing physiological properties such as blood acidity. Other supplements such as caffeine have been touted as endurance enhancers by stimulating the central nervous system. The mechanisms by which each supplement allegedly enhances endurance performance will be investigated. Furthermore, the safety and effectiveness of each supplement will be examined.

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 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.

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.

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.

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.

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.