Leucine, isoleucine, and valine are essential amino acids and are collectively termed the branched-chain amino acids (BCAAs). BCAAs comprise approximately one-third of muscle protein, and of these three amino acids, leucine has been researched the most extensively. Significant decreases in plasma or serum levels of leucine 01-33%) have been shown to occur after aerobic exercise. Exercise has also been shown to increase the tryptophan/BCAA ratio, which has been touted as support for the central fatigue hypothesis. This hypothesis suggests that an increase in the uptake of tryptophan by the brain will cause an increase in the release of serotonin. This release will ultimately impair endurance performance.

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.

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Endurance athletes (e.g., marathon runners, triathletes, etc.) are known to use Creatine for the purpose of enhancing performance. Of the three energy systems, these athletes performance depends primarily on oxidative phosphorylation and glycolysis. By increasing the available concentrations of glucose and free fatty acids, some of these so-called endurance supplements may enhance performance. These substances are usually termed nutritional supplements and include carbohydrates and various amino acids. It has been suggested that an average diet may lack certain nutrients that could aid in one’s performance.

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.

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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.

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Coenzyme Q10 (CoQ10), sometimes referred to as ubiquinone, is a lipid-soluble coenzyme produced by respiring organisms and some photosynthetic bacteria. CoQ10 aids in the transport of electrons between enzyme complexes of the inner mitochondrial membrane. Through the process of oxidation phosphorylation, CoQ10 also aids in the production of ATP.

Human Studies

The effects of CoQ10 supplementation have been studied using patients with chronic obstructive pulmonary disease (COPD). Eight patients ingested 90 mg/day of CoQ10 for 8 weeks and showed a significant increase in serum CoQ10 levels with a decrease in hypoxemia at rest. Tread­mill time tended to increase (12.0-14.0 min) with a significant decrease in heart rate during exercise, whereas lactate production decreased. However, pulmonary function and oxygen consumption during exercise were unaltered.

Studies have also been conducted on elite athletes. Twentyfive Finnish top-level cross-country skiers ingested 90 mg/day of CoQ10 in a double-blind, crossover fashion. Supplementation significantly improved the subjects . Also, 94% of the athletes felt their performance and recovery times were improved during the supplementation period versus only 33% during the placebo period.

Conversely, ten male bicycle racers performed graded cycle ergometry before and after supplementation with 100 mg/day of CoQ10 or a placebo for 8 weeks. There was a significant difference in serum CoQ10 levels between groups. Both groups showed improvements in exercise performance, but there were no significant differences between groups.

Snider et al. supplemented 11 highly trained male triathletes with three daily doses of a combination of 100 mg of CoQ10, 500 mg of cytochrome C, 100 mg of inosine, and 200 IU of vitamin E or a placebo for two, 4-week periods. There was a 4-week washout between treatment periods in this double-blind crossover design study. After each treatment period, the subjects ran on a treadmill at 70% for 90 minutes followed by a period of cycling at 70% until exhaustion. There were no significant differences between groups for time to exhaustion, blood glucose levels, lactate levels, and free fatty acid concentrations.

Eighteen male road cyclists and triathletes were supplemented with 1 mg/kg/day of CoQ10 or a placebo for 28 days The subjects were evaluated during and after graded cycling exercise tests. Plasma CoQ10 levels were significantly increased from baseline. Nonetheless, CoQ10 had no consistently significant effect on oxygen uptake, anaerobic and respiratory compensation thresholds, blood lactate, glucose and triglyceride kinetics, heart rate, or blood pressure during and following the exercise protocol.

In 1996, MaIm et al. conducted research on CoQ10 using healthy males. The results showed that CoQ10 might actually cause cell damage under intense exercise conditions. MaIm et al also conducted a follow-up study on CoQ10. Subjects ingested CoQ10 for 22 days while performing aerobic exercise, except on days through the subjects performed high-intensity anaerobic training. The results showed that during an anaerobic cycling test, the placebo group performed significantly better than the CoQ10 group on day of supplementation (9.7 versus 9.3 W/kg for the placebo and CoQ10 groups, respectively). Furthermore, the CoQ10 group had a significantly lower increase in total work performed. Overall, there were no significant differences between the groups , rate of perceived exertion (RPE), respiratory quotient, blood lactate concentration, or heart rate.

CoQ10 may aid in the transportation of electrons with­in the mitochondria and also aid in the production of ATP However, it probably does not enhance endurance performance.

Safety and Toxicity

Studies have been conducted on the safety and effectiveness of CoQ10 supplementation in patients who suffer from heart failure. These studies showed an improvement in the patient’s health status However, the results from a study using healthy males showed that supplementation with CoQ10 may cause some cell damage in the intramembrane compartment of the mitochondria.

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L-carnitine is a creatine which contains a short-chain carboxylic acid and has a potential effect on endurance performance because it is a physiological carrier of activated long-chain fatty acids across the inner mitochondrial membrane. Once inside the mitochondria, the long-chain fatty acids are beta-oxidized and carnitine exports acylcoenzyme A compounds. The oxidation of fatty acids in the mitochondria is the main fuel source for skeletal muscle. Also, the carnitine shuttle of a muscle controls the efficiency of the use of fatty acids and the activation of branched-chain amino acid oxidation in the muscle.

The ingestion of carnitine has been speculated to enhance fatty acid oxidation and thus spare skeletal muscle glycogen, and this glycogen-sparing effect may aid endurance performance.

Human Studies

Marconi et al. were the first to investigate the use of carnitine supplementation on endurance performance. Six long distance competitive walkers ingested 4 g/day of L-carnitine for 2 weeks. After the 2-week training period, the subjects’ increased 6% . On the other hand, when the subjects walked 120 minutes at 65%, heart rate, pulmonary ventilation, oxygen consumption, and respiratory quotient remained unchanged. The authors concluded that the slight, but significant increase was probably due to an activation of substrate flow through the TCA cycle.

In a study by Greig et al. two groups of untrained individuals were used in a double-blind, crossover designed study. In the first trial, 2 g of L-carnitine were ingested per day for 2 weeks, and in the second trial, the same dose was given for 4 weeks. Maximal and sub maximal exercise capacity was assessed with a cycle ergometer at 70 rpm. The results showed no significant increase or maximum heart rate.

Gorostiaga et al. conducted a study on ten endurance­trained athletes . The subjects first performed a control test consisting of 45 minutes of cycling at 66% of followed by 60 minutes of seated rest. After 28 days of supplementation with 2 g/day of L-carnitine or a placebo (double-blind, crossover design), the subjects performed the same routine. The results showed a lower respiratory quotient in the treatment group, and there were also trends for an improvement in oxygen uptake and heart rate, but no significant improvements in performance were seen.

In a double-blind, crossover design field study, seven male subjects were given 2 g of L-carnitine 2 hours before the start of a marathon and 20 km into the run. The subjects’ respiratory exchange ratio (RER) was determined before and after the race, and a submaximal performance test was conducted on a treadmill the morning after the race. Supplementation with L-carnitine showed no significant change in marathon running time or RER. Moreover, there were no changes in the sub maximal treadmill test conducted the morning after the run.

One could reasonably conclude at this point that carnitine does not have any consistent effect on endurance performance.

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HMB is a metabolite of the essential amino acid leucine. HMB is usually promoted as a muscle-building supplement. It has been claimed to increase strength and lean body mass via an antiproteolytic effect. Recently, of carbohydrate loading as it relates to ameliorating exercise­induced hypoglycemia. HMB has been touted as an endurance enhancer. However, the literature on HMB and endurance performance is scant.

Human Studies

A recent study was conducted by Knitter et al on the effects of HMB on muscle damage after a prolonged run. Thirteen subjects randomly received 3 g/day of HMB or a placebo for 6 weeks. After the training period, all subjects completed a 20-km run. Creatine phosphokinase and lactate dehydrogenase (LDH) activities were measured before and after the prolonged run to assess muscle damage. The placebo group had a significantly greater increase in creatine phosphokinase activity when compared with the HMB-supplemented group. Also, LDH activity was significantly lower in the HMB-supplemented group. These results suggest that supplementation with HMB may prevent exercise-induced muscle damage. However, it is not clear if this could translate into an enhanced endurance performance.

Safety and Toxicity

The use of HMB has been reported to be safe. A summary of safety data was collected in nine studies in which humans were ingesting 3 g of HMB per day. The duration of the studies lasted from 3 to 8 weeks and included young and old, male and female, and exercising and nonexercising subjects. HMB supplementation did not affect any markers of tissue health and function. Furthermore, HMB resulted in a significant decrease in total cholesterol (5.8%), LDL cholesterol (7.3%), and systolic blood pressure (4.4 mm Hg).

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Creatine is a natural nutrient found in our bodies. Most of the needs of creatine of the human body can be fulfilled through a balanced diet. However, bodybuilders, athletes and a vast majority of individuals following a fitness regime, resort to creatine supplements because it has proven to increase body mass and lean muscle formation, in a very short span of time.

Though creatine supplements allegedly do not have side effects, users have reported that they suffer from mental mood swings, anger, and increased aggressive behavior among other short term side effects. There have been reports from users of upset stomach, diarrhea, cramps, and bloating of the body when starting off on creatine monohydrate, but these side effects become fewer as the body gets used to the supplement. Due to the property of creatine by which lean muscle mass is increased by water retention, some users have experienced obesity and reports of dehydration are also there.

Anger and aggressive behavior seems to be one of the most reported side effect among users, both male and female. Independent users have claimed that they suffered from bouts of depression, and increased aggressiveness when they took creatine. When they stopped taking it, or when they took a break from creatine, they felt “happy” and “light”. The bouts of depression returned when creatine intake was resumed. A reason for this could be the increase of testosterone levels in the users. Testosterone – a male hormone, besides being responsible for growth of muscle mass, increased bone density and development of sex organs, is also said to increase aggressiveness in behavior.

To alleviate such mood swings, users are advised to take lots of water. This also prevents from dehydration which the body suffers due to creatine intake. Creatine should be used responsibly and physicians suggest that the ideal way to do this would be to limit dosages during the cycling of creatine. Users should limit intake to 3 to 5 grams almost every day for three weeks followed by 3 grams two to four times a week. It is also recommended that users take a break from creatine for at least a week, in a month.

Most physicians are of the opinion that not enough studies have been completed on the long and short term effects creatine may have on teenagers. Even when such studies are conducted, the period of study remains, on an average, around two weeks, which physicians claim is a very short span of time to actually adjudge whether creatine is harmful or beneficial.

Not all creatine supplements have obtained the FDA approval. FDA approval to creatine is termed as “loose” by many industry experts, since though creatine is approved, a lot of marketers add more chemicals to pure creatine to lessen side effects and increase effectiveness. For example, one seller alleges that its product does not get converted to creatinine in the human stomach, a compound which is nullify all expected benefits from ingesting creatine. The company claims that it does this by addition of chemicals to prevent conversion of creatine into creatinine. The effects of such additives on the human body haven’t been studied.

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Over the years, numerous nutritional supplements have been purported to affect physiological responses to exercise, enhance training adaptations, and/or improve exercise performance. Although research has generally indicated that many of these nutrients do not affect performance, creatine has consistently proven to be one of the most effective nutritional supplements available to athletes. To date, over 200 research studies have evaluated the safety and effectiveness of short- and/or long-term creatine supplementation in various untrained, trained, and diseased populations. The majority of these studies indicate that short-term creatine supplementation (0.3 g/kg/day for 5 to 7 days) increases muscle creatine and phosphocreatine content by 10-30%, has the ability to improve the ability to maintain high-intensity single effort and/or repetitive sprint performance, and may improve work output during repeated sets of muscle contractions. There is also evidence that creatine supplementation may affect exercise bouts involving anaerobic glycolysis (30 to 150 sec) and high-intensity endurance exercise (150 to 600 see). The improved exercise capacity has been attributed to a creatine­stimulated enhancement of the phosphagen energy system, the buffering of acidity, and the shuttling of mitochondrial ATP by phosphocreatine into the cytoplasm. Additionally, long­term creatine supplementation during training (e.g., 0.3 g/kg/ day for 5-7 days followed by 0.03 to 0.3 g/kg/day) has been reported to increase strength, sprint performance, and training volume, and promote greater gains in fat-free mass and muscle fiber diameter. These findings suggest that creatine supplementation may improve the quality of training, leading to greater training adaptations. Although not all studies report ergogenic benefit, it is my view that, with the exception of carbohydrate, creatine is the most effective nutritional supplement for athletes involved in high-intensity exercise bouts that rely on anaerobic energy systems.

Although creatine has been reported to be an effective ergogenic aid, there have been some concerns regarding the medical safety of creatine supplementation. Some reports, primarily in the popular media, suggest that creatine supplementation may adversely affect renal and liver function, cause long-term suppression of creatine synthesis, alter fluid and electrolyte status-promoting dehydration and muscle cramping, and/or increase the incidence of musculoskeletal injury in athletes. Additionally, some have expressed concern regarding possible side effects of long-term creatine use. Note that there is no evidence from well-controlled short­and/or long-term clinical studies (up to 5 yrs) to support any of these concerns. Furthermore, a number of recent studies that have attempted to evaluate the validity of these concerns have found no adverse effects of short- or long-term creatine supplementation on markers of clinical status.

This said, the question still remains as to whether athletes should take creatine to enhance performance. Adolescent athletes involved in serious training should consider creatine supplementation only with the approval and supervision of parents, trainers, coaches, and qualified health professionals. If the athlete plans to take creatine, quality supplements should be purchased from reputable vendors. Athletic administrators in organized sports who want to establish policies on creatine supplementation for teams should base such policies on the scientific literature. Any formal administration policy should be supervised by a qualified health professional. Although more research is needed, available studies indicate that creatine supplementation does not appear to pose a health risk when taken at recommended doses and may provide therapeutic benefits for various medical populations.

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Creatine or methyl guanidine – acetic acid is a natural energy providing protein which is found in the bodies of vertebrates. Methionine, Arginine and Glycine combine in the liver to form the metabolite we know as creatine.  Ones diet also acts as a source of creatine. Health freaks, body builders and athletes take creatine as a dietary supplement to gain energy for workouts. Skeletal muscles store around 95% of the body’s creatine while the rest is stored in various other parts.

Though creatine is allegedly free of side effects, users have reported several counter effects of creatine. Though most of the side effects reported are not serious and not for a long term, it is advised that users carefully evaluate the use of creatine for their work out regime. Also, physicians and trainers should be contacted to ascertain the dosage and the time of taking creatine.

There have been reports from users of upset stomach, diarrhea, cramps, and bloating of the body when starting off on creatine monohydrate, but these side effects become fewer as the body gets used to the supplement. Due to the property of creatine by which lean muscle mass is increased by water retention, some users have experienced obesity and reports of dehydration are also there.

Anger and aggressive behavior seems to be one of the most reported side effect among users, both male and female. A reason for this could be the increase of testosterone levels in the users. Testosterone – a male hormone, besides being responsible for growth of muscle mass, increased bone density and development of sex organs, is also said to increase aggressiveness in behavior. Independent users have claimed that they suffered from bouts of depression, and increased aggressiveness when they took creatine. When they stopped taking creatine, or when they took a break from creatine, they felt “happy” and “light”. The bouts of depression returned when creatine intake was resumed.

An independent study proclaimed that increased mood swings, depression and anger in creatine users is found because creatine users fail to drink enough water while taking creatine. The study stated that dehydration was the main reason behind such mood swings and, though creatine users are usually advised to drink lots of water, few comply with the advise. It has been recommended that to mitigate side effects, creatine should be taken in a cycle. In the 1st phase or the loading creatine should be taken in large quantities to ‘shock’ the body into accepting it. In the 2nd phase or maintenance phase intake should be lower. After this, creatine intake should be stopped for a period, and then the cycle should be renewed.

To alleviate such mood swings, creatine should be used responsibly and and physicians suggest that the ideal way to do this would be to limit dosages during the cycling of creatine. Users should limit intake to 3 to 5 grams almost every day for three weeks followed by 3 grams two to four times a week. It is also recommended that users take a break from creatine for at least a week, in a month.

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Creatine or methyl guanidine – acetic acid is a natural energy providing protein which is found in the bodies of vertebrates. Skeletal muscles store around 95% of the body’s creatine while the rest is stored in various other parts. Methionine, Arginine and Glycine combine in the liver to form the metabolite we know as creatine.  Ones diet also acts as a source of creatine. Health freaks, body builders and athletes take creatine as a dietary supplement to gain energy for workouts. The most common creatine for dietary supplement purposes is creatine monohydrate.

Creatine Monohydrate is highly reputed diet supplement which improves athletic performance. Creatine is widely used by athletes and bodybuilders for anaerobic exercises, such as weight training. Creatine increases energy reserves, thus by the virtue of its use more energy becomes available for high intensity exercises and recovery is faster after workouts. Creatine monohydrate affects nitrogen production within the body to delay fatigue. When used in a training program creatine allegedly also facilitates muscle repair, and stimulates muscle strength.

Dosage has been a bone of contention among users. “How much is enough?” – is a frequently asked question. When using it, one should keep in mind that not everyone reacts to creatine in the same way. Users having less creatine in the body, like vegetarians, show a quicker and more perceptible reaction to creatine. Meat eaters, who have presence of creatine in their body in comparatively larger quantities, will have a slower reaction. This should not lead the latter group to take higher dosages of creatine.

Athletes using creatine take a “loading dose” of 20 to 25 grams a day for one week; then begin a “maintenance cycle” of 3 to 5 grams per day. The “loading” and “maintenance” dosage recommendations differ from manufacturer to manufacturer. Usually the “maintenance cycle” is continued for a month after which athletes “cycle off” from creatine for a week or so. This follows a resumption of creatine with the “loading dose”. Cycling creatine dosages help athletes to overcome any immunity which the body builds against creatine and take advantage of the extra water weight and strength which comes from reloading.

Manufacturers have claimed that the consumption of creatine monohydrate has no serious adverse effects. There have been reports from users of upset stomach, cramps, and bloating of the body when starting off on creatine monohydrate, but these side effects become fewer as the body gets used to the supplement. Due to the property of creatine by which lean muscle mass is increased by water retention, some users have experienced obesity and reports of dehydration are also there.

It is also important to note here that not all creatine supplements have obtained the FDA approval. FDA approval to Creatine is termed as “loose” by many industry experts, since though creatine is approved, a lot of marketers add more chemicals to pure creatine to lessen side effects and increase effectiveness. For example, one seller alleges that its product does not get converted to creatinine in the human stomach, a compound which is nullify all expected benefits from ingesting creatine. The company claims that it does this by addition of chemicals to prevent conversion of creatine into creatinine. The effects of such additives on the human body haven’t been studied.

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