Exercise Supplementation

A dietary supplement is something used to provide nutrients to the body that may be lacking in sufficient and necessary quantities. Dietary supplements are commonly used by those involved in certain athletic activities and recreation. They may be used to help replace meals, increase lean muscle mass/decrease fat composition and/or improve performance in a particular physical activity.

Some common supplements include: vitamins, protein powders, creatine, glutamine, omega-3 fish oils, branched chained amino acids (BCAAs), etc.

Creatine (also known as alpha-methyl-guandino-acetic acid) is a nitrogen containing organic acidic compound that is naturally occurring in vertebrates. It is an “instant energy” supply to skeletal muscle cells.

Creatine is widely distributed throughout the body with 95% of it in skeletal muscle and 5% in the brain, kidney, liver and testicles. It can be obtained through the diet (approx. 1g/day) and is synthesized by the body (approx. 1g/day). Liver and kidney are perhaps the largest producers of this substance. (1)

Steps of biological creatine synthesis:

1. Glycine + arginine catalyzed by AGAT (Arginine:glycine amidinotransferase) gives you ornithine (1)

2. 5-adenosylmethionine donates a methyl group to guandinoacetic acid and ornithine and guanidinoacetic acid gives you creatine, catalyzed by GAMT (Guanidinoacetate N-methyltransferase) (1)

3. Creatine becomes phosphorylated by creatine kinase to become phosphocreatine, this reaction is spontaneous (1)

4. Creatine and/or phosphocreatine gets catalyzed by creatine amidohydrolase to become creatinine (1)

5. Creatine may also become catalyzed by glycine oxidase to become urea (1)

Very little Cr is found at the sites of production (liver and kidneys) and therefore require transportation to areas of storage and utilization. Organs with the highest amount of AGAT and GAMT contain the least creatine kinase, which is the enzyme responsible for the conversion of creatine (Cr) to phosphocreatine (PCr) (the biologically active form of creatine). Thus it enters blood to reach other tissue systems through a transporter known as CreaT (a concentration gradient sodium and chloride dependent transporter), this transporter is found in kidneys, heart, skeletal muscle, brain, testicles and colon; but not in liver, pancreas and intestine. The highest proportion of Cr is found in type II skeletal muscle fibres. (1)

If there is excess ATP, creatine gets phosphorylated to become PCr. This PCr acts like a storage molecule (temporal and spatial buffer) and when ATP is needed during intense activity, PCr can readily and anaerobically donate a phosphate group to ADP to regenerate ATP following the first 10 seconds of intense muscular/physical effort. Cr gets phosphorylated with ATP to form PCr and ADP. The large negative charge on phosphocreatine prevents diffusion across biological membranes thus locking phosphocreatine in the muscle cell. (1)

The purpose of using creatine as an exercise supplement is to give an individual a final burst of energy to push through the last set of their routine, resulting in a more efficient workout.

A 28 day-long study by Kreider et al. (1998) on 28 NCAA division IA football players during the off-season was done to test the use of creatine on their athletic performance. It was made sure that no participants were taking anabolic steroids or any other form of ergogenic aids, and all maintained their normal diets and their foods were mostly similar with little variation. This was a double-blind study, and the drinks made with the control and experimental groups had similar taste so there would be no subjective bias. (2)

The results showed that both groups increased in total body weight, however the experimental group had significantly greater gains in total body weight, had an increase in bench press lifting volume, and an increased sprint performance. (2)

Although there are some reservations about using creatine due to probable side effects, there were no reports of ill side effects in this study (e.g. gastrointestinal distress and/or other symptoms). There were also no significant differences in nutritional intake, and no significant blood chemistry alterations other than a higher concentration of creatinine (waste product of creatine). (2)

The study concluded that creatine may provide ergogenic benefit with little cost. (2)

There have been numerous anecdotal reports of Cr supplementation causing gastrointestinal, cardiovascular and muscular problems but they remain indefinite.

Nausea, vomiting and diarrhea have been reported, however many blind performances failed to reproduce this observation. It is possible that the co-ingestion of other substances may have partially accounted for these reports. However, taking creatine during exercise had increased reports of post-exercise distress.

Renal function was altered due to the increased amounts of urinary creatine and creatinine. However, it is important to state that the only individuals who experienced distress after creatine supplementation had pre-existing renal dysfunction (e.g. nephritis). (3)

Muscle cramps, strain, damage and particular “stiffness” have been reported in athletes supplementing with Cr. However, there is no definite evidence from controlled studies that implicate Cr supplementation in muscle dysfunction in healthy individuals and/or patients with neuromuscular disease. It is recommended to consume adequate amounts of water and electrolytes to try to minimize the risk of cramps and discomfort during physical strenuous activity. (3)

Pediatrics and pregnancy (lactation) have no definite evidence for creatine supplementation in terms of safety and efficacy. Therefore it is not advised for the pediatric population (under 18 years of age) as well as pregnant and lactating mothers to supplement with Cr. (3)

In conclusion, the myths surrounding the dangers of creatine supplementation seem to be unfounded, however many studies always look at short-term creatine usage. The fact that Cr is a naturally occurring compound does not necessarily make it safe. It may be essential in moderation but can always be detrimental in excess. It is recommended that you take 5g/day for a month then go off for a month. Safe loading phases can go as high as 20g/day for a week, lowering the dose every week. (3)

Branched chain amino acids include 3 of the 9 essential amino acids, leucine, isoleucine and valine. They account for approximately 35% of the essential amino acids in muscle proteins and 40% of the preformed amino acids required by mammals. Supposed benefits of BCAAs include improved immune function, reduced fatigue, reduced levels of exercise-induced muscle damage and increased levels of post-exercise muscle growth. It is also believed that these BCAAs play a role in contributing as an energy source. (4)

Exercise increases oxidation of BCAAs in body, these oxidation products are toxic in high concentrations (e.g. branched-chain alpha-keto acids [BCKA], therefore they must be disposed of to maintain homeostasis. (4)

BCAA Catabolism

1. Reversible transanimation of BCAA to produce BCKA, catalyzed by branched-chain amino transferase (4)

2. Irreversible oxidative decarboxylation of BCKA to form coenzyme A (CoA) compounds, catalyzed by branched-chain alpha keto acid dehydrogenase (BCKDH) complex; this is the rate-limiting step of BCAA catabolism and is therefore subject to very tight regulation; the BCKDH complex is regulated by a phosphorylation-desphosphorylation cycle and BCKDH kinase is responsible for the inactivation of the complex by phosphorylation of the E1 component of the complex and BCKDH phosphatase (less certain about this enzyme, not as much information in the scientific literature) is responsible for the reaction of the complex by dephosphorylation. (4)

Essentially, increasing exercise decreases the activity of the BCKDH kinase in skeletal muscle and increasing the activity of the BCKDH complex causing breakdown of BCAAs (4)

In this study, young healthy male and female adults who did not exercise regularly were recruited to test the effects of BCAAs on the human body. (5)

An oral BCAA supplement in the proportion of 77 mg/kg body weight, was given to the test subjects before exercise. The results of this study show that an intake of 5g BCAA supplementation increased intracellular and arterial BCAA levels during exercise, which resulted in decreased muscle protein breakdown, and therefore decreased delayed-onset muscle fatigue, and fatigue in general. (5)

Research commonly cited include test subjects who don’t normally consume the adequate amount of protein and do not exercise on a daily basis. This does not make any logical sense in that those who do not exercise on a regular basis are not very likely to take any exercise supplements, and the bodies of those who are more used to exercise may react differently than those who are not as active. Not a lot of conclusive research has been done on active or athletic people who could benefit from this nutritional supplement. (6)

BCAAs are commonly found in foods such as chicken breast, eggs, salmon, peanuts, etc. It seems like a waste of money to buy the BCAA supplement when they are readily available from healthy, nutrient-rich foods like those listed above. (6)

Amino acid imbalances may occur with the use of BCAAs, simply because inducing the same few amino acids may offset the healthy proportion of these amino acids with the others that are present in the human body.(6)

(1)Persky, A. M., & Brazeau, G. A. (2001). Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacological Reviews, 53(2), 161-176.

(2)Kreider, R. B., Ferreira, M., Wilson, M., Grindstaff, P., Plisk, S., Reinardy, J., … & Almada, A. L. (1998). Effects of creatine supplementation on body composition, strength, and sprint performance. Medicine and science in sports and exercise, 30(1), 73-82.

(3)Terjung, R. L., Clarkson, P., Eichner, E. R., Greenhaff, P. L., Hespel, P. J., Israel, R. G., … & Williams, M. H. (2000). American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Medicine and Science in Sports and Exercise, 32(3), 706-717.

(4)Shimomura, Y., Murakami, T., Nakai, N., Nagasaki, M., & Harris, R. A. (2004). Exercise promotes BCAA catabolism: effects of BCAA supplementation on skeletal muscle during exercise. The Journal of nutrition, 134(6), 1583S-1587S.

(5)Shimomura, Y., Yamamoto, Y., Bajotto, G., Sato, J., Murakami, T., Shimomura, N., … & Mawatari, K. (2006). Nutraceutical effects of branched-chain amino acids on skeletal muscle. The Journal of nutrition, 136(2), 529S-532S.

(6)http://www.muscleforlife.com/bcaa-supplement/