Sports Nutrition: a Review of Selected Nutritional Supplements for Bodybuilders and Strength Athletes

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Sports Nutrition: A Review of Selected Nutritional Supplements For Bodybuilders and Strength Athletes

Gregory S. Kelly, N.D.

Abstract Because there is widespread belief among athletes that special nutritional practices will enhance their achievements in competition, the use of supplements has become common. Accompanying the growth in supplementation by athletes has been a corresponding increase in exaggerated claims or misleading information. This article reviews several supplements currently popular among bodybuilders and other strength athletes in order to clarify which products can be expected to produce results. Included in the discussion are creatine monohydrate, beta-hydroxy beta-methylbutyrate, whey protein, phosphatidylserine, and selected amino acids and minerals. (Alt Med Rev 1997; 2(3):184-201)

Introduction The increased focus on fitness and subsequent research in the exercise field has ex- panded the role of nutrition as it relates to sports performance. Because there is widespread belief among athletes that special nutritional practices will enhance their achievements in competition, the use of supplements has become common. Although some of the supplements have proven benefits, historically a great deal of the information on products is either misleading or exaggerated. This is perhaps best witnessed in the products marketed to bodybuilders and other athletes concerned with size, strength, and body composition. This article reviews some of the supplements currently promoted in this market in an effort to determine which contribute to maximizing results. Included in the review are creatine monohydrate, beta-hydroxy beta- methylbutyrate (HMB), whey protein, phosphatidylserine, and selected amino acids and minerals.

Creatine Monohydrate Creatine monohydrate has become one of the most popular supplements in the history of bodybuilding. It is used primarily to increase strength and lean body mass and has shown consistent results in promoting these effects in experimental subjects. In humans, over 95% of the total creatine content is located in skeletal muscle, of which approximately one third is in its free form as creatine, also known as methyl-guanidinoacetic acid, while the remainder is present in a phosphorylated form as creatine phosphate (also called phosphocreatine). Creatine phosphate is utilized within skeletal muscle as a means for storing high energy phosphate bonds.

Creatine is formed in the liver, kidney, In addition to its use in skeletal muscle, and pancreas. Initially, arginine and glycine some creatine is used by cardiac muscle. In combine to produce guanidinoacetate. A me- fact, chronic heart failure patients might have thyl group from S-adenosylmethionine (SAM) decreased stores of creatine and have been is then transferred, resulting in the formation shown to have improved exercise capacity of creatine. The byproduct of this reaction, following administration of creatine.4 One S-adenosylhomocysteine, is subsequently hy- week of creatine supplementation (20 g/d) to drolyzed into homocysteine and adenosine. In patients with chronic heart failure increased order to optimize endogenous production of skeletal muscle energy-rich phosphagens and creatine, the amino acids arginine, glycine, and performance as regards both strength and en- methionine must be available as substrates. durance.4 Additionally, magnesium is required as a cofactor to form SAM from methionine, and B12, folic acid and betaine are required to Figure 1. Formulation of Creatine, Creatine recycle the homocysteine to methionine for Phosphate, and Creatinine reuse as SAM. See Figure 1. While creatine can be synthesized Arginine+G Glycine uanidinoacetic Acid+ Ornithine endogenously as described above, creatine is also found in a variety of foods in varying concentrations. The richest source is con- SAM sidered to be wild game, but in domesticated

meats, beef (lean red meat) is the richest SAH source; 1.1 kg of fresh uncooked steak contains about 5 g of creatine.1 Fish is also a good source, especially herring, salmon, and ATP ADP tuna. However, it is believed creatine in foods might be destroyed or reduced signifi- Creatine Creatine Phosphate cantly by cooking. Creatine is transported to muscle tissue where it exists in equilibrium with creatine phosphate. Creatine phosphate spon- Creatinine taneously converts to creatinine (estimated to be at a rate of about 2 g per day for a 150 pound male)2 and is then excreted in the urine. While part of this turnover can be re- Creatine phosphate produces energy in placed through dietary sources of creatine, es- the form of ATP in muscle cells for about 10 pecially meat and fish, the remainder must be seconds of activity. After it is depleted, the supplied by endogenous synthesis. Because of muscle must shift to anaerobic glycolysis for this, there is a constant drain on arginine, gly- fuel. It is thought skeletal muscles are capable cine, methionine, and nutritional cofactors to of storing significantly more creatine than is maintain a supply of creatine and creatine generally supplied by the diet and by phosphate. In vegetarians, daily needs must endogenous synthesis. Because of this, be met exclusively by endogenous synthesis. increased serum creatine, following an oral When dietary creatine is high, the synthetic dose of creatine monohydrate, will be available pathway is correspondingly regulated for storage in muscle tissue. Over time, this downward.3

Alternative Medicine Review ◆ Volume 2, Number 3 ◆ 1997 Page 185 Copyright©1997 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission increased dietary consumption can allow the of 20 g creatine/day. In five of the eight muscle to become saturated with creatine. subjects, there was substantially increased When the muscle has this extra creatine, it muscle total creatine concentration and should theoretically be able to delay fatigue creatine phosphate resynthesis during and refuel itself quicker during high intensity, recovery. In the remaining subjects, creatine short duration exercise, and so should be supplementation slightly increased total capable of greater work. creatine concentration and did not increase When muscle absorbs creatine, it is hy- creatine phosphate resynthesis.6 In three pothesized it also brings water intracellularly subjects measured, uptake into muscle was with it, so the muscle becomes more “hy- greatest during the first two days of drated.” It is estimated muscles are about 70% supplementation, accounting for 32% of the water, so this results in a larger, fuller muscle. total 30 g of creatine monohydrate given orally Evidence suggests when a cell is well hydrated per day. In these subjects, renal excretion was it might accelerate its synthesis of new pro- 40%, 61% and 68% of the creatine dose over teins and might also minimize protein degra- the first three days, respectively. dation.5 Approximately 20% or more of the creatine One gram of creatine monohydrate or taken up was measured as phosphocreatine, less in water produces only a modest rise in while no changes were observed in the muscle plasma creatine concentration; however, a 5 g ATP content.1 oral dose has been shown to significantly in- Oral creatine monohydrate supplemen- crease plasma creatine concentration. Re- tation has also been shown, in a patient with peated dosing with 5 g of creatine monohy- extra pyramidal movement disorder and ex- drate every two hours then sustains the plasma tremely low creatinine concentrations in se- concentration at around 1000 mmmol/l.1 rum and urine, to significantly increase brain Recent studies have shown feeding creatine levels. Phosphorus magnetic reso- large amounts of creatine (typically 20-30 g nance spectroscopy of the brain revealed no per day for five days) increases muscle total detectable creatine-phosphate before oral sub- creatine (and phosphocreatine) content.1, 6 The stitution of creatine and a significant increase extent of the increase normally observed is afterward. Partial restoration of cerebral cre- inversely related to the pre-supplementation atine concentrations was accompanied by im- level.1, 6 Vegetarians, because they have a very provement of the patient’s neurologic symp- low dietary creatine intake and low-normal toms. Oral substitution of arginine, a substrate total creatine content,1 would be expected to for creatine synthesis, was unable to elevate show large increases. Muscle creatine uptake cerebral creatine levels.8 appears to be augmented substantially in indi- Creatine supplementation has been viduals adhering to a program of repeated shown to improve performance in situations high-intensity exercise during the period of where the availability of creatine phosphate is supplementation.1 Adequate vitamin E status important; thus, performance is improved in might also be needed to optimize creatine up- very high-intensity exercise, especially where take.7 Resynthesis of phosphocreatine follow- repeated bursts of energy are required with ing one minute of recovery from intense mus- short recovery periods.9-13 Several studies have cular contraction is accelerated in individuals documented creatine monohydrate’s effect on consuming creatine.6 muscle size and strength. Typically, after a 5- In eight subjects studied, biopsy 7 day loading dose, there is an increase in the samples were taken after five days of ingestion amount of work done in repeated bouts of

maximal exercise and a gain in body mass of Typically, dosing of creatine between 0.5-1.0 kg.10,12 Earnest et al reported monohydrate follows a loading and a following 28 days of supplementation (20g/ maintenance cycle. During the loading period, day), fat-free mass increased by 1.7 kg.9 larger doses of creatine monohydrate are While creatine supplementation in- ingested for 5-7 days. A typical dose for creased performance in sprint-trained cyclists, individuals weighing less than 225 pounds is it does not appear to improve endurance per- 5 g q.i.d., while heavier individuals might take formance.14 Balsom et al actually reported a up to six doses per day. The maintenance dose worsening in performance during prolonged would be 0.03 g/kg body weight.17,18 Larger continuous exercise following creatine supple- doses are probably not of any greater benefit mentation. This finding remains unexplained, since the capability of muscle to take in and although the authors believe the increase in store creatine is finite.1 In fact, this dosing body mass due to supplementation might be a schedule might exceed the ability of most contributing factor.15 Results show creatine individuals to incorporate creatine into muscle supplementation has no measurable effect on tissue as evidenced by the renal excretion rate respiratory gas exchange and blood lactate of creatine (40-68% of the supplemented dose) concentrations during either incremental reported in individuals given 30 grams per submaximal exercise or recovery, suggesting day.1 A recent study supports the possible use creatine phosphate produces energy in the form of lower oral doses. Hultman, et al found 3 g/ of ATP in muscle cells for about 10 seconds d for 28 days increased muscle creatine and of activity. After it is depleted, the muscle must creatine phosphate stores to a level comparable shift to anaerobic glycolysis for fuel. Creatine to a loading phase.17 supplementation does not influence substrate Most of the gains in size and strength utilization during and after this type of exer- occur within the first month, after which cise.16 muscles are generally saturated with creatine. Results from an unpublished human Evidence indicates these gains will remain trial indicate insulin might be a potent while supplementation continues, but will upregulator of a muscle’s ability to take in cre- gradually disappear over time when the atine. This has resulted in many users supple- supplement is discontinued. Typically, levels menting creatine monohydrate with a carbo- of creatine drop back to pre-supplementation hydrate, such as glucose, dextrose, or maltose, levels about one month after discontinuing which simultaneously causes a release in in- supplementation. The size and strength insulin. In a four-week trial, a large increase in creases resulting from improved muscle cell speed, anaerobic power, and lean body mass, hydration also disappear over this same time along with a decrease in body fat was reported interval; however, actual gains in muscle mass in individuals receiving doses of 20 g of cre- due to increased work capacity while on creatine per day for the first five days followed atine will remain. by 10 g a day for the remainder of the four Anecdotal reports suggest 20-30% of weeks. An even greater response in these pa- individuals who take creatine do not respond rameters was reported in the athletes using the with increased muscle mass or strength. Pres- creatine/carbohydrate mix, which contained ently, this finding is unexplained; however, creatine monohydrate, dextrose, taurine, diso- individuals with lower initial tissue levels are dium phosphate, magnesium phosphate, and most likely to benefit.1 Because of the success potassium phosphate. of creatine monohydrate, several other forms have become available, including creatine

Alternative Medicine Review ◆ Volume 2, Number 3 ◆ 1997 Page 187 Copyright©1997 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission phosphate and creatine citrate. These are high-intensity exercise, creatine monohydrate claimed to produce similar results; however, can be incorporated into any supplementation creatine monohydrate is the only form shown protocol. Although quicker results will be seen to date to increase strength, lean body mass, following a loading dose, the cost- and tissue creatine phosphate levels. effectiveness of the 3 g/day dose might be a Reported side effects from creatine more appealing option for many athletes. supplementation include gastric disturbance, headaches, clenched teeth, and the sound of HMB blood rushing in the ear. Creatine HMB (beta-hydroxy beta- supplementation might cause serum creatinine methylbutyrate) is a new product only avail- levels to increase. This is due to the increase able in limited supply since the end of 1995. in muscle creatine phosphate and its The nutritional use of HMB for nitrogen re- subsequent spontaneous conversion to tention has been patented by the Iowa State creatinine. Since most of the studies have only University Research Foundation and is li- supplemented creatine for short periods of censed to Metabolic Technologies. time, and in the single study reporting long HMB is a leucine metabolite. It has not term supplementation only 1 g/day was yet been established how HMB is synthesized utilized,19 it is not currently known whether from leucine in humans; however, in animals long-term, high-dose supplementation has evidence suggests the majority of circulating adverse side-effects. HMB is formed following the transamination Some concern exists that caffeine use of leucine to alpha-ketoisocaproate with its (0.5 mg/kg per day) can have a negative im- subsequent oxidation to HMB.20 It has not been pact on the effectiveness of creatine. However, determined either to what extent HMB is nor- in at least one study, participants were in- mally produced in vivo or which specific co- structed to dissolve the creatine monohydrate factors might influence its production. in tea or coffee before ingestion. Body weight While the mechanism of action of increase was still observed in 7 of 8 subjects HMB is still equivocal, it is hypothesized and all subjects had increased muscle total cre- HMB decreases muscle-protein turnover and atine and phosphocreatine resynthesis.6 Al- might work primarily by minimizing protein though these results suggest caffeine does not degradation. Suggestive evidence of HMB’s negate the results of creatine supplementation, effect at blocking catabolism is based on its until more is known it might be best to mini- ability to decrease urinary 3-methylhistidine mize caffeinated substances, or drink them (a marker of muscle breakdown), and to de- several hours away from supplementation, if crease plasma levels of creatine phosphoki- seeking optimal results. nase and lactic dehydrogenase.21 Anecdotal Creatine supplementation is widely reports indicate individuals who work out practiced by athletes in many sports and does more often and most intensely get the best re- not contravene current doping regulations.3 sults with HMB. This is important since typi- Since creatine supplementation does not cally the more an individual works out, the enhance performance in endurance athletes more muscle catabolism also occurs; so at a and evidence suggests an actual decline in certain point, the anabolic gains achieved by performance, I recommend endurance athletes stimulating the muscles through training are avoid creatine supplementation. In athletes offset by the catabolic effects of frequent, high concerned with improving strength, body intensity workouts. HMB’s anti-catabolic ef- composition, or short-duration repetitive fects might move this balance point further in

the direction of anabolic growth, allowing an similar protein intake of between 120-175 g/ individual to train more often and still receive day for athletes supplementing with HMB. positive results in strength and mass gains. In a human study conducted over a Whey Protein three-week period, 3 g/d of oral HMB Whey protein, often referred to as lac- supplementation was shown to decrease body talbumin, is currently the supplemental pro- fat, increase lean mass and strength, and reduce tein source of choice for many bodybuilders muscle damage in individuals beginning and strength athletes. Whey proteins represent resistance-training exercises. In this trial, the major proteins in human breast milk, as participants also consumed either 117 or 175 opposed to bovine milk which is comprised g/day of protein. While protein intake did not primarily of casein with lesser amounts of seem to impact strength, participants with whey. Whey is comprised of alpha-lactoglo- higher protein intakes, independent of HMB bulin, beta-lactoglobulin, bovine serum albu- supplementation, appeared to have greater min (BSA), and immunoglobulins (IgG1, increases in lean body mass.21 Because these IgG2, Secretory IgA, and IgM). Other com- results were on individuals who had not ponents of the lactalbumin fraction include: previously engaged in weight training, doubt enzymes, iron binding proteins, calcium, po- existed as to whether these results would also tassium, sodium, phosphorous, and vitamins be reproducible in bodybuilders or other A, C, B1, B2, B3, B5, B12, folic acid, and athletes who had already engaged in long-term biotin. Whey is a balanced source of essential resistance training. However, in a subsequent amino acids and peptides with a high protein study, not yet published as a full paper, efficiency ratio. It is considered to be an ex- researchers indicate HMB feeding resulted in cellent source of sulfur amino acids (methion- equal increases in strength, body composition, ine and cysteine), as well as the branched chain and decreased fat in trained and untrained amino acids (leucine, isoleucine and valine), individuals.22 and glutamine. (See sections on branched At this point, the primary concern re- chain amino acids and glutamine for informa- garding HMB is anecdotal evidence which in- tion on their potential benefits). dicates many individuals have not experienced Whey transits the stomach quickly and expected results with this supplement. Since is rapidly absorbed from the human intestine. HMB is thought to function primarily as an The beta-lactoglobulin component remains anti-catabolic substance, it is possible these soluble in the stomach and empties rapidly as individuals did not train with enough inten- an intact protein needing further hydrolysis by sity to optimize its effect. The other possibil- pancreatic enzymes. Casein, on the other hand, ity is, similar to creatine monohydrate, HMB transits the stomach slowly.23 might be ineffective in some individuals. Since Skeletal muscle is the largest reposi- this is such a new supplement, no information tory of metabolically active protein and a ma- is available on its long-term safety. jor contributor to total body nitrogen balance. For athletes wishing to experiment Supplying energy alone (i.e., carbohydrate and with this product, the recommended dosage lipids) cannot prevent negative nitrogen bal- for HMB is 3 g/day. Since relatively high pro- ance (net protein catabolism) in animals or hu- tein intake was reported in the study demon- mans; only provision of protein or amino ac- strating HMB’s efficacy, and because it is un- ids allows the attainment of nitrogen balance. known whether the same results will occur While no studies exist comparing the while on a low-protein diet, I recommend a impact on nitrogen balance, body composition,

Acetyl choline peroxidation but has not been shown to en- CoA hance exercise performance.29 Acetyl CoA (B5 dependent) Glutathione levels have been shown to Choline Phosphatidyl choline decrease with exercise.30 Additionally, running B2 a marathon causes a large increase in the tis- SAM sue content of oxidized glutathione (189%) at B3 the expense of reduced glutathione (-18%).31 Phosphatidyl ethanolamine While no information is available on the ef- Betaine fects of resistance exercise and glutathione

Homocysteine Mg++ levels, it is hypothesized an increased intake Methionine of antioxidants might protect the active per- son against minor muscle injuries.32 Phosphatidyl serine DMG B6 Whey protein is more efficient at in- B2 ducing supernormal glutathione levels than a 33 MN2+ cysteine-enriched casein diet. A whey-rich Glycine Serine CDPdiacylglycerol B6 diet has been shown to increase heart and liver tissue glutathione content in rats. The whey protein diet appeared to also increase longev- ity when fed at the onset of senescence.33 or performance of different protein sources in Whey-based formula enhances cysteine reten- trained athletes, whey has been shown to pro- tion and results in greater taurine excretion, mote growth and enhance nitrogen balance in thought to be a reflection of greater taurine experimental animals, low birth-weight in- stores.34 Whey protein fed to three HIV-sero- fants, and burn victims.24-26 positive individuals over a period of three Whey protein is rich in substrates for months, at doses increasing progressively from glutathione synthesis,27 containing 8.4 to 39.2 g per day, resulted in progressive substantially more cysteine, which is weight gain and increased glutathione levels considered to be a rate-limiting step in in all three cases.35 glutathione synthesis, than does casein. Whey Experimental studies suggest the whey also contains high amounts of glutamine and protein component of milk might exert an in- glycine. hibitory effect on the development of several Glutathione is a powerful antioxidant types of tumors. It is thought the rich supply and is involved in metabolic detoxification of substrates for glutathione synthesis contrib- pathways. The role free radicals play in the utes to this inhibitory effect.36 In experimental development of exercise-induced tissue dam- animals, a diet consisting of 20 g of whey/100 age, or the protective role antioxidants might g diet has been shown to be more protective play, remains to be completely elucidated. Re- than similar diets utilizing casein, soybean, or search has indicated free radical production red meat against dimethylhydrazine-induced and subsequent lipid peroxidation are normal intestinal cancers.37 Peptides from whey pro- sequelae to the rise in oxygen consumption tein have also been shown to have with exercise.28 However, physical training has antithrombotic38 and immunoenhancing been shown to result in an augmented antioxi- activities.38, 39 dant system and a reduction in lipid The primary concerns about supple- peroxidation. Supplementation with antioxi- menting whey protein are the possibility of dants appears to further reduce lipid food allergies, its lactose content, and proposed

links to insulin-dependent diabetes mellitus composition. It is probably in this manner (IDDM). While the possibility of food aller- whey can be best utilized by athletes concerned gies from whey has to be considered, it is prob- with maximizing lean body mass and strength. able it is no more and possibly less antigenic Amino acid availability following a than soy, casein, or egg-based protein supple- workout regulates protein synthesis and deg- ments. A significant concern might be the radation. Because of the anabolic effects of method of processing of the whey protein, insulin on protein synthesis and protein deg- since high temperatures during heating or dry- radation, a rapid synergistic response occurs ing can generate browning reaction products when both amino acids and insulin increase by covalent interaction of proteins and lactose. after a protein-containing meal.43 It is thought Browned proteins have lowered digestibility the body is highly insulin sensitive after exer- and are thought to result in more uptake of cise and preferentially shuttles carbohydrates intact protein through intestinal mucosa. All and protein into muscle cells rather than fat whey protein available contains some degree cells. Experts think this sensitivity gradually of lactose, although many have very low declines post-workout for about two hours amounts. until it again reaches normal sensitivity. The BSA component of whey has been A carbohydrate-whey protein implicated as a possible trigger for IDDM in supplement has been shown to be more children. A similarity exists between the amino effective in generating a plasma insulin acid sequence of the beta cell protein, found response than either a carbohydrate or a protein on the insulin-secreting beta cells of the pan- supplement alone during recovery from creas, and BSA. Because elevated levels of prolonged exhaustive exercise. The rate of anti-BSA antibodies have been found in sera muscle glycogen storage was also significantly from children developing IDDM, it has been faster during the carbohydrate-protein proposed that absorption of BSA, or partially treatment. The participants in this study digested fragments of BSA, stimulate the im- ingested 112.0 g carbohydrate and 40.7 g mune system which then incorrectly destroys protein immediately after each exercise bout.44 beta cells.40 Pardini et al found the prevalence Whey is an excellent choice as a pro- of anti-BSA antibodies was 52% in children tein source for the post-workout shake because with less than one year of IDDM, 47% in chil- of its rapid transit into the small intestine and dren with greater than one year of IDDM, and because of its high levels of branched chain 28% in the control group. They concluded the amino acids and glutamine. Glucose-polymers prevalence of anti-BSA antibodies is higher or maltodextrins are considered to be the best in IDDM subjects than in control subjects; form of carbohydrates to use because of their however, because of the large overlap of anti- ability to stimulate an insulin response. Fat body titers observed in patients and control should not be added because it might slow tran- subjects, anti-BSA antibodies were not sensi- sit and decrease the insulin response. tive nor specific markers of IDDM.41 Ivarsson et al found IgG antibodies to BSA were not Phosphatidylserine significantly increased at onset of IDDM.42 Phosphatidylserine is becoming Currently, the exact nature of the relationship widely used by individuals engaged in between BSA and IDDM remains unclear. resistance training, primarily due to its The routine use of a post-workout presumed ability to prevent muscle tissue shake might be the most important nutritional degradation. Phosphatidylserine has been supplementation habit for enhancing body shown to have an effect on the body’s

Alternative Medicine Review ◆ Volume 2, Number 3 ◆ 1997 Page 191 Copyright©1997 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission production of glucocorticoids. While the Arginine mechanism of action of phosphatidylserine is Arginine is an amino acid which is still unknown, it is proposed it exerts an effect used occasionally by body-builders to stimu- on the hypothalamic-pituitary-adrenal axis.45 late growth hormone secretion. It was very Phosphatidylserine is formed by add- popular in the mid-1980’s; however, interest ing a serine to a phosphatidyl group. This re- in it has since waned. Several studies have quires pyridoxal 5'-phosphate (active B6), and shown its ability to stimulate growth hormone occurs in the same biochemical loop involved and insulin-like growth factor-1 secretion and with phosphatidylcholine, choline, betaine, improve nitrogen balance after IV administra- and dimethylglycine metabolism. tion; however, equivocal results have been ob- (See Figure 2.) tained following oral supplementation. Physical exercise induces a clear-cut Corpas et al found oral arginine/lysine increase in plasma epinephrine, (3 g of each per day) was not a practical means norepinephrine, adrenocorticotropic hormone of chronically enhancing GH secretion in older (ACTH), cortisol, growth hormone (GH), and men.47 Additionally, it is debated whether in- prolactin (PRL). It is theorized if the increase creasing growth hormone levels in people not in cortisol subsequent to intense exercise is already deficient has an anabolic effect. prevented, excess muscle tissue breakdown Arginine is required for creatine might be prevented. Pretreatment of eight synthesis and some believe it will enhance healthy men with both 50 and 75 mg of synthesis if supplemented. In rats, arginine and intravenous brain cortex-derived glycine supplementation increased muscle phosphatidylserine within 10 minutes of the creatine.48 start of exercise blunted the ACTH and cortisol Elam et al reported individuals receiv- responses to physical stress.46 Oral ing arginine and ornithine, five days a week administration of phosphatidylserine derived for five weeks, had higher gains in strength from brain cortex, 800 mg/d for 10 days, and enhancement of lean body mass when significantly blunted the ACTH and cortisol compared with controls. Dosages amounted to responses to physical exercise (P = 0.003 and 2 g or 1 g each of L-arginine and L-ornithine P = 0.03, respectively), without affecting the taken orally, and 600 mg of calcium and 1 g rise in plasma GH and PRL. Although of vitamin C as placebos. Subjects taking the participants also experienced reductions in arginine and ornithine also had significantly plasma cortisol concentrations at a dose of 400 lower urinary hydroxyproline, a marker of tis- mg/day of phosphatidylserine, the area under sue breakdown, than subjects receiving pla- the curve of plasma cortisol was significantly cebo. The authors concluded arginine and or- lower after the higher dose of 800 mg/day.45 nithine, in conjunction with a high-intensity While the results of the work of strength training program, can increase Monteleone et al appear promising, to date no strength and lean body mass, and minimize trials have reported an increase in strength or tissue breakdown.49 an improvement in body composition after Based upon the results of Elam et al it phosphatidylserine supplementation. Until appears a combination of arginine and orni- these results are determined, claims of thine might exert a positive impact on body phosphatidylserine’s ability to decrease muscle composition and strength; however, no addi- tissue catabolism should be considered unsub- tional research has substantiated these stantiated. findings.

Branched-Chain Amino Acids Glutamine Leucine, isoleucine, and valine are Glutamine is the most abundant amino considered branched-chain amino acids acid in the blood and in the free amino acid (BCAAs) because of their similar chemical pool of skeletal muscle. Glutamine stimulates structures and interlocking methyl groups. the synthesis and inhibits the degradation of Exercise results in marked alterations in amino proteins, is an important vehicle for the trans- acid metabolism within the body. The port of nitrogen and carbon within the tissues, branched-chain amino acids, especially leu- stimulates the synthesis of hepatic glycogen, cine, are particularly important since they con- and is an energy source for cell division.54 tribute as energy substrates and as nitrogen Because glutamine deficiency can occur dur- donors in the formation of alanine, glutamine ing periods of metabolic stress, it has led to and aspartate. Calculations indicate the rec- the reclassification of glutamine as a condi- ommended dietary intake of leucine is inad- tionally essential amino acid.55 Glutamine is equate, since it is lower than the measured also a precursor for the synthesis of amino whole-body rates of leucine oxidation. This acids, proteins, nucleotides, glutathione, and inadequacy is exacerbated in individuals who other biologically important molecules. are physically active.50 Glutamine is considered to have an Results indicate an increased supply of anabolic effect on skeletal muscle. It stimu- BCAA might have a sparing effect on muscle lates the synthesis and inhibits the degrada- glycogen degradation during exercise.51 Short- tion of proteins. Experiments with various term (3-4 hours) infusion of branched-chain animal models have demonstrated glutamine amino acids has been shown to suppress supplementation can result in better nitrogen muscle protein breakdown.52 In humans homeostasis, with conservation of skeletal nourished parenterally, provision of balanced muscle.55 The mechanism by which glutamine amino acid solutions or of only the three affects skeletal muscle protein turnover, and BCAA cause similar improvements in nitrogen thus muscle protein balance, is unknown. balance for several days.43 However, glutamine has an anabolic effect of Administration of BCAA can greatly promoting protein synthesis and also might increase their concentration in plasma and sub- reduce protein breakdown.56 sequently their uptake by muscle during exer- Glutamine was shown to increase cell cise.51 Long-term exercise following BCAA volume, while insulin and glutamine together administration results in significantly greater seem to work synergistically to enhance cel- muscle NH3, alanine and glutamine produc- lular hydration. The effects of glutamine in tion, as well as lower lactate production, than skeletal muscle include the stimulation of pro- is observed during exercise without BCAA tein synthesis, which occurs in the absence or supplementation.53 presence of insulin, the response being greater While evidence indicates BCAA might with insulin.57 be significant in enhancing protein synthesis During various catabolic states, such or minimizing protein degradation, supple- as infection, surgery, burns, and trauma, mentation with these amino acids has not pro- glutamine homeostasis is placed under stress, duced significant changes in body composi- and glutamine reserves, particularly in the tion. Because of this I would not recommend skeletal muscle, are depleted. In these condi- additional supplementation if consuming a tions, the body requirements of glutamine ap- protein drink. If whey or another top quality pear to exceed the individual’s muscle depo- protein formula is being used, adequate sits, resulting in a loss of muscle mass.58 In amounts of BCAA are provided.

Alternative Medicine Review ◆ Volume 2, Number 3 ◆ 1997 Page 193 Copyright©1997 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission critically ill patients, parenteral glutamine re- minutes after the glutamine administration duces nitrogen loss and causes a reduction in load, both plasma bicarbonate concentration mortality.54 and circulating plasma growth hormone con- With regard to glutamine metabolism, centration were elevated.63 exercise stress can be viewed in a similar light Although some advocates recommend to other catabolic stresses. Plasma glutamine as much as 30 g, it is likely only marginal ben- concentrations increase during prolonged, efits are found at supplementary levels higher high-intensity exercise. However, during the than 2-3 g per day. post-exercise recovery period, plasma concentrations decrease significantly. Several Ornithine Alpha Keto-Glutarate hours of recovery are required before plasma (OKG) levels are restored to pre-exercise levels. If Ornithine alpha-ketoglutarate (OKG) recovery between exercise bouts is inadequate, is a salt formed of two molecules of ornithine the acute effects of exercise on plasma and one molecule of alpha-ketoglutarate. OKG glutamine concentrations can be cumulative. has been successfully used by the enteral and It has been observed that overtrained athletes parenteral route in burn, traumatized, and sur- appear to maintain low plasma glutamine gical patients, and in chronically malnourished levels for months or years.59 Some experts subjects. According to the metabolic situation, believe reduced concentration of plasma OKG treatment decreases muscle protein ca- glutamine can provide a good indication of tabolism and/or increases synthesis. In addi- severe exercise stress.60 tion, OKG promotes wound healing. The Results suggest, after exercise, the mechanism of action of OKG is not fully un- increased availability of glutamine promotes derstood, but the secretion of anabolic hor- muscle glycogen accumulation by mones (insulin, human growth hormone), and mechanisms possibly including diversion of the synthesis of metabolites (glutamine, glutamine carbon to glycogen.61 polyamines, arginine, ketoacids) might be in- Following trauma there is a loss of ni- volved.64 trogen, with a concomitant reduction of skel- This supplement has been available for etal muscle protein synthesis. This is accom- several years. It has been used successfully in panied by a decrease in the stores of muscle hospitalized burn victims to slow protein loss. free glutamine. Nutritional support with either In one study on physical performance, OKG glutamine or its carbon skeleton, alpha-keto- (10 g/day with 75 g of carbohydrates) was glutarate, has been shown to counteract the given for six weeks. The OKG group experi- postoperative fall of muscle free glutamine and enced a significant increase in bench press of muscle protein synthesis.62 strength and biceps circumference. Body Evidence suggests oral glutamine weight and percent fat were not different be- supplementation results in an increased release tween groups. No differences in growth hor- of growth hormone. An oral glutamine load mone levels were seen between groups. Body (2 g) was administered to nine healthy sub- composition changes were seen among sev- jects to determine the effect on plasma eral individuals in the OKG group but no sig- glutamine, bicarbonate, and circulating growth nificance was found either within or between hormone concentrations. Eight of nine subjects experimental groups.64 responded with an increase in plasma Anecdotal reports from some individu- glutamine at 30 and 60 minutes before return- als supplementing with OKG indicate in- ing to the control value at 90 minutes. Ninety creased appetite and better disposition to train.

Some anecdotal reports claim great results Boron while others experience no results. If OKG is Recently, a proliferation of athletic utilized as a supplement, the dosage recom- supplements has been marketed touting boron mended is 10 g along with a 75 g carbohy- as an ergogenic aid capable of increasing tes- drate drink. tosterone. While this might to be true in some populations under specific conditions, boron’s Vitamin C impact on testosterone is still equivocal. There have been several investigations Boron appears to increase testosterone during the past four decades of the potential levels in rats in a time- and dose-dependent effect of high-dose vitamin C supplementation manner.69 In postmenopausal women, on physical performance. However, the results increasing dietary intake of boron from 0.25 have been equivocal. Most studies could not to 3.25 mg/d has been reported to more than demonstrate an effect. On the other hand, a double plasma testosterone.70 In a subsequent suboptimal vitamin C status results in an im- study of healthy men, boron supplementation paired working capacity which can be normal- resulted in an increase in the concentrations ized by restoring vitamin C body pools.65 of both plasma estrogen and testosterone.71 A potent antioxidant required for However, Beattie and Peace reported changing collagen synthesis, ascorbic acid might help boron intake had no impact on testosterone protect muscles from excessive damage due levels in postmenopausal women.72 to training or trauma. Data suggests prior The effect of boron supplementation vitamin C supplementation might exert a was investigated in 19 male bodybuilders ages protective effect against exercise-induced 20-27 years. Ten were given a 2.5-mg boron muscle damage.66 supplement, while nine were given a placebo Ascorbic acid might decrease cortisol every day for seven weeks. Both groups production.67 It has also been suggested ascor- demonstrated significant increases in total bic acid might have a role in facilitating an testosterone, lean body mass, and one- adequate response to stress.68 repetition maximum squat and bench press; Because of ascorbic acid’s potential for however, analysis of variance indicated no minimizing muscle damage and cortisol-in- significant effect of boron supplementation on duced muscle catabolism, it is recommended any of the dependent variables. The authors that 1-3 grams be supplemented daily. concluded the gains were a result of seven weeks of bodybuilding, not of boron Minerals supplementation.73 There are at least 60 trace minerals It is prudent to supplement the diet with having some impact on health in animal mod- 3 mg of boron per day to ensure against defi- els. Many of these have not been adequately ciency; however, an expectation of increased studied in humans, and even fewer have been strength and improved body composition is un- looked at for their effect on athletic perfor- realistic. mance. While it is possible deficiency in any of these trace minerals would detrimentally Chromium impact performance, this review will selec- Chromium is highly promoted in body- tively focus on boron, chromium, selenium, building circles as a fat-burning supplement vanadium, and zinc. and as an aid in increasing lean mass. Avail- able research does not support either of these claims.

Alternative Medicine Review ◆ Volume 2, Number 3 ◆ 1997 Page 195 Copyright©1997 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission Changes in body weight, a sum of three suggest routine chromium supplementation body circumferences, a sum of three skinfolds, has no beneficial effects on body composition and the one-repetition maximum for the squat or strength gain in men, although it must be and bench press were examined in 59 college- noted the placebo group received a trace level age students over a 12-week weightlifting pro- of chromium.78 gram. Half of the students were given 200 mcg/ Evidence strongly indicates supple- day elemental chromium as chromium mentation of chromium will not enhance picolinate, while the other half received a pla- strength or body composition. Similar to bo- cebo. No treatment effects were seen for the ron, chromium-rich foods or a supplement strength measurements. The only significant containing chromium should be included in treatment effect found was an increase in body the diet to avoid deficiency; however, it is weight observed in the females supplement- unrealistic to expect gains in strength or im- ing with chromium.74 provement in body composition. The effects of nine weeks of daily chromium supplementation (200 mcg chromium Selenium as picolinate) were investigated in a double- Selenium is a trace mineral which is blind design in football players during spring utilized as a cofactor in several enzymes. It is training. Chromium picolinate supplementa- commonly found in antioxidant formulas be- tion was ineffective in bringing about changes cause of its role as a cofactor in the enzyme in body composition or strength.75 glutathione peroxidase. Evidence suggests the Hallmark et al found 200 mcg of administration of organic selenium partially chromium supplemented to untrained males compensates for and decreases the intensity (23 +/- 4 yr), in conjunction with a progressive, of oxidative stress in athletes.79 While optimal resistive exercise training program, did not antioxidant status is critical to athletes, sele- promote a significant increase in strength and nium might have an additional role in the de- lean body mass, or a significant decrease in termination of body composition. Selenium percent body fat.76 deficiency can affect the metabolism of thy- Trent et al conducted a double-blind, roid hormones. Iodothyronine 5'-deiodinase, placebo-controlled protocol for 16 weeks. which is mainly responsible for peripheral T3 Chromium as picolinate (400 mcg) or a pla- production, has been demonstrated to be a se- cebo were distributed to designated individu- lenium-containing enzyme.80 In rats fed a se- als. At the end of 16 weeks, the chromium lenium-deficient diet, hepatic iodothyronine 5'- group failed to show a significantly greater re- deiodinase is decreased by 47%. Lower con- duction in either percent body fat or body centrations of T3 and T4 have also been dem- weight, or a greater increase in lean body mass, onstrated in selenium-deficient animals.81 Re- than did the placebo group. It was concluded duced peripheral conversion of T4 to T3 sec- chromium picolinate was ineffective in en- ondary to a selenium deficiency might create hancing body fat reduction in this group.77 a functional hypothyroidism which would be Lukaski et al investigated the effects expected to adversely impact body of eight weeks of daily chromium composition. supplementation in 36 men in a double-blind design. Strength, mesomorphy, fat-free mass, Vanadium (Vanadyl Sulfate) and muscle mass increased with resistance Vanadium as vanadyl sulfate is widely training independently of chromium utilized by athletes seeking to improve body supplementation (P < 0.0001). These findings composition. It is generally promoted as

having an anabolic effect which enhances the abnormalities of puberty, growth, or muscu- transport of amino acids into cells. Several lar performance.86 studies have indicated its ability to reduce Some investigators have concluded fasting glucose and improve hepatic and zinc might play an important role in modulat- peripheral insulin sensitivity in non-insulin- ing serum testosterone levels in normal men. dependent diabetic humans.82-84 However, Prasad et al observed dietary zinc restriction vanadyl sulfate does not appear to alter insulin in normal young men is associated with a sig- sensitivity in nondiabetic subjects.84 A single nificant decrease in serum testosterone con- study reported the effect of oral vanadyl sulfate centrations. They also reported zinc supple- (0.5 mg/kg/day) on anthropometry, body mentation of marginally zinc-deficient normal composition, and performance in a 12-week, elderly men resulted in an increase in serum double-blind, placebo-controlled trial testosterone from 8.3 +/- 6.3 to 16.0 +/- 4.4 involving 31 weight-training volunteers. No nmol/L (p = 0.02).87 It is important to remem- significant treatment effects for ber, while zinc deficiency might inhibit test- anthropometric parameters and body osterone production, zinc supplementation to composition were observed. Both groups had an individual with adequate levels has not been similar improvements in performance in most shown to produce excess testosterone. exercises; however, a significant improvement Zinc deficiency might result in reduced in one repetition-maximum leg extension was production of growth hormone (GH) and/or found in the treatment group. The authors insulin-like growth factor-I (IGF-I).88 Oral zinc concluded that although vanadyl sulfate was replacement has normalized growth hormone ineffective in changing body composition in levels and increased growth rate in teenagers weight-training athletes, its performance- found to be GH deficient.89 Zinc enhancing effect required further supplementation causes a significant increase investigation.85 Anecdotal reports indicate in liver synthesis of IGF-I (somatomedin C). bodybuilders often supplement 15 mg t.i.d., In chronic zinc deficiency, reduced liver however, this practice is ill-advised due to both production of IGF-I is responsible for reduced the lack of demonstrated efficacy and the lack physical growth; moreover, in this situation, of information regarding long-term toxicity of receptor resistance to IGF-I (in addition to GH) high doses of vanadium. has been demonstrated. Receptor sensitivity is reestablished after supplementation with Zinc zinc. Zinc also might play a role in increasing Dietary deficiency of zinc is prevalent. the number of receptors.90 Because of this, zinc supplements have been Zinc deficiency might affect the me- widely advocated for athletes. While it might tabolism of thyroid hormones. The structure not be wise to indiscriminately administer zinc, of nuclear thyroid hormone receptors contains suggestive evidence indicates zinc might im- zinc ions, crucial for the functional properties pact body composition due to its interaction of the protein.80 In experimental animals, zinc with a variety of hormones. deficiency decreases concentrations of tri- It is thought intense exercise can re- iodothyronine (T3) and free thyroxine (fT4) sult in changes in zinc metabolism. Zinc has in serum by approximately 30% when com- been demonstrated to be lowered in trained pared with zinc-adequate controls. The con- adolescent gymnasts and even lower in fe- centration of thyroxine (T4) in serum was not males in the general population. Brun et al affected by zinc deficiency. In these animals, suggested this reduction might play a role in zinc deficiency also decreased the activity of hepatic iodothyronine 5'-deiodinase by 67%.81

Alternative Medicine Review ◆ Volume 2, Number 3 ◆ 1997 Page 197 Copyright©1997 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission Because of the multiple interactions of 2. Walker JB. Creatine biosynthesis, regulation zinc with hormones critical to strength and and function. Adv Enzymol 1979;50:117-242. body composition, it is recommended athletes 3. Maughan RJ. Creatine supplementation and exercise performance. Int J Sport Nutr get a determination of zinc nutriture and 1995;5:94-101. supplement if required. 4. Gordon A, Hultman E, Kaijser L, et al. Creatine supplementation in chronic heart Conclusion failure increases skeletal muscle creatine phosphate and muscle performance. Based upon available information, Cardiovasc Res 1995;30:413-418. strength athletes are likely to obtain improved 5. Haussinger D, Roth E, Lang F, Gerok W. results by following a supplementation rou- Cellular hydration state: an important determi- tine which includes creatine monohydrate (at nant of protein catabolism in health and least 3 g/d), a post-workout protein shake (40 disease. Lancet 1993;341:1330-1332. g of protein), vitamin C (1-3 g/d), and a multi- 6. Greenhaff PL, Bodin K, Soderlund K, Hultman E. Effect of oral creatine supplemen- vitamin/mineral formulation which contains tation on skeletal muscle phosphocreatine approximately 3 mg of boron, 200 mcg of resynthesis. Am J Physiol 1994;266:E725- chromium, 200 mcg of selenium, 100 mcg of E730. vanadium, and 15 mg of zinc. The published 7. Gerber GB, Gerber G, Koszalka TR, et al. results to date on HMB are impressive; how- Creatine metabolism in vitamin E deficiency ever, because of its high price, it should be in the rat. Am J Physiol 1962;202:453-460. 8. Stöckler S, Holzbach U, Hanefeld F, et al. tried only if results either plateau or are not Creatine deficiency in the brain: a new, obtained with the above supplementation pro- treatable inborn error of metabolism. Pediatr tocol. I do not currently recommend Res 1994;36:409-413. phosphatidylserine for several reasons. It has 9. Earnest CP, Snell PG, Rodriguez R, et al. The not been demonstrated yet to produce bottom- effect of creatine monohydrate ingestion on aerobic power indices, muscular strength and line results of improved strength or body com- body composition. Acta Physiol Scand position, and it is very expensive to dose at 1995;153:207-209. 800 mg/d. I also do not routinely recommend 10. Balsom PD, Söderlund K, Sjödin B, Ekblom isolated amino acids, with the exception of B. Skeletal muscle metabolism during short glutamine. Although compelling evidence duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand could be used to make an argument for many 1995;154:303-310. of the isolated amino acids, my bias is that a 11. Dawson B, Cutler M, Moody A, et al. Effects high-quality protein supplement, such as whey, of oral creatine loading on single and repeated provides adequate levels of all of the amino maximal short sprints. Aust J Sci Med Sport acids for the majority of athletes. Because of 1995;27:56-61. the correlation of low glutamine levels and 12. Greenhaff PL, Casey A, Short AH, et al. over-training, supplementation with two grams Influence of oral creatine supplementation of muscle torque during repeated bouts of per day of glutamine, in addition to a protein maximal voluntary exercise in man. Clin Sci supplement, should be considered in individu- 1993;84:565-571. als whose training regimen places them at risk 13. Birch R, Noble D, Greenhaff PL. The influ- for over-training. ence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man. Eur J Appl Physiol References 1994;69:268-276. 1. Harris RC, Söderlund K, Hultman E. Elevation 14. Cooke WH, Grandjean PW, Barnes WS. Effect of creatine in resting and exercised muscle of of oral creatine supplementation on power normal subjects by creatine supplementation. output and fatigue during bicycle ergometry. J Clin Sci 1992;83:367-374. Appl Physiol 1995;78:670-673.

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