EFFECTS OF PROTEIN AND AMINO-ACID SUPPLEMENTATION ON ATHLETIC PERFORMANCE
Richard B Kreider PhD
Exercise & Sport Nutrition Laboratory, Department of Human Movement Sciences & Education, The University of Memphis, Memphis, Tennessee 38152. Email: email@example.com
Sportscience 3(1), sportsci.org/jour/9901/rbk.html, 1999 (5579 words)
Reviewed by Brian Leutholtz PhD, Department of Exercise Science, Physical Education, and Recreation, Old Dominion University, Norfolk, Virginia
Amino acids are the building blocks of protein in the body; assuch they are essential for the synthesis of structural proteins,enzymes, and some hormones and neurotransmitters. Amino acids arealso involved in numerous metabolic pathways that affect exercisemetabolism. Consequently, it has been suggested that athletesinvolved in intense training require additional protein in the dietor that they should supplement their diet with specific amino acids.I review here the rationale and the evidence for the potentialergogenic effect of short-term supplementation with protein and aminoacids and the evidence for the potential anabolic effect oflonger-term use when supplementation is combined with training. Ideal first with protein, then with the amino acids under thefollowing headings: the potentially anabolic amino acids; thebranched-chain amino acids, which have a somewhat different role inmetabolism and in their potential effect on performance; glutamine,which is in a class of its own for its effects on the immune system;creatine, an amino acid that is not one of the building blocks ofprotein but is involved in short-term energy production in muscle;and hydroxymethylbutyrate (HMB), a potentially anabolic metabolite ofthe amino acid leucine.
This review is an update rather than an exhaustive account of allpublished works on the topic. I have cited two books, 60 researcharticles, 10 published abstracts, and 18 review articles/bookchapters from my own database of references. In my database there area further 97 research articles, 78 abstracts, and 38 reviewarticles/book chapters on the topic. These additional references arereviewed elsewhere (Kreider, 1999; Kreider,1998; Williams et al., 1999). Downloadthe complete list as a Word 97 file by clicking on thislink.
More recently, there has been interest in determining the effectsof pre- and post-exercise carbohydrate and protein feedings onhormonal responses to exercise (Cade et al.,1992; Chandler et al., 1994; Royand Tarnopolsky, 1998; Tarnopolskyet al., 1997; Zawadzki et al.,1992). Ingestion of protein with carbohydrate has been reportedto increase insulin and/or growth hormone levels to a greater degreethan ingestion of carbohydrate alone (Chandleret al., 1994; Zawadzki et al.,1992). Consequently, ingesting protein and carbohydrate prior toexercise may serve as an anti-catabolic nutritional strategy(Carli et al., 1992). Further, ingestingcarbohydrate and protein following exercise may promote a moreanabolic hormonal profile, glycogen resynthesis, and/or hastenrecovery from intense exercise (Roy andTarnopolsky, 1998; Roy et al., 1997).Over time these alterations may allow an athlete to tolerate trainingto a greater degree and/or promote greater training adaptations, butthe evidence is not yet clear.
One of the commonly purported benefits of amino acidsupplementation is that certain amino acids (e.g., arginine,histidine, lysine, methionine, ornithine, and phenylalanine) maystimulate the release of growth hormone, insulin, and/orglucocorticoids, thereby promoting anabolic processes (Kreider,1993). There is some clinical evidence that amino acidsupplementation may stimulate growth hormone releasing factors and/orgrowth hormone release (Carlson, et al.,1989;; Garlick and Grant, 1988;Iwasaki et al., 1987; Merimeeet al., 1969). For example, intravenous arginine and ornithineinfusion have been used clinically for stimulating growth hormonerelease (Carlson et al., 1989; Iwasakiet al., 1987). In addition, preliminary clinical studiesindicated that protein (20 to 60 g); arginine and lysine (1.2 g); andornithine (70 mg/kg) increased growth hormone and somatomedinconcentrations in the blood (Bucci et al., 1990;Jackson et al., 1968; Isidoriet al., 1981). However, other researchers have not replicatedthese findings, particularly in healthy individuals (Lemon,1991). There is also little evidence that supplementation ofthese amino acids during training significantly affects bodycomposition, strength, and/or muscle hypertrophy (Kreider,1999). Consequently, the effects of amino acid supplementation ongrowth-hormone release and training adaptations are as yetunclear.
Researchers have expended a considerable amount of effort onevaluating the effects of supplementation of branched-chain aminoacids (BCAAs: leucine, isoleucine, and valine) on physiological andpsychological responses to exercise (Blomstrandet al., 1991; Kreider, 1998; Wagenmakers,1998). There are two primary hypotheses regarding the ergogenicvalue of supplementation with these amino acids.
First, BCAA supplementation has been reported to decreaseexercise-induced protein degradation and/or muscle enzyme release (anindicator of muscle damage) possibly by promoting an anti-catabolichormonal profile (Carli et al., 1992;Coombes and McNaughton, 1995).Theoretically, BCAA supplementation during intense training may helpminimize protein degradation and thereby lead to greater gains infat-free mass. Although several studies support this hypothesis,additional research is necessary to determine the long-term effectsof BCAA supplementation during training on markers of catabolism,body composition, and strength (Kreider,1998).
Second, the availability of BCAA during exercise has beentheorized to contribute to central fatigue (Newsholmeet al., 1991). During endurance exercise, BCAAs are taken up bythe muscles rather than the liver in order to contribute to oxidativemetabolism. The source of BCAAs for muscular oxidative metabolismduring exercise is the plasma BCAA pool, which is replenished throughthe catabolism of whole body proteins during endurance exercise(Davis, 1995; Kreider,1998; Newsholme et al., 1991).However, the oxidation of BCAAs in the muscle during prolongedexercise may exceed the catabolic capacity to increase BCAAavailability, so plasma BCAA concentration may decline duringprolonged endurance exercise (Blomstrand etal., 1988; Blomstrand et al., 1991).The decline in plasma BCAAs during endurance exercise can result inan increase in the ratio of free tryptophan to BCAAs. Free tryptophanand BCAAs compete for entry into the brain via the same amino-acidcarrier (Newsholme et al., 1991).Therefore, a decrease in BCAAs in the blood facilitates entry oftryptophan into the brain. Moreover, most tryptophan in the blood isbound to albumin, and the proportion of tryptophan bound to albuminis influenced by the availability of long-chained fatty acids(Davis et al., 1992; Newsholmeet al., 1991). In endurance exercise free fatty-acidconcentration rises, so the amount of tryptophan bound to albuminfalls, increasing the concentration of free tryptophan in the blood(Davis, 1995).
Collectively, the decline in plasma BCAAs and increase in freetryptophan during prolonged endurance exercise alters the ratio offree tryptophan to BCAAs and increases the entry of tryptophan intothe brain (Newsholme et al., 1991). Anincreased concentration of tryptophan in the brain promotes theformation of the neurotransmitter 5-hydroxytryptamine (5-HT). 5-HThas been shown to induce sleep, depress motor neuron excitability,influence autonomic and endocrine function, and suppress appetite inanimal and human studies. An exercise-induced imbalance in the ratioof free tryptophan to BCAAs has been implicated as a possible causeof acute physiological and psychological fatigue (central fatigue).It has also been hypothesized that chronic elevations in 5-HTconcentration, which may occur in athletes maintaining high-volumetraining, explains some of the reported signs and symptoms of theovertraining syndrome: postural hypotension, anemia, amenorrhea,immunosuppression, appetite suppression, weight loss, depression, anddecreased performance (Newsholme et al.,1991; Gastmann and Lehmann, 1998;Kreider, 1998).
A number of studies have recently been conducted to evaluatewhether carbohydrate and/or BCAA supplementation affects centralfatigue during exercise and/or signs and symptoms of overtraining.Analysis of this literature indicates that carbohydrate and/or BCAAsupplementation during exercise can affect the ratio of freetryptophan to BCAA. For example, carbohydrate administration duringexercise has been reported to attenuate FFA release and minimizeincreases in the free tryptophan:BCAA ratio (Daviset al., 1992). In addition, BCAA supplementation has beenreported to increase plasma BCAA concentration and minimize and/orprevent increases in the ratio of free tryptophan to BCAAs (Blomstrandet al., 1991). Studies also indicate that BCAA administrationwith or without carbohydrate prior to and during exercise can affectphysiological and psychological responses to exercise (Coombesand McNaughton, 1995; Hefler et al.,1993; Kreider et al., 1992; Kreiderand Jackson, 1994).
Nevertheless, the effect of these nutritionally-inducedalterations in the free tryptophan to BCAA ratio on physicalperformance is still not clear. Most studies indicate that BCAAsupplementation does not improve single-bout endurance performance,but these studies almost certainly lacked power to delimit small butuseful enhancements of performance (Davis,1995; Gastmann and Lehmann, 1998;Kreider, 1998). Additional research is alsonecessary to determine the effect of long-term BCAA supplementationon training adaptations and the signs and symptoms of overtraining(Kreider, 1998).
Rennie and colleagues have suggested glutamine supplementation asa strategy to promote muscle growth (Rennie etal., 1994; Rennie, 1996). They based thesuggestion on animal and human studies of the effect of glutamine onprotein synthesis, cell volume, and glycogen synthesis (Rennieet al., 1994; Varnier et al., 1995;Rennie, 1996; Low et al.,1996). Glutamine is also an important fuel for white blood cells,so reductions in blood glutamine concentration following intenseexercise may contribute to immune suppression in overtrained athletes(Parry-Billings et al., 1990a; Parry-Billingset al., 1990b; Parry-Billings et al.,1992; Kargotich et al., 1996;Newsholme and Calder, 1997).
Preliminary studies indicate that supplementation withbranched-chain amino acids (4 to 16 g) and/or glutamine (4 to 12 g)can prevent the decline or even increase glutamine concentrationduring exercise (Kreider, 1998). In theorythese changes in glutamine concentration could have beneficialeffects on protein synthesis and immune function. However, in the fewstudies of increased glutamine availability, there was little or noeffect on performance or immune status (Rohde etal., 1998; Nieman and Pedersen, 1999). Itis also unclear whether long-term supplementation of glutamineaffects protein synthesis, body composition, or the incidence ofupper respiratory-tract infections during training.
Creatine is a naturally occurring amino acid derived from theamino acids glycine, arginine, and methionine (Balsomet al., 1994; Williams et al., 1999).Most creatine is stored in skeletal muscle, primarily asphosphocreatine; the rest is found in the heart, brain, and testes(Balsom et al., 1994; Kreider,1998). The daily requirement of creatine is approximately 2 to 3g; half is obtained from the diet, primarily from meat and fish,while the remainder is synthesized (Williams etal., 1999). Creatine supplementation has been proposed as a meansto "load" muscle with creatine and phosphocreatine (PCr). In theory,an increased store of creatine or phosphocreatine would improve theability to produce energy during high intensity exercise as well asimprove the speed of recovery from high-intensity exercise.
A number of studies have been conducted to determine the effectsof creatine supplementation on muscle concentrations and performance.Creatine supplementation (20 g per day or 0.3 g per kg body mass perday for 4 to 7 days) has been reported to increase intramuscularcreatine and phosphocreatine content by 10 to 30% (Caseyet al., 1996; Febbraio et al, 1995;Green et al., 1996a; Greenet al., 1996b; Greenhaff et al.,1993a; Hultman et al., 1996; Smithet al., 1998b, Vandenberghe et al.,1997). There is also evidence that creatine supplementationenhances the rate of PCr resynthesis following intense exercise(Greenhaff et al., 1993b; Greenhaffet al., 1994a; Greenhaff et al.,1994b). Most studies indicate that short-term creatinesupplementation increases total body mass (Hultmanet al., 1996; Williams et al., 1999),work performed during multiple sets of maximal effort musclecontractions (Greenhaff et al., 1993a;Volek et al., 1997), and single and/orrepetitive sprint capacity (Birch et al.,1994; Grindstaff et al., 1997;Prevost et al., 1997). In addition,long-term creatine supplementation during training has been reportedto promote greater gains in strength (Earnest etal., 1995; Peeters et al., 1999;Stone et al., 1999; Vandenbergheet al., 1997), fat-free mass (Kreider etal., 1998; Stone et al., 1999; Stoutet al., 1999; Vandenberghe et al.,1997), and sprint performance (Kreider etal., 1998; Peyreburne et al., 1998;Stout et al., 1999). However, it should benoted that not all studies report ergogenic benefit (Burkeet al., 1996; Redondo et al., 1996;Terrillion et al., 1997) and thatcaffeine has been reported to counteract the potential ergogenicvalue of creatine supplementation (Vanakoskiet al., 1998; Vandenburghe et al.,1996). Although more research is needed, creatine supplementationappears to be a safe and effective nutritional strategy to enhancehigh intensity exercise performance and improve training adaptations(Williams et al., 1999).
The leucine metabolite hydroxymethylbutyrate (more exactly thecalcium salt of b -hydroxy-b-methylbutyric acid) has recently become a popular dietary supplementpurported to promote gains in fat-free mass and strength duringresistance training (Kreider, 1999). Therationale is that leucine and its metabolite a-ketoisocaproate (KIC) appear to inhibit protein degradation(Nair et al., 1992; Nissenet al., 1996), and this anti-proteolytic effect may be mediatedby HMB. Animal studies indicate that approximately 5% of oxidizedleucine is converted to HMB via KIC (Nissen etal., 1994; Van Koevering et al.,1994). The addition of HMB to dietary feed improved colostralmilk fat and growth of sows (Nissen et al.,1994), tended to improve the carcass quality of steers (VanKoevering et al., 1994), and decreased markers of catabolismduring training in horses (Miller et al.,1997). Supplementing with leucine and/or HMB may thereforeinhibit protein degradation during periods associated with increasedproteolysis, such as resistance training.
Although much of the available literature on HMB supplementationin humans is preliminary in nature, several recently publishedarticles and abstracts support this hypothesis. Leucine infusionappears to decrease protein degradation in humans (Nairet al., 1992). HMB supplementation during 3 to 8 weeks oftraining has been reported to promote significantly greater gains offat-free mass and strength in untrained men and women initiatingresistance training (Nissen et al., 1996;Nissen et al., 1997; Vukovichet al., 1997). In some instances these gains were associated withsigns of significantly less muscle damage (efflux of muscle enzymesand urinary 3-methylhistidine excretion) (Nissenet al., 1996). Although these findings suggest that HMBsupplementation during training may enhance training adaptations inuntrained individuals initiating training, it is less clear whetherHMB supplementation reduces markers of catabolism or promotes greatergains in fat-free mass and strength during resistance training inwell-trained athletes. Indeed, there are several reports of nosignificant effects of HMB supplementation (3 to 6 g per day) inwell-trained athletes (Almada et al., 1997;Kreider et al., 1997; Kreideret al., 1999). More research is needed (Kreider,1999).
Over the last few decades researchers have found that amino acidsplay multiple roles in metabolism. For this reason, researchers andathletes are interested in the effects of amino-acid supplementationon exercise metabolism, exercise performance, and trainingadaptations. Although significant advances have been made, muchremains to be learned about these effects. Researchers should alsoevaluate the long-term safety of amino-acid supplementation, as wellas the potential medical value in the treatment of variousdiseases.
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