The human body is endowed with the capacity to adapt to training such that it can maintain low to moderately high contractions for extended periods. For example, the world record marathon time is 2:03:59 run by Haile Gebrselassie of Ethiopia. At the opposite end of the spectrum, strength and power athletes can exert extreme torques and forces such that today a 1,000 lb back squat is no longer unthinkable in the world of powerlifting. In between these extremes lie sports such as hockey, basketball, and speed skating, which require brief intermittent bouts of high-intensity activity. Although the time to fatigue differs among categories of activities, the end result of each are declines in force generating capacity and ultimately impairments in performance. While fatigue is characterized by a decrease in energy stores (adenosine triphosphate, phosphocreatine, and glycogenic substrates) and the intracellular accumulation of metabolites (adenosine diphosphate, inorganic phosphate, hydrogen ions [H+], and magnesium), 2 primary mechanisms thought to underlie fatigue include the accumulation of H+ ions and oxidative stress. An acute accumulation of H+ results in a decrease in intramuscular pH, which may contribute to fatigue in some models of exercise. Chronically, intense training can stimulate oxidative stress, with both excess H+ and oxidative stress demonstrating to impair excitation-contraction coupling (EC coupling) processes, leading to reported decrements in force.
An athletes' ability to resist fatigue may determine the intensity and duration of their training and ultimately dictate performance outcomes. Resistance to fatigue is thought to be limited, in part, by intramuscular concentrations of carnosine (29). Carnosine appears to enhance fatigue resistance by a conglomeration of factors including an increased physiological buffering capacity (22), decreased oxidative stress (18), and through the direct facilitation of EC coupling processes (2). Isolated skeletal muscle fiber studies suggest that the EC coupling response and its maintenance over multiple bouts of stimulation is optimized at a neutral pH (7.1) and degrades when tested at an acidic pH (e.g., 6.1) (22). Intramuscular concentrations of lactate and H+ rise as individual's reliance on glycolysis increases. Research, however, indicates that large amounts of lactate can accumulate without impairing function in the presence of carnosine, thus supporting its role as a physiological buffer (24). In addition to its role as a buffer, carnosine has been demonstrated to lower oxidative damage to lipids and proteins, which theoretically should delay fatigue induced losses of contractile function (18). Finally, exposure of isolated muscle fibers to carnosine may sensitize Ca++ release channels (ryanodine 1 receptors) to various stimuli such as caffeine and Ca++ (2).
Carnosine is synthesized by carnosine synthase from the amino acids beta-alanine and histidine. Plasma and intramuscular concentrations of histidine are high relative to its Michaelis-Menten constant (Km) with carnosine synthase (Km = 0.0168 mM), whereas beta-alanine concentration is lower and has a much higher Km for carnosine synthase (Km = 1.0-2.3 mM) (14,23). This low Km demonstrates a smaller amount of beta-alanine availability than needed for carnosine synthesis. Moreover, it has been demonstrated that supplementing with an isomolar concentration of carnosine (i.e., equal amounts of histidine and beta-alanine) is no more effective at increasing carnosine levels than beta-alanine supplementation alone (9). For this reason, beta-alanine is thought to be limiting to carnosine synthesis. As such, a number of recent studies have investigated the effects of beta-alanine supplementation on intramuscular carnosine concentrations and changes in exercise performance (8-10). Intriguingly, beta-alanine supplementation has been found to increase intramuscular carnosine levels (8-10), strength (11-13), power (30), volume per training session (11-13), and a host of other indices of aerobic and anaerobic capacity (31). However, there is a need to synthesize this research so that the athlete and strength coach alike can optimally benefit from beta-alanine supplementation. The purpose of this review is to provide an analysis of studies conducted on beta-alanine. The review will cover the optimal dosage of beta-alanine and its use in resistance training, intermittent, and endurance-based exercises in trained and untrained individuals. An additional section is provided to discuss the possible role that creatine may have in augmenting the effects of beta-alanine.
OPTIMIZING THE DOSE AND FREQUENCY OF BETA-ALANINE
Thus far, human research has been limited to a range of 1.6-6.4 gram doses of beta-alanine daily for 28 days (9,10). Within this range, the amino acid appears to increase intramuscular carnosine concentrations in dose-dependent fashion. For example, 3.2 and 6.4 grams of beta-alanine per day increased the carnosine content of the vastus lateralis by 42 and 61%, respectively (9,10). In the latter, it was estimated that the total muscle buffering capacity of carnosine would have increased from 9 to 14%. When fractionated into fiber types, carnosine increased buffering capacity from 6.4 and 11.2 to 10 and 18% in type I and II muscle fibers, respectively. Changes in intramuscular carnosine are also time dependent, demonstrated by elevations in carnosine concentrations of active males by 58 and 80% at 4 and 10 weeks of beta-alanine (3.2-6.4 g/kg/d) supplementation, respectively.
The daily dose of beta-alanine appears to be limited by the flushing symptoms experienced by its users. This was illustrated by Harris et al. (9) who found that a single 3.2 gram bolus of beta-alanine resulted in a flushing sensation characterized by a skin-deep, prickly, irritating reaction, which radiated from the ears, scalp, upper trunk, and finally, the base of the spine (i.e., paresthesia). Although lower in severity, these symptoms were still present at half the dosage but were only mild and experienced by 25% of participants at 0.8-g servings. The flushing effect from beta-alanine supplementation is because of the release of histidine, to form carnosine. This is a similar response to a release of histamines during an allergic reaction; although the effect is not toxic and does not affect everyone, it is uncomfortable. For this reason, scientists have administered beta-alanine in frequent (every 3 hours) and small boluses (0.8 g) over the duration of the day until the desired dose is reached (8-10). Three-hour spacing between dosing was chosen because beta-alanine returns to baseline levels after this time. More recently, a controlled release formula has been administered at 1.6 grams 4 times per day for 4 week to reduce flushing symptoms. At this high dose, no symptoms of paresthesia were reported (31).
In summary, within the range of doses (1.6-6.4 grams) tested thus far, beta-alanine appears to increase intramuscular carnosine levels in a dose-dependent fashion and in a 28-day loading phase. However, because of flushing effects, a single serving is generally limited to 0.8 grams, administered every 3 hours until the desired dose is reached.
BETA-ALANINE FOR RESISTANCE TRAINING ATHLETES
Resistance training exercise is the direct tool of the powerlifter, weightlifter, and bodybuilder, as well as an indirect means of increasing performance in nearly every sport. Generally, repetitions for strength/power and hypertrophy are thought to lie within the 1-5 and 8-12 ranges, respectively (20). The former is primarily reliant on immediate phosphagen (ATP-CP) energy production for contraction, whereas the latter causes the individual to depend primarily on glycolytic energy production. Although beta-alanine supplementation during 4-10 weeks of resistance training has resulted in an increase in training volume and strength, it appears to be optimized under moderately high repetition ranges (8-12% or 70-85% 1 repetition maximum), which use short rest periods (30-90 seconds) (11,12). To illustrate, 30 days of beta-alanine supplementation (4.8 g/day) in experienced resistance-trained men placed on a moderately high-intensity training regimen, with short rest periods (1.5 minutes), led to a 22% increase in total training volume per workout. Furthermore, Hoffman et al. (12) demonstrated significant increases in training volume for 4 sets (6-8 repetitions [reps]) for bench press with individuals supplementing with beta-alanine. In contrast, a more recent 10-week long study using a higher intensity level of training (e.g., 5 × 5 on squats and bench press exercises) with longer rest periods (2-5 minutes) resulted in no significant changes in any indices of strength or lean body mass (LBM) (15). Possible explanations for these results were the longer rest periods (2-5 minutes) and limited resistance training experience in this group of athletes.
It has been suggested that greater training volume resulting from beta-alanine supplementation may augment endocrine responses. However, no changes in endocrine responses both at rest and after resistance training exercise have been found for growth hormone, testosterone, blood lactate, cortisol, IGF-1, or sex hormone-binding globulin (11,13).
Thus far beta-alanine alone has had not led to significant changes in LBM (12,13,15). It is possible that this outcome may be attributed to an inadequate training stimulus or length of time over which studies have been conducted. For example, Hoffman et al. (13) found that neither control or beta-alanine groups were able to increase LBM after 4 weeks of training in experienced weightlifters. In such cases, a long duration periodized strength routine may be necessary to accurately examine the effects of beta-alanine on LBM.
BETA-ALANINE FOR BRIEF INTERMITTENT/INTERVAL TRAINING EXERCISE
Brief, intermittent, high-intensity exercise is generally characterized by maximal work outputs within a 30- to 120-second time frame. This type of exercise results in the accumulation of large amounts of lactate, H+, and other metabolites and thus theoretically may be positively influenced with beta-alanine supplementation. In a recent study, active males were asked to cycle at 110% of their mean power output obtained during the final 60 seconds of an incremental cycling test to exhaustion (10). Mean cycling time to exhaustion was 156 seconds pretest and increased by 12 and 16% after 4 and 10 weeks of supplementation. Intriguingly, these changes paralleled the increase seen in intramuscular carnosine concentrations, which rose by 58 to 80% at weeks 4 and 10, respectively. Likewise, trained sprint athletes supplementing with 4.8 grams of beta-alanine daily increased average torque during the final 2 sets of 5 maximal sets of 30 isokinetic contractions (5). However, 400-m sprint time was not increased, suggesting that this event may not be limited by H+ buffering capacity in highly trained sprinters. Moreover, recent literature suggests compounded improvements when combining beta-alanine supplementation and high-intensity interval training on endurance performance (V̇o2max), time to exhaustion during a graded exercise test, and total work done at supramaximal workloads (110%) (24). Furthermore, this training-supplementing strategy may foster an environment for greater training volume at moderate and high intensities, possibly leading to considerable physiological adaptations.
BETA-ALANINE SUPPLEMENTATION FOR ENDURANCE EXERCISE
Endurance exercise is limited by maximal aerobic capacity (V̇o2max), economy, and the percentage of an athlete's V̇o2max that can be maintained for a given race (3). The final factor is largely dependent on lactate threshold (LT). LT is thought to lead to a nonlinear increase in ventilation (ventilatory threshold [VT]) and the onset of neuromuscular fatigue. Stout et al. (26-28) have investigated the effects of beta-alanine supplementation on a number of variables underlying aerobic capacity and neuromuscular fatigue. These researchers found that 28 days of beta-alanine supplementation (3.2 g/d) in untrained males resulted in a 16% increase in physical working capacity at neuromuscular fatigue in a continuous cycling bout. Similarly, untrained females increased physical working capacity at neuromuscular fatigue by 13%, with concomitant elevations in VT (14%) and cycling time to exhaustion (2.5%). These results suggest that beta-alanine supplementation alone may allow endurance athletes to perform at a higher percentage of their maximal aerobic capacity before experiencing fatigue.
THE ADDITION OF CREATINE TO BETA-ALANINE
Creatine supplementation has been demonstrated to decrease blood lactic acid accumulation during high-intensity and submaximal exercises (1,21). The rationale is based on augmented phosphocreatine (PCr) concentrations lowering the reliance on glycolysis during intermittent exercise, thereby lowering lactate accumulation. Moreover, there is recent data using animal models suggesting that creatine may increase intramuscular carnosine levels, perhaps by acting as a free radical scavenger and sparing carnosine from this process (4). Because the administration of creatine may facilitate the maintenance of muscle pH during exercise, researchers have postulated that it may support beta-alanine supplementation.
In this context, Zoeller et al. (31) found that beta-alanine and creatine alone were able to increase 1-2 indices of aerobic capacity, whereas the combination of the 2 increased 5 of 8 indices. These included an increase in LT and VT (5.7-8%), power at LT and VT (9-10.5%), and V̇o2peak at VT (7.8%).
The combined effects of beta-alanine and creatine have extended to the resistance training domain. Alone, beta-alanine has been able to increase training volume and strength, without any effects on LBM (11). It is intriguing to note that when combined with creatine, this supplement has resulted in greater increases in strength, training volume, and LBM, compared with both a creatine only and placebo conditions (11).
In summary, it appears that the addition of creatine to beta-alanine, in both aerobic and resistance exercise trainings, may provide greater benefits than with separate supplementation of each. More research is needed to show whether these effects are synergistic or simply additive.
BETA-ALANINE SUPPLEMENTATION-MODERATOR VARIABLES (AGE, SEX, AND TRAINING EXPERIENCE)
The majority of studies using beta-alanine supplementation have been conducted in young (age = 20-29 years) males. We were only able to locate one study in young untrained women. Similar to young men, women who supplemented with beta-alanine improved their gains in LT, VT, neuromuscular fatigue, and time to exhaustion (27).
Age, however, does appear to moderate the effects of beta-alanine. While men and women have demonstrated 12-15% increases in work capacity at neuromuscular fatigue (26,27), elderly men and women demonstrate nearly double the increase (28%) (28). According to Stout et al. (28), this may reflect lower starting levels of intramuscular carnosine (45% lower) relative to young individuals.
A final variable is training experience. Sprinters and bodybuilders have demonstrated higher carnosine concentrations than endurance athletes and untrained individuals (19,30), yet research has established that 4-10 weeks of resistance and/or interval training is not effective for augmenting carnosine levels (15,16). Although training alone has failed to induce significant increases in carnosine levels, combining beta-alanine supplementation with training has stimulated a 2-fold increase in carnosine levels, compared with beta-alanine supplementation alone (6,8). Notably, the change in intramuscular carnosine levels with beta-alanine supplementation appears to be similar between trained and relatively untrained individuals (5,10,15), illustrating the practicality in both populations. However, it is difficult to quantify differences in the effectiveness of beta-alanine between trained and untrained individuals because no direct comparisons have been made. Moreover, outcome measures have differed between trained and untrained subjects across the current body of literature. What is known is that supplementation has been demonstrated efficacious regardless of training status (Table).
The goal of supplementation with beta-alanine is to increase muscle carnosine levels and ultimately augment performance. Carnosine is thought to be a powerful hydrogen ion buffer, thereby delaying the onset of fatigue. Twelve studies reported in this review investigated the effects of beta-alanine on muscle carnosine and various parameters of performance (Table). Supplementation ranging from 3 to 6.5 g of beta-alanine daily, divided into 0.8-1.6 g doses, for 4-10 weeks has irrefutably augmented carnosine levels by 30-80% (8-10,15).
For athletes, we recommend a dose of 6.4 g daily, divided into four 1.6-g doses throughout day. Dosing should be spaced in a minimum of 3-hour intervals so as to avoid negative flushing effects. It may also be wise to pyramid the dosage, starting from lower (3.2 g/d) during the first week, to moderate (4.8 g/d) during the second week, to higher (6.4 g/d) the remainder of the supplemental period (9). For the athlete looking to enhance performance during an event, it should be realized that intramuscular carnosine concentrations increase over time (e.g., from 4 to 10 weeks). Thus, we recommend a minimum of 4 weeks and optimally triple this time before a competition (10). More so, it has recently been shown that carnosine levels remain elevated for up to 9 weeks devoid of supplementation (7).
Beta-alanine supplementation appears to be optimized when lactate production is greatest. Therefore, resistance training athletes will most likely experience the greatest increases in volume and strength in a moderately high-intensity (8-12 reps or 60-85% repetition maximum) (11-13) as opposed to very high-intensity (1-5 reps or 85-100% 1 repetition maximum) (15) training regimen. Similarly, intermittent or interval training athletes will experience greater gains when performing over 30-90 seconds (e.g., hockey shift) than when performing the 100-m dash. We predict that endurance athletes will benefit greatly when performing closer to their LT. It is also important to note that these effects may be magnified with increasing age (28). Finally, beta-alanine combined with creatine may augment performance to a greater extent than when administered separately (11,26,31), most likely as a result of a decreased accumulation of H+ ions during submaximal and maximal intensity exercises.
For scientists, we suggest that the research continues to diversify its subject population and perform longer experiments to ascertain if beta-alanine with or without endurance and/or resistance training results in changes in body composition, strength, and functionality across age spans over a period of months to years. Furthermore, a sound research design implementing a double-blind, placebo-controlled, repeated measures design comparing between-group differences will be most valuable to the research community.
1. Balsom PD, Soderlund K, Sjodin B, and Ekblom B. Skeletal muscle metabolism during short duration high-intensity exercise: Influence of creatine supplementation. Acta Physiol Scand
154: 303-310, 1995.
2. Batrukova MA and Rubtsov AM. Histidine-containing dipeptides as endogenous regulators of the activity of sarcoplasmic reticulum Ca-release channels. Biochim Biophys Acta
1324: 142-150, 1997.
3. Conley DL and Krahenbuhl GS. Running economy and distance running performance of highly trained athletes. Med Sci Sports Exerc
12: 357-360, 1980.
4. Derave W, Jones G, Hespel P, and Harris RC. Creatine supplementation augments skeletal muscle carnosine content in senescence-accelerated mice (SAMP8). Rejuvenation Res
11: 641-647, 2008.
5. Derave W, Ozdemir MS, Harris RC, Pottier A, Reyngoudt H, Koppo K, Wise JA, and Achten E. Beta-alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. J Appl Physiol
103: 1736-1743, 2007.
6. Harris R, Edge J, Kendrick I, Bishop D, Goodman C, and Wise J. The effect of very high interval training on the carnosine content and buffering capacity of V lateralis from humans. FASEB J
21: 761, 2007.
7. Harris R, Jones G, Kim H, Kim C, Price K, and Wise J. Changes in muscle carnosine of subjects with 4 weeks of supplementation with a controlled release formulation of beta-alanine (Carnosyn), and for 6 weeks post. FASEB J
23: 599.4, 2009.
8. Harris R, Kendrick IP, Kim C, Kim H, Dang VH, and Lam TQ. Effect of physical training on the carnosine content of v. lateralis using a one-leg training model. Med Sci Sports Exerc
39: S91, 2007.
9. Harris RC, Tallon MJ, Dunnett M, Boobis L, Coakley J, Kim HJ, Fallowfield JL, Hill CA, Sale C, and Wise JA. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids
30: 279-289, 2006.
10. Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, and Wise JA. Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids
32: 225-233, 2007.
11. Hoffman J, Ratamess N, Kang J, Mangine G, Faigenbaum A, and Stout J. Effect of creatine and beta-alanine supplementation on performance and endocrine responses in strength/power athletes. Int J Sport Nutr Exerc Metab
16: 430-446, 2006.
12. Hoffman JR, Ratamess NA, Faigenbaum AD, Ross R, Kang J, Stout JR, and Wise JA. Short-duration beta-alanine supplementation increases training volume and reduces subjective feelings of fatigue in college football players. Nutr Res
28: 31-35, 2008.
13. Hoffman J, Ratamess NA, Ross R, Kang J, Magrelli J, Neese K, Faigenbaum AD, and Wise JA. Beta-alanine and the hormonal response to exercise. Int J Sports Med
29: 952-958, 2008.
14. Horinishi H, Grillo M, and Margolis FL. Purification and characterization of carnosine synthetase from mouse olfactory bulbs. J Neurochem
31: 909-919, 1978.
15. Kendrick IP, Harris RC, Kim HJ, Kim CK, Dang VH, Lam TQ, Bui TT, Smith M, and Wise JA. The effects of 10 weeks of resistance training combined with beta-alanine supplementation on whole body strength, force production, muscular endurance and body composition. Amino Acids
34: 547-554, 2008.
16. Kendrick IP, Kim HJ, Harris RC, Kim CK, Dang VH, Lam TQ, Bui TT, and Wise JA. The effect of 4 weeks beta-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres. Eur J Appl Physiol
106: 131-138, 2009.
17. Kern B and Robinson T. Effects of beta-alanine supplementation on performance and body composition in collegiate wrestlers and football players. J Int Soc Sports Nutr
6(Suppl 1): P2, 2009.
18. Nagasawa T, Yonekura T, Nishizawa N, and Kitts DD. In vitro and in vivo inhibition of muscle lipid and protein oxidation by carnosine. Mol Cell Biochem
225: 29-34, 2001.
19. Parkhouse WS, McKenzie DC, Hochachka PW, and Ovalle WK. Buffering capacity of deproteinized human vastus lateralis muscle. J Appl Physiol
58: 14-17, 1985.
20. Peterson MD, Rhea MR, and Alvar BA. Maximizing strength development in athletes: A meta-analysis to determine the dose-response relationship. J Strength Cond Res
18: 377-382, 2004.
21. Prevost MC, Nelson AG, and Morris GS. Creatine supplementation enhances intermittent work performance. Res Q Exerc Sport
68: 233-240, 1997.
22. Rousseau E and Pinkos J. pH modulates conducting and gating behaviour of single calcium release channels. Pflugers Arch
415: 645-647, 1990.
23. Skaper SD, Das S, and Marshall FD. Some properties of a homocarnosine-carnosine synthetase isolated from rat brain. J Neurochem
21: 1429-1445, 1973.
24. Skulachev VP. Biological role of carnosine in the functioning of excitable tissues. Centenary of Gulewitsch's discovery. Biochemistry (Mosc)
65: 749-750, 2000.
25. Smith AE, Moon JR, Kendall KL, Graef JL, Lockwood CM, Walter AA, Beck TW, Cramer JT, and Stout JR. The effects of beta-alanine supplementation and high-intensity interval training on neuromuscular fatigue and muscle function. Eur J Appl Physiol
105: 357-363, 2009.
26. Stout JR, Cramer JT, Mielke M, O'Kroy J, Torok DJ, and Zoeller RF. Effects of twenty-eight days of beta-alanine and creatine monohydrate supplementation on the physical working capacity at neuromuscular fatigue threshold. J Strength Cond Res
20: 928-931, 2006.
27. Stout JR, Cramer JT, Zoeller RF, Torok D, Costa P, Hoffman JR, Harris RC, and O'Kroy J. Effects of beta-alanine supplementation on the onset of neuromuscular fatigue and ventilatory threshold in women. Amino Acids
32: 381-386, 2007.
28. Stout JR, Graves BS, Smith AE, Hartman MJ, Cramer JT, Beck TW, and Harris RC. The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55-92 years): A double-blind randomized study. J Int Soc Sports Nutr
5: 21, 2008.
29. Suzuki Y, Ito O, Mukai N, Takahashi H, and Takamatsu K. High level of skeletal muscle carnosine contributes to the latter half of exercise performance during 30-s maximal cycle ergometer sprinting. Jpn J Physiol
52: 199-205, 2002.
30. Tallon MJ, Harris RC, Boobis LH, Fallowfield JL, and Wise JA. The carnosine content of vastus lateralis is elevated in resistance-trained bodybuilders. J Strength Cond Res
19: 725-729, 2005.
31. Zoeller RF, Stout JR, O'Kroy AJ, Torok DJ, and Mielke M. Effects of 28 days of beta-alanine and creatine monohydrate supplementation on aerobic power, ventilatory and lactate thresholds, and time to exhaustion. Amino Acids
33: 505-510, 2007.