ISSN exercise & sports nutrition review update: research & recommendations

HMB is a metabolite of the amino acid leucine. It is well-documented that supplementing with 1.5 to 3 g/day of calcium HMB during resistance training can increase muscle mass (+ 0.5–1 kg greater than controls during 3–6 weeks of training) and strength particularly among untrained subjects initiating training [168‐173] and the elderly [174]. The currently established minimal effective dose of HMB is 1.5 g per day, with 3 g per day offering additional benefits on lean body mass, while 6 g per day do not provide any additional gains in lean mass beyond what was reported with a 3 g dose [169]. To optimize HMB retention, its recommend to split the daily dose of 3 g into three equal doses of 1 g each (with breakfast, lunch or pre-exercise, bedtime) [174]. From a safety perspective, dosages of 1.5–6 g per day have been well tolerated [15, 169, 170]. The effects of HMB supplementation in trained athletes are less clear with selected studies reporting non-significant gains in muscle mass [175‐177]. In this respect, it has been suggested by Wilson and colleagues [15] that program design (periodized resistance training models) and duration of supplementation (minimum of 6 weeks) likely operate as key factors. In 2015, Durkalec-Michalski and investigators [178] supplemented highly trained rowers (n = 16) in a randomized, double-blind, crossover fashion with either 3 g per day of calcium-HMB or a placebo. Before and after each supplementation period, body composition and performance parameters were assessed. When HMB was provided, fat mass was significantly reduced while changes in lean mass were not significant between groups. The same research group published data of 58 highly trained males athletes who supplemented with either 3 g of calcium-HMB or placebo for 12 weeks in a randomized, double-blind, crossover fashion [179]. In this report, fat mass was found to be significantly reduced while fat-free mass was significantly increased. Finally, Durkalec-Michalski and investigators [180] supplemented 42 highly-trained combat sport athletes for 12 weeks with either a placebo or 3 g of calcium-HMB in a randomized, double-blind, crossover fashion. When HMB was provided, fat-free mass was shown to increase (p = 0.049) while fat mass was significantly reduced in comparison to the changes seen when placebo was provided. In conclusion, a growing body of literature continues to offer support that HMB supplementation at dosages of 1.5–3 g for durations as short as three to 4 weeks in untrained populations and longer durations (12 weeks) in trained populations can lead to improvements in fat mass and fat-free mass while participating in various forms of exercise training.

In our view, the most effective nutritional supplement available to athletes to increase high intensity exercise capacity and muscle mass during training is creatine monohydrate. Numerous studies have indicated that creatine supplementation increases body mass and/or muscle mass during training [181, 182]. Body mass increases are typically one to two kilograms greater than controls during 4–12 weeks of training [182]. The gains in muscle mass appear to be a result of an improved ability to perform high intensity exercise enabling an athlete to train harder and thereby promote greater training adaptations and muscle hypertrophy [183‐186]. The only clinically significant side effect occasionally reported from creatine monohydrate supplementation has been the potential for weight gain [181, 182, 187, 188]. Although concerns have been raised about the safety and possible side effects of creatine supplementation [189, 190], multiple shorter [191‐193] and long-term safety studies have reported no apparent side effects [188, 194, 195] and/or that creatine monohydrate may lessen the incidence of injury during training [196‐199]. Consequently, supplementing the diet with creatine monohydrate and/or creatine containing formulations seems to be a safe and effective method to increase muscle mass. The ISSN position stand on creatine monohydrate [10] summarizes their findings as this:

Research examining the impact of the essential amino acids on stimulating muscle protein synthesis is an extremely popular area. Collectively, this data indicates that ingesting 6–12 g of the essential amino acids (EAA) in the absence of feeding [200] and prior to [201, 202] and/or following resistance exercise stimulates protein synthesis [202‐208], with this response being largely independent of the protein source or food type [209]. Theoretically, this may enhance increases in fat-free mass, but to date limited evidence exists to demonstrate that supplementation with non-intact sources of EAAs (e.g., free form amino acids) while resistance training positively impacts fat-free mass accretion. Moreover, other research has indicated that changes in muscle protein synthesis may not correlate with phenotypic adaptations to exercise training [210]. An abundance of evidence is available, however, to indicate that ingestion of high-quality protein sources can heighten adaptations to resistance training [211]. While various methods of protein quality assessment exist, most of these approaches center upon the amount of EAAs that are found within the protein source, and in nearly all situations, the highest quality protein sources are those containing the highest amounts of EAAs. To this point, a number of published studies are available that state the EAAs operate as a prerequisite to stimulate peak rates of muscle protein synthesis [212‐215]. To better understand the impact of ingesting free-form amino acids versus an intact protein source, Katsanos et al. [216] administered similar doses of the essential amino acids (6.72 g) as part of an intact protein (15 g of whey protein isolate) source or as free amino acids while completing a resistance training program in elderly adults. Protein accrual was greater when the amino acid dose was provided in an intact source. While the age of the participants in this study may have impacted outcomes [217], this study’s results do highlight the need for more research to better understand to what extent training adaptations are due to the EAA content or if additional benefits are present from ingesting an intact protein source.

While the EAAs are comprised of nine separate amino acids, some individual EAAs have received considerable attention for their potential role in impacting protein translation and muscle protein synthesis. In this respect, the branched-chain amino acids have been highlighted for their predominant role in stimulating muscle protein synthesis [218, 219]. To this point, Karlsson and colleagues [220] demonstrated significantly higher increases in p70s6k expression in recovery from a single bout of lower-body resistance exercise in seven male participants after ingesting a BCAA solution containing 100 mg/kg BCAA when compared to ingesting a placebo. Interestingly, Moberg and investigators [221] had trained volunteers complete a standardized bout of resistance training in conjunction with ingestion of placebo, leucine, BCAA or EAA while measuring changes in post-exercise activation of p70s6k. They concluded that EAA ingestion led to a nine-fold greater increase in p70s6k activation and that these results were primarily attributable to the BCAAs. Finally, a 2017 study by Jackman et al. [222] compared the ability of a 5.6 g dose of BCAAs (versus a placebo) to stimulate increases in muscle protein synthesis. Myofibrillar muscle protein synthesis rates were increased significantly (~ 20%, p < 0.05) in comparison to a placebo. While significant, this magnitude of change was notably less than the post-exercise MPS responses seen when doses of whey protein that delivered similar amounts of the BCAAs were consumed [88, 223]. These outcomes led the authors to conclude that the full complement of EAAs was advised to maximally stimulate increases in MPS.

Of all the interest captured by the BCAAs, leucine is accepted to be the primary driver of acute changes in protein translation. In this respect, Dreyer et al. [224] and others [225] have reported that providing leucine after completion of resistance exercise can further potentiate increases in mTOR signalling and protein translation. In this respect, Jager et al. [11] have highlighted that an ideal dose of leucine to stimulate increases in protein translation is likely somewhere between 1.7–3.5 g.

A growing body of literature is available that suggests higher amounts of protein are needed by exercising individuals to optimize exercise training adaptations [11, 83, 211, 226]. Collectively, these sources indicate that people undergoing intense training with the primary intention to promote accretion of fat-free mass should consume between 1.4–2.0 g of protein per kilogram of body weight per day [83, 226]. Tang and colleagues [95] conducted a classic study that examined the ability of three different sources of protein (hydrolyzed whey isolate, micellar casein and soy isolate) to stimulate acute changes in muscle protein synthesis both at rest and after a single bout of resistance exercise. These authors concluded that all three protein sources significantly increased muscle protein synthesis rates both at rest and in response to resistance exercise. When this response is extrapolated over the course of several weeks, multiple studies have reported on the ability of different forms of protein to significantly increase fat-free mass while resistance training [70, 227‐232]. Cermak et al. [211] performed a meta-analysis that examined the impact of protein supplementation on changes in strength and fat-free mass. Data from 22 separate published studies that included 680 research participants were included in the analysis. These authors concluded that protein supplementation demonstrated a positive effect of fat-free mass and lower-body strength in both younger and older participants. Similarly, Morton and investigators [83] published results from a meta-analysis that also included a meta-regression approach involving data from 49 studies and 1863 participants. They concluded that the ability of protein to positively impact fat-free mass accretion increases up to approximately 1.62 g of protein per kilogram of body weight per day whereby higher amounts beyond that do not appear to promote greater gains in fat-free mass. Although more research is necessary in this area, evidence clearly indicates that protein needs of individuals engaged in intense training are elevated and consequently those athletes who achieve higher intakes of protein while training promote greater changes in fat-free mass. Beyond the impact of protein to foster greater training-induced adaptations such as increases in strength and muscle mass, several studies have examined the ability of different types of protein to stimulate changes in fat-free mass [229, 231, 233‐235] while several studies and reviews have critically explored the role protein may play in achieving weight loss in athletes [236, 237] as well as during periods of caloric restriction [238, 239]. Therefore, it is simplistic and misleading to suggest that there is no data supporting contentions that athletes need more protein in their diet and/or there is no potential ergogenic value of incorporating different types of protein into the diet. It is the position stand of ISSN that exercising individuals need approximately 1.4 to 2.0 g of protein per kilogram of bodyweight per day [11].

ATP is the primary intracellular energy source and in addition, has extensive extracellular functions including the increase in skeletal muscle calcium permeability and vasodilation. While intravenous administration of ATP is bioavailable [240], several studies have shown that oral ATP is not systematically bioavailable [241]. However, chronic supplementation with ATP increases the capacity to synthesize ATP within the erythrocytes without increasing resting concentrations in the plasma, thereby minimizing exercise-induced drops in ATP levels [242]. Oral ATP supplementation has demonstrated initial ergogenic properties, after a single dose, improving total weight lifted and total number of repetitions [243]. ATP may increase blood flow to the exercising muscle [244] and may reduce fatigue and increase peak power output during later bouts of repeated bouts exercise [242]. ATP may also support greater recovery and lean mass maintenance under high volume training [245], however, this has only been reported in one previous study. In addition, ATP supplementation in clinical populations has been shown to improve strength, reduce pain after knee surgery, and reduce the length of the hospital stay [246]. However, given the limited number of human studies of ATP on increasing exercise-induced gains in muscle mass, more chronic human training studies are warranted.

BCAA supplementation has been reported to decrease exercise-induced protein degradation and/or muscle enzyme release (an indicator of muscle damage) possibly by promoting an anti-catabolic hormonal profile [118, 247, 248] and more recent studies support their ability to favorably promote responses to damaging eccentric muscle contractions [249, 250]. Leucine, in particular, is recognized as a keystone of sorts that when provided in the correct amounts (3–6 g) activates the mTORC1 complex resulting in favorable initiation of translation [251]. To highlight this impact for leucine, varying doses of whey protein and leucine levels were provided to exercising men at rest and in response to an acute bout of lower-body resistance exercise to examine the muscle protein synthetic response. Interestingly, when a low dose of whey protein (6.25 g) was enriched with leucine to equal the leucine content found in a 25-g dose of whey protein, the ability to stimulate muscle protein synthesis was retained. While the 25-g dose of whey protein did favorably sustain the increases in muscle protein synthesis, the added leucine highlights an important role for leucine in stimulating muscle protein synthesis in response to resistance exercise [223]. For these reasons, it has been speculated that the leucine content of whey protein and other high-quality protein sources have been suggested to be primary reasons for their ability to stimulate favorable adaptations to resistance training [252, 253]. Theoretically, BCAA supplementation during intense training may help minimize protein degradation and thereby lead to greater gains in (or limit losses of) fat-free mass, but only limited evidence exists to support this hypothesis. For example, Schena and colleagues [254] reported that BCAA supplementation (~ 10 g/d) during 21-days of trekking at altitude increased fat free mass (1.5%) while subjects ingesting a placebo had no change in muscle mass. Bigard and associates [255] reported that BCAA supplementation appeared to minimize loss of muscle mass in subjects training at altitude for 6 weeks. Finally, Candeloro and coworkers [256] reported that 30 days of BCAA supplementation (14 g/day) promoted a significant increase in muscle mass (1.3%) and grip strength (+ 8.1%) in untrained subjects. Alternatively, Spillane and colleagues [257] reported that 8 weeks of resistance training while supplementing with either 9 g of BCAAs or placebo did not impact body composition or muscle performance. Most recently, Jackman et al. [222] examined the ability of an acute dose of branched-chain amino acids to stimulate increases in muscle protein synthesis. While acute ingestion of BCAAs did promote a 22% greater increase in muscle protein synthesis when compared to a placebo, the determined rates were 50% lower than what is commonly seen when a dose of whey protein containing similar amounts of BCAAs is ingested. As mixed outcomes cloud the ability to make clear determinations, studies strongly suggest a mechanistic role for BCAAs and in particular leucine, yet translational data fails to consistently support the need for BCAA supplementation. Alternatively, multiple studies do support BCAAs ability to mitigate recovery from damaging exercise while their ability to favorably impact resistance training adaptations needs further research. This will be discussed in a later section.

Phosphatidic acid (PA) is a diacyl-glycerophospholipid that is enriched in eukaryotic cell membranes and it can act as a signalling lipid [258]. Interestingly, PA has been repeatedly shown to activate the mammalian target of rapamycin (mTOR) signalling in muscle; an effect which ultimately leads to increases in muscle protein synthesis. For instance, Fang et al. [259] demonstrated that PA activates mTOR in vitro. Hornberger et al. [260] also reported that mechanical stretching of skeletal muscle in situ promotes an increase in intramuscular PA levels and this effect was associated with the activation of mTOR signalling. To date, two chronic human supplementation studies have been performed whereby PA supplementation (750 mg/day) occurred in subjects engaged in resistance training. Hoffman et al. [261] reported that PA supplementation increased whole-body lean body mass (LBM) by 1.7 kg, whereas the placebo group demonstrated no relative change in LBM (0.1 kg; p = 0.065 between groups). Joy et al. [262] performed a similar eight-week study with more participants and supervised training sessions, and reported that PA supplementation significantly increased LBM by 2.4 kg, whereas the placebo group demonstrated marginal increases in LBM (1.2 kg; p < 0.05 between groups). A third study confirmed the beneficial effects of PA on exercise-induced gains in lean body mass [263]. The currently established dose of PA is 750 mg per day and another study investigating lower doses, 375 and 250 mg per day, failed to show significant benefits on lean body mass [264]. Hence, preliminary human research suggests that PA supplementation can increase anabolic signalling in skeletal muscle and enhance gains in muscle mass with resistance training. Given that PA supplementation studies are in their infancy relative to other muscle-building supplements (e.g., whey protein, creatine, HMB, etc.), future studies are needed in order to determine the optimal dosage, timing, and duration of supplementation needed for optimal muscle mass gains.

ß-alanine, a non-essential amino acid, has ergogenic potential based on its role in carnosine synthesis [12]. Carnosine is a dipeptide comprised of the amino acids, histidine and ß-alanine, that naturally occur in large amounts in skeletal muscles. Carnosine is believed to be one of the primary muscle-buffering substances available in skeletal muscle. Studies have demonstrated that taking four to 6 g of ß-alanine orally, in divided doses, over a 28-day period is effective in increasing carnosine levels [418, 419], while more recent studies have demonstrated increased carnosine and efficacy up to 12 g per day [420]. According to the ISSN position statement, evaluating the existing body of ß-alanine research suggests improvements in exercise performance with more pronounced effects on activities lasting one to 4 min; improvements in neuromuscular fatigue, particularly in older subjects, and lastly; potential benefits in tactical personnel [12]. Other studies have shown that ß-alanine supplementation can increase the number of repetitions one can do [421], increase lean body mass [422], increase knee extension torque [423], and increase training volume [421]. In fact, one study also showed that adding ß-alanine to creatine improves performance over creatine alone [424]. While it appears that ß-alanine supplementation can improve performance, other studies have failed to demonstrate a performance benefit [425, 426].

Caffeine is a naturally derived stimulant found in many nutritional supplements typically as guarana, bissey nut, or kola. Caffeine can also be found in coffee, tea, soft drinks, energy drinks, and chocolate. Caffeine has also been shown to be an effective ergogenic aid for aerobic and anaerobic exercise with a documented ability to increase energy expenditure and promote weight loss [14]. Research investigating the effects of caffeine on time trial performance in trained cyclists found that caffeine improved speed, peak power, and mean power [427]. Similar results were observed in a recent study that found cyclists who ingested a caffeine drink prior to a time trial demonstrated improvements in performance [428, 429]. Studies indicate that ingestion of caffeine (e.g., 3–9 mg/kg taken 30–90 min before exercise) can spare carbohydrate use during exercise and thereby improve endurance exercise capacity [430, 431]. In addition to the apparent positive effects on endurance performance, caffeine has also been shown to improve repeated sprint performance benefiting the anaerobic athlete [432‐434]. Research examining caffeine’s ability to increase maximal strength and repetitions to fatigue are largely mixed in their outcomes. For example, Trexler, et al. [434] reported that caffeine can improve repeated sprint performance but failed to impact maximal strength and repetitions to fatigue using both upper-body and lower-body exercises. In agreement, Astorino and colleagues [435] revealed no change in upper-body and lower-body strength after resistance trained males ingested 6 mg/kg of caffeine. Similarly, Beck and investigators [436] provided resistance trained males with 201 mg caffeine (2.1–3.0 mg/kg) and reported no impact on lower-body strength, lower-body muscular endurance or upper-body muscular endurance. Maximal upper-body strength, however, was improved. In contrast, other studies have indicated that caffeine may favorably impact muscular performance. For example, Goldstein et al. [437] reported that caffeine ingestion (6 mg/kg) significantly increased bench press strength in a group of women but did not impact repetitions to fatigue. Studies by Duncan and colleagues [438‐441] have examined the impact of caffeine on strength and endurance performance as well various parameters of mood state while performing maximal resistance exercise. Briefly, these authors have reported improvements in strength and repetitions to failure using the bench press [438, 439] and other exercises [440, 441]. In addition to potential ergogenic impact, these authors also reported that caffeine significantly improved various indicators of mood state [438, 440], lowered ratings of perceived exertion and decreased perception of muscle pain [439, 441] when acute doses of caffeine (5 mg/kg) were provided before maximal resistance exercise. As illustrated, when evaluating the research on caffeine for its ability to impact strength and muscular performance, the findings are equivocal, and, subsequently, more research is needed to better determine what situations may best predict caffeine’s ability to impact strength performance. For example, trained subjects have demonstrated more ergogenic effects compared to untrained subjects [442, 443]. Also, people who drink caffeinated drinks regularly, however, appear to experience less ergogenic benefits from caffeine [444]. Some concern has been expressed that ingestion of caffeine prior to exercise may contribute to dehydration, although several studies have not supported this concern [430, 445, 446]. Caffeine, from anhydrous and coffee sources are both equally ergogenic [434]. Caffeine doses above 9 mg/kg can result in urinary caffeine levels that surpass the doping threshold for many sport organizations. In summary, consistent scientific evidence is available to indicate that caffeine operates as an ergogenic aid in several sporting situations.

One of the best ergogenic aids available for athletes and active individuals alike, is carbohydrate. Optimal carbohydrate in the diet on a daily basis, in the hours leading up to exercise, throughout exercise and in the hours after exercise can ensure endogenous glycogen stores are maintained and support many types of exercise performance [41‐43, 50]. In this respect, athletes and active individuals should consume a diet high in carbohydrate (e.g., 55–65% of calories or 5–8 g/kg/day) to maintain muscle and liver carbohydrate stores [41, 50, 54]. Research has clearly identified carbohydrate as an ergogenic aid that can prolong exercise [41, 68]. For example, Below and colleagues [447] provided research that ingesting carbohydrate throughout a time to exhaustion protocol after nearly an hour of moderate intensity cycling can significantly extend the time cycling is performed. Moreover, Widrick et al. [129] systematically examined all four possible combinations of high and low pre-exercise intramuscular glycogen levels with and without carbohydrate provision before a standard bout of cycling exercise. When carbohydrate was provided, performance was improved. In addition to traditional endurance exercise models, Williams and Hawley [42] summarized the literature involving carbohydrate delivery and performance of team sports that are typically characterized by variable intensities and intermittent periods of heavy exertion and concluded that carbohydrate intake can increase performance. Pochmuller et al. [68] and Colombani et al. [69] have critically pointed to the duration of the involved exercise bout, the intensity of exercise involved, and the fasting status of the individuals as key factors that may impact exercise performance. Further, Burke and colleagues [23, 50], Hawley et al. [43] and Rodriguez et al. [54] have all emphasized the importance of optimal carbohydrate delivery throughout various types of sport and recovery scenarios to support performance. Beyond ingestion, a growing body of literature has drawn attention to the potential impact of carbohydrate mouth rinsing as an ergogenic strategy. Initial work by Carter and colleagues [448] where they demonstrated an increase in time to exhaustion performance while cycling after rinsing (but not swallowing) the oral cavity with a carbohydrate solution versus a no carbohydrate rinse revealed that receptors in the brain might be linked to the mere presence of carbohydrate in the mouth, which subsequently can work to improve various types of exercise performance. While this concept is still emerging, some [449‐452] but not all [453‐455] of the studies have supported the ability of carbohydrate mouth rinsing to increase performance. Another carbohydrate manipulation strategy has included utilizing high molecular weight carbohydrates solutions, in contrast to traditional low molecular weight beverages, to theoretically accelerate glucose absorption and energy availability. Importantly, the majority of the literature suggests that utilizing a high molecular weight solution can impart changes in oxidized substrates, or patterns of fuel usage, but appears to have no ergogenic effect on performance in males or females [63, 456‐459].

As indicated earlier, creatine supplementation is a well-supported strategy to increase muscle mass and strength during training. However, creatine has also been reported to improve exercise capacity in a variety of settings [182, 460‐462]. Specifically, and as discussed by Kreider et al. [10], studies have documented improvements in: a) single and multiple sprints, b) work completed across multiple sets of maximal effort, c) anaerobic threshold, d) glycogen loading, e) work capacity, f) recovery, and g) greater training tolerance. Consequently, team sports, individual activities or sports that consist of high intensity, intermittent exercise such as soccer, tennis, basketball, lacrosse, field hockey and rugby can all benefit from creatine use [182]. Moreover, a 2009 study found that in addition to high intensity interval training creatine improved critical power [460]. Less research is available involving creatine supplementation and endurance exercise, but creatine’s ability to promote glycogen loading [463] and storage of carbohydrate [464‐466], key fuels during endurance exercise, may translate into improved endurance exercise performance. Indeed, a 2003 study found that ingesting 20 g of creatine for 5 days improved endurance and anaerobic performance in elite rowers [467]. Since creatine has been reported to enhance interval sprint performance, creatine supplementation during training may improve training adaptations in endurance and anaerobic athletes, anaerobic capacity, and allow athletes to complete greater volumes of training at or above anaerobic threshold [468, 469]. Notably, for athletes who struggle to maintain their body mass throughout their competitive season, creatine use may help athletes in this respect. Importantly and in addition to creatine being an effective ergogenic aid in a wide variety of sports, studies have documented these outcomes (improvements in acute exercise capacity, work completed during multiple sets and training adaptations) in adolescents [470‐474], younger adults [231, 424, 462, 475‐483], and older individuals [484‐490]. Regarding creatine and athletic performance, there appears to be a misunderstanding that creatine may result in muscle cramps and dehydration. However, based on many available studies, there is no clinical evidence that creatine supplementation will increase susceptibility of dehydration, muscle cramps, or heat related illness [196, 491].

During high intensity exercise, acid (H+) and carbon dioxide (CO₂) accumulate in the muscle and blood. The bicarbonate system is the primary means the body rids itself of the acidity and CO₂ via their conversion to bicarbonate prior to subsequent removal in the lungs. Bicarbonate loading (e.g., 0.3 g per kg taken 60–90 min prior to exercise or 5 g taken two times per day for 5 days) as sodium bicarbonate has been shown to be an effective way to buffer acidity during high intensity exercise lasting one to 3 min in duration [431, 492‐494]. Matson et al. [495] reported improvements in exercise capacity in events like the 400–800 m run while Lindh and colleagues [496] reported that bicarbonate can improve 200 m freestyle swimming performance in elite male swimmers. Similarly, studies have reported the ability of bicarbonate to improve 3 km cycling time trials [497]. Marriott et al. [498] published findings that sodium bicarbonate significantly improved intermittent running performance by 23% and reduced perceived exertion in male team-sport athletes. Interestingly, Percival and investigators [499] reported that sodium bicarbonate supplementation resulted in significantly higher levels of PGC-1-α, a key protein known to drive mitochondrial adaptations. Finally, a meta-analysis by Peart and investigators [500] involving sodium bicarbonate reported the overall treatment effect to be moderate at improving performance with nearly all measured ergogenic outcomes being influenced by the training status of the participants.

In addition, other studies have examined the potential additive benefit of ingesting sodium bicarbonate with either caffeine or beta-alanine. In this respect, Kilding et al. [497] reported significant independent effects of caffeine and bicarbonate on three-kilometer cycling time trial performance, but no additive benefit. Alternatively, Tobias and associates [501] also reported a significant improvement in upper-body power production in trained martial arts athletes after ingesting either beta-alanine or sodium bicarbonate, but noted a distinct synergistic improvement in upper-body power and performance when beta-alanine and sodium bicarbonate were ingested together. In contrast, Danaher et al. [502] had eight healthy males supplement with either beta-alanine, sodium bicarbonate or their combination for 6 weeks in a crossover fashion before completing a repeated sprint ability test while cycling. While buffering capacity was increased, performance was only improved when beta-alanine was provided. Due to the mixed outcomes and relative lack of available studies, more research is recommended examining the synergistic impact of sodium bicarbonate and other ingredients. It is important to highlight that a common complaint surrounding the ingestion of sodium bicarbonate is gastrointestinal distress, thus athletes should experiment with its use prior to performance to evaluate tolerance.

Phosphate is best known as an essential mineral found in many common food sources (e.g., red meat, fish, dairy, cereal, etc.) with key functions in bone, cell membranes, RNA/DNA structure and as backbones of phosphocreatine and various nucleotides. In addition, phosphate has been suggested to operate in an ergogenic fashion due to its potential to improve oxygen transport through modulation of 2,3-diphosphoglycerate (DPG) and other lactic-acid-buffering components. Sodium phosphate (NaPO₄) supplementation has been reported in multiple studies to improve aerobic capacity by 5–12% [503‐505], anaerobic threshold by 5–10% [504‐507], mean power output [503, 508] and intermittent running performance [509‐511]. Collectively these studies have employed a dosing regimen that required 1 g of NaPO₄ to be taken four times daily for three to 6 days. Not all studies, however [512‐514], have reported ergogenic outcomes while factors that impact phosphate absorption, training status and gender posed as potential reasons why supplementation has not universally impacted performance. Brewer and colleagues [513] reported modest (non-significant) effects of NaPO₄ supplementation on repeated supplementation regimens in trained cyclists completing a time trial. Furthermore, West and investigators [514] used a mixed gender cohort and concluded no change in VO₂Max resulted after supplementation. Buck et al. [515] were the first to solely examine the impact of NaPO4 in female athletes when they had 13 trained female cyclists complete a 500-kJ time trial after supplementing with either 25, 50, or 75 mg/kg of NaPO₄ in a randomized, double-blind manner. No significant impact of supplementation was seen at any dosage leading the authors to conclude that females may not respond in the same manner as men. However, the same authors on two occasions [510, 511] examined the impact of NaPO4 in female team sport athletes completing repeated bouts of sprint running and found that NaPO4 significantly improved best and total sprint times when compared to a placebo. Consequently, the impact of gender on the ergogenic potential of NaPO4 remains unclear with consistent benefits in females when repeated sprints are performed but no such benefits during time-trial work.

Adopting strategies to limit the loss of body mass due to sweating is critical to maintain exercise performance (particularly in hot/humid environments). People engaged in intense exercise or work in the heat are commonly recommended to regularly ingest water or sports drinks (e.g., 12–16 fluid ounces every 10–15 min) with the overarching goal being to minimize the loss of body mass commonly seen as a result of exercising in a hot and humid environment [516]. Below and colleagues [447] demonstrated the independent ability of both fluid (no carbohydrate) and carbohydrate ingestion to significantly increase cycling performance. Moreover, when the two treatments were combined a synergistic impact on performance was observed. Studies show that ingestion of sports drinks during exercise in hot/humid environments can help prevent dehydration and improve endurance exercise capacity [517‐519]. Of note and like carbohydrate, it appears that exercise factors such as the duration and intensity of the exercise bout operate as strong predictors of cycling time-trial performance [520, 521]. Consequently, frequent ingestion of water and/or sports drinks during exercise is one of the easiest and most effective ergogenic aids due to its ability to support thermoregulation and reduce cardiovascular strain during prolonged bouts of exercise, particularly when completed in hot and humid conditions [162, 516].

Operating under the same theoretical framework as glutamine, interest in supplementing with L-alanyl-L-glutamine has increased in recent years. The ingredient has two parts: L-alanine and L-glutamine, both of which are amino acids that are mainstays in the transamination processes involving amino acids. Rogero and colleagues [522] supplemented rats with L-alanyl-L-glutamine for the final 21 days of a six-week exercise training program. Supplementation did not impact time to exhaustion performance, but higher levels of glutamine were found when compared to a control group. Cruzat and Tirapequi [523] also reported increases in plasma and intramuscular glutamine along with an improved antioxidative profile in blood, muscle and liver tissue samples of laboratory rats. These results were extended in 2010 to also report an attenuation of inflammation and plasma creatine kinase levels in laboratory rats after exercise training [523].

Since 2010, five peer-reviewed studies have been published using human subjects. Hoffman and colleagues [524] reported, in a group of ten physically active males, that L-alanyl-L-glutamine increased time to exhaustion on a cycle ergometer when exposed to mild dehydration stress. Two years later, the same research group reported that rehydration with L-alanyl-L-glutamine after 2.3% dehydration in a basketball scrimmage led to an improvement in basketball skill performance and visual reaction time when compared to water [525]. A 2016 study indicated that L-alanyl-L-glutamine maintained reaction time in an upper and lower-body activities after an exhaustive bout of treadmill running [526]. Finally, a 2015 paper determined that L-alanyl-L-glutamine significantly improved treadmill running performance when compared to no hydration [527]. Collectively this research indicates that L-alanyl-L-glutamine at dosages ranging 300–1000 mg per 500 mL of fluid can favorably influence hydration status and performance when compared to no fluid ingestion or water only ingestion.

Arachidonic acid (ARA) is a long-chain polyunsaturated fatty acid (20:4, n-6) that resides within the phospholipid bi-layer of cell membranes at concentrations that are dependent upon dietary intake [528]. ARA is not found in high amounts in the typical American diet [529]. However, as little as 1.5 g per day of supplementation over a 50-day period has been shown to increase tissue cell membrane stores of ARA [530]. In skeletal muscle, there is evidence that ARA drives some of the inflammatory response to strength training via enhanced prostaglandin signalling [531]. Specifically, exercise liberates ARA from the muscle cell membrane via phospholipase A₂ activation. Resultant free intracellular ARA is subsequently converted into certain prostaglandins (i.e., PGE₂ or PGF_2α) via cyclooxygenase (COX) enzymes [532], and these prostaglandins can signal associated receptors in an autocrine and paracrine manner to up-regulate signalling associated with increases in muscle protein synthesis. Roberts and colleagues [533] were the first group to examine the impact of ARA supplementation on changes in strength and body composition. Over an eight-week period, resistance-trained, college-aged males were supplemented in a double-blind fashion with either a placebo or ARA at a dosage of 1 g per day in conjunction with 90 g/day of whey protein. A significant increase in anaerobic peak power was found in the ARA group, but no other changes in strength or body composition were found. The second study by DeSouza et al. [534] investigated the effects of ARA supplementation (0.6 g/d vs. placebo) in strength-trained college-aged males for 8 weeks with concomitant resistance training and without protein supplementation. These authors reported that lean body mass (2.9%, p < 0.05), upper-body strength (8.7%, p < 0.05), and anaerobic peak power (12.7%, p < 0.05) significantly increased only in the ARA group. Mitchell and colleagues [535] have also published data in 19 resistance-trained men who supplemented, in a double-blind, placebo-controlled fashion, with 1.5 g per day of ARA for 4 weeks and found that ARA supplementation did not impact acute changes in muscle protein synthesis and other mechanistic links to protein translation. The authors concluded that ARA supplementation did not support a mechanistic link between ARA supplementation and short-term anabolism, but may increase translation capacity. Given the limited human data and inconsistent nature (two positive outcomes, one negative outcome) of the findings regarding the efficacy of ARA, it is too early to recommend ARA at this time. In this respect, more chronic human studies testing different doses of ARA supplementation are needed to fully examine its safety and potential efficacy as a performance enhancing or muscle building aid. From a safety perspective and due to ARA being a known pro-inflammatory fatty acid, use of ARA may be contraindicated in populations that have compromised inflammatory health (i.e., inflammatory bowel syndrome, Chron’s disease, etc.).

Ingestion of BCAA (e.g., 6–10 g per hour) with sports drinks during prolonged exercise has long been suggested to improve psychological perception of fatigue (i.e., central fatigue). Accordingly, Mikulski and investigators [536] used 11 endurance trained men to examine the impact of ingesting 16 g of BCAAs and 12 g of ornithine aspartate over a 90-min cycling exercise bout and found that the amino acid combination significantly improved reaction time, but no ergogenic impact was seen when BCAAs were ingested independently. Although a strong rationale and data exist to support an ergogenic outcome, mixed outcomes currently prevail as other studies have failed to report an ergogenic impact of BCAAs [247, 537]. Consequently, more research is needed to fully determine the ergogenic impact, if any, of BCAAs. An important point to highlight surrounding BCAAs is the growing body of literature supporting their ability to mitigate outcomes surrounding muscle damage. In this respect, multiple studies have investigated and offered support for BCAA’s ability to promote recovery, mitigate soreness and attenuate losses in force production [249, 250, 537, 538].

Citrulline (2-Amino-5-(carbamoylamino)pentanoic acid or L-Carnitine) is endogenously produced from ornithine and carbamoyl phosphate in the urea cycle. In the body, citrulline is efficiently recycled into arginine for subsequent nitric oxide production through the citrulline-nitric oxide cycle [539]. Unlike arginine, citrulline catabolism is limited in the intestines [540] as well as its extraction from hepatic tissue [541] resulting in the majority of citrulline passing into systemic circulation before conversion to arginine [542]. Due to this and its non-competitive uptake for cell transport [542], oral citrulline supplementation has been shown to be more effective in increasing arginine [543, 544] and activation of nitric oxide synthase (NOS) [544] as well as various biomarkers of nitric oxide [545]. Multiple studies have employed aerobic exercise models to examine citrulline’s impact on performance. Suzuki et al. [546] showed that 2.4 g/day of L-citrulline for 7 days increased plasma nitric oxide metabolites, plasma arginine and 4-km time trial performance. Using a finger flexor exercise model and P31 nuclear magnetic resonance spectroscopy, Bailey and colleagues [547] reported that 7 days of citrulline (6 g/day) significantly increased plasma arginine and nitrite levels and significantly improved VO₂ kinetics and exercise performance. However, not all studies reported an ergogenic effect whereby Cunniffe et al. [548] reported no impact of 12 g of citrulline malate on the performance of a single bout of high-intensity cycling. In addition to aerobic exercise research, three studies examined the impact of an 8-g citrulline dose while resistance training on various performance outcomes [549‐551]. One study [550] evaluated the effects on the number of repetitions performed for chin-ups, reverse chin-ups, and push-ups to failure in trained males. A second study [551] evaluated the effect of citrulline supplementation on the number of repetitions performed for five sequential sets (60% 1RM) to failure on the leg press, hack squat, and leg extension exercises in trained males. The third study [549] evaluated the effects of citrulline supplementation on the number of repetitions performed during six sets each of bench press and leg press exercises to failure at 80% 1RM in trained females. In all three studies, citrulline malate was shown to significantly increase performance during upper- and lower-body multiple-bout resistance exercise performance. Alternatively, Cultrufello and colleagues [552] reported that a 6 g dose of L-citrulline failed to impact both aerobic and anaerobic indicators of exercise performance. The role of malate in combination with citrulline is largely undetermined. Since malate is an important tricarboxylic acid cycle intermediate, this could possibly account for improvements in muscle function [553]. Therefore, it is presently unclear whether these benefits can be solely attributed to citrulline, as well as what role citrulline may play in aerobic and anaerobic performance.

Research exploring the impact of essential amino acids with various forms of exercise has exploded. To date, it is well accepted that ingestion of at least 2 g of the essential amino acid, leucine, is required to stimulate cellular mechanisms controlling muscle hypertrophy [225, 554] and that ingestion of 6–12 g of a complete essential amino acid mixture are needed to maximize muscle protein synthesis [201‐208, 555]. However, their impact on performance remains largely unexplored. While sound theoretical rationale exists and multiple acute study designs provide supportive evidence, it is currently unclear whether following this strategy would lead to greater training adaptations and/or whether EAA supplementation would be better than simply ingesting carbohydrate and a quality protein following exercise. Moreover, very little research is available that has examined the ability of EAAs to impact exercise performance. For these reasons, many authors and review articles have encouraged the prioritization of intact protein sources over ingestion of free form amino acids [11, 13, 54, 222] to promote accretion of fat-free mass, but, as mentioned, the impact of this recommendation on performance changes remains undetermined.

Ingesting glycerol with water has been reported to increase fluid retention, and maintain hydration status [556‐558]. Theoretically, this should help athletes prevent dehydration and improve thermoregulatory and cardiovascular changes. Although studies indicate that glycerol can significantly enhance body fluid, results are mixed on whether it can improve exercise capacity [166, 559‐564]. Regarding endurance performance Coutts and investigators [565] had ten trained endurance athletes complete an Olympic distance triathlon under both placebo and glycerol hyperhydration (1.2 g/kg) + 25 mL/kg fluid solution) 2 h before completion of each triathlon and reported that completion time was significantly improved with glycerol hyperhydration over placebo. These findings were corroborated by Goulet et al. [566] when they had six endurance-trained subjects hyperhydrate with glycerol or water 2 h before a prolonged (2 h) bout of cycling at 65% VO₂max in hot conditions (26-27 °C) followed two-minute intervals at 80% VO₂max and concluded that glycerol hyperhydration significantly improved performance. In contrast, Marino et al. [567] reported that a similar glycerol hyperhydration protocol did not improve the total distance covered when moderately trained cyclists completed a variable-intensity cycling protocol. Additionally, Goulet et al. [568] combined a hyperhydration strategy (1.2 g/kg glycerol + 26 mL/kg water) 2 h before commencing a two-hour cycling bout at 66% VO₂max and 25 °C with consuming (500 mL/hour) a sports drink and reported that glycerol hyperhydration failed to impact cardiovascular or thermoregulatory functions as well as endurance performance. McKenna and investigators [569] were one of the only research groups to examine glycerol’s potential to impact anaerobic power after glycerol hyperhydration. After following a double-blind hyperhydration protocol, male collegiate wrestlers lost 3% of their body mass from fluid and completed an anaerobic test where no impact on performance was found. Variable outcomes surrounding glycerol continue to undermine its potential and the ability to offer a recommendation for its use. Consequently, as pointed out by Goulet et al. [556], it is concluded that more research needs to be completed to work through the nuance surrounding glycerol’s potential efficacy, a key point previously summarized by Nelson et al. [570].

For several years, beta-hydroxy-beta-methyl-butyrate (HMB) has received interest for its ability to enhance training adaptations and performance while also delaying or preventing muscle damage [15, 168, 571]. Initial work by Nissen and colleagues [171] showed significant increases in lean body mass and strength with doses 1.5 and 3 g/day in untrained males, with the 3 g dose showing additional benefits over the lower dose. Gallagher and colleagues [169] indicated that a dose of 38 mg/kg/day (approximately 3 g/day) promoted improvements in fat-free mass, peak isometric force and isokinetic torque production, while no changes in maximal strength were seen. In agreement, Thomson and researchers [572] had 22 resistance trained men supplement, in a double-blind fashion, with either HMB or placebo for 9 weeks and concluded that HMB was responsible for a significant increase in lower-body strength. Not all studies, however, have provided support. For example, Kreider et al. [175] used a dose-response, placebo-controlled approach and concluded that three or 6 g of calcium-HMB did not impact body composition or strength adaptations in individuals experienced with resistance exercise after 4 weeks of supplementation and resistance training. Similarly, Hoffman and colleagues [573] reported that HMB supplementation failed to improve anaerobic power production in collegiate football players, a conclusion which aligns with other previous studies [172, 574]. Differences in training regimens (intensities), randomization, and supervision varied in the initial studies and may have contributed to the mixed results. HMB appears to have the greatest effects on performance when training intensity is maximized.

While many of the previous studies have examined, with mixed results, the ergogenic potential of calcium-HMB supplementation in active, recreationally active individuals, Durkalec-Michalski and colleagues completed three investigations [178‐180] that all sought to determine the impact of calcium-HMB supplementation in different athlete types. For instance, HMB supplementation (3 g/day) in elite rowers over a 12-week period significantly improved aerobic (VO₂max, time to reach ventilatory threshold) performance markers and decreased fat mass when compared to changes seen with placebo [178]. Later, Durkalec-Michalski and Jeszka [179] required 58 highly trained males to supplement with calcium-HMB (3 g/day) for 12 weeks. In this study, fat-free mass increased and fat mass decreased along with multiple markers of aerobic capacity when HMB was provided in comparison to a placebo. Most recently, HMB supplementation over 12 weeks in highly-trained combat sport athletes significantly increased (in comparison to placebo) several indicators of aerobic and anaerobic exercise performance [180]. The recent studies by Durkalec-Michalski and colleagues confirmed earlier works by Vukovich [575] and Lamboley [576] that HMB does have a positive effect on increasing aerobic capacity.

HMB is available as calcium-HMB and as free acid. In comparison to calcium HMB, HMB-free acid shows greater and faster absorption (approx. 30 min vs. 2–3 h) [577]. Much of the initial research used calcium-HMB with largely mixed outcomes while studies using the free acid form are more limited. Studies by Wilson and colleagues using the free acid form have indicated robust changes in strength, vertical jump power and skeletal muscle hypertrophy while heavy resistance training alone [578] and in combination with supplemental ATP [579], but others have critically questioned these outcomes [580]. A recent systematic review by Silva and investigators [581] concluded that the free acid form of HMB may improve muscle and strength and attenuate muscle damage when combined with heavy resistance training but stated that more research is needed before definitive conclusions can be determined.

Nitrate supplementation has received much attention due to their effects on vasodilation, blood pressure, improved work efficiency, modulation of force production, and reduced phosphocreatine degradation [582‐584] all of which can potentially improve sports performance. Nitrate supplementation is most commonly consumed two to 3 h prior to exercise as beetroot juice or sodium nitrate [585] and is prescribed in both absolute and relative amounts ranging from 300 to 600 mg [585] or 0.1 mmol per kilogram of body mass per day, respectively [583, 586]. These dosing amounts appear to be well tolerated when consumed as both supplemental [587] and supplemental sources [588] without significant alterations in hemodynamics or clinical boundaries of hepatorenal and muscle enzyme status [478, 589]. Supplementing highly trained cyclists with sodium nitrate (10 mg per kilogram of body mass) significantly reduced VO₂peak without influencing time to exhaustion or maximal power outputs [590]. Additionally, 600 mg of nitrate supplementation (given 2 h prior) non-significantly improved the performance of a 500-m time trial performance in elite-level kayak athletes by 2 s [591]. Of practical significance, it should be noted that first place and last place in the 2008 Beijing Olympics, was separated by 1.47 s in the 500-m men’s canoe/kayak flatwater race. Amateur cyclists at simulated altitude (~ 2500 m) observed improved 16.1 km time trial performance with a concomitant decrease in oxygen consumption after beetroot juice (310 mg nitrate) supplementation [592]. Not all findings, however, have reported performance benefits with nitrate supplementation. Nitrate supplementation (~ 385 mg nitrate) 2.5 h before a 50-mile time trial in well-trained cyclists failed to improve performance [593], which was also reported by MacLeod et al. [594] after examining nitrate supplementation (~ 400 mg nitrate) on 10-km time trial performance in normoxia or simulated altitude (~ 2500 m). In well-trained runners, nitrate supplementation (~ 430 mg nitrate) did not improve performance during an incremental exercise test to exhaustion (simulated altitude 4000 m) or a 10-km time trial (simulated altitude, 2500 m) [595] and Nyakayiru et al. [596] reported no impact of nitrate supplementation on changes in VO₂ and time trial performance in highly trained cyclists. Other studies have also reported an additive or synergistic effects of high-intensity intermittent exercise, endurance exercise, or resistance training when nitrate supplementation is combined with sodium phosphate [511], caffeine [597], or creatine [478], respectively. It is important to mention that dietary nitrates have a health benefit in some, but not all populations [598]. Daily consumption of beetroot juice (~ 320–640 mg nitrate/d) significantly decreased resting systolic blood pressure in older adults by approximately 6 mmHg [599, 600]. Nitrate supplementation (560 mg – 700 mg nitrate) significantly increased blood flow to working muscle and exercise time in older adults with peripheral artery disease [601] as well as significantly improved endothelial function via increased flow-mediated dilation and blood flow velocity in older adults with risk factors of cardiovascular disease [602]. Collectively, these results indicate that nitrate supplementation may improve aerobic exercise performance and cardiovascular health in some populations.

Ingesting carbohydrate with protein following exercise has been a popular strategy to heighten adaptations seen as part of a resistance training program. The rationale behind this strategy centers upon providing an energy source to stimulate MPS via key signal transduction pathways. Additionally, carbohydrate intake will impact insulin status which could promote MPS, limit protein breakdown or both [603‐605]. Furthermore, combining carbohydrate with protein can heighten glycogen resynthesis rates, particularly when carbohydrate intake is not optimal [120] and can improve muscle damage responses after exhaustive exercise [606]. A key point for readers to consider when interpreting findings from this literature is the amount of protein, essential amino acids or leucine being delivered by the protein source [11]. In the last few years many studies have agreed that post workout supplementation is vital to recovery and training adaptations [133, 230, 232, 607, 608]. However, the need for adding carbohydrate to protein to maximize hypertrophic adaptations continues to be questioned. For example, Staples and investigators [605] used an acute study design involving stable isotope methodology to investigate the impact of adding 50 g of carbohydrate to 25 g of whey protein ingestion after a single bout of lower body resistance exercise. The authors concluded that the combination of carbohydrate and protein was no more effective at stimulating muscle protein synthesis or blunting rates of muscle protein breakdown than protein alone. Furthermore, Hulmi and colleagues [609] had participants resistance train for 12 weeks and supplement with equivalent doses of whey protein, carbohydrate or whey protein + carbohydrate while having strength and body composition assessed. Overall, changes in strength were similar in all groups while changes in fat-free mass were greater in the protein group when compared to the carbohydrate group. Fat mass was found to significantly decrease in both groups that contained protein in comparison to carbohydrate, but no differences between the two protein-containing groups were noted. In conclusion, these findings underscore the importance of ingesting adequate protein to stimulate resistance training adaptations. Whether or not the addition of carbohydrate can heighten these changes at the current time seems unlikely. This outcome, however, should not distract the reader from appreciating the fact that optimal carbohydrate delivery will absolutely support glycogen recovery, aid in mitigating soreness and inflammation and fuel other recovery demands.

Quercetin is a flavonoid commonly found in fruits, vegetables and flowers, and is known for having some health benefits with therapeutic use. In addition, quercetin has been purported in both animal and human models to improve endurance performance. In this respect, Cureton and colleagues [610] supplemented 30 recreationally active, but not highly trained men in a double-blind fashion to ingest either quercetin (1 g/day) or placebo. No changes in total work performed, substrate utilization, or perception of effort were found after supplementation. Similarly, Bigelman and investigators [611] supplemented ROTC cadets with either 1 g of quercetin or a placebo and concluded that VO₂max was unchanged as a result. These results correspond with the outcomes of other studies that failed to document ergogenic potential for quercetin [612, 613]. In contrast, Nieman et al. [614] supplemented untrained adult males with 1 g of quercetin in a double-blind fashion for 2 weeks and reported that treadmill performance and markers of mitochondrial biogenesis were improved. Similarly, Patrizio et al. [615] used a resistance exercise model and reported quercetin may improve neuromuscular performance while Davis et al. [616] had 12 study participants supplement with either quercetin and placebo and found that quercetin may improve VO₂max and endurance capacity. A meta-analysis was completed by Pelletier and researchers [617] to summarize the potential impact of quercetin supplementation on endurance performance. This analysis involved seven published studies representing 288 research participants. Only in untrained participants was quercetin found to significantly increase endurance performance. A 2011 meta-analysis by Kressler et al. [618] drew a similar conclusion whereby they indicated quercetin does have benefit, but the size of this effect is trivial and small. Consequently, more research needs to be completed to better identify what situations may exist that support quercetin’s ability to impact exercise performance.

Taurine is an amino acid found in high abundance in human skeletal muscle [619, 620] derived from cysteine metabolism that plays a role in a wide variety of physiological functions [621‐623]. Studies have indicated that training status (higher in trained vs. untrained muscle, reviewed in [624]) and fiber type (higher in type I vs. type II, reviewed in [619]) impact the amount of taurine found in muscle. It has been reported in some [625, 626] but not all studies [627, 628] that taurine may improve exercise performance and mitigate recovery from damaging and stressful exercise [629]. In recent years, many studies have examined the impact of taurine ingestion on various types of exercise performance. In accordance with previous work, ergogenic outcomes related to taurine administration continue to be mixed. Milioni and investigators [628] failed to show an improvement in performance with a 6 g dose of taurine while completing high-intensity treadmill running. Similarly, Balshaw et al. [625] indicated that taurine failed to positively impact 3-km running performance in trained runners. In contrast, a 2017 study by Warnock et al. [630] reported that a 50 mg/kg dose of taurine outperformed caffeine, placebo and caffeine + taurine on performance changes after repeated Wingate anaerobic capacity tests. Finally, a 2018 meta-analysis by Waldron et al. [631] reported that single daily dosages ranging from one to 6 g for up to 2 weeks can significantly improve endurance exercise performance in a range of study participants. Two studies [632, 633] have been completed that examined taurine’s ability to mitigate decrements associated with muscle damage and resistance exercise performance. Notably, oral ingestion at a dosage of 50 mg/kg for 14 days prior to damage and for 7 days after damage significantly increased strength, and decreased soreness and markers of muscle damage [633]. Finally, studies have also supported the ability of taurine to function in an anti-oxidative role, which may promote an improved cellular environment to tolerate exercise stress [634, 635]. While more research continues to be published involving taurine, the consensus of these outcomes continue to be mixed regarding taurine’s potential to enhance physical performance.

Arginine is known as a conditionally essential amino acid which has been linked with the ability to increase exercise performance, increase growth hormone production, support immune function, increase training tolerance and promote accretion of fat-free mass [273, 636]. Several studies have sought to examine the ergogenic potential of arginine using both endurance and resistance exercise models with largely mixed results. For example, Greer and investigators [637] examined the ability of arginine + alpha-ketoglutarate and reported that the combination did not significantly impact muscle endurance and significantly reduced the number of chin-ups completed. Similar outcomes were found by Aguiar et al. [638] in older women whereby arginine supplementation failed to impact muscle performance. Sunderland et al. [639] supplemented 18 endurance-trained cyclists for 28 days with either arginine (12 g/day) or corn starch and concluded that arginine did not impact VO₂Max or ventilatory threshold. In accordance, several other studies have failed to positively report on the ability of arginine to operate as an ergogenic aid [278, 640‐644]. Alternatively, a few studies have provided evidence of ergogenic potential for arginine. For example, Campbell and researchers [271] supplemented 35 resistance-trained males in a double-blind fashion with arginine (2 g) + alpha-ketoglutarate (2 g) or a placebo and concluded that maximal upper-body strength and wingate peak power were significantly increased after supplementation. Similarly, Bailey and colleagues [645] concluded that acute arginine supplementation reduced the oxygen cost of moderate-intensity exercise and increased tolerance to high-intensity training. Moreover, Pahlavani et al. [646] supplemented male athletes with arginine in a double-blind fashion and concluded that arginine supplementation significantly increased sport performance. As it stands, most of the published literature that has examined the ability of arginine to operate in an ergogenic fashion has failed to report positive outcomes. While more research is certainly indicated, consumers should exercise caution when using arginine to enhance exercise performance.

Carnitine is produced endogenously by the liver and kidneys and plays a pivotal role in lipid metabolism. Consequently, many are led to believe that carnitine ingestion will increase the concentration of endogenous carnitine, thereby increasing lipid metabolism and decrease adipose reserves. To date, the majority of the data continues to suggest that carnitine supplementation does not markedly affect muscle carnitine content [647‐649], fat metabolism [648, 650, 651], exercise performance [648, 649, 652, 653], or weight loss in overweight [650, 654], obese [651, 655, 656] or trained subjects [657]. For example, Burrus and investigators [658] had ten cyclists ingest combinations of carbohydrate and carnitine while completing a 40-min ride at 65% VO₂peak before completing an exhaustion ride at 85% VO₂Peak. No differences in power outputs or times to exhaustion were found with cycling at 85% VO₂Peak. Of note, studies have suggested that co-ingesting carnitine with carbohydrate can lead to significant increases in intramuscular carnitine [659, 660]. Later, Wall and colleagues [661] reported that endurance exercise performance was improved and improvements in fuel selection appeared to occur. While interesting, more research is needed regarding changes in performance before further recommendations can be made.

As outlined above, a strong theoretical framework exists for glutamine’s ability to help an individual tolerate stress, particularly when relying on animal studies. A close examination into the available human research on glutamine makes it more challenging to characterize glutamine’s potential. Theoretically, glutamine supplementation during training should enhance gains in strength and muscle mass, but evidence in this respect has not been consistent. Glutamine supplementation has been shown to improve glycogen stores which could go on to impact certain types of exercise performance [331] and two recent studies suggest that glutamine provision may help support recovery from damaging resistance exercise. In this respect, Street and colleagues [662] concluded that adding glutamine (0.3 g/kg) to a carbohydrate drink significantly improved muscle soreness and force production, but did not impact changes in creatine kinase, when compared to carbohydrate only ingestion. A similar outcome was found by Legault and colleagues [337] who reported that glutamine supplementation significantly lowered perceived soreness levels and led to improved recovery of force production after a damaging bout of eccentric muscle contractions. From an ergogenic perspective, limited research is available, but Antonio et al. [334] reported that 0.3 g/kg glutamine ingestion did not impact the number of repetitions completed with the leg press or bench press exercises. Consequently, minimal research is available to support glutamine’s ability to operate as an ergogenic aid.

Inosine is a building block for DNA and RNA that is found in muscle. Inosine possesses important roles that may enhance training and/or exercise performance [663]. Although there is some theoretical rationale, available studies indicate that inosine supplementation has no apparent effect on aerobic or anaerobic exercise performance [664‐666].

Medium chain triglycerides (MCT’s) are shorter chain fatty acids known to readily enter the mitochondria and be converted to energy through beta-oxidation [667]. Studies are mixed as to whether MCT’s are ergogenic and can serve as an effective source of fat during exercise [667‐671]. A 2001 study found that 60 g/day of MCT oil for 2 weeks did improve running performance [672]. Additionally, Van Zyl and colleagues [671] reported that while MCTs negatively influenced cycling time trial performance when ingested alone in comparison to carbohydrate ingestion, performance was improved when MCTs were combined with carbohydrate. Using a similar exercise model, Goedecke et al. [668] also reported that MCT administration throughout a two-hour moderate intensity cycle ride resulted in a similar performance in completing a 40-km time trial by trained cyclists. A similar outcome was also reported by Vistisen et al. [673]. Beyond equivocal findings, Goedecke et al. [674] and Jeukendrup et al. [667] both reported ergolytic outcomes of MCT administration on sprint performance in trained cyclists and cycling time trial performance, respectively, while the incidence of gastrointestinal complaints increased in both studies. These findings have been confirmed by others that MCT oils are not sufficient to induce positive training adaptations and may cause gastric distress [675, 676]. Consequently, it does not appear likely that MCT favorably impacts acute exercise performance and no evidence exists that training adaptations may be positively impacted either, while multiple studies have reported that MCT ingestion may cause gastrointestinal upset and decrease exercise performance.

Ribose is a 5-carbon carbohydrate that is involved in the synthesis of adenosine triphosphate (ATP) and other adenine nucleotides. Clinical studies have shown that ribose supplementation can increase exercise capacity in heart patients [677‐681] leading to the development of theories that it can operate as ergogenic aid for athletes. Of the available research, most fail to show an ergogenic value for ribose supplementation on exercise capacity in healthy untrained or trained populations [682‐684]. A 2006 study [685] investigated the effects of supplementing with either ribose or dextrose over 8 weeks on rowing performance and concluded that ribose was outperformed by the dextrose control [685]. Kreider and associates [684] and Kerksick and colleagues [686] investigated ribose supplementation on measures of anaerobic capacity in trained cyclists and concluded ribose had no positive impact on performance. In 2017, Seifert and investigators [687] had 26 healthy subjects supplement with either 10 g of ribose or 10 g of dextrose for 5 days while completing a single bout of interval exercise and a two-minute power output test. When splitting the participants into high vs. low oxygen uptake levels, the people with low peak VO₂ experienced significant increases in mean and peak power output along with reductions in ratings of perceived exertion and creatine kinase. No such changes were reported in individuals with high peak VO₂. As it stands, clinical findings provide support while studies in healthy, trained populations generally fail to report a positive outcome for ribose supplementation. Healthy individuals with lower fitness levels may afford some benefit.