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What is ZMA supplement

ZMA is short for zinc magnesium aspartate (ZMA). ZMA supplement is a commercial supplement containing zinc monomethionine aspartate, magnesium aspartate, and vitamin B-6 (ZMA). ZMA supplementation is based upon the rationale that zinc and magnesium deficiency may reduce the production of testosterone and insulin like growth factor (IGF-1) 1. Consequently, ZMA supplementation is advocated for its ability to increase testosterone and IGF-1, which is further suggested to promote recovery, anabolism, and strength during training.

Two studies with contrasting outcomes have examined the ability of acute ZMA administration to increase anabolic hormone concentrations. Initially, Brilla and Conte 2 reported that a zinc-magnesium formulation increased testosterone and IGF-1 (two anabolic hormones) leading to greater strength gains in football players participating in spring training while Koehler et al. 3 reported that ZMA supplementation increased serum zinc and excretion, but failed to change free and total testosterone levels. Wilborn et al. 4 had resistance trained males ingest a ZMA supplement or placebo in a double-blind fashion and resistance train for 8 weeks and found no change in free or total testosterone, strength or fat-free mass (via DXA). It is noted that previous deficiencies in zinc may negatively impact endogenous production of testosterone secondary to its role in androgen metabolism and steroid receptor interaction 5. To this point, Brilla and Conte 2 did report depletions of both zinc and magnesium, thus increases in testosterone levels could have been attributed to deficient nutritional status rather than a pharmacologic effect. More research is needed to further evaluate the role of ZMA on body composition and strength during training before definitive conclusions can be drawn. These findings are in contrast with the notion that ZMA supplementation can increase zinc and magnesium status, anabolic hormone status, and/or strength gains during training. These findings refute claims that ZMA supplementation in the amount and manner investigated provides performance enhancing effect to experienced resistance trained athletes. Whether higher levels of ZMA is needed to promote these adaptations in experienced resistance-trained males; ZMA supplementation may influence zinc and magnesium status and/or training adaptations in individuals with low zinc and magnesium status; and/or, whether ZMA supplementation may have therapeutic and/or performance enhancing effect in other populations (e.g., untrained, females, elders, etc) remains to be determined.

Zinc is an essential trace element involved in a range of vital biochemical processes and is required for the activity of more than 300 enzymes 4. Zinc-containing enzymes participate in many components of macronutrient metabolism, particularly cell replication. In addition, zinc-containing enzymes such as carbonic anhydrase and lactate debydrogenase are involved in exercise metabolism while superoxide dismutase protects against free radical damage. Zinc deficiencies have been shown to be higher in athletes and/or individuals who recreationally train 6. Zinc deficiencies in athletes have been suggested to contribute to impaired immune function and decreased performance 7.

Magnesium is a ubiquitous element that plays a fundamental role in many cellular reactions. More than 300 metabolic reactions require magnesium as a cofactor 4. Some important examples include glycolysis, fat and protein metabolism, adenosine triphosphate synthesis, and second messenger system. Magnesium also serves as a physiological regulator of membrane stability and in neuromuscular, cardiovascular, immune, and hormonal function. It also appears that there is a relationship between magnesium levels and cortisol, which has been reported to have negative effects on strength gains and muscle mass during training. A 1984 8 study found that 14 days of magnesium supplementation decreased cortisol which would theoretically reduce catabolism during training. Another study reported similar results concluding that magnesium supplementation reduced the stress response without affecting competitive potential 9.

Athletes have been reported to have lower levels of zinc and magnesium possibly due to increased sweating while training or inadequate intake in their diets 10. Additionally, zinc and magnesium supplementation has been reported to have positive effects on resistance training athletes 11. Theoretically, zinc and magnesium supplementation may enhance anabolic hormonal profiles, reduce catabolism, improve immune status, and/or improve adaptations to resistance training. In support of this theory, Brilla and Conte 11 reported that ZMA supplementation during off-season football resistance training promoted significant increases in testosterone, IGF-1, and muscle strength. However, it is clear that more research is needed before conclusions can be drawn.

Lastly, companies selling nutritional supplements or promoting exercise, diet or supplementation protocols should develop scientifically based products, conduct research on their products, and honestly market the results of studies so consumers can make informed decisions.

Does ZMA work?

The major findings of this study was that dietary supplementation of a commercially available ZMA supplement resulted in a non-significant 12–17% increase in serum zinc levels but did not appear to effect anabolic or catabolic responses to resistance training, body composition, or training adaptations 4. These findings do not support contentions that ZMA supplementation during training increases muscle mass and/or enhances training adaptations. The following provides additional insight to results observed.

Zinc and Magnesium Status

Athletes have been reported to have low zinc and magnesium levels which have been found to negatively impact performance 12. Brilla and Conte 11 reported that ZMA supplementation (i.e., 30 mg zinc monomethionine aspartate, 450 mg magnesium aspartate, and 10.5 mg vitamin B-6) promoted a 30% increase in plasma zinc levels (0.8 ± 0.1 to 1.04 ± 0.14 μg/mL) and a 6.1% increase in plasma magnesium levels (19.43 ± 1.2 to 20.63 ± 0.73 μg/mL). In the a study by Wilborn and colleagues (subjects from Baylor University and the American College of Sports Medicine: age 27 ± 9 years; height 178 ± 8 cm, average weight 85.15 kg, and 18.6 ± 6% body fat) 4, fasting zinc and magnesium levels were within normal ranges (1.04 ± 0.24 to 1.08 ± 0.2 μg/mL) and training did not negatively impact on zinc or magnesium status. ZMA supplementation promoted only a modest but non-significant increase in plasma zinc levels (12–17%) while magnesium levels were not significantly affected. These findings indicate that within the population and sample tested, ZMA supplementation had no discernable effects on plasma zinc or magnesium status. While the present study did not assess tissue levels of these minerals, these findings suggest that ZMA supplementation may not be needed or beneficial in this population of athletes. In support of this finding, Lukasi 6 concluded that although some studies 13 have suggested that zinc and magnesium levels are diminished in athletes, most athletes get adequate dietary intake of booth zinc and magnesium.

Training Adaptations

ZMA supplementation has been purported to increase zinc and magnesium status, anabolic hormones, and promote greater gains in strength during training. In support of this contention, Brilla and Conte 11 reported that ZMA supplementation significantly increased free testosterone, IGF-1, and isokinetic strength gains during training. However, the results of another study do not support these findings 4. In this regard, ZMA supplementation had no significant effects on total and free testosterone, IGF-1, growth hormone, cortisol, the ratio of cortisol to testosterone, or muscle and liver enzymes in response to training 4. Moreover, no significant effects were observed between groups in changes in 1-RM strength, upper or lower body muscle endurance, or anaerobic sprint capacity. Interestingly, while some contend that ZMA supplementation may increase muscle mass during training, the Brilla and Conte 11 paper reported that ZMA supplementation had no effect on body mass changes during training. Results of the this study support these findings in that ZMA supplementation had no significant effects on body mass or DEXA determined body composition values 4. However, it should be noted that some potentially favorable trends were observed in fat free mass, fat mass, and body fat that deserve additional study.

What works?

Strong evidence to support efficacy and apparently safe

ß-alanine

ß-alanine, a non-essential amino acid, has physical performance enhancing (ergogenic) potential based on its role in carnosine synthesis 14. 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 grams of ß-alanine orally, in divided doses, over a 28-day period is effective in increasing carnosine levels 15, while more recent studies have demonstrated increased carnosine and efficacy up to 12 grams per day 16. According to the International Society of Sports Nutrition (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 minutes; improvements in neuromuscular fatigue, particularly in older subjects, and lastly; potential benefits in tactical personnel 17. Other studies have shown that ß-alanine supplementation can increase the number of repetitions one can do 18, increase lean body mass 19, increase knee extension torque 20, and increase training volume 18. In fact, one study also showed that adding ß-alanine to creatine improves performance over creatine alone 21. While it appears that ß-alanine supplementation can improve performance, other studies have failed to demonstrate a performance benefit 22.

Caffeine

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 performance enhancing (ergogenic) aid for aerobic and anaerobic exercise with a documented ability to increase energy expenditure and promote weight loss 23. Research investigating the effects of caffeine on time trial performance in trained cyclists found that caffeine improved speed, peak power, and mean power 24. 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 25. 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 26. In addition to the apparent positive effects on endurance performance, caffeine has also been shown to improve repeated sprint performance benefiting the anaerobic athlete 27. Research examining caffeine’s ability to increase maximal strength and repetitions to fatigue are largely mixed in their outcomes. For example, Trexler, et al. 27 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 28 revealed no change in upper-body and lower-body strength after resistance trained males ingested 6 mg/kg of caffeine. Similarly, Beck and investigators 29 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. 30 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 31 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 32 and other exercises 31. In addition to potential ergogenic impact, these authors also reported that caffeine significantly improved various indicators of mood state 33, lowered ratings of perceived exertion and decreased perception of muscle pain 31 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 34. Also, people who drink caffeinated drinks regularly, however, appear to experience less ergogenic benefits from caffeine 35. Some concern has been expressed that ingestion of caffeine prior to exercise may contribute to dehydration, although several studies have not supported this concern 36. Caffeine, from anhydrous and coffee sources are both equally ergogenic 27. 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.

Carbohydrate

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 37. 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 body weight per day) to maintain muscle and liver carbohydrate stores 38. Research has clearly identified carbohydrate as an ergogenic aid that can prolong exercise 38. For example, Below and colleagues 39 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. 40 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 41 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. 42 and Colombani et al. 43 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 44, Hawley et al. 37 and Rodriguez et al. 45 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 46 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 47 but not all 48 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 49.

Creatine monohydrate

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 50. Specifically, and as discussed by Kreider et al. 51, 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 52. Moreover, a 2009 study found that in addition to high intensity interval training creatine improved critical power 50. Less research is available involving creatine supplementation and endurance exercise, but creatine’s ability to promote glycogen loading 53 and storage of carbohydrate 54, 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 55. 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 56. 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 57, younger adults 58, and older individuals 59. 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 60.

Sodium bicarbonate (baking soda)

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 minutes in duration 61. Matson et al. 62 reported improvements in exercise capacity in events like the 400–800 m run while Lindh and colleagues 63 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 64. Marriott et al. 65 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 66 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 67 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. 64 reported significant independent effects of caffeine and bicarbonate on three-kilometer cycling time trial performance, but no additive benefit. Alternatively, Tobias and associates 68 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. 69 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.

Sodium phosphate

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% 70, anaerobic threshold by 5–10% 71, mean power output 70 and intermittent running performance 72. 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 73, 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 74 reported modest (non-significant) effects of NaPO4 supplementation on repeated supplementation regimens in trained cyclists completing a time trial. Furthermore, West and investigators 75 used a mixed gender cohort and concluded no change in VO2Max resulted after supplementation. Buck et al. 76 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 77 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.

Water and sports drinks

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 minutes) 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 78. Below and colleagues 39 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 79. 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 80. 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 78.
Limited or mixed evidence to support efficacy

L-alanyl-L-glutamine

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 81 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 82 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 82.

Since 2010, five peer-reviewed studies have been published using human subjects. Hoffman and colleagues 83 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 84. 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 85. Finally, a 2015 paper determined that L-alanyl-L-glutamine significantly improved treadmill running performance when compared to no hydration 86. 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

Arachidonic acid 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 87. Arachidonic acid is not found in high amounts in the typical American diet 88. 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 arachidonic acid 89. In skeletal muscle, there is evidence that arachidonic acid drives some of the inflammatory response to strength training via enhanced prostaglandin signalling 90. Specifically, exercise liberates arachidonic acid from the muscle cell membrane via phospholipase A2 activation. Resultant free intracellular arachidonic acid is subsequently converted into certain prostaglandins (i.e., PGE2 or PGF2α) via cyclooxygenase (COX) enzymes 91, 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 92 were the first group to examine the impact of arachidonic acid 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 arachidonic acid 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 arachidonic acid group, but no other changes in strength or body composition were found. The second study by DeSouza et al. 93 investigated the effects of arachidonic acid supplementation (0.6 g/day 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%), upper-body strength (8.7%), and anaerobic peak power (12.7%) significantly increased only in the arachidonic acid group. Mitchell and colleagues 94 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 arachidonic acid for 4 weeks and found that arachidonic acid supplementation did not impact acute changes in muscle protein synthesis and other mechanistic links to protein translation. The authors concluded that arachidonic acid supplementation did not support a mechanistic link between arachidonic acid 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 arachidonic acid, it is too early to recommend arachidonic acid at this time. In this respect, more chronic human studies testing different doses of arachidonic acid 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 arachidonic acid being a known pro-inflammatory fatty acid, use of arachidonic acid may be contraindicated in populations that have compromised inflammatory health (i.e., inflammatory bowel syndrome, Chron’s disease, etc.).

Branched chain amino acids (BCAA)

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 95 used 11 endurance trained men to examine the impact of ingesting 16 g of BCAAs and 12 g of ornithine aspartate over a 90-minutes 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 96. 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 96, 97.

Citrulline

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 98. Unlike arginine, citrulline catabolism is limited in the intestines 99 as well as its extraction from hepatic tissue 100 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 101, oral citrulline supplementation has been shown to be more effective in increasing arginine 102 and activation of nitric oxide synthase (NOS) 102 as well as various biomarkers of nitric oxide 103. Multiple studies have employed aerobic exercise models to examine citrulline’s impact on performance. Suzuki et al. 104 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 105 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. 106 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 107. One study 108 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 109 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 107 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 110 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 111. 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.

Essential amino acids (EAA)

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 112 and that ingestion of 6–12 g of a complete essential amino acid mixture are needed to maximize muscle protein synthesis 113. 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 essential amino acid 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 essential amino acids 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 114 to promote accretion of fat-free mass, but, as mentioned, the impact of this recommendation on performance changes remains undetermined.

Glycerol

Ingesting glycerol with water has been reported to increase fluid retention, and maintain hydration status 115. 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 116. Regarding endurance performance Coutts and investigators 117 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 hours 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. 117 when they had six endurance-trained subjects hyperhydrate with glycerol or water 2 hour before a prolonged (2 hour) 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. 118 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. 119 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 120 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. 121, 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. 122.

β-hydroxy β-methylbutyrate (HMB)

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 123. Initial work by Nissen and colleagues 124 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 125 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 126 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. 127 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 128 reported that HMB supplementation failed to improve anaerobic power production in collegiate football players, a conclusion which aligns with other previous studies 129. 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 130 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 131. Later, Durkalec-Michalski and Jeszka 132 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 130. The recent studies by Durkalec-Michalski and colleagues confirmed earlier works by Vukovich 133 and Lamboley 134 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) 135. 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 136 and in combination with supplemental ATP 137, but others have critically questioned these outcomes 138. A recent systematic review by Silva and investigators 139 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.

Nitrates

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 140 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 141 and is prescribed in both absolute and relative amounts ranging from 300 to 600 mg 141 or 0.1 mmol per kilogram of body mass per day, respectively 142. These dosing amounts appear to be well tolerated when consumed as both supplemental 143 and supplemental sources 144 without significant alterations in hemodynamics or clinical boundaries of hepatorenal and muscle enzyme status 145. 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 146. 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 147. 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 148. 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 149, which was also reported by MacLeod et al. 150 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) 151 and Nyakayiru et al. 152 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 153, caffeine 154, or creatine 155, respectively. It is important to mention that dietary nitrates have a health benefit in some, but not all populations 156. Daily consumption of beetroot juice (~ 320–640 mg nitrate/d) significantly decreased resting systolic blood pressure in older adults by approximately 6 mmHg 157. Nitrate supplementation (560 mg – 700 mg nitrate) significantly increased blood flow to working muscle and exercise time in older adults with peripheral artery disease 158 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 159. Collectively, these results indicate that nitrate supplementation may improve aerobic exercise performance and cardiovascular health in some populations.

Post-exercise carbohydrate and protein

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 muscle protein synthesis via key signal transduction pathways. Additionally, carbohydrate intake will impact insulin status which could promote muscle protein synthesis, limit protein breakdown or both 160. Furthermore, combining carbohydrate with protein can heighten glycogen resynthesis rates, particularly when carbohydrate intake is not optimal 161 and can improve muscle damage responses after exhaustive exercise 162. 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 114. In the last few years many studies have agreed that post workout supplementation is vital to recovery and training adaptations 163. However, the need for adding carbohydrate to protein to maximize hypertrophic adaptations continues to be questioned. For example, Staples and investigators 164 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 165 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

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 166 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 167 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 168. In contrast, Nieman et al. 169 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. 170 used a resistance exercise model and reported quercetin may improve neuromuscular performance while Davis et al. 171 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 172 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. Kressler J, Millard-Stafford M, Warren GL. Quercetin and endurance exercise capacity: a systematic review and meta-analysis. Med Sci Sports Exerc. 2011;43(12):2396–2404. doi: 10.1249/MSS.0b013e31822495a7 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

Taurine is an amino acid found in high abundance in human skeletal muscle 173 derived from cysteine metabolism that plays a role in a wide variety of physiological functions 174. 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) impact the amount of taurine found in muscle. It has been reported in some 175 but not all studies 176 that taurine may improve exercise performance and mitigate recovery from damaging and stressful exercise 177. 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 178 failed to show an improvement in performance with a 6 g dose of taurine while completing high-intensity treadmill running. Similarly, Balshaw et al. 175 indicated that taurine failed to positively impact 3-km running performance in trained runners. In contrast, a 2017 study by Warnock et al. 179 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. 180 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 181, 182 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 182. 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 183. 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.

Supplements to promote general health

Although daily vitamin and mineral supplementation has not been found to improve exercise capacity in athletes, it may make sense to take a daily vitamin supplement for health reasons. Vitamin D is often recommended to athletes, especially those participating in indoor sports or in cloudy geographies 184. Although direct evidence linking vitamin D with performance is equivocal, it is clear that vitamin D has a role in regulating immune function, cardiovascular health, and growth and repair. Dosing should be dependent upon baseline levels, which can be measured by any physician 185. Glucosamine and chondroitin have been reported to slow cartilage degeneration and reduce the degree of joint pain in active individuals which may help athletes postpone and/or prevent joint problems 186. Meanwhile, other ingredients including undenatured type II collagen (UC-II) may be helpful as well although more research is needed involving athletic applications 187. Supplemental vitamin C, glutamine, echinacea, quercetin, and zinc have been reported to enhance immune function 188. However, consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression [699]. Similarly, although additional research is necessary, vitamin E, vitamin C, selenium, alpha-lipoic acid and other antioxidants may help restore overwhelmed antioxidant defenses exhibited by athletes 189. One countering argument against higher doses is the potential for these to interfere with adaptive responses to training 190. Finally, the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapantaenoic acid (EPA), in supplemental form, are now endorsed by the American Heart Association for heart health in certain individuals stemming from initial scientific statements made in 2002 191. This supportive supplement position stems from: 1) an inability to consume cardio-protective amounts by diet alone; and, 2) the mercury contamination sometimes present in whole-food sources of DHA and EPA found in fatty fish. For general health, dosing recommendations range from 3000 mg-5000 mg daily of deep, cold water fish 192. Consequently, prudent use of these types of nutrients at various times during training may help athletes stay healthy and/or tolerate training to a greater degree.

High intensity exercise can compromise an athlete’s immune health. Infection risk and exercise workload follow a J-Shape curve with moderate intensity exercise reducing the infection risk, and high intensity exercise actually increasing the risk of infection 193. Immune suppression in athletes further worsens by the psychological stress, foreign travel, disturbed sleep, environmental extremes, exposure to large crowds or an increase exposure to pathogens due to elevated breathing during exercise or competition. Athletes have several nutritional options to reduce the risk and symptoms of upper respiratory tract infections, including probiotics and baker’s yeast beta-glucan. Beta-glucan is a natural gluco polysaccharide derived from the cell walls of highly purified yeast (Saccharomyces cerevisiae) and has been shown to significantly decrease upper-respiratory tract infection symptoms in men and women participating in the Carlsbad marathon 194. Probiotics, often referred to as “friendly” or “good” bacteria, are live microorganisms which when administered in adequate amounts confer a health benefit on the host. An estimated 70% of our immune system is located in your digestive system indicating the importance of a balanced gut microflora on immune health. Probiotics have been shown to reduce the number, duration and severity of upper-respiratory tract infections and gastrointestinal distress in the general population and in athletes, certain strains of probiotics have been shown to significantly reduce the number of upper-respiratory tract infection episodes a well as their severity 195. Health benefits of probiotics are strain specific and dose dependent, and some strains have failed to show beneficial effects in athletes 196. Also, consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression 188.

Conclusion

Several factors operate as cornerstones to enhance athletic performance and optimize training adaptations including the consumption of a balanced, nutrient and energy dense diet, prudent training, and obtaining adequate rest. Use of a limited number of nutritional supplements that research has supported to improve energy availability (e.g., sports drinks, carbohydrate, creatine, caffeine, β-alanine, etc.) and/or promote recovery (carbohydrate, protein, essential amino acids, etc.) can provide additional benefit in certain instances 1. Dietitians and sport nutritionists should stay up to date on current research regarding the role of nutrition on exercise so they can provide honest and accurate information to their students, clients, and/or athletes about the role of nutrition and dietary supplements on performance and training. Furthermore, these professionals should actively participate in exercise nutrition research, write unbiased scholarly reviews for journals and lay publications, and help disseminate the latest research findings to the public. Through these actions, consumers and other professionals can make informed decisions about appropriate methods of exercise, dieting, and/or whether various nutritional supplements can affect health, performance, and/or training. In all situations, individuals are expected and ethically obligated to disclose any commercial or financial conflicts of interest during such promulgations. Finally, companies selling nutritional supplements or promoting exercise, diet or supplementation protocols should develop scientifically based products, conduct research on their products, and honestly market the results of studies so consumers can make informed decisions.

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