Updated research and advice on exercise and sports nutrition from ISSN

Congress passed the Dietary Supplement Health and Education Act of 1994 (DSHEA), placing dietary supplements in a special category of “foods”. In October 1994, President Clinton signed DSHEA into law. This statute was enacted amid claims that the Food and Drug Administration (FDA) was distorting the then-existing provisions of the Food, Drug, and Cosmetic Act (FDCA) to improperly deprive the public of safe and popular dietary supplement products.

The law defines a “dietary supplement” as a product that is intended to supplement the diet and contains a “dietary ingredient”. By definition, “dietary ingredients” in these products may include vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, and glandular extracts. Further, dietary ingredients may also include extracts, metabolites, or concentrates of those substances. Dietary supplements may be found in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders, but may only be intended for oral ingestion. Dietary supplements cannot be marketed or promoted for sublingual, intranasal, transdermal, injected, or in any other route of administration except oral ingestion. A supplement can be in other forms, such as a bar, as long as the information on its label does not represent the product as a conventional food or a sole item of a meal or diet.

Indeed, DSHEA clearly defines “dietary supplements” and “dietary ingredients,” it sets certain criteria for “new dietary ingredients,” and the law prevents the FDA from overreaching. Additionally, and contrary to widespread opinion, DSHEA did not leave the industry unregulated. The dietary supplement industry is in fact regulated by the FDA as a result of DSHEA. The law ensures the authority of the FDA to provide legitimate protections for the public health. The Federal Trade Commission (FTC) also continues to have jurisdiction over the marketing claims that dietary supplement manufacturers or companies make about their products. The FDA and FTC operate in a cooperative fashion to regulate the dietary supplement industry. In this respect, the extent to which information is shared and jurisdiction between these two entities overlaps with regard to marketing and advertising dietary supplements continues to increase.

In the United States, dietary supplements are classified as food products, not drugs, and there is generally no mandate to register products with the FDA or obtain FDA approval before producing or selling supplements to consumers. However, if a dietary supplement manufacturer is making a claim about their product, the company must submit the claims to FDA within 30 days of marketing the product. Compare this, for example, with Canada where under the Natural Health Product (NHP) Regulations enacted in 2004 supplements must be reviewed, approved, and registered with Health Canada. The rationale for the U.S. model is based on a presumed long history of safe use; hence there is no need to require additional safety data.

DSHEA also requires supplement marketers to include on any label displaying structure/function claims (i.e., claims that the product affects the structure or function of the body) the mandatory FDA disclaimer “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.” Opponents of dietary supplements often cite this statement as evidence that the FDA does not review or approve dietary supplements. However, most dietary ingredients have been “grandfathered in” as DSHEA-compliant ingredients due to a long history of safe use, and those products containing new ingredients must be submitted by a notification to the FDA for a safety review prior to being brought to market. Although many dietary ingredients have been introduced into dietary supplements since October 1994 and have not been submitted to the FDA for a safety review, nutritional supplementation writ large is generally safe. In this regard, while there are over 50,000 dietary supplements registered with the Office of Dietary Supplement’s “Dietary Supplement Label Database”, a 2013 Annual Report (released in 2015) of the American Association of Poison Control Centers revealed zero fatalities occurred due to dietary supplements compared to 1692 deaths due to drugs [5]. Perhaps more alarming is a 2015 report by the Centers for Disease Control suggesting 2,287,273 emergency room visits were due to prescription drug-related events which dwarfs the 3266 emergency room visits due to dietary supplements (adjusted from 23,000 visits after excluding cases of older adults choking on pills, allergic reactions, unsupervised children consuming too many vitamins, and persons consuming ingredients not defined by DSHEA as a dietary supplement) [5]. Furthermore, a recent Healthcare Cost and Utilization Project Statistical Brief by Lucado et al. [6] reported approximately one in six Americans suffered from food borne illnesses in 2010, and food borne illnesses were associated with over 3.7 million treat-and-release emergency department visits, 1.3 million inpatient hospital stays, and 3000 deaths. Notwithstanding, there have been case reports of liver and kidney toxicity potentially caused by supplements containing herbal extracts [7] as well as overdoses associated with pure caffeine anhydrous ingestion [8]. Collectively, the aforementioned statistics and case reports demonstrate that while generally safe, as with food or prescription drug consumption, dietary supplement consumption can lead to adverse events in spite of DSHEA and current FDA regulations described below.

Recognizing that new and untested dietary supplement products may pose unknown health issues, DSHEA distinguishes between products containing dietary ingredients that were already on the market and products containing new dietary ingredients that were not marketed prior to the enactment of the law. A “new dietary ingredient” (NDI) is defined as a dietary ingredient that was not marketed in the United States before October 15, 1994. DSHEA grants the FDA greater control over supplements containing NDIs. A product containing an NDI is deemed adulterated and subject to FDA enforcement sanctions unless it meets one of two exemption criteria: either (1) the supplement in question contains “only dietary ingredients which have been present in the food supply as an article used for food in a form in which the food has not been chemically altered”; or (2) there is a “history of use or other evidence of safety” provided by the manufacturer or distributor to the FDA at least 75 days before introducing the product into interstate commerce. The first criterion is silent as to how and by whom presence in the food supply as food articles without chemical alteration is to be established. The second criterion—applicable only to new dietary ingredients that have not been present in the food supply—requires manufacturers and distributors of the product to take certain actions. Those actions include submitting, at least 75 days before the product is introduced into interstate commerce, information that is the basis on which a product containing the new dietary ingredient is “reasonably expected to be safe.” That information would include: (1) the name of the new dietary ingredient and, if it is an herb or botanical, the Latin binomial name; (2) a description of the dietary supplement that contains the new dietary ingredient, including (a) the level of the new dietary ingredient in the product, (b) conditions of use of the product stated in the labeling, or if no conditions of use are stated, the ordinary conditions of use, and (c) a history of use or other evidence of safety establishing that the dietary ingredient, when used under the conditions recommended or suggested in the labeling of the dietary supplement, is reasonably expected to be safe.

In July 2011, the FDA released a Draft Guidance for Industry, entitled “Dietary Supplements: New Dietary Ingredient Notifications and Related Issues.” While a guidance does not carry the authority or the enforceability of a law or regulation, the FDA’s NDI draft guidance represented the agency’s current thinking on the topic. The guidance prompted great controversy, and FDA agreed to issue a revised draft guidance to address some of the issues raised by industry. In August 2016, FDA released a revised Draft Guidance that replaced the 2011 Draft Guidance. The purpose of the 2016 Draft Guidance was to help manufacturers and distributors decide whether to submit a premarket safety notification to FDA, help prepare NDI notifications in a manner that allows FDA to review and respond more efficiently and quickly, and to improve the quality of NDI notifications. The 2016 Draft Guidance has been criticized by industry and trade associations for its lack of clarity and other problems. Some of these issues include the lack of clarity regarding Pre-DSHEA, (Grandfathered), ingredients and FDA requiring an NDI notification even if another manufacturer has submitted a notification.

The lack of clarity surrounding the “new” Draft Guidance has led to many NDI notifications being rejected by FDA for lack of safety data and other issues. Other companies have opted to utilize the “Self-Affirmed Generally Recognized as Safe (GRAS)” route in order to “bypass” the NDI notification process. Self-Affirmed GRAS is when a company has a team of scientific experts evaluate the safety of their ingredient. There is no requirement that the safety dossier be submitted to FDA but is used by the company as an internal document that may be relied upon if the ingredient is challenged by the FDA. FDA has expressed its concern with this practice and does not encourage dietary supplement manufacturers to use Self-Affirmed GRAS to avoid submitting NDI notifications. In any event, the likelihood of another revised Draft Guidance from FDA becoming available in the future is high, and possibly more enforcement actions taken against companies that market an NDI without submitting a notification.

In response to growing criticism of the dietary supplement industry, the 109th Congress passed the first mandatory Adverse Event Reporting (AER) legislation for the dietary supplement industry. In December 2006, President Bush signed into law the Dietary Supplement and Nonprescription Drug Consumer Protection Act, which took effect on December 22, 2007. After much debate in Congress and input from the FDA, the American Medical Association (AMA), many of the major supplement trade associations, and a host of others all agreed that the legislation was necessary and the final version was approved by all. In short, the Act requires that all “serious adverse events” regarding dietary supplements be reported to the Secretary of Health and Human Services. The law strengthens the regulatory structure for dietary supplements and builds greater consumer confidence, as consumers have a right to expect that if they report a serious adverse event to a dietary supplement marketer the FDA will be advised about it.

An adverse event is any health-related event associated with the use of a dietary supplement that is adverse. A serious adverse event is an adverse event that (A) results in (i) death, (ii) a life-threatening experience, (iii) inpatient hospitalization, (iv) a persistent or significant disability or incapacity, or (v) a congenital anomaly or birth defect; or (B) requires, based on reasonable medical judgment, a medical or surgical intervention to prevent an outcome described under subparagraph (A). Once it is determined that a serious adverse event has occurred, the manufacturer, packer, or distributor (responsible person) of a dietary supplement whose name appears on the label of the supplement shall submit to the Secretary of Health and Human Services any report received of the serious adverse event accompanied by a copy of the label on or within the retail packaging of the dietary supplement. The responsible person has 15 business days to submit the report to FDA after being notified of the serious adverse event. Following the initial report, the responsible person must submit follow-up reports of new medical information that they receive for one-year.

The FDA has various options to protect consumers from unsafe supplements. The Secretary of the Department of Health and Human Services (which falls under FDA oversight) has the power to declare a dangerous supplement to be an “imminent hazard” to public health or safety and immediately suspend sales of the product. The FDA also has the authority to protect consumers from dietary supplements that do not present an imminent hazard to the public but do present certain risks of illness or injury to consumers. The law prohibits introducing adulterated products into interstate commerce. A supplement shall be deemed adulterated if it presents “a significant or unreasonable risk of illness or injury”. The standard does not require proof that consumers have actually been harmed or even that a product will harm anyone. It was under this provision that the FDA concluded that dietary supplements containing ephedra, androstenedione, and DMAA presented an unreasonable risk. Most recently, FDA imposed an importation ban on the botanical Mitragyna speciose, better known as Kratom. In 2016, FDA issued Import Alert #54–15, which allows for detention without physical examination of dietary supplements and bulk dietary ingredients that are, or contain, Kratom. Criminal penalties are present for a conviction of introducing adulterated supplement products into interstate commerce. While the harms associated with dietary supplements may pale in comparison to those linked to prescription drugs, recent pronouncements from the U.S. Department of Justice confirm that the supplement industry is being watched vigilantly to protect the health and safety of the American public.

When DSHEA was passed in 1994, it contained a provision requiring that the FDA establish and enforce current Good Manufacturing Practices (cGMPs) for dietary supplements. However, it was not until 2007 that the cGMPs were finally approved, and not until 2010 that the cGMPs applied across the industry, to large and small companies alike. The adherence to cGMPs has helped protect against contamination issues and should serve to improve consumer confidence in dietary supplements. The market improved as companies became compliant with cGMPs, as these regulations imposed more stringent requirements such as Vendor Certification, Document Control Procedures, and Identity Testing. These compliance criteria addressed the problems that had damaged the reputation of the industry with a focus on quality control, record keeping, and documentation.

However, it does appear that some within the industry continue to struggle with compliance. In Fiscal Year 2017, it was reported that approximately 23.48% of the FDA’s 656 total cGMP inspections resulted in citations for failing to establish specifications for the identity, purity, strength, and composition of dietary supplements. Further, 18.47% of those inspected were cited for failing to establish and/or follow written procedures for quality control operations. Undoubtedly, relying on certificates of analysis from the raw materials supplier without further testing, or failing to conduct identity testing of a finished product, can result in the creation of a product that contains something it should not contain such as synthetic chemicals or even pharmaceutical drugs. All members of the industry need to ensure compliance with cGMPs.

An initial question that should be asked is whether the supplement is legal and/or safe. Some athletic associations have banned the use of various nutritional supplements (e.g., prohormones, ephedra that contains ephedrine, “muscle building” supplements, etc.) and many professional sports organization have now written language into their collective bargaining agreements that products made available by the team must be NSF certified as safe for sport. Obviously, if the supplement is banned, the sports nutrition specialist should discourage its use. In addition, many supplements lack appropriate long-term safety data. People who consider taking nutritional supplements should be well aware of the potential side effects so they can make an informed decision whether to use a supplement. Additionally, they should consult with a knowledgeable physician to see if any underlying medical problems exist that may contraindicate its use. When evaluating the safety of a supplement, it is suggested to determine if any side effects have been reported in the scientific or medical literature. In particular, we suggest determining how long a particular supplement has been studied, the dosages evaluated, and whether any side effects were observed. We also recommend consulting the Physician’s Desk Reference (PDR) for nutritional supplements and herbal supplements to see if any side effects have been reported and/or if there are any known drug interactions. If no side effects have been reported in the scientific/medical literature, we generally will view the supplement as safe for the length of time and dosages evaluated. Unfortunately, many available supplements have not had basic safety studies completed that replicate the length of time and dosages being used.

The next question to ask is whether any well-controlled data are available showing effectiveness of the proposed ergogenic aid in athletic populations or people regularly involved in exercise training. The first place to look is the list of references cited in marketing material supporting their claims. Are the abstracts or articles cited just general references or specific studies that have evaluated the efficacy of the nutrients included in the formulation or of the actual supplement? From there, one can critically evaluate the cited abstracts and articles by asking a series of questions:

The primary component to optimize training and performance through nutrition is to ensure the athlete is consuming enough calories to offset energy expenditure [22–26]. People who participate in a general fitness program (e.g., exercising 30–40 min per day, 3 times per week) can typically meet nutritional needs following a normal diet (e.g., 1800–2400 kcals/day or about 25–35 kcals/kg/day for a 50–80 kg individual) because their caloric demands from exercise are not too great (e.g., 200–400 kcals/session). However, athletes involved in moderate levels of intense training (e.g., 2–3 h per day of intense exercise performed 5–6 times per week) or high volume intense training (e.g., 3–6 h per day of intense training in 1–2 workouts for 5–6 days per week) may expend 600–1200 kcals or more per hour during exercise [24]. For this reason, their caloric needs may approach 40–70 kcals/kg/day (2000–7000 kcals/day for a 50–100 kg athlete). For elite athletes, energy expenditure during heavy training or competition will further exceed these levels [27, 28]. For example, energy expenditure for cyclists to compete in the Tour de France has been estimated as high as 12,000 kcals/day (150–200 kcals/kg/day for a 60–80 kg athlete) [29, 30]. Additionally, caloric needs for large athletes (i.e., 100–150 kg) may range between 6000 and 12,000 kcals/day depending on the volume and intensity of different training phases [31].

Although some argue that athletes can meet caloric needs simply by consuming a well-balanced diet, it is often very difficult for larger athletes and athletes engaged in high volume/intense training to be able to eat enough food, on a daily basis, to meet caloric needs [2, 29, 30, 32–34]. This point was clearly highlighted in a review by Burke who demonstrated that carbohydrate needs are largely unmet by high-level athletes [22]. Additionally it is difficult to consume enough food and maintain gastrointestinal comfort to train or race at peak levels [35]. Maintaining an energy deficient diet during training often leads to a number of physical (i.e., loss of fat-free mass, illness, reduced sleep quality, incomplete recovery, hormonal fluctuations, increased resting heart rate, etc.) and psychological (i.e., apathy towards training, heightened stress) adverse outcomes [23, 27]. Nutritional analyses of athletes’ diets have revealed that many are susceptible to maintaining negative energy intakes during training. It is still a question whether there may be specific individualized occasions when negative energy balance may enhance performance in the days prior to running performance [36]. Populations susceptible to negative energy balance include runners, cyclists, swimmers, triathletes, gymnasts, skaters, dancers, wrestlers, boxers, and athletes attempting to lose weight too quickly [37]. Additionally, female athletes are at particular risk of under fueling due to both competitive and aesthetic demands of their sport and their surrounding culture. Female athletes have been reported to have a high incidence of eating disorders [38]. Low or reduced energy availability (LEA) is linked to functional hypothalamic oligomenorrhea/amenorrhea (FHA), which is frequently reported in weight sensitive sports. This makes LEA a major nutritional concern for female athletes [39]. Consequently, it is important for the sports nutrition specialist working with athletes to assess athletes individually to ensure that athletes are well fed according to the goals of their sport and their health, and consume enough calories to offset the increased energy demands of training, and maintain body weight. Although this sounds relatively simple, intense training often suppresses appetite and/or alters hunger patterns so that many athletes do not feel like eating [37, 38]. Some athletes prefer not to exercise within several hours after eating because of sensations of fullness and/or a predisposition to cause gastrointestinal distress. Further, travel and training schedules may limit food availability or the types of food athletes are accustomed to eating. This means that care should be taken to plan meal times in concert with training, as well as to make sure athletes have sufficient availability of nutrient dense foods throughout the day for snacking between meals (e.g., fluids, carbohydrate/protein-rich foods and supplemental bars, etc.) [2, 33, 40]. For this reason, sports nutritionists’ often recommend that athletes consume four to six meals per day and snacks in between meals to meet energy needs. Due to these practical concerns, the use of nutrient dense energy foods, energy bars and high calorie carbohydrate/protein supplements provides a convenient way for athletes to supplement their diet in order to maintain energy intake during training.

Beyond optimal energy intake, consuming adequate amounts of carbohydrate, protein, and fat is important for athletes to optimize their training and performance. In particular and as it relates to exercise performance, the need for optimal carbohydrates before, during and after intense and high-volume bouts of training and competition is evident [41]. Excellent reviews [42, 43] and original investigations [44–49] continue to highlight the known dependence on carbohydrates that exists for athletes competing to win various endurance and team sport activities. A complete discussion of the needs of carbohydrates and strategies to deliver optimal carbohydrate and replenish lost muscle and liver glycogen extend beyond the scope of this paper, but the reader is referred to several informative reviews on the topic [23, 41, 50–53].

As such, individuals engaged in a general fitness program and are not necessarily training to meet any type of performance goal can typically meet daily carbohydrate needs by consuming a normal diet (i.e., 45–55% CHO [3–5 g/kg/day], 15–20% PRO [0.8–1.2 g/kg/day], and 25–35% fat [0.5–1.5 g/kg/day]). However, athletes involved in moderate and high-volume training need greater amounts of carbohydrate and protein (discussed later) in their diet to meet macronutrient needs [50]. In terms of carbohydrate needs, athletes involved in moderate amounts of intense training (e.g., 2–3 h per day of intense exercise performed 5–6 times per week) typically need to consume a diet consisting of 5–8 g/kg/day or 250–1200 g/day for 50–150 kg athletes of carbohydrate to maintain liver and muscle glycogen stores [23, 24, 50]. Research has also shown that athletes involved in high volume intense training (e.g., 3–6 h per day of intense training in 1–2 daily workouts for 5–6 days per week) may need to consume 8–10 g/day of carbohydrate (i.e., 400–1500 g/day for 50–150 kg athletes) in order to maintain muscle glycogen levels [50]. Preferably, the majority of dietary carbohydrate should come from whole grains, vegetables, fruits, etc. while foods that empty quickly from the stomach such as refined sugars, starches and engineered sports nutrition products should be reserved for situations in which glycogen resynthesis needs to occur at accelerated rates [53]. In these situations, the absolute delivery of carbohydrate (> 8 g of carbohydrate/kg/day or at least 1.2 g of carbohydrate/kg/hour for the first four hours into recovery) takes precedence over other strategies such as those that may relate to timing or concomitant ingestion of other macronutrients (e.g., protein) or non-nutrients (e.g., caffeine) or carbohydrate type (i.e., glycemic index) [50].

When considering the carbohydrate needs throughout an exercise session, several key factors should be considered. Previous research has indicated athletes undergoing prolonged bouts (2–3 h) of exercise training can oxidize carbohydrates at a rate of 1–1.1 g per minute or about 60 g per hour [41]. Several reviews advocate the ingestion of 0.7 g of carbohydrate/kg/hr. during exercise in a 6–8% solution (i.e., 6–8 g per 100 ml of fluid) [41, 42, 50, 54]. It is now well established that different types of carbohydrates can be oxidized at different rates in skeletal muscle due to the involvement of different transporter proteins that result in carbohydrate uptake [55–59]. Interestingly, combinations of glucose and sucrose or maltodextrin and fructose have been reported to promote greater exogenous rates of carbohydrate oxidation when compared to situations when single sources of carbohydrate are ingested [55–63]. These studies generally indicate a ratio of 1–1.2 for maltodextrin to 0.8–1.0 fructose seems to support the greatest rates of carbohydrate oxidation during exercise. Additional research on high molecular weight amylopectin indicates that there may be a benefit to the lower osmolality of the starch, allowing for greater consumption (100 g/hour) and possibly greater oxidation rates and performance improvement [64–67]. In addition to oxidation rates and carbohydrate types, the fasting status and duration of the exercise bout also function as key variables for athletes and coaches to consider. When considering duration, associated reviews have documented that bouts of moderate to intense exercise need to reach exercise durations that extend well into 90th minute of exercise before carbohydrate is shown to consistently yield an ergogenic outcome [41, 68, 69]. Of interest, however, not all studies indicate that shorter (60–75 min) bouts of higher intensity work may benefit from carbohydrate delivery. Currently the mechanisms surrounding these findings are, respectively, thought to be replacement of depleted carbohydrate stores during longer duration of moderate intensity while benefits seen during shorter, more intense exercise bouts are thought to operate in a central fashion. Moreover, these reviews have also pointed to the impact of fasting status on documentation of ergogenic outcomes [41, 68, 69]. In this respect, when studies require study participants to commence exercise in a fasted state, ergogenic outcomes are more consistently reported, yet other authors have questioned the ecological validity of this approach for competing athletes [43].

As it stands, the need for optimal carbohydrates in the diet for those athletes seeking maximal physical performance is unquestioned. Daily consumption of appropriate amounts of carbohydrate is the first and most important step for any competing athlete. As durations extend into 2 h, the need to deliver carbohydrate goes up, particularly when commencing exercise in a state of fasting or incomplete recovery. Once exercise ceases, several dietary strategies can be considered to maximally replace lost muscle and liver glycogen, particularly if a limited window of recovery exists. In these situations, the first priority should lie with achieving aggressive intakes of carbohydrate while strategies such as ingesting protein with lower carbohydrate amounts, carbohydrate and caffeine co-ingestion or certain forms of carbohydrate may also help to facilitate rapid assimilation of lost glycogen.

Considerable debate exists surrounding the amount of protein needed in an athlete’s diet [70–74]. Initially, it was recommended that athletes do not need to ingest more than the RDA for protein (i.e., 0.8 to 1.0 g/kg/d for children, adolescents and adults). However, research spanning the past 30 years has indicated that athletes engaged in intense training may benefit from ingesting about two times the RDA of protein in their diet (1.4–1.8 g/kg/d) to maintain protein balance [11, 70, 71, 73, 75–80]. If an insufficient amount of protein is consumed, an athlete will develop and maintain a negative nitrogen balance, indicating protein catabolism and slow recovery. Over time, this may lead to muscle wasting, injuries, illness, and training intolerance [76, 77, 81].

For people involved in a general fitness program or simply interested in optimizing their health, recent research suggests protein needs may also be above the RDA. Phillips and colleagues [76], Witard et al. [82], Jager et al. [11] and Tipton et al. [79] report that current evidence indicates optimal protein intakes in the range of 1.2–2.0 g/kg/day should be considered. In this respect, Morton and investigators [83] performed a meta-review and meta-regression involving 49 studies and 1863 participants and concluded that a daily protein intake of 1.62 g/kg/day may be an ideal place to start, with intakes beyond that providing no further contribution to increases in fat-free mass. In addition and in comparison to the RDA, non-exercising, older individuals (53–71 years) may also benefit from a higher daily protein intake (e.g., 1.0–1.2 g/kg/day of protein). Recent reports suggest that older muscle may be slower to respond and less sensitive to protein ingestion, typically requiring 40 g doses to robustly stimulate muscle protein synthesis [84–86]. Studies in younger individuals, however, have indicated that in the absence of exercise, a 20 g dose can maximize muscle protein synthesis [87, 88] and if consumed after a multiple set workout consisting of several exercises that target large muscle groups a 40 g dose might be needed [89]. Consequently, it is recommended that athletes involved in moderate amounts of intense training consume 1.2–2.0 g/kg/day of protein (60–300 g/day for a 50–150 kg athlete) while athletes involved in high volume, intense training consume 1.7–2.2 g/kg/day of protein (85–330 g/day for a 50–150 kg athlete) [78, 90]. This protein need would be equivalent to ingesting 3–15 three-ounce servings of chicken or fish per day for a 50–150 kg athlete [78]. Although smaller athletes typically can ingest this amount of protein, on a daily basis, in their normal diet, larger athletes often have difficulty consuming this much dietary protein. Additionally, a number of athletic populations are known to be susceptible to protein malnutrition (e.g., runners, cyclists, swimmers, triathletes, gymnasts, dancers, skaters, wrestlers, boxers, etc.) and consequently, additional counseling and education may be needed to help these athletes meet their daily protein needs. To this point, the periods of energy restriction to meet weight or aesthetic demands of their sports that are seemingly a part of the sport’s fabric creates an arguably greater need to understand that protein intake, quality and timing as well as combination with carbohydrate is particularly important to maintain lean body mass, training effects, and performance [25]. Overall, it goes without saying that care should be taken to ensure that athletes consume a sufficient amount of quality protein in their diet to maintain nitrogen balance.

Proteins differ based on their source, amino acid profile, and the methods of processing or isolating the protein undergoes [11]. These differences influence the availability of amino acids and peptides, which may possess biological activity (e.g., α-lactalbumin, ß-lactoglobulin, glycomacropeptides, immunoglobulins, lactoperoxidases, lactoferrin, etc.). Additionally, the rate of digestion and/or absorption and metabolic activity of the protein also are important considerations [91]. For example, different types of proteins (e.g., casein, whey, and soy) are digested at different rates, which may affect whole body catabolism and anabolism and acute stimulation of muscle protein synthesis (MPS) [91–96]. Therefore, care should be taken not only to make sure the athlete consumes enough protein in their diet but also that the protein is high quality. The best dietary sources of low fat, high quality protein are light skinless chicken, fish, egg whites, very lean cuts of beef and skim milk (casein and whey) while protein supplements routinely contain whey, casein, milk and egg protein. In what is still an emerging area of research, various plant sources of protein have been examined for their ability to stimulate increases in muscle protein synthesis [77, 97] and promote exercise training adaptations [98]. While amino acid absorption from plant proteins is generally slower, leucine from rice protein has been found to be absorbed even faster than from whey [99], while digestive enzymes [100], probiotics [101] and HMB [102] can be used to overcome differences in protein quality. Preliminary findings suggest that rice [98] and pea protein [103] may be able to stimulate similar changes in fat-free mass and strength as whey protein, although the reader should understand that many other factors (dose provided, training status of participants, duration of training and supplementation, etc.) will ultimately impact these outcomes and consequently more research is needed.

While many reasons and scenarios exist for why an athlete may choose to supplement their diet with protein powders or other forms of protein supplements, this practice is not considered to be an absolute requirement for increased performance and adaptations. Due to nutritional, societal, emotional and psychological reasons, it is preferable for the majority of daily protein consumed by athletes to occur as part of a food or meal. However, we recognize and embrace the reality that situations commonly arise where efficiently delivering a high-quality source of protein takes precedence. Jager and colleagues [11] published an updated position statement of the International Society of Sports Nutrition that is summarized by the following points:

The dietary recommendations of fat intake for athletes are similar to or slightly greater than dietary recommendations made to non-athletes to promote health. Maintenance of energy balance, replenishment of intramuscular triacylglycerol stores and adequate consumption of essential fatty acids are important for athletes, and all serve as reasons for an increased intake of dietary fat [104]. Depending upon the athlete’s training status or goals, the amount of dietary fat recommended for daily intake can change. For example, higher-fat diets appear to maintain circulating testosterone concentrations better than low-fat diets [105–107]. Additionally, higher fat intakes may provide valuable translational evidence to the documented testosterone suppression which can occur during volume-type overtraining [108]. Generally, it is recommended that athletes consume a moderate amount of fat (approximately 30% of their daily caloric intake), while proportions up to 50% of daily calories can be safely ingested by athletes during regular high-volume training [104]. In situations where an athlete may be interested in reducing their body fat, dietary fat intakes ranging from 0.5 to 1 g/kg/day have been recommended results in situations where daily fat intake might comprise as little as 20% of total calories in the diet [2]. This recommendation stems largely from available evidence in weight loss studies involving non-athletic individuals that people who are most successful in losing weight and maintaining the weight loss are those who ingest reduced amounts of fat in their diet [109, 110] although this is not always the case [111]. Strategies to help athletes manage dietary fat intake include teaching them which foods contain various types of fat so that they can make better food choices and how to count fat grams [2, 33].

For years, high-fat diets have been used by athletes with the majority of evidence showing no ergogenic benefit and consistent gastrointestinal challenges [112]. In recent years, significant debate has swirled regarding the impact of increasing dietary fat. One strategy, “train low, compete high”, refers to an acute pattern of dietary periodization whereby an athlete first follows a high-fat, low carbohydrate diet for one to 3 weeks while training before reintroducing carbohydrates back into the diet. While intramuscular adaptations result that may theoretically impact performance [113, 114], no consistent, favorable impact on performance has been documented [112, 115]. A variant of high-fat diets, ketogenic diets, have increased in popularity. While no exact prescription exists, nearly all ketogenic diet prescriptions derive at least 70–80% of their daily calories from dietary fat, prescribe a moderate amount of protein (20–25% total calories or 2.0–2.5 g/kg/day) and are largely devoid of carbohydrate (10–40 g per day). This diet prescription leads to a greater reliance on ketones as a fuel source. Currently, limited and mixed evidence remains regarding the overall efficacy of a ketogenic diet for athletes. In favor, Cox et al. [116] demonstrated that ketogenic dieting can improve exercise endurance by shifting fuel oxidation while Burke and colleagues [115] failed to show an increase in performance in a cohort of Olympic-caliber race walkers. Additionally, Jabekk and colleagues [117] reported decreases in body fat with no change in lean mass in overweight women who resistance trained for 10 weeks and followed a ketogenic diet. In light of the available evidence being limited and mixed, more human research needs to be completed before appropriate recommendations can be made towards the use of high fat diets for athletic performance.

In addition to the general nutritional guidelines described above, research has also demonstrated that timing and composition of meals consumed may play a role in optimizing performance, training adaptations, and preventing overtraining [2, 25, 40]. In this regard, it takes about 4 h for carbohydrate to be digested and assimilated into muscle and liver tissues as glycogen. Consequently, pre-exercise meals should be consumed about four to 6 h before exercise [40]. This means that if an athlete trains in the afternoon, breakfast can be viewed to have great importance to top off muscle and liver glycogen levels. Research has also indicated that ingesting a light carbohydrate and protein snack 30 to 60 min prior to exercise (e.g., 50 g of carbohydrate and 5 to 10 g of protein) serves to increase carbohydrate availability toward the end of an intense exercise bout [118, 119]. This also serves to increase availability of amino acids, decrease exercise-induced catabolism of protein, and minimize muscle damage [120–122]. Additionally, athletes who are going through periods of energy restriction to meet weight or aesthetic demands of sports should understand that protein intake, quality and timing as well as combination with carbohydrate is particularly important to maintain lean body mass, training effects, and performance [25]. When exercise lasts more than 1 h and especially as duration extends beyond 90 min, athletes should ingest glucose/electrolyte solutions (GES) to maintain blood glucose levels, prevent dehydration, and reduce the immunosuppressive effects of intense exercise [40, 123–128]. Notably, this strategy becomes even more important if the athlete is under-fueled prior to the exercise task or is fasted vs. unfasted at the start of exercise [68, 69, 129]. Following intense exercise, athletes should consume carbohydrate and protein (e.g., 1 g/kg of carbohydrate and 0.5 g/kg of protein) within 30 min after exercise and consume a high carbohydrate meal within 2 h following exercise [2, 74]. This nutritional strategy has been found to accelerate glycogen resynthesis as well as promote a more anabolic hormonal profile that may hasten recovery [120, 130, 131], but as mentioned above only when rapid glycogen restoration is needed or if the carbohydrate intake in the diet is adequate (< 6 g/kg/day) [53, 132]. In other words, the total carbohydrate consumption and timing of carbohydrate consumption should be individualized to each athlete’s needs according to the goals of the training cycle and bout [112]. Finally, for two to 3 days prior to competition, athletes should taper training by 30 to 50% and consume an additional 200 to 300 g of carbohydrate each day in their diet. This eating strategy has been shown to supersaturate carbohydrate stores prior to competition and improve endurance exercise capacity [2, 40]. Thus, the type of meal, amount of carbohydrate consumed, and timing of eating are important factors to maximize glycogen storage and in maintaining carbohydrate availability during training while also potentially decreasing the incidence of overtraining. The ISSN has adopted a position stand on nutrient timing in 2008 [133] that has been subsequently revised [13] and can be summarized with the following points:

Vitamins are essential organic compounds that serve to regulate metabolic and neurological processes, energy synthesis, and prevent destruction of cells. Fat-soluble vitamins include vitamins A, D, E, & K and the body stores fat-soluble vitamins in various tissues, which can result in toxicity if consumed in excessive amounts. Water-soluble vitamins consist of the entire complex of B-vitamins and vitamin C. Since these vitamins are water-soluble, excessive intake of these vitamins are eliminated in urine, with few exceptions (e.g. vitamin B6, which can cause peripheral nerve damage when consumed in excessive amounts). Table 1 describes the RDA, proposed ergogenic benefit, and summary of research findings for fat and water-soluble vitamins. Research has demonstrated that specific vitamins possess various health benefits (e.g., Vitamin E, niacin, folic acid, vitamin C, etc.), while few published studies have reported to find an ergogenic value of vitamins for athletes [134–138]. Alternatively, if an athlete is deficient in a vitamin, supplementation or diet modifications to improve vitamin status can consistently improve health and performance [139]. For example, Paschalis and colleagues [140] supplemented individuals who were low in vitamin C for 30 days and reported these individuals had significantly lower VO₂Max levels than a group of males who were high in vitamin C. Further, after 30 days of supplementation, VO₂Max significantly improved in the low vitamin C cohort as did baseline levels of oxidative stress of oxidative stress. Importantly, one must consider that some vitamins may help athletes tolerate training to a greater degree by reducing oxidative damage (Vitamin E, C) and/or help to maintain a healthy immune system during heavy training (Vitamin C). Alternatively, conflicting evidence has accumulated that ingesting high doses of Vitamins C and E may negatively impact intracellular adaptations seen in response to exercise training [141–144], which may consequently negatively impact an athlete’s performance. Furthermore, while optimal levels of vitamin D have been linked to improved muscle health [145] and strength [146] in general populations, research studies conducted in athletes generally fail to report on the ergogenic impact of vitamin D in athletes [147, 148]. However, equivocal evidence from Wyon et al. [149] suggests vitamin D supplementation in elite ballet dancers improved strength and reduced risk for injuries. The remaining vitamins reviewed appear to have little ergogenic value for athletes who consume a normal, nutrient dense diet. Since dietary analyses of athletes commonly indicate that athletes fail to consume enough calories and subsequently may not be consuming adequate amounts of each vitamin, many sport dietitians and nutritionists recommend that athletes consume a low-dose daily multivitamin and/or a vitamin enriched post-workout carbohydrate/protein supplement during periods of heavy training [150]. Finally, athletes may desire to consume a vitamin or mineral for various health (non-performance) related reasons including niacin to elevate high density lipoprotein (HDL) cholesterol levels and decrease risk of heart disease (niacin), vitamin E for its antioxidant potential, vitamin D for its ability to preserve musculoskeletal function, or vitamin C to promote and maintain a healthy immune system.

Minerals are essential inorganic elements necessary for a host of metabolic processes. Minerals serve as structure for tissue, important components of enzymes and hormones, and regulators of metabolic and neural control. In athletic populations, some minerals have been found to be deficient while other minerals are reduced secondary to training and/or prolonged exercise. Notably, acute changes in sodium, potassium and magnesium throughout a continued bout of moderate to high intensity exercise are considerable. In these situations, athletes must work to ingest foods and fluids to replace these losses, while physiological adaptations to sweat composition and fluid retention will also occur to promote a necessary balance. Like vitamins, when mineral status is inadequate, exercise capacity may be reduced and when minerals are supplemented in deficient athletes, exercise capacity has been shown to improve [151]. However, scientific reports consistently fail to document a performance improvement due to mineral supplementation when vitamin and mineral status is adequate [134, 152, 153]. Table 2 describes minerals that have been purported to affect exercise capacity in athletes. Of the minerals reviewed, several appear to possess health and/or ergogenic value for athletes under certain conditions. For example, calcium supplementation in athletes susceptible to premature osteoporosis may help maintain bone mass [151]. For years, the importance of iron status in female athletes has been discussed [154] and more recent efforts have highlighted that iron supplementation in athletes prone to iron deficiencies and/or anaemia can improve exercise capacity [155, 156]. Sodium phosphate loading can increase maximal oxygen uptake, anaerobic threshold, and improve endurance exercise capacity by 8 to 10% [157]. Increasing dietary availability of salt (sodium chloride) during the initial days of exercise training in the heat helps to maintain fluid balance and prevent dehydration. The American College of Sports Medicine (ACSM) recommendations for sodium levels (340 mg) represent the amount of sodium in less than 1/8 teaspoon of salt and recommended guidelines for sodium ingestion during exercise (300–600 mg per hour or 1.7–2.9 g of salt during a prolonged exercise bout) [158–161]. Finally, zinc supplementation during training can support changes in immune status in response to exercise training. Consequently, several minerals may enhance exercise capacity and/or training adaptations for athletes under certain conditions. However, there is little evidence that boron, chromium, magnesium, or vanadium affect exercise capacity or training adaptations in healthy individuals eating a normal diet. Sport nutritionists and dietitians should be aware of the specialized situations in which different types of minerals may provide support to bolster an athlete’s health or physical performance.

The most important nutritional ergogenic aid for athletes is water and limiting dehydration during exercise is one of the most effective ways to maintain exercise capacity. Before starting exercise, it is highly recommended that individuals are adequately hydrated [162]. Exercise performance can be significantly impaired when 2% or more of body weight is lost through sweat (i.e., a 1.4 kg body weight loss from a 70-kg athlete). When one considers that average sweat rates are reported to be 0.5–2.0 L/hour during exercise and training [128, 162], performance losses due to water loss can occur after just 60–90 min of exercise. Further, weight loss of more than 4% of body weight during exercise may lead to heat illness, heat exhaustion, heat stroke, and possibly death [128]. For this reason, it is critical that athletes adopt a mind set to prevent dehydration first by promoting optimal levels of pre-exercise hydration. Throughout the day and without any consideration of when exercise is occurring, a key goal is for an athlete to drink enough fluids to maintain their body weight. Next, athletes can promote optimal pre-exercise hydration by ingesting 500 mL of water or sports drinks the night before a competition, another 500 mL upon waking and then another 400–600 mL of cool water or sports drink 20–30 min before the onset of exercise. Once exercise commences, the athlete should strive to consume a sufficient amount of water and/or glucose-electrolyte solutions (i.e., sports drinks) during exercise to maintain hydration status. Consequently, to maintain fluid balance and prevent dehydration, athletes need to plan on ingesting 0.5 to 2 L/hour of fluid to offset weight loss. This requires frequent (every 5–15 min) ingestion of 12–16 fluid ounces of cold water or a sports drink during exercise [128, 163–166]. Athletes should not depend on thirst to prompt them to drink because people do not typically get thirsty until they have lost a significant amount of fluid through sweat. Additionally, athletes should weigh themselves prior to and following exercise training to monitor changes in fluid balance and then can work to replace their lost fluid [128, 163–166]. During and after exercise, athletes should consume three cups of water for every pound lost during exercise to promote adequate rehydration [128]. A primary goal soon after exercise should be to completely replace lost fluid and electrolytes during a training session or competition. Additionally, sodium intake in the form of glucose-electrolyte solutions (vs. only drinking water) and making food choices and modifications (added salt to foods) should be considered during the rehydration process to further promote euhydration [167]. Athletes should train themselves to tolerate drinking greater amounts of water during training and make sure that they consume more fluid in hotter/humid environments. Beyond nutrition, allowing one’s physiology the chance to acclimatize to the exercising environment for 10–14 days can help improve heat tolerance and promote thermoregulation. Finally, inappropriate and excessive weight loss techniques (e.g., cutting weight in saunas, wearing rubber suits, severe dieting, vomiting, using diuretics, etc.) are considered dangerous and should be prohibited. Sport nutritionists, dietitians, and athletic trainers can play an important role in educating athletes and coaches about proper hydration methods and supervising fluid intake during training and competition.

Agmatine, the decarboxylation product of the amino acid L-arginine, has shown different biological effects in different in vitro and animal models [265] indicating potential benefits in an athletic population. Agmatine is thought to improve insulin release and glucose uptake, assist in the secretion of luteinizing hormone, influence the nitric oxide signalling pathway, offer protection from oxidative stress, and is potentially involved in neurotransmission [266]. It is mostly found in fermented foods [267], with higher levels found in alcoholic beverages. Currently, nearly all research involving agmatine is commonly from animal research models and no human studies have been conducted to examine its impact on blood flow or impacting resistance training adaptations such as strength and body composition. There does not appear to be any scientific evidence that Agmatine supports increases in lean body mass or muscular performance.

α-ketoglutarate (α-KG) is an intermediate in the Krebs cycle that is involved in aerobic energy metabolism and may function to stimulate nitric oxide production. There is some clinical evidence that α-KG may serve as an anticatabolic nutrient after surgery [268, 269]. However, it is unclear whether α-KG supplementation during training may affect training adaptations. Very little research has been conducted on just alpha-ketoglutarate in humans to examine exercise outcomes. For example, Little and colleagues [270] supplemented with creatine, a combination of creatine, α-KG, taurine, BCAA and medium-chain triglycerides, or a placebo. The combination of nutrients increased the maximal number of bench press repetitions completed and Wingate peak power while no changes were reported in the placebo group. Campbell and investigators [271] supplemented 35 healthy trained men with 2 g of arginine and 2 g of α-KG or placebo in a double-blind manner while resistance training for 8 weeks. Supplementation with arginine + α-KG increased bench press strength and Wingate peak power, but did not impact body composition. Finally, Willoughby and colleagues [272] examined the results of arginine α-KG supplementation in relation to increasing nitric oxide production (vasodilation during resistance exercise), hemodynamics, brachial artery flow, circulating levels of l-arginine, and asymmetric dimethyl arginine in active males. This study found that although plasma L-arginine increased, there was no significant impact of supplementation on nitric oxide production after a bout of resistance exercise. Due to the lack of research on α-KG examining its impact on exercise training adaptations, its use cannot be recommended at this time.

Arginine is commonly classified as a conditionally essential amino acid and has been linked to nitric oxide production and increases in blood flow that are purported to then stimulate enhanced nutrient and hormone delivery and favorably impact resistance training adaptations [273]. To date, few studies have examined the independent impact of arginine on the ability to enhance fat-free mass increases while resistance training. Tang and colleagues [274] used an acute model to examine the ability of an oral 10-g dose of arginine to stimulate changes in muscle protein synthesis. These authors reported that arginine administration failed to impact muscle protein synthesis or femoral artery blood flow. Growth hormone levels did rise in response to arginine ingestion, which contrasts with the findings of Forbes et al., [275] who reported a blunting of growth hormone production after acute ingestion of arginine in strength trained males. Regardless, the Tang study [274] and others [276, 277] failed to link the increase in growth hormone to changes in rates of muscle protein synthesis. Notably, other studies have also failed to show a change in blood flow after arginine ingestion, one of its key purported benefits [272, 278]. Campbell and colleagues published outcomes from an 8 week resistance training study that supplemented healthy men in a double-blind fashion with either a placebo or 2 g of arginine and 2 g of α-ketoglutarate. No changes in fat mass or fat-free mass were reported in this study. Therefore, due to the limited data of arginine supplementation on stimulating further increases of exercise in muscle mass, its use for is not recommended at this time.

Boron is a trace mineral whose physiological role is not clearly understood. A number of proposed functions have been touted for boron: vitamin D metabolism, macromineral metabolism, immune support, increase testosterone levels and promote anabolism [279]. Due to a lack of scientific evidence surrounding boron, no official Daily Reference Intake (DRI) is established. Several studies have evaluated the effects of boron supplementation during training on strength and body composition alterations. However, these studies (conducted on male bodybuilders) indicate that boron supplementation (2.5 mg/d) had no significant impact on muscle mass or strength [280, 281]. Further, two investigations [282, 283] examined the impact of boron supplementation on bone mineral density in athletic and sedentary populations. In both investigations, boron supplementation did not significantly influence bone mineral density. Therefore, due to the limited findings on boron supplementation, its use is not recommended, and more research is warranted to determine its physiological impact.

Chromium is a trace mineral that is actively involved in macronutrient metabolism. Clinical studies have suggested that chromium potentiates the effects of insulin, particularly in diabetic populations. Due to its close interaction with insulin, chromium supplementation has been theorized to impact anabolism and exercise training adaptations. Initial research was promising with chromium supplementation being associated with increases in muscle and strength, particularly in women [284–286]. Subsequent well-controlled research studies [287] since that time have consistently failed to report a benefit for chromium supplementation (200–800 μg/d for 4–16 weeks) [288–294]. Most recently, chromium supplementation was investigated for its ability to impact glycogen synthesis after high-intensity exercise and was found to exert no impact over recovery of glycogen [295]. In summary, chromium supplementation appears to exert very little potential for its ability to stimulate or support improvements in fat-free mass. Therefore, due to the limited data of arginine supplementation on stimulating further increases of exercise in muscle mass, its use for is not recommended at this time.

Animal studies indicate that adding CLA to dietary feed decreases body fat, increases muscle and bone mass, has anti-cancer properties, enhances immunity, and inhibits progression of heart disease [296–298]. Although animal studies are impressive [299–301], human studies, at best, suggest a modest ability, independent of exercise or diet changes, of CLA to stimulate fat loss [302–305]. Moreover, very little research has been conducted on CLA to better understand if any scenario exists where its use may be justified. Initial work by Pinkoski et al. [306] suggested that CLA supplementation may help minimize catabolism while resistance training, but overall improvements in body composition from this study failed to yield positive outcomes. Two studies are available that supplemented exercising younger [307] and older individuals [308] with a combination of CLA and creatine and reported significant improvements in strength and body composition, but these results are thought to be the result of creatine. Currently, it seems there is little evidence that CLA supplementation during training can affect lean tissue accretion and has limited efficacy [309].

Also known as aspartate, aspartic acid is a non-essential amino acid. Two isomers exist within aspartic acid: L-Aspartic acid and D-Aspartic acid. D-Aspartic acid is thought to help boost athletic performance and function as a testosterone booster. It is also used to conserve muscle mass. While limited research is available in humans examining D-aspartic, Willoughby and Leutholtz [310] published a study to determine the impact of D-aspartic acid in relation to testosterone levels and performance in resistance-trained males. The results showed D-aspartic acid did not impact testosterone levels nor did it improve any aspect of performance. In agreement, Melville and colleagues [311] had participants supplement with either three or 6 g of D-aspartic acid and concluded that neither dose of D-aspartic acid stimulated any changes in testosterone and other anabolic hormones. Later, Melville et al. [312] supplemented 22 men in a randomized, double-blind fashion with either a placebo or 6 g of D-aspartic acid and concluded that 12 weeks of supplementation exerted no impact on resting levels of free or total testosterone and all changes observed in strength or hypertrophy were similar to what was experienced in the placebo group. Based on the currently available literature, D-aspartic acid is not recommended to improve muscle health.

Ecdysterones (also known as ectysterone, 20 β-Hydroxyecdysterone, turkesterone, ponasterone, ecdysone, or ecdystene) are naturally derived phytoecdysteroids (i.e., insect hormones). They are typically extracted from the herbs Leuza rhaptonticum sp., Rhaponticum carthamoides, or Cyanotis vaga. They can also be found in high concentrations in the herb Suma (also known as Brazilian Ginseng or Pfaffia). Initial interest was generated for ecdysterones due to reports of research from Russia and Czechoslovakia that indicated a potential physiological benefit in insects and animals [313–316]. A review by Bucci on various herbals and exercise performance also mentioned suma (ecdysterone) [317]. Unfortunately, the initial work was available in obscure journals with sub-standard study designs and presentation of results. In 2006, Wilborn and coworkers [318] completed what remains as the only study in humans to examine the impact of ecdysterones while resistance training. Herein, a 200 mg daily dose of 20-hydroxyecdysone over 8 weeks yielded no impact on changes in fat free mass or anabolic/catabolic hormone status. Ecdysterones are not recommended for supplementation to increase training adaptations or performance.

Fenugreek (trigonella foenum-graecum) is an Ayurvedic herb historically used to enhance masculinity and libido. Fenugreek extract has been shown to increase testosterone levels by decreasing the activity of the aromatase enzyme metabolizing testosterone into estradiol [319, 320]. Initial research by Poole et al. [321] supplemented resistance trained men in a randomized, double-blind fashion with a placebo or 500 mg of Fenugreek extract. After 8 weeks of supplementing and resistance training, significantly greater improvements in body fat, lower body strength, and upper body strength were observed. Wankhede and colleagues [320] reported a significant increase in repetitions performed to failure using the bench press and a reduction in body fat when 600 mg Fenugreek extract was consumed while following a resistance training program. Initial research using Fenugreek extract suggests it may help improve resistance-training adaptations, but more research in different populations is needed before any further recommendations can be made.

Gamma oryzanol is a mixture of a plant sterol and ferulic acid theorized to increase anabolic hormonal responses, strength and muscle mass during training [322, 323]. Although data are limited, one study reported no effect of 0.5 g/d of gamma oryzanol supplementation on strength, muscle mass, or anabolic hormonal profiles during 9 weeks of training [324]. Most recently, Eslami and colleagues [325] supplemented healthy male volunteers with either gamma oryzanol or placebo for 9 weeks while resistance training. In this study, changes in body composition were not realized, but a significant increase in strength was found in the bench press and leg curl exercise. With limited research of mixed outcomes at this point, no conclusive recommendation can be made at this time as more research is needed to fully determine what impact, if any, gamma oryzanol supplementation may have in exercising individuals.

Glutamine is the most plentiful non-essential amino acid in the body and plays several important physiological roles [74, 326, 327]. Glutamine has been reported to increase cell volume and stimulate protein [328–330] and glycogen synthesis [331]. Despite its important role in physiological processes, there is no compelling evidence to support the use of glutamine supplementation in terms of increasing lean body mass and a 2008 review by Gleeson concluded that minimal evidence is available to support glutamine’s purported role in exercise and sport training [332]. Initial research by Colker and associates [333] reported that subjects who supplemented their diet with glutamine (5 g) and BCAA (3 g) enriched whey protein (40 g) during resistance training promoted about a two pound greater gain in muscle mass and greater gains in strength than ingesting whey protein alone. In contrast, Kerksick and colleagues [232] reported no additional impact on strength, endurance, body composition and anaerobic power of combining 5 g of glutamine and 3 g of BCAAs to 40 g of whey protein in healthy men and women who resistance trained for 10 weeks. In addition, Antonio et al. [334] reported that high-dose glutamine ingestion (0.3 g/kg) offered no impact of the number of repetitions completed using the leg press or bench press exercises. In a well-designed investigation, Candow and co-workers [335] studied the effects of oral glutamine supplementation combined with resistance training in young adults. Thirty-one participants were randomly allocated to receive either glutamine (0.9 g/kg of lean tissue mass) or a maltodextrin placebo (0.9 g/kg of lean tissue mass) during 6 weeks of total body resistance training. The authors concluded glutamine supplementation during resistance training had no significant effect on muscle performance, body composition or muscle protein degradation in young healthy adults. While there may be other beneficial uses for glutamine supplementation (i.e. gastrointestinal health and peptide uptake in stressed populations [336] and, as mentioned previously, mitigation of soreness and recovery of lost force production [337]), there does not appear to be any scientific evidence that it supports increases in lean body mass or muscular performance.

Growth hormone releasing peptides (GHRP) and other non-peptide compounds (secretagogues) facilitate growth hormone (GH) release [338, 339], and can impact sleep patterns, food intake and cardiovascular functioning [340] along with improvements in lean mass in clinical wasting states [341]. These observations have served as the basis for development of nutritionally-based GH stimulators (e.g., amino acids, pituitary peptides, “pituitary substances”, Macuna pruriens, broad bean, alpha-GPC, etc.) and continue to capture interest by sporting populations for their potential to impact growth hormone secretion, recovery and robustness of training [342]. Although there is clinical evidence that pharmaceutical grade GHRP’s and some non-peptide secretagogues can increase GH and IGF-1 levels at rest and in response to exercise, it has not been demonstrated that such increases lead to an increase in skeletal muscle mass [343]. Finally, Chromiak and Antonio [344] reported that oral ingestion of many secretagogues fail to consistently stimulate hormone increases in growth hormone and fail to stimulate greater changes in muscle mass or strength. Currently, there is no convincing scientific evidence that secretagogues support increases in lean body mass or muscular performance.

Isoflavones are naturally occurring non-steroidal phytoestrogens that have a similar chemical structure as ipriflavone (a synthetic flavonoid drug used in the treatment of osteoporosis) [345–347]. For this reason, soy protein (which is an excellent source of isoflavones) and isoflavone extracts have been investigated in the possible treatment of osteoporosis as well as their role in body composition changes and changes in cardiovascular health markers. In this respect, multiple studies have supported the ability of isoflavone supplementation in older women alone [348] and in combination with exercise over the course of 6–12 months to improve various body composition parameters [349–351]. Findings from these studies have some applications to sedentary, postmenopausal women. However, there are currently no peer-reviewed data indicating that isoflavone supplementation affects exercise, body composition, or training adaptations in physically active individuals. For example, Wilborn and colleagues [318] reported that 8 weeks of supplementing with isoflavones with resistance training did not significantly impact strength or body composition.

OKG (via enteral feeding) has been shown to significantly shorten wound healing time and improve nitrogen balance in severe burn patients [352, 353]. A 2004 review by Cynober postulated that OKG may operate as a precursor to arginine and nitric oxide, but the overall lack of efficacy for arginine and other precursors limits the potential of OKG. Because of its ability to improve nitrogen balance, OKG may provide some value for athletes engaged in intense training. A study by Chetlin and colleagues [354] reported that OKG supplementation (10 g/day) during 6 weeks of resistance training significantly increased upper body strength. However, no significant differences were observed in lower body strength, training volume, gains in muscle mass, or fasting insulin and growth hormone. Since the previously published version of this review, no additional human research has been published and consequently, no further recommendations can be made regarding OKG’s potential as an ergogenic aid.

Testosterone and growth hormone are two primary hormones in the body that serve to promote gains in muscle mass (i.e., anabolism) and strength while decreasing muscle breakdown (catabolism) and fat mass [355–362]. Testosterone also promotes male sex characteristics (e.g., hair, deep voice, etc.) [356]. Low level anabolic steroids are often prescribed by physicians to prevent loss of muscle mass for people with various diseases and illnesses [363–374]. It is well known that athletes have experimented with large doses of anabolic steroids in an attempt to enhance training adaptations, increase muscle mass, and/or promote recovery during intense training [356–358, 361, 362, 375]. Research has generally shown that use of anabolic steroids and growth hormone during training can promote gains in strength and muscle mass [355, 360, 362, 368, 371, 376–383]. However, a number of potentially life threatening adverse effects of steroid abuse have been reported including liver and hormonal dysfunction, hyperlipidemia (high cholesterol), increased risk to cardiovascular disease, and behavioral changes (i.e., steroid rage) [378, 384–388]. Some of the adverse effects associated with the use of these agents are irreversible, particularly in women [385]. For these reason, anabolic steroids have been banned by most sport organizations and should be avoided unless prescribed by a physician to treat an illness.

Prohormones (e.g., androstenedione, 4-androstenediol, 19-nor-4-androstenedione, 19-nor-4-androstenediol, 7-keto DHEA, and DHEA, etc.) are naturally derived precursors to testosterone or other anabolic steroids. Their use has been suggested to naturally boost levels of these anabolic hormones. While data is available demonstrating increases in testosterone [389, 390], virtually no evidence exists demonstrating heightened training adaptations in younger men with normal hormone levels. In fact, most studies indicate that they do not affect testosterone and that some may actually increase estrogen levels and reduce HDL-cholesterol [378, 389, 391–396]. On a related note, studies have examined the ability of various ingredients to increase testosterone via inhibition of aromatase and 5-alpha-reductase [397]. Rohle et al. [398] and Willoughby et al. [399] reported that significant increases in free testosterone and dihydrotesterone occurred, but soft tissue composition either was not measured [398] or wasn’t changed as a result of supplementation [399]. Consequently, although there may be some potential applications for older individuals to replace diminishing androgen levels, it appears that prohormones have no training value. Since prohormones are “steroid-like compounds”, most athletic organizations have banned their use. Use of nutritional supplements containing prohormones will result in a positive drug test for anabolic steroids. Use of supplements (knowingly or unknowingly) containing prohormones have been believed to have contributed to a number of recent positive drug tests among athletes. Consequently, care should be taken to make sure that any supplement an athlete considers taking does not contain prohormone precursors particularly if their sport bans and tests for use of such compounds. Companies such as Informed Choice (www.informed-choice.org↗) and National Sanitation Foundation, NSF (aka, NSF Certified for Sport) www.nsf.org↗) have developed assurance programs to test and screen various nutrition products. Moreover, several professional sporting organizations have incorporated language into the collective bargaining that requires all products provided by teams or sporting organizations must provide products that have achieved certain 3rd party approvals for safety, banned substances and/or label claims. It is noteworthy to mention that many prohormones are not lawful for sale in the USA since the passage of the Anabolic Steroid Control Act of 2004. The distinctive exception to this is dehydroepiandrosterone (DHEA), which has been the subject of numerous clinical studies in aging populations.

Myostatin or growth differentiation factor 8 (GDF-8) is a transforming growth factor known as a negative regulator of skeletal muscle hypertrophy [400]. In humans, inhibiting myostatin gene expression has been theorized as a way to prevent or slow down muscle wasting in various diseases, speed up recovery of injured muscles, and/or promote increases in muscle mass and strength in athletes [401]. Since 2010, no additional research has been published that examined the impact of any nutritional ingredient or strategy to inhibit myostatin expression. In humans, myostatin clearly plays a role in regulating skeletal muscle mass. For example, a study by Ivey and colleagues [401] reported that female athletes with a less common myostatin allele experienced greater gains in muscle mass during training and reduced atrophy during detraining. Interestingly, no such changes were reported for men. Willoughby and colleagues [402] supplemented untrained males with 1200 mg/day of Cytoseira Canariensis (a form of sea algae), a purported myostatin inhibitor, and reported no changes for fat-free mass, strength and blood concentrations of myostatin. These results were corroborated by Wilborn et al. [318] who reported no impact of sulfo-polysaccaride supplementation on body composition or performance changes. As it stands, there is currently no published data supporting the use of sulfo-polysaccharides or any other ingredient touted to act as a myostatin inhibitor for their ability to increase strength or muscle mass.

Tribulus terrestris (also known as puncture weed/vine or caltrops) is a plant extract that has been suggested to stimulate leutinizing hormone which stimulates the natural production of testosterone [403]. Consequently, tribulus is marketed as a supplement that can increase testosterone and promote greater gains in strength and muscle mass during training. In human research models, several studies have indicated that tribulus supplementation alone [404, 405] or in combination with other segragotogues and androgen precusors [406, 407] appears to have no effects on body composition or strength during resistance training.

Vanadyl sulfate is a trace mineral that has been found to affect insulin-sensitivity (similar to chromium) and may affect protein and glucose metabolism [403, 408]. In this regard, reports have highlighted the potential efficacy and support for vanadium to improve insulin sensitivity [409] and assist with the management of diabetes [410]. In relation to its potential ability to impact protein and glucose metabolism, vanadyl sulfate supplementation has been purported to positively impact strength and muscle mass [74, 411]. However, no studies are available that support the ability of vanadyl sulfate supplementation to impact strength or muscle mass in non-diabetic individuals who are currently resistance training [412, 413].

The main ingredients in ZMA formulations are zinc monomethionine aspartate, magnesium aspartate, and vitamin B-6. 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). 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 [414] 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. [415] reported that ZMA supplementation increased serum zinc and excretion, but failed to change free and total testosterone levels. Wilborn et al. [416] 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 [417]. To this point, Brilla and Conte [414] did report depletions of both zinc and magnesium, thus increases in testosterone levels could have been attributed to deificient 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.