International Society of Sports Nutrition position stand: energy drinks
- Bill Campbell†1,
- Colin Wilborn†2,
- Paul La Bounty3,
- Lem Taylor†2,
- Mike T Nelson4,
- Mike Greenwood†5,
- Tim N Ziegenfuss6,
- Hector L Lopez6,
- Jay R Hoffman7,
- Jeffrey R Stout7,
- Stephen Schmitz†8,
- Rick Collins†9,
- Doug S Kalman10,
- Jose Antonio†11 and
- Richard B Kreider5Email author
© Campbell et al.; licensee BioMed Central Ltd. 2013
Received: 28 December 2012
Accepted: 31 December 2012
Published: 3 January 2013
Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the safety and efficacy of the use of energy drinks (ED) or energy shots (ES). The ISSN has concluded the following. 1. Although ED and ES contain a number of nutrients that are purported to affect mental and/or physical performance, the primary ergogenic nutrients in most ED and ES appear to be carbohydrate and/or caffeine. 2. The ergogenic value of caffeine on mental and physical performance has been well-established but the potential additive benefits of other nutrients contained in ED and ES remains to be determined. 3. Consuming ED 10-60 minutes before exercise can improve mental focus, alertness, anaerobic performance, and/or endurance performance. 4. Many ED and ES contain numerous ingredients; these products in particular merit further study to demonstrate their safety and potential effects on physical and mental performance. 5. There is some limited evidence that consumption of low-calorie ED during training and/or weight loss trials may provide ergogenic benefit and/or promote a small amount of additional fat loss. However, ingestion of higher calorie ED may promote weight gain if the energy intake from consumption of ED is not carefully considered as part of the total daily energy intake. 6. Athletes should consider the impact of ingesting high glycemic load carbohydrates on metabolic health, blood glucose and insulin levels, as well as the effects of caffeine and other stimulants on motor skill performance. 7. Children and adolescents should only consider use of ED or ES with parental approval after consideration of the amount of carbohydrate, caffeine, and other nutrients contained in the ED or ES and a thorough understanding of the potential side effects. 8. Indiscriminant use of ED or ES, especially if more than one serving per day is consumed, may lead to adverse events and harmful side effects. 9. Diabetics and individuals with pre-existing cardiovascular, metabolic, hepatorenal, and neurologic disease who are taking medications that may be affected by high glycemic load foods, caffeine, and/or other stimulants should avoid use of ED and/or ES unless approved by their physician.
According to published research, energy drinks (ED) are the most popular dietary supplement besides multivitamins in the American adolescent and young adult population [1–3]. ED are also reported to be the most popular supplement among British athletes . More recently, energy shots (ES) have also been purported to possess ergogenic value on mental focus and/or performance . It is important to make a distinction between ED, ES, and sports drinks. Sports drinks are a unique category within the beverage industry and are marketed to consumers with the primary function of promoting hydration, replacing electrolytes and sustaining endurance performance capacity. They typically provide a small amount of carbohydrate (e.g., 6-8 grams/100 ml) and electrolytes (sodium, potassium, calcium, magnesium). ED, on the other hand, typically contain higher amounts of carbohydrate along with nutrients purported to improve perceptions of attention and/or mental alertness. Low calorie ED are also marketed to increase mental alertness, energy metabolism, and performance. Energy shots are typically 2-4 oz. servings of concentrated fluid containing various purported ergogens. Since ED and ES contain carbohydrate, caffeine, and/or nutrients that may affect mental focus and concentration, they have the potential to affect exercise capacity and perceptions of energy and/or fatigue. The purpose of this position stand is to critically evaluate the scientific literature and make recommendations in regards to the role that ED and/or ES may have on exercise performance and energy expenditure/metabolism. Additionally, we will discuss safety considerations in regards to the use of ED and/or ES.
This analysis represents a systematic review of the literature on the effects of “energy drinks” on exercise and cognitive performance as well as primary ingredients contained in popular energy drinks. A comprehensive literature search was performed by searching the Medline database of the US National Library of Medicine of the National Institutes of Health. The search strategy involved entering “energy drinks” and commercial names of energy drinks and/or caffeinated beverages as well as a search of primary nutrients contained in popular energy drinks (e.g., caffeine, carbohydrate, taurine, glucoronolactone, Guarana, Yerba Mate, etc.). It is important to note, from a United States regulatory perspective, several of these ED are marketed as dietary supplements and not beverages, and the label on the product will indicate which category of Food and Drug Administration (FDA) authority the product falls under. Each category has its own set of governing laws and regulations. For example, depending on the category, the labels will include Supplement Facts (dietary supplements) or Nutrition Facts (beverages). A paper summarizing the literature related to ED was presented at the 2011 International Society of Sports Nutrition Annual meeting. Thereafter, a position stand writing team was organized to develop this paper. Drafts of this position stand were then reviewed by all authors as well as the Research Committee of the International Society of Sports Nutrition (ISSN). The final version of this paper was then adopted as the official position of the ISSN.
List of ingredients described on nutrient panels found in some energy drinks
Calories from Fat
2,500 mg L-Carnitine, Glucose, Caffeine, Guarana, Inositol, Glucuronolactone, Maltodextrin
Caffeine (77 mg)
325 mg Ginko Biloba (150 mg), Caffeine (80 mg), Guarana (25 mg), Inositol (25 mg), L-Carnitine (25 mg), Milk Thistle (20 mg)
Guarana, maltodextrin, caffeine, taurine, panax ginseng, calcium
Citrulline Malate, L-Glutamine, L-Arginine, Quercetin, L-Leucine, L-Valine,
List of ingredients described on nutrient panels found in some energy shots
Calories from Fat
Taurine, Glucuronolactone, Malic Acid, N-Acetyl L-Tyrosine, L-Phenylalanine, Caffeine, Citicoline
Glucouronolactone (425 mg), N-Acetyl L-Tyrosine (400 mg), L-Phenylalanine (375 mg), Taurine (350 mg), Malic Acid 300 mg), Caffeine (200 mg), Green Tea Extract (150 mg), Ginseng Extract (150 mg)
Glucouronolactone (420 mg), L-Phenylalanine (380 mg), D-Ribose (350 mg), N-Acetyl L-Tyrosine (325 mg), Malic Acid (300 mg), Caffeine (175 mg), Green Tea Extract (150 mg), Ginseng Extract (100 mg)
Caffeine Citrate, Caffeine Anhydrous, Evoburn, Octapomine, Gugulsterone E & Z, Yerbe Mate, Green Tea, Synephrine, cAMP, Vinpocetine, Yohimbe HCL
Beta-Alanine, Vitamin C, Caffeine Anhydrous (158 mg), Evoburn, N-Acetyl-L-Tyrosine, Hordinine, 5-Hydroxy-L-Trypotophan (5-HTP), Potassium, N-methyl Tyramine, Sulbutlamine, Vinpocetine, Yohimbine HCI, St. John’s Wort Extract
Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg·kgBM-1) and overall does not result in further enhancement in performance when consumed in higher dosages (≥ 9 mg·kgBM-1).
Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared to coffee.
It has been shown that caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation.
Caffeine is ergogenic for sustained maximal endurance exercise, and has been shown to be highly effective for time-trial performance.
Caffeine supplementation is beneficial for high-intensity exercise, including team sports such as soccer and rugby, both of which are categorized by intermittent activity within a period of prolonged duration.
The literature is equivocal when considering the effects of caffeine supplementation on strength-power performance, and additional research in this area is warranted.
The scientific literature does not support caffeine-induced diuresis during exercise, or any harmful change in fluid balance that would negatively affect performance.
As demonstrated below, several studies have reported significant improvements in both aerobic and resistance exercise with a relative dosage of approximately 2 mg·kgBM-1of caffeine. This is less than the amount recommended (3-6 mg·kgBM-1) to enhance performance , and may contribute to the hypothesis that the synergistic effects of the various ingredients contained in ED/ES are responsible for the reported improvements in exercise performance.
Another common ingredient in most ED is some type of carbohydrate source (e.g., glucose, sucrose, maltodextrin, etc.). Energy drinks also typically contain glucuronolactone, an ingredient which is involved in ascorbic acid synthesis and is metabolized into xylulose . Evidence from numerous studies indicates that carbohydrate feeding during exercise of about 45 minutes or longer can improve endurance capacity and performance [13, 14]. Mechanisms by which carbohydrate feeding prior to and during exercise improves endurance performance include maintaining blood glucose levels, maintaining high levels of carbohydrate oxidation, and the sparing of liver and possibly skeletal muscle glycogen . Peak rates of carbohydrate oxidation are commonly around 1 g of carbohydrate per minute or 60 g·hr-1. Glucose, sucrose, maltodextrins and amylopectin are oxidized at high rates, while fructose, galactose and amylose are oxidized at lower rates (approximately 25-50% lower) . Consequently, sports drinks typically contain a mixture of various types of carbohydrates designed to optimize exogenous carbohydrate oxidation .
ED’s contain approximately 25-30 grams of carbohydrate per 240 mL (8 fluid ounces) serving. This amount nearly meets the lower value of 30 grams/hour recommended during endurance exercise, but falls short of the upper range of 60 g·hr-1. In order to meet this upper level of 60 grams of carbohydrate per hour during endurance exercise, approximately 530 mL (18 fluid ounces) of a typical ED per hour would need to be consumed. While the total carbohydrate content of typical ED is quite high, a shortcoming exists in regards to the concentration of commercially available energy drinks. The American College of Sports Medicine  and the ISSN [6, 17] recommend ingesting carbohydrate in a 6-8% solution (6-8 grams per 100 ml of fluid) during endurance exercise. A typical ED provides carbohydrates at a greater concentration, typically around an 11-12% solution. Ingesting higher percentages (>10%) of carbohydrate in fluids has been reported to delay gastric emptying and increase gastrointestinal distress [19, 20]. Consequently, athletes who want to use ED as sports drinks may need to dilute the beverage and/or alternate consumption of ED and water during exercise.
Potential ergogenic nutrients contained in energy drinks that may affect cognition and/or mental performance
Potential ergogenic value
Improve memory and mental concentration
Some supportive evidence on cognition (e.g., 2 g/d, 150 mg acute ingestion with cold exposure) [41, 43, 46, 48, 49]. No effects on performance capacity [42, 50]. No known effects at dosages found in ED or ES.
Some supportive evidence with large doses (8.5 g prior to and during exercise) and in fed animals . No known effects at dosages found in ED or ES.
St. John’s Wort
Potential stimulants contained in energy drinks that may affect performance capacity
Potential ergogenic value
Natural source of caffeine. Similar properties to caffeine.
Similar to caffeine effects.
Green Tea Extract
Alternative to ephedrine. Naturally derived from Citrus aurantium. Stimulant with less cardiovascular effects than ephedrine. Purported to increase metabolism and promote weight loss.
Contains three xanthines (caffeine, theobromine, and theophylline). Similar properties to caffeine
Similar to caffeine effects. Effects at dosages found in ED are unknown.
Naturally-occurring monoamine derived from tyrosine. Acts as a catecholamine (dopamine, NE, Epi) releasing agent. Degraded to octopine. Increases blood pressure and can serve as neurotransmitter [91–93].
Mild cardiovascular stimulant. Effects at dosages found in ED / ES are unknown.
No known effects at dosages found in ED or ES.
Other potential ergogenic nutrients contained in energy drinks that may affect performance
Potential ergogenic value
Contains ginsenosides which are purported to have anti-inflammatory, antioxidant, and anticancer effects. Purported to enhance perceptions of energy, increase stamina and improve nitrogen balance .
Involved in shuttling long chain fatty acids into mitochondria. Purported to promote lipolysis .
Limited supportive ergogenic value in athletes or on weight loss . No known effects at dosages found in ED and ES.
Involved in ATP synthesis. Theoretically, D-ribose supplementation can increase ATP availability.
Some evidence of improved exercise capacity in clinical populations  but limited evidence that high dose ribose supplementation affects exercise capacity [114–119]. No known effects at dosages found in ED and ES.
Carbohydrate that is not classified as sugar. Involved in insulin signaling, nerve transmission, serotonin modulation, and fat oxidation .
No known effects at dosages found in ED or ES.
Reported to have antioxidant, anti-inflammatory, antiviral, and immune-modulatory effects .
Several studies have investigated the effects of ED consumption prior to exercise. The types of exercise that were evaluated include resistance exercise [167, 168], anaerobic exercise , and aerobic/endurance exercise [62, 170–172].
Ingestion prior to anaerobic exercise
Many of the studies investigating the effects of ED ingestion on anaerobic performance measures have been conducted within the past several years. In a crossover study (separated by seven days), Forbes and colleagues  gave 15 physically active college-aged students a commercially available energy drink standardized with 2 mg·kgBM-1of caffeine or an isoenergetic, isovolumetric, non-caffeinated placebo 60-minutes prior to exercise. The exercise consisted of three sets of 70% one repetition maximum (1RM) bench press conducted to failure on each set with one minute of rest between each set. Following the resistance exercise bout, three x 30-second Wingate Anaerobic Capacity tests were also conducted with two minutes of rest between each test. The ED significantly increased total bench press repetitions over three sets (approximately 6% more repetitions completed) but had no effect on Wingate peak or average power.
In a similarly designed study, a commercially available energy drink (providing an average of 2.1 mg of caffeine per kg of body mass) given to physically active male and female participants 45 minutes prior to exercise resulted in a significant increase in leg press total lifting volume (12% increase as compared to a carbohydrate placebo) but had no effect on bench press total lifting volume  or multiple 20-second Wingate-type cycle sprints . Hoffman and colleagues  gave male strength/power athletes an ED containing an average of 1.8 mg·kgBM-1of caffeine or a placebo beverage that was similar in taste and appearance but contained only inert substances. Following the ingestion of the ED, three separate 20-second Wingate tests separated by about 15 minutes were performed. Results revealed that there were no significant differences between trials in any anaerobic power measure. In a recent publication, 12 healthy male and female non-resistance trained participants ingested a commercially available ED standardized at either 1 or 3 mg·kgBM-1of caffeine or a placebo beverage (containing no caffeine) in a randomized, repeated measures design . Sixty minutes following beverage ingestion, each participant completed 10-to-100% 1RM power-load tests for the bench press and half-squat. Ingestion of the ED with 1 mg·kgBM-1of caffeine was not enough to raise the power output during the power-load tests. However, the ingestion of an ED with 3 mg·kgBM-1of caffeine increased maximal power output by 7% in both the half-squat and bench-press as compared to the ingestion of a placebo . A recent study by Gonzalez and colleagues  indicated that an energy matrix consisting of caffeine, taurine and glucoronolactone consumed 10-min prior to a workout resulted in an 11.9% improvement (p < 0.05) in the number of repetitions performed during 4 sets of the squat or bench press exercise using 80% of the subject’s 1-RM. In addition, the average power output for the workout was significantly higher for subjects consuming the energy drink compared to subjects consuming the placebo.
In addition to resistance and high intensity anaerobic exercise, the effects that ED exert on speed/agility performance has also been investigated. Collegiate female soccer players ingested an ED containing 1.3 mg·kgBM-1of caffeine and 1 gram of taurine or a caffeine and taurine-free placebo 60 minutes prior to repeated agility t-tests . No difference in agility t-test performance between the ED and placebo groups was reported. Specifically, the highest difference reported between the two groups was during the third set of eight agility t-tests, and the difference reached only 1.15% between the groups. It is unlikely that the carbohydrate content alone in ED is responsible for improvements in resistance exercise performance. In support of this view, the majority of studies in which supplemental carbohydrate was ingested prior to a resistance-training bout did not report improvements in resistance training performance [176–178].
ED (containing approximately 2 mg·kgBM-1caffeine) consumed 45 to 60 minutes prior to anaerobic/resistance exercise may improve upper- and lower- body total lifting volume, but has no effect on repeated high intensity sprint exercise, or on agility performance.
Ingestion prior to endurance exercise
Several studies have investigated the effects of ED ingestion prior to aerobic exercise [62, 170–172, 179]. In the earliest of these studies, Alford and colleagues  investigated the effects of ingesting a commercial ED on aerobic endurance. In a repeated measures, crossover design, young healthy participants ingested 250 mL of a commercial ED (containing 80 mg of caffeine and 26 grams of carbohydrate), a carbonated water beverage, or no beverage at all 30 minutes prior to performing an endurance exercise bout. Test days for separate treatments were assessed within a week. Aerobic performance was analyzed by the amount of time that exercise could be maintained at 65-75% of maximum heart rate on a cycle ergometer. Significant improvements in aerobic performance were reported for the commercial ED treatment. Aerobic performance was 8% and 14% longer after ingesting the commercial ED as compared to the carbonated water and no beverage treatment, respectively.
In one of only two studies that have investigated the effects of ingesting a sugar/carbohydrate-free ED on performance capacity, Candow and colleagues  reported no improvements in high intensity run time-to-exhaustion performed at 80% of VO2max on a treadmill in physically active college-aged participants. The sugar-free ED contained 2 mg·kgBM-1caffeine and was ingested one-hour prior to the exercise bout . In contrast, Walsh and colleagues  reported significant improvements in treadmill run time to exhaustion following ingestion of a carbohydrate-free ED. In this randomized cross-over investigation, 15 recreationally active participants ingested an ED 10-minutes prior to engaging in a treadmill run-to exhaustion test at 70% VO2max . The ED utilized in this study did not contain any carbohydrate, and unlike other ED products, contained nearly eight grams of the amino acids L-leucine, L-isoleucine, L-valine, L-arginine and L-glutamine. Unfortunately, the published study did not disclose the precise amount of caffeine contained in the ED, but instead referred to a ~2 g “proprietary blend” of caffeine, taurine, and glucoronolactone. The placebo used as a comparison was sweetened water that was similar in color and volume. It was reported that participants consuming the ED were able to run 12.5% longer than during the placebo treatment .
The two most common protocols used to assess aerobic performance are time to exhaustion at a given exercise intensity (e.g., exercise at 70% of maximum oxygen uptake until exhaustion) and time trial performance for a set distance (e.g., 40 km time trial). Time trials have greater validity than time to exhaustion because they provide a good physiological simulation of actual performance and correlate with actual performance [180, 181]. Ivy and colleagues  were the first research group to utilize a time trial component in conjunction with ED consumption. In this investigation, trained male and female cyclists completed two trials in a repeated measures crossover design separated by one week. After a 12 hour fast, the cyclists ingested a commercially available ED providing approximately 2.3 mg·kgBM-1caffeine or an artificially colored, flavored, and sweetened-water placebo 40-minute prior to the exercise bout. Performance during the exercise bout was measured as the time to complete a standardized amount of work equal to 1 hr of cycling at 70% of maximal power output. Results revealed a significant difference between the treatments in relation to performance with the ED treatment completing the time trial ~4.7% faster than the placebo treatment .
ED containing approximately 2 mg·kgBM-1caffeine consumed 10 to 40 minutes prior to aerobic exercise improve cycling and running performance in both trained cyclists and recreationally active participants. In the one investigation in which no aerobic performance improvement was reported, the ED (containing 2 mg·kgBM-1caffeine) was ingested 60-minutes prior to the performance assessment. In light of the other findings, ingestion of the caffeine-containing ED 60-minutes prior to the exercise bout may be too long of a period to realize improvements in aerobic exercise performance.
Reaction time, concentration, alertness, and subjective feelings of energy/vitality are important in many competitive activities such as hitting a baseball, returning a serve in tennis, and dodging strikes and kicks in a mixed martial arts competition. Strategies to improve these attributes are often sought after by individuals competing in certain athletic endeavors. Over the past several years, research has investigated the effects that ED ingestion has on these (and other) variables.
Seidl and coworkers  conducted a study utilizing three common ingredients (i.e., caffeine, taurine, glucuronolactone) typically found in ED and compared it to a placebo group. Participants were evaluated at night to see if ingestion of these nutrients affected mood and motor function in fatigued participants. Interestingly, the investigators found that at the end of the experiment, reaction time was significantly longer in the placebo group, but remained unchanged in the group that consumed the ED ingredients. Similarly, vitality scores, feelings of well-being, and social extrovertedness were all significantly decreased in the placebo group, but did not change in the ED group .
Scholey and colleagues  investigated the effects of an ED (containing primarily caffeine, glucose, ginseng and ginkgo biloba drink) or a placebo beverage on five aspects of cognitive performance and mood. Thirty minutes after consuming ED, two of the five variables (i.e., “secondary memory” and “speed of attention”) were significantly improved as compared to the placebo beverage . Other investigators also reported that when caffeine was combined with carbohydrates in a carbonated beverage, performance and mood were improved and/or maintained during fatiguing and cognitively demanding tasks relative to placebo . Similarly, ED containing caffeine and glucose have also been shown to enhance event related potentials (i.e., a measure of brain activity in real time obtained from an electroencephalogram), which may translate to improvements in reaction time .
Hoffman and colleagues  reported that when male strength/power athletes consumed 120 ml of a commercially available ED or a placebo, reaction time and subjective feelings of energy and focus were significantly improved in those consuming the ED. Furthermore, the investigators also noted a statistical trend (p=0.06) towards an increase in alertness. In a similar study, Walsh and colleagues  examined the effects of ingesting an “energy matrix” (2.05 g of caffeine, taurine, glucuronolactone), amino acids (7.9 g of L-leucine, L-isoleucine, L-valine, L-arginine and L-glutamine), di-creatine citrate (5 g), and β-alanine (2.5 g) mixed with 500 ml of water or a placebo) 10-minutes prior to exercise on aerobic performance and subjective measures of focus, energy, and fatigue in recreationally active male and females. Results revealed that participants ingesting the ED increased time to exhaustion while running at 70% of VO2max by 12.5% (p = 0.012), they reported greater focus (p = 0.031), energy (p = 0.016), and less fatigue (p = 0.005) prior to exercise; and, that their ratings of focus (p = 0.026) and energy (p = 0.004) were greater 10 minutes into exercise . However, no significant differences in energy, fatigue, and focus were observed between groups immediately post-exercise .
Howard and coworkers  evaluated the effects of acute ingestion of a glucose containing ED on behavioral control. In this study, 80 participants were randomly assigned to consume 1.8, 3.6, or 5.4 ml/kg of an ED, a placebo, or no drink in a counterbalanced manner. Participants completed a behavioral control task and subjective measures of stimulation, sedation, and mental fatigue before and 30-minutes after ingestion of the assigned drinks. Results revealed that those consuming the ED decreased reaction times on the behavioral control task, increased subjective ratings of stimulation and decreased ratings of mental fatigue. The greatest improvements in reaction times and subjective measures were observed with the lower dose and improvements diminished as the dose increased. Earlier research conducted by Alford and associates  supported these findings by demonstrating that individuals ingesting 250 ml of this same ED had significantly better reaction time, concentration, memory, and subjective alertness compared to a placebo. Smit and coworkers  suggested that caffeine is most likely the primary ingredient that improves mood and performance during fatiguing and cognitively demanding tasks, with carbohydrates playing a minor role. However, caffeine and carbohydrate may act in a synergistic manner . To support this view, a recent paper by Pettitt et al  reported that while ingestion of an ED prior to exercise affected aerobic metabolism during and following cycling exercise, the secondary ingredients found in the ED had no additive effects.
To date, most studies on ED have reported improvements in mood, reaction time, and/or markers of alertness, even though the relative importance of the various ingredients is not fully understood. The primary ergogenic value appears to be due to the caffeine and/or carbohydrate contained in these drinks. Individuals looking to enhance reaction time, mental alertness, and/or focus may benefit from consuming an ED prior to exercise.
Energy drinks and their role in energy expenditure and weight loss
As shown in Table 4, ED and some commercial beverages designed to increase metabolism typically contain a number of stimulants (e.g., caffeine, Guarana, Green Tea, synephrine, Yerba mate, Yohimbine, Tyramine, Vinocetine, etc.). Several low-calorie ED and beverages have been marketed as “thermogenic blends” with a focus on increasing metabolism. Theoretically, ingestion of ED prior to exercise may increase energy expenditure which over time could help manage and/or promote weight loss. In support of this theory, studies have shown that ingestion of caffeine (e.g., 200-500 mg) can increase acute (1-24 hours) energy expenditure [187–193], chronic (28 days) energy expenditure , and elevate plasma free-fatty acid and glycerol levels [187, 194, 195]. Collectively, these findings suggest that the stimulant properties of caffeine contained in ED can elevate an individual’s metabolic rate as well as elevate the rate of lipolysis in the body. However, these studies used various types of caffeine/stimulant/vitamin-enriched coffee [189–193], a caffeine/stimulant blend supplement [187, 189, 193], and various calorie-free thermogenic ED [190, 194–197]. Additionally, the dosage of caffeine used in some of these beverages that are marketed as a thermogenic supplements is typically higher (e.g., 200-500 mg) than the concentrations found in ED and ES marketed for increasing athletic performance or alertness (i.e., about 80 – 200 mg). With this said, there is some data that indicates that acute ingestion of ED has been shown to enhance energy expenditure, metabolic rate, catecholamine secretion, and/or lipolysis [187, 198]
In terms of weight loss, Roberts and colleagues  reported that 28 days of consumption of a calorie free ED (336 ml/day) promoted small (i.e., 18.9 ± 1.5 to 18.3 ± 1.5 kg) but statistically significant (p<0.05) reductions in fat mass compared to controls (i.e., 18.1 ± 1.3 to 18.4 3± 1.2 kg). Similarly, Stout and associates  evaluated the effects of consuming an ED or placebo 15-minutes prior to exercise training and ad-libitum on non-training days for 10-weeks on changes in body composition and fitness. Results revealed that those consuming the ED experienced greater changes in fat mass (-6.6% vs. -0.35%, p<0.05), peak aerobic capacity (+13.8% vs. 5.4%, p<0.01), and treadmill time to exhaustion (+19.7% vs. 14.0%, p<0.01). These findings suggest that consumption of ED during training and/or weight loss may provide some additive ergogenic benefits. However, it should be noted that recent review on ED by Higgins and associates  found that many of the commonly used additional ingredients (e.g., Ma Huang, willow bark, synephrine, calcium, cayenne/black pepper extracts) that are contained in the “thermogenic blends” of several of these products are not contained in some of the most commonly used ED. It is also important to note that daily consumption of high calorie ED could promote weight gain. Consequently, additional research is necessary to determine whether ingesting low-calorie ED or ES may affect training adaptations and/or weight loss.
Consumption of low calorie ED and thermogenic beverages have been reported to increase resting energy expenditure and fat metabolism on an acute basis. Preliminary studies suggest that ingesting some types of ED and thermogenic beverages prior to exercise during training could promote positive adaptations in body composition. However, more research is needed to determine whether daily use of ED would affect long-term energy balance and body composition.
Very often, ED also contain various stimulants with the most common being caffeine. Some concern has been raised about excessive caffeine intake that could be obtained from consuming too many ED and/or from a lack of knowledge that that some ingredients contained in ED may contain caffeine [201, 202]. Currently in the United States, the FDA has regulated the limit of caffeine in soft drinks to 0.02 percent (10mg/oz.) of the product, but this is not currently enforced for ED or ES. As of December 2012, the US-FDA along with the US Congress has begun to study products marketed as ED or ES, however no formal new guidelines have been published. The Nutrition Facts Panel on food labels are not required to always list caffeine since it is not a nutrient. However, if caffeine is added to a food, it must then be listed ; therefore many individuals may consume more caffeine than they realize [201, 202]. In Canada, caffeine levels are limited to 180 mg per drink . The caffeine content of common ED and ES has been reported to range from about 100 to 286 mg . As a comparison, the average cup of coffee or contains between 40 and 150 mg caffeine, while a 20 oz. cup of Starbucks regular drip coffee has been found to contain as much as 480 mg of caffeine .
The potential side effects of caffeine include: insomnia, nervousness, restlessness, gastric irritation, nausea, vomiting, tachycardia, tremors, and anxiety; which have been reported at doses as low as 250 to 300 mg [5, 201–204, 209]. Caffeine availability is ubiquitous and it is one of the most extensively studied substances in the food supply with a long history as generally regarded as safe when consumed in moderation . However, all substances may be toxic under the right conditions, with toxicity being a function of the interaction of many physiologic variables that include the following: acute and chronic dosing, route of administration, genetics, age, sex, environment, and intrinsic health of the individual being exposed. Young adults have been found to have subclinical coronary atherosclerosis . In addition, post-mortem assessment of sudden cardiac death in young persons (<35 years) reveals a variety of anatomic abnormalities of the coronary arteries, myocardium, valves and the conduction system . Such unknown pre-existing risk factors may increase the risk of adverse events, particularly cardiovascular ones, in individuals consuming EDs, due to underlying disease. In fact, even water can be toxic given certain conditions with an LD50 (lethal acute dose for 50 percent in test species) of greater than 90 mL/kg in rats . It is possible to overdose on caffeine and there are a handful of case reports in the literature [5, 209, 216–218]. A lethal dose of caffeine has been typically in excess of 5 g , which equates to about 42 cups of coffee at 120 mg of caffeine per cup. Sepkowitz  recently suggested that an intake of 3 grams of caffeine (equivalent to ingesting 12 or so highly caffeinated ED within a few hours) could elicit significant adverse effects. The average caffeine per serving in most ED and ES range between 75 and 200 mg, an amount similar to the caffeine found in a premium cup of coffee .
Nawrot and colleagues  stated that in a healthy adult population, up to 400 mg of caffeine daily was not associated with any adverse effects. In another review, Higdon et al.  presented data in children stating no adverse effects were seen with doses under 3 mg·kgBM-1·day-1. As with most drugs, the exact amount of caffeine where side effects will occur varies from person to person based on genetics, age, liver cytochrome P450-CYP1A2 isozyme function, concurrent medications or substances that may affect hepatic metabolism, body mass, and sensitivity. Additionally, it is unknown whether inclusion of other stimulants in ED and/or ES may increase or decrease the threshold for experiencing side effects. For this reason, some groups do not recommend ED or ES for athletes participating in exercise lasting less than 1 hour , despite the admission of inadequate long-term data. The longest duration studies on ED or ES we were able to find was 10 weeks and these studies did not report any change in clinical safety markers [199, 206]. Nevertheless, since ED and ES often contain other stimulants that can have a synergistic effect with caffeine, more research is needed to determine the long-term effects of habitual intake of ED and ES before definitive conclusions can be drawn.
Several reports have expressed concern about the safety of ED [5, 200, 205, 221]. For example, Worthley and associates  tested 50 young male and female adults one hour before and one hour after consuming 250 ml of a sugar-free ED containing approximately 80 mg of caffeine. The investigators found that mean arterial pressure increased by approximately 3.8 mmHg while resting heart rate was not affected. Additionally, platelet aggregation increased by 13.7% compared to only a 0.3% change in the control group while endothelial function decreased. The researchers noted that the component of the ED that was associated with these results was not clear. However, they suggested that since endothelial dysfunction and impaired platelet function are associated with elevated glucose levels, it is possible that glucuronolactone contained in the ED might have contributed to the observed detrimental effects of energy drinks . More research is needed to corroborate these findings as well as to determine whether these acute changes would pose any long-term health risk.
Bichler and cohorts  investigated a combination of caffeine and taurine (two common ingredients in ED) in a double-blind study of college students. Subjects consumed either caffeine and taurine pills or a placebo and then completed a memory assessment while heart rate and blood pressure were monitored. The combination caused a significant decline in heart rate and an increase in mean arterial blood pressure. Steinke et al.  studied 15 healthy adults who abstained from caffeine for 48 hours prior to and during the study in addition to being fasted overnight. Baseline measurements of blood pressure and heart rate were measured. On day one of the study, each participant consumed 500 mL (2 cans) of an ED and measurements were repeated 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours later. Participants also drank 500 mL of the ED drink daily for the next 5 days. The experiment was then repeated after 7-days. The investigators found that maximum mean heart rate occurred at 4 hours with significant increases of 7.8% and 11.0% on days 1 and 7, respectively. Blood pressures were increased approximately 7% after acute ingestion of the ED on day 1 (significant increase) but no differences were seen on day 7. Finally, in a case report, Usman and coworkers  reported that a young boy presented with palpitations and high blood pressure after consumption of an ED containing carbohydrate (40 g), sodium citrate, taurine (124 mg), caffeine, inositol (17 mg), Panax ginseng (6.98 mg), and other nutrients. The tachycardia and hypertension returned to normal after discontinuation of ED consumption.
Individuals with certain medical conditions (e.g., metabolic syndrome or diabetes mellitus) should avoid consumption of high glycemic drinks and/or foods and therefore should not consume the high calorie versions of ED. It would be prudent for individuals with known cardiovascular disease to avoid altogether their use of ED and/or ES, or other products with known cardio-stimulant effects. While ED containing caffeine and other stimulants may have negative effects upon health and cardiac parameters in individuals with such pre-existing health conditions, the current evidence (although small) suggests that consumption of ED and ES are safe in healthy populations and similar to ingesting other foods and beverages containing caffeine. Finally, although it is estimated that only 1% of all dietary supplement adverse events are reported to FDA , given the number of servings of these products that are consumed daily, the rate of adverse events appears low in the population of consumers. Nevertheless, it is acknowledged that additional short- and long-term studies are needed to better determine any factors that increase the risk for adverse events. Additionally, since ED often contain several nutrients that contain caffeine and/or other stimulants, care should be taken to make sure that an excessive number of ED are not consumed within a short period of time.
Conclusions and recommendations
Although ED and ES contain a number of nutrients that are purported to affect mental and/or physical performance, the primary ergogenic nutrients in most ED and ES appear to be carbohydrate and/or caffeine.
The ergogenic value of caffeine on mental and physical performance has been well-established but the potential additive benefits of other nutrients contained in ED and ES remains to be determined.
Consuming ED 10-60 minutes before exercise can improve mental focus, alertness, anaerobic performance, and/or endurance performance.
Many ED and ES contain numerous ingredients; these products in particular merit further study to demonstrate their safety and potential effects on physical and mental performance.
There is some limited evidence that consumption of low-calorie ED during training and/or weight loss trials may provide ergogenic benefit and/or promote a small amount of additional fat loss. However, ingestion of higher calorie ED may promote weight gain if the energy intake from consumption of ED is not carefully considered as part of the total daily energy intake.
Athletes should consider the impact of ingesting high glycemic load carbohydrates on metabolic health, blood glucose and insulin levels, as well as the effects of caffeine and other stimulants on motor skill performance.
Children and adolescents should only consider use of ED or ES with parental approval after consideration of the amount of carbohydrate, caffeine, and other nutrients contained in the ED or ES and a thorough understanding of the potential side effects.
Indiscriminant use of ED or ES, especially if more than one serving per day is consumed, may lead to adverse events and harmful side effects.
Diabetics and individuals with pre-existing cardiovascular, metabolic, hepatorenal, and neurologic disease who are taking medications that may be affected by high glycemic load foods, caffeine, and/or other stimulants should avoid use of ED and/or ES unless approved by their physician.
- Froiland K, Koszewski W, Hingst J, Kopecky L: Nutritional supplement use among college athletes and their sources of information. Int J Sport Nutr Exerc Metab. 2004, 14: 104-120.PubMedGoogle Scholar
- Hoffman : Caffeine and Energy Drinks. Strength Cond J. 2010, 32: 15-20. 10.1519/SSC.0b013e3181bdafa0.View ArticleGoogle Scholar
- Hoffman JR, Faigenbaum AD, Ratamess NA, Ross R, Kang J, Tenenbaum G: Nutritional supplementation and anabolic steroid use in adolescents. Med Sci Sports Exerc. 2008, 40: 15-24.PubMedView ArticleGoogle Scholar
- Petroczi A, Naughton DP, Pearce G, Bailey R, Bloodworth A, McNamee M: Nutritional supplement use by elite young UK athletes: fallacies of advice regarding efficacy. J Int Soc Sports Nutr. 2008, 5: 22-10.1186/1550-2783-5-22.PubMed CentralPubMedView ArticleGoogle Scholar
- Wolk BJ, Ganetsky M, Babu KM: Toxicity of energy drinks. Curr Opin Pediatr. 2012, 24: 243-251. 10.1097/MOP.0b013e3283506827.PubMedView ArticleGoogle Scholar
- Kerksick C, Harvey T, Stout J, Campbell B, Wilborn C, Kreider R, Kalman D, Ziegenfuss T, Lopez H, Landis J, et al, et al.: International Society of Sports Nutrition position stand: nutrient timing. J Int Soc Sports Nutr. 2008, 5: 17-10.1186/1550-2783-5-17.PubMed CentralPubMedView ArticleGoogle Scholar
- Goldstein ER, Ziegenfuss T, Kalman D, Kreider R, Campbell B, Wilborn C, Taylor L, Willoughby D, Stout J, Graves BS, et al, et al.: International society of sports nutrition position stand: caffeine and performance. J Int Soc Sports Nutr. 2010, 7: 5-10.1186/1550-2783-7-5.PubMed CentralPubMedView ArticleGoogle Scholar
- Bonati M, Latini R, Galletti F, Young JF, Tognoni G, Garattini S: Caffeine disposition after oral doses. Clin Pharmacol Ther. 1982, 32: 98-106. 10.1038/clpt.1982.132.PubMedView ArticleGoogle Scholar
- Graham TE, Hibbert E, Sathasivam P: Metabolic and exercise endurance effects of coffee and caffeine ingestion. J Appl Physiol. 1998, 85: 883-889.PubMedGoogle Scholar
- McLellan TM, Bell DG: The impact of prior coffee consumption on the subsequent ergogenic effect of anhydrous caffeine. Int J Sport Nutr Exerc Metab. 2004, 14: 698-708.PubMedGoogle Scholar
- Kovacs EM, Stegen J, Brouns F: Effect of caffeinated drinks on substrate metabolism, caffeine excretion, and performance. J Appl Physiol. 1998, 85: 709-715.PubMedGoogle Scholar
- Oka H, Suzuki S, Suzuki H, Oda T: Increased urinary excretion of L-xylulose in patients with liver cirrhosis. Clin Chim Acta. 1976, 67: 131-136. 10.1016/0009-8981(76)90251-5.PubMedView ArticleGoogle Scholar
- Jeukendrup A, Brouns F, Wagenmakers AJ, Saris WH: Carbohydrate-electrolyte feedings improve 1 h time trial cycling performance. Int J Sports Med. 1997, 18: 125-129. 10.1055/s-2007-972607.PubMedView ArticleGoogle Scholar
- Jeukendrup AE: Carbohydrate intake during exercise and performance. Nutrition. 2004, 20: 669-677. 10.1016/j.nut.2004.04.017.PubMedView ArticleGoogle Scholar
- Coyle EF, Coggan AR, Hemmert MK, Ivy JL: Muscle glycogen utilization during prolonged strenuous exercise when fed carbohydrate. J Appl Physiol. 1986, 61: 165-172.PubMedGoogle Scholar
- Jeukendrup AE, Jentjens R: Oxidation of carbohydrate feedings during prolonged exercise: current thoughts, guidelines and directions for future research. Sports Med. 2000, 29: 407-424. 10.2165/00007256-200029060-00004.PubMedView ArticleGoogle Scholar
- Kreider RB, Wilborn CD, Taylor L, Campbell B, Almada AL, Collins R, Cooke M, Earnest CP, Greenwood M, Kalman DS, et al, et al.: ISSN exercise & sport nutrition review: research & recommendations. J Int Soc Sports Nutr. 2010, 7: 7-10.1186/1550-2783-7-7.PubMed CentralPubMedView ArticleGoogle Scholar
- Rodriguez NR, Di Marco NM, Langley S: American College of Sports Medicine position stand. Nutrition and athletic performance. Med Sci Sports Exerc. 2009, 41: 709-731. 10.1249/MSS.0b013e31890eb86.PubMedView ArticleGoogle Scholar
- Murray R, Bartoli W, Stofan J, Horn M, Eddy D: A comparison of the gastric emptying characteristics of selected sports drinks. Int J Sport Nutr. 1999, 9: 263-274.PubMedGoogle Scholar
- Maughan RJ, Leiper JB: Limitations to fluid replacement during exercise. Can J Appl Physiol. 1999, 24: 173-187. 10.1139/h99-015.PubMedView ArticleGoogle Scholar
- Franconi F, Loizzo A, Ghirlanda G, Seghieri G: Taurine supplementation and diabetes mellitus. Curr Opin Clin Nutr Metab Care. 2006, 9: 32-36. 10.1097/01.mco.0000196141.65362.46.PubMedView ArticleGoogle Scholar
- Dawson R, Biasetti M, Messina S, Dominy J: The cytoprotective role of taurine in exercise-induced muscle injury. Amino Acids. 2002, 22: 309-324. 10.1007/s007260200017.PubMedView ArticleGoogle Scholar
- Zhang M, Izumi I, Kagamimori S, Sokejima S, Yamagami T, Liu Z, Qi B: Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men. Amino Acids. 2004, 26: 203-207. 10.1007/s00726-003-0002-3.PubMedView ArticleGoogle Scholar
- Obrosova IG, Stevens MJ: Effect of dietary taurine supplementation on GSH and NAD(P)-redox status, lipid peroxidation, and energy metabolism in diabetic precataractous lens. Invest Ophthalmol Vis Sci. 1999, 40: 680-688.PubMedGoogle Scholar
- Bakker AJ, Berg HM: Effect of taurine on sarcoplasmic reticulum function and force in skinned fast-twitch skeletal muscle fibres of the rat. J Physiol. 2002, 538: 185-194. 10.1113/jphysiol.2001.012872.PubMed CentralPubMedView ArticleGoogle Scholar
- Bichler A, Swenson A, Harris MA: A combination of caffeine and taurine has no effect on short term memory but induces changes in heart rate and mean arterial blood pressure. Amino Acids. 2006, 31: 471-476. 10.1007/s00726-005-0302-x.PubMedView ArticleGoogle Scholar
- Galloway SD, Talanian JL, Shoveller AK, Heigenhauser GJ, Spriet LL: Seven days of oral taurine supplementation does not increase muscle taurine content or alter substrate metabolism during prolonged exercise in humans. J Appl Physiol. 2008, 105: 643-651. 10.1152/japplphysiol.90525.2008.PubMedView ArticleGoogle Scholar
- Matsuzaki Y, Miyazaki T, Miyakawa S, Bouscarel B, Ikegami T, Tanaka N: Decreased taurine concentration in skeletal muscles after exercise for various durations. Med Sci Sports Exerc. 2002, 34: 793-797. 10.1097/00005768-200205000-00011.PubMedView ArticleGoogle Scholar
- Rutherford JA, Spriet LL, Stellingwerff T: The effect of acute taurine ingestion on endurance performance and metabolism in well-trained cyclists. Int J Sport Nutr Exerc Metab. 2010, 20: 322-329.PubMedGoogle Scholar
- Ward RJ, Francaux M, Cuisinier C, Sturbois X, De Witte P: Changes in plasma taurine levels after different endurance events. Amino Acids. 1999, 16: 71-77. 10.1007/BF01318886.PubMedView ArticleGoogle Scholar
- Seidl R, Peyrl A, Nicham R, Hauser E: A taurine and caffeine-containing drink stimulates cognitive performance and well-being. Amino Acids. 2000, 19: 635-642. 10.1007/s007260070013.PubMedView ArticleGoogle Scholar
- Goodman CA, Horvath D, Stathis C, Mori T, Croft K, Murphy RM, Hayes A: Taurine supplementation increases skeletal muscle force production and protects muscle function during and after high-frequency in vitro stimulation. J Appl Physiol. 2009, 107: 144-154. 10.1152/japplphysiol.00040.2009.PubMed CentralPubMedView ArticleGoogle Scholar
- Wang FR, Dong XF, Tong JM, Zhang XM, Zhang Q, Wu YY: Effects of dietary taurine supplementation on growth performance and immune status in growing Japanese quail (Coturnix coturnix japonica). Poult Sci. 2009, 88: 1394-1398. 10.3382/ps.2009-00022.PubMedView ArticleGoogle Scholar
- Pierno S, De Luca A, Camerino C, Huxtable RJ, Camerino DC: Chronic administration of taurine to aged rats improves the electrical and contractile properties of skeletal muscle fibers. J Pharmacol Exp Ther. 1998, 286: 1183-1190.PubMedGoogle Scholar
- Warburton DM, Bersellini E, Sweeney E: An evaluation of a caffeinated taurine drink on mood, memory and information processing in healthy volunteers without caffeine abstinence. Psychopharmacology (Berl). 2001, 158: 322-328. 10.1007/s002130100884.View ArticleGoogle Scholar
- Jorm AF, Rodgers B, Christensen H: Use of medications to enhance memory in a large community sample of 60-64 year olds. Int Psychogeriatr. 2004, 16: 209-217. 10.1017/S1041610204000298.PubMedView ArticleGoogle Scholar
- Elsabagh S, Hartley DE, File SE: Limited cognitive benefits in Stage +2 postmenopausal women after 6 weeks of treatment with Ginkgo biloba. J Psychopharmacol. 2005, 19: 173-181. 10.1177/0269881105049038.PubMedView ArticleGoogle Scholar
- Walesiuk A, Trofimiuk E, Braszko JJ: Gingko biloba extract diminishes stress-induced memory deficits in rats. Pharmacol Rep. 2005, 57: 176-187.PubMedGoogle Scholar
- Stoll S, Scheuer K, Pohl O, Muller WE: Ginkgo biloba extract (EGb 761) independently improves changes in passive avoidance learning and brain membrane fluidity in the aging mouse. Pharmacopsychiatry. 1996, 29: 144-149.PubMedView ArticleGoogle Scholar
- Grevet EH, Tietzmann MR, Shansis FM, Hastenpflugl C, Santana LC, Forster L, Kapczinskil F, Izquierdo I: Behavioural effects of acute phenylalanine and tyrosine depletion in healthy male volunteers. J Psychopharmacol. 2002, 16: 51-55. 10.1177/026988110201600103.PubMedView ArticleGoogle Scholar
- Mahoney CR, Castellani J, Kramer FM, Young A, Lieberman HR: Tyrosine supplementation mitigates working memory decrements during cold exposure. Physiol Behav. 2007, 92: 575-582. 10.1016/j.physbeh.2007.05.003.PubMedView ArticleGoogle Scholar
- Chinevere TD, Sawyer RD, Creer AR, Conlee RK, Parcell AC: Effects of L-tyrosine and carbohydrate ingestion on endurance exercise performance. J Appl Physiol. 2002, 93: 1590-1597.PubMedView ArticleGoogle Scholar
- Deijen JB, Wientjes CJ, Vullinghs HF, Cloin PA, Langefeld JJ: Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Brain Res Bull. 1999, 48: 203-209. 10.1016/S0361-9230(98)00163-4.PubMedView ArticleGoogle Scholar
- Salter CA: Dietary tyrosine as an aid to stress resistance among troops. Mil Med. 1989, 154: 144-146.PubMedGoogle Scholar
- Smith ML, Hanley WB, Clarke JT, Klim P, Schoonheyt W, Austin V, Lehotay DC: Randomised controlled trial of tyrosine supplementation on neuropsychological performance in phenylketonuria. Arch Dis Child. 1998, 78: 116-121. 10.1136/adc.78.2.116.PubMed CentralPubMedView ArticleGoogle Scholar
- Magill RA, Waters WF, Bray GA, Volaufova J, Smith SR, Lieberman HR, McNevin N, Ryan DH: Effects of tyrosine, phentermine, caffeine D-amphetamine, and placebo on cognitive and motor performance deficits during sleep deprivation. Nutr Neurosci. 2003, 6: 237-246. 10.1080/1028415031000120552.PubMedView ArticleGoogle Scholar
- Waters WF, Magill RA, Bray GA, Volaufova J, Smith SR, Lieberman HR, Rood J, Hurry M, Anderson T, Ryan DH: A comparison of tyrosine against placebo, phentermine, caffeine, and D-amphetamine during sleep deprivation. Nutr Neurosci. 2003, 6: 221-235. 10.1080/1028415031000120543.PubMedView ArticleGoogle Scholar
- O’Brien C, Mahoney C, Tharion WJ, Sils IV, Castellani JW: Dietary tyrosine benefits cognitive and psychomotor performance during body cooling. Physiol Behav. 2007, 90: 301-307. 10.1016/j.physbeh.2006.09.027.PubMedView ArticleGoogle Scholar
- Wiesel FA, Edman G, Flyckt L, Eriksson A, Nyman H, Venizelos N, Bjerkenstedt L: Kinetics of tyrosine transport and cognitive functioning in schizophrenia. Schizophr Res. 2005, 74: 81-89. 10.1016/j.schres.2004.07.009.PubMedView ArticleGoogle Scholar
- Struder HK, Hollmann W, Platen P, Donike M, Gotzmann A, Weber K: Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans. Horm Metab Res. 1998, 30: 188-194. 10.1055/s-2007-978864.PubMedView ArticleGoogle Scholar
- Jager R, Purpura M, Kingsley M: Phospholipids and sports performance. J Int Soc Sports Nutr. 2007, 4: 5-10.1186/1550-2783-4-5.PubMed CentralPubMedView ArticleGoogle Scholar
- Warber JP, Patton JF, Tharion WJ, Zeisel SH, Mello RP, Kemnitz CP, Lieberman HR: The effects of choline supplementation on physical performance. Int J Sport Nutr Exerc Metab. 2000, 10: 170-181.PubMedGoogle Scholar
- Turner EH, Loftis JM, Blackwell AD: Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006, 109: 325-338. 10.1016/j.pharmthera.2005.06.004.PubMedView ArticleGoogle Scholar
- Chaouloff F, Laude D, Elghozi JL: Physical exercise: evidence for differential consequences of tryptophan on 5-HT synthesis and metabolism in central serotonergic cell bodies and terminals. J Neural Transm. 1989, 78: 121-130. 10.1007/BF01252498.PubMedView ArticleGoogle Scholar
- Leu-Semenescu S, Arnulf I, Decaix C, Moussa F, Clot F, Boniol C, Touitou Y, Levy R, Vidailhet M, Roze E: Sleep and rhythm consequences of a genetically induced loss of serotonin. Sleep. 2010, 33: 307-314.PubMed CentralPubMedGoogle Scholar
- Freeman MP, Helgason C, Hill RA: Selected integrative medicine treatments for depression: considerations for women. J Am Med Womens Assoc. 2004, 59: 216-224.PubMedGoogle Scholar
- Larzelere MM, Wiseman P: Anxiety, depression, and insomnia. Prim Care. 2002, 29: 339-360. 10.1016/S0095-4543(01)00003-3. viiPubMedView ArticleGoogle Scholar
- Thachil AF, Mohan R, Bhugra D: The evidence base of complementary and alternative therapies in depression. J Affect Disord. 2007, 97: 23-35. 10.1016/j.jad.2006.06.021.PubMedView ArticleGoogle Scholar
- Hayashi Y, Jacob-Vadakot S, Dugan EA, McBride S, Olexa R, Simansky K, Murray M, Shumsky JS: 5-HT precursor loading, but not 5-HT receptor agonists, increases motor function after spinal cord contusion in adult rats. Exp Neurol. 2010, 221: 68-78. 10.1016/j.expneurol.2009.10.003.PubMed CentralPubMedView ArticleGoogle Scholar
- Yamamoto T, Newsholme EA: Diminished central fatigue by inhibition of the L-system transporter for the uptake of tryptophan. Brain Res Bull. 2000, 52: 35-38. 10.1016/S0361-9230(99)00276-2.PubMedView ArticleGoogle Scholar
- Heckman MA, Weil J, Gonzalez de Mejia E: Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci. 2010, 75: R77-87. 10.1111/j.1750-3841.2010.01561.x.PubMedView ArticleGoogle Scholar
- Ivy JL, Kammer L, Ding Z, Wang B, Bernard JR, Liao YH, Hwang J: Improved cycling time-trial performance after ingestion of a caffeine energy drink. Int J Sport Nutr Exerc Metab. 2009, 19: 61-78.PubMedGoogle Scholar
- Goldstein E, Jacobs PL, Whitehurst M, Penhollow T, Antonio J: Caffeine enhances upper body strength in resistance-trained women. J Int Soc Sports Nutr. 2010, 7: 18-10.1186/1550-2783-7-18.PubMed CentralPubMedView ArticleGoogle Scholar
- Del Coso J, Muñoz-Fernández VE, Muñoz G, Fernández-Elías VE, Ortega JF, Hamouti N, Barbero JC, Muñoz-Guerra J: Effects of a Caffeine-Containing Energy Drink on Simulated Soccer Performance. PLoS One. 2012, 7: e31380-10.1371/journal.pone.0031380.PubMed CentralPubMedView ArticleGoogle Scholar
- Del Coso J, Salinero JJ, Gonzalez-Millan C, Abian-Vicen J, Perez-Gonzalez B: Dose response effects of a caffeine-containing energy drink on muscle performance: a repeated measures design. J Int Soc Sports Nutr. 2012, 9: 21-10.1186/1550-2783-9-21.PubMed CentralPubMedView ArticleGoogle Scholar
- Berube-Parent S, Pelletier C, Dore J, Tremblay A: Effects of encapsulated green tea and Guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men. Br J Nutr. 2005, 94: 432-436. 10.1079/BJN20051502.PubMedView ArticleGoogle Scholar
- Belza A, Toubro S, Astrup A: The effect of caffeine, green tea and tyrosine on thermogenesis and energy intake. Eur J Clin Nutr. 2009, 63: 57-64. 10.1038/sj.ejcn.1602901.PubMedView ArticleGoogle Scholar
- Eichenberger P, Colombani PC, Mettler S: Effects of 3-week consumption of green tea extracts on whole-body metabolism during cycling exercise in endurance-trained men. Int J Vitam Nutr Res. 2009, 79: 24-33. 10.1024/0300-98188.8.131.52.PubMedView ArticleGoogle Scholar
- Venables MC, Hulston CJ, Cox HR, Jeukendrup AE: Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans. Am J Clin Nutr. 2008, 87: 778-784.PubMedGoogle Scholar
- Eichenberger P, Mettler S, Arnold M, Colombani PC: No Effects of Three-week Consumption of a Green Tea Extract on Time Trial Performance in Endurance-trained Men. Int J Vitam Nutr Res. 2010, 80: 54-64. 10.1024/0300-9831/a000006.PubMedView ArticleGoogle Scholar
- Chen N, Bezzina R, Hinch E, Lewandowski PA, Cameron-Smith D, Mathai ML, Jois M, Sinclair AJ, Begg DP, Wark JD, et al, et al.: Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet. Nutr Res. 2009, 29: 784-793. 10.1016/j.nutres.2009.10.003.PubMedView ArticleGoogle Scholar
- Hursel R, Westerterp-Plantenga MS: Green tea catechin plus caffeine supplementation to a high-protein diet has no additional effect on body weight maintenance after weight loss. Am J Clin Nutr. 2009, 89: 822-830. 10.3945/ajcn.2008.27043.PubMedView ArticleGoogle Scholar
- Auvichayapat P, Prapochanung M, Tunkamnerdthai O, Sripanidkulchai BO, Auvichayapat N, Thinkhamrop B, Kunhasura S, Wongpratoom S, Sinawat S, Hongprapas P: Effectiveness of green tea on weight reduction in obese Thais: A randomized, controlled trial. Physiol Behav. 2008, 93: 486-491. 10.1016/j.physbeh.2007.10.009.PubMedView ArticleGoogle Scholar
- Diepvens K, Kovacs EM, Nijs IM, Vogels N, Westerterp-Plantenga MS: Effect of green tea on resting energy expenditure and substrate oxidation during weight loss in overweight females. Br J Nutr. 2005, 94: 1026-1034. 10.1079/BJN20051580.PubMedView ArticleGoogle Scholar
- Diepvens K, Westerterp KR, Westerterp-Plantenga MS: Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol. 2007, 292: R77-85.PubMedView ArticleGoogle Scholar
- Murase T, Haramizu S, Shimotoyodome A, Tokimitsu I, Hase T: Green tea extract improves running endurance in mice by stimulating lipid utilization during exercise. Am J Physiol Regul Integr Comp Physiol. 2006, 290: R1550-1556. 10.1152/ajpregu.00752.2005.PubMedView ArticleGoogle Scholar
- Fugh-Berman A, Myers A: Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood). 2004, 229: 698-704.Google Scholar
- Haller CA, Benowitz NL, Jacob P: Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med. 2005, 118: 998-1003. 10.1016/j.amjmed.2005.02.034.PubMedView ArticleGoogle Scholar
- Kim GS, Park HJ, Woo JH, Kim MK, Koh PO, Min W, Ko YG, Kim CH, Won CK, Cho JH: Citrus aurantium flavonoids inhibit adipogenesis through the Akt signaling pathway in 3T3-L1 cells. BMC Complement Altern Med. 2012, 12: 31-10.1186/1472-6882-12-31.PubMed CentralPubMedView ArticleGoogle Scholar
- Peixoto JS, Comar JF, Moreira CT, Soares AA, de Oliveira AL, Bracht A, Peralta RM: Effects of Citrus aurantium (bitter orange) fruit extracts and p-synephrine on metabolic fluxes in the rat liver. Molecules. 2012, 17: 5854-5869. 10.3390/molecules17055854.PubMedView ArticleGoogle Scholar
- Preuss HG, DiFerdinando D, Bagchi M, Bagchi D: Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: an overview. J Med. 2002, 33: 247-264.PubMedGoogle Scholar
- Stohs SJ, Preuss HG, Keith SC, Keith PL, Miller H, Kaats GR: Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med Sci. 2011, 8: 295-301.PubMed CentralPubMedView ArticleGoogle Scholar
- Pittler MH, Ernst E: Dietary supplements for body-weight reduction: a systematic review. Am J Clin Nutr. 2004, 79: 529-536.PubMedGoogle Scholar
- Pittler MH, Schmidt K, Ernst E: Adverse events of herbal food supplements for body weight reduction: systematic review. Obes Rev. 2005, 6: 93-111. 10.1111/j.1467-789X.2005.00169.x.PubMedView ArticleGoogle Scholar
- Kang YR, Lee HY, Kim JH, Moon DI, Seo MY, Park SH, Choi KH, Kim CR, Kim SH, Oh JH, et al, et al.: Anti-obesity and anti-diabetic effects of Yerba Mate (Ilex paraguariensis) in C57BL/6J mice fed a high-fat diet. Lab Anim Res. 2012, 28: 23-29. 10.5625/lar.2012.28.1.23.PubMed CentralPubMedView ArticleGoogle Scholar
- Riley AJ: Yohimbine in the treatment of erectile disorder. Br J Clin Pract. 1994, 48: 133-136.PubMedGoogle Scholar
- Gupta RS, Sharma R, Sharma A, Bhatnager AK, Dobhal MP, Joshi YC, Sharma MC: Effect of Alstonia scholaris bark extract on testicular function of Wistar rats. Asian J Androl. 2002, 4: 175-178.PubMedGoogle Scholar
- Porst H: The future of erectile dysfunction (ED). Arch Esp Urol. 2010, 63: 740-747.PubMedGoogle Scholar
- Kucio C, Jonderko K, Piskorska D: Does yohimbine act as a slimming drug?. Isr J Med Sci. 1991, 27: 550-556.PubMedGoogle Scholar
- Sax L: Yohimbine does not affect fat distribution in men. Int J Obes. 1991, 15: 561-565.PubMedGoogle Scholar
- deMarcaida JA, Schwid SR, White WB, Blindauer K, Fahn S, Kieburtz K, Stern M, Shoulson I: Effects of tyramine administration in Parkinson’s disease patients treated with selective MAO-B inhibitor rasagiline. Mov Disord. 2006, 21: 1716-1721. 10.1002/mds.21048.PubMedView ArticleGoogle Scholar
- Conlay LA, Maher TJ, Wurtman RJ: Tyrosine’s pressor effect in hypotensive rats is not mediated by tyramine. Life Sci. 1984, 35: 1207-1212. 10.1016/0024-3205(84)90192-9.PubMedView ArticleGoogle Scholar
- Edwards DJ: Possible role of octopamine and tyramine in the antihypertensive and antidepressant effects of tyrosine. Life Sci. 1982, 30: 1427-1434. 10.1016/0024-3205(82)90556-2.PubMedView ArticleGoogle Scholar
- McDaniel MA, Maier SF, Einstein GO: “Brain-specific” nutrients: a memory cure?. Nutrition. 2003, 19: 957-975. 10.1016/S0899-9007(03)00024-8.PubMedView ArticleGoogle Scholar
- Polich J, Gloria R: Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory. Hum Psychopharmacol. 2001, 16: 409-416. 10.1002/hup.308.PubMedView ArticleGoogle Scholar
- Bahrke MS, Morgan WP, Stegner A: Is ginseng an ergogenic aid?. Int J Sport Nutr Exerc Metab. 2009, 19: 298-322.PubMedGoogle Scholar
- Engels HJ, Fahlman MM, Wirth JC: Effects of ginseng on secretory IgA, performance, and recovery from interval exercise. Med Sci Sports Exerc. 2003, 35: 690-696. 10.1249/01.MSS.0000058363.23986.D2.PubMedView ArticleGoogle Scholar
- Goulet ED, Dionne IJ: Assessment of the effects of eleutherococcus senticosus on endurance performance. Int J Sport Nutr Exerc Metab. 2005, 15: 75-83.PubMedGoogle Scholar
- Hsu CC, Ho MC, Lin LC, Su B, Hsu MC: American ginseng supplementation attenuates creatine kinase level induced by submaximal exercise in human beings. World J Gastroenterol. 2005, 11: 5327-5331.PubMed CentralPubMedView ArticleGoogle Scholar
- Hwang HJ, Kwak YS, Yoon GA, Kang MH, Park JH, Lee BK, Kim SJ, Um SY, Kim YM: Combined effects of swim training and ginseng supplementation on exercise performance time, ROS, lymphocyte proliferation, and DNA damage following exhaustive exercise stress. Int J Vitam Nutr Res. 2007, 77: 289-296. 10.1024/0300-98184.108.40.2069.PubMedView ArticleGoogle Scholar
- Kulaputana O, Thanakomsirichot S, Anomasiri W: Ginseng supplementation does not change lactate threshold and physical performances in physically active Thai men. J Med Assoc Thai. 2007, 90: 1172-1179.PubMedGoogle Scholar
- Liang MT, Podolka TD, Chuang WJ: Panax notoginseng supplementation enhances physical performance during endurance exercise. J Strength Cond Res. 2005, 19: 108-114. 10.1519/00124278-200502000-00019.PubMedView ArticleGoogle Scholar
- Reay JL, Scholey AB, Milne A, Fenwick J, Kennedy DO: Panax ginseng has no effect on indices of glucose regulation following acute or chronic ingestion in healthy volunteers. Br J Nutr. 2009, 101: 1673-1678. 10.1017/S0007114508123418.PubMedView ArticleGoogle Scholar
- Engels HJ, Kolokouri I, Cieslak TJ, Wirth JC: Effects of ginseng supplementation on supramaximal exercise performance and short-term recovery. J Strength Cond Res. 2001, 15: 290-295.PubMedGoogle Scholar
- Eschbach LF, Webster MJ, Boyd JC, McArthur PD, Evetovich TK: The effect of siberian ginseng (Eleutherococcus senticosus) on substrate utilization and performance. Int J Sport Nutr Exerc Metab. 2000, 10: 444-451.PubMedGoogle Scholar
- Ferrando A, Vila L, Voces JA, Cabral AC, Alvarez AI, Prieto JG: Effects of ginseng extract on various haematological parameters during aerobic exercise in the rat. Planta Med. 1999, 65: 288-290. 10.1055/s-2006-960783.PubMedView ArticleGoogle Scholar
- Ferrando A, Vila L, Voces JA, Cabral AC, Alvarez AI, Prieto JG: Effects of a standardized Panax ginseng extract on the skeletal muscle of the rat: a comparative study in animals at rest and under exercise. Planta Med. 1999, 65: 239-244. 10.1055/s-1999-14081.PubMedView ArticleGoogle Scholar
- Ziemba AW, Chmura J, Kaciuba-Uscilko H, Nazar K, Wisnik P, Gawronski W: Ginseng treatment improves psychomotor performance at rest and during graded exercise in young athletes. Int J Sport Nutr. 1999, 9: 371-377.PubMedGoogle Scholar
- Allen JD, McLung J, Nelson AG, Welsch M: Ginseng supplementation does not enhance healthy young adults’ peak aerobic exercise performance. J Am Coll Nutr. 1998, 17: 462-466.PubMedView ArticleGoogle Scholar
- Engels HJ, Wirth JC: No ergogenic effects of ginseng (Panax ginseng C.A. Meyer) during graded maximal aerobic exercise. J Am Diet Assoc. 1997, 97: 1110-1115. 10.1016/S0002-8223(97)00271-X.PubMedView ArticleGoogle Scholar
- Pieralisi G, Ripari P, Vecchiet L: Effects of a standardized ginseng extract combined with dimethylaminoethanol bitartrate, vitamins, minerals, and trace elements on physical performance during exercise. Clin Ther. 1991, 13: 373-382.PubMedGoogle Scholar
- Karlic H, Lohninger A: Supplementation of L-carnitine in athletes: does it make sense?. Nutrition. 2004, 20: 709-715. 10.1016/j.nut.2004.04.003.PubMedView ArticleGoogle Scholar
- Pauly DF, Pepine CJ: D-Ribose as a supplement for cardiac energy metabolism. J Cardiovasc Pharmacol Ther. 2000, 5: 249-258. 10.1054/JCPT.2000.18011.PubMedView ArticleGoogle Scholar
- Kerksick C, Rasmussen C, Bowden R, Leutholtz B, Harvey T, Earnest C, Greenwood M, Almada A, Kreider R: Effects of ribose supplementation prior to and during intense exercise on anaerobic capacity and metabolic markers. Int J Sport Nutr Exerc Metab. 2005, 15: 653-664.PubMedGoogle Scholar
- Kreider RB, Melton C, Greenwood M, Rasmussen C, Lundberg J, Earnest C, Almada A: Effects of oral D-ribose supplementation on anaerobic capacity and selected metabolic markers in healthy males. Int J Sport Nutr Exerc Metab. 2003, 13: 76-86.PubMedGoogle Scholar
- Berardi JM, Ziegenfuss TN: Effects of ribose supplementation on repeated sprint performance in men. J Strength Cond Res. 2003, 17: 47-52.PubMedGoogle Scholar
- Dunne L, Worley S, Macknin M: Ribose versus dextrose supplementation, association with rowing performance: a double-blind study. Clin J Sport Med. 2006, 16: 68-71. 10.1097/01.jsm.0000180022.44889.94.PubMedView ArticleGoogle Scholar
- Eijnde BO, Van Leemputte M, Brouns F, Van Der Vusse GJ, Labarque V, Ramaekers M, Van Schuylenberg R, Verbessem P, Wijnen H, Hespel P: No effects of oral ribose supplementation on repeated maximal exercise and de novo ATP resynthesis. J Appl Physiol. 2001, 91: 2275-2281.PubMedGoogle Scholar
- Hellsten Y, Skadhauge L, Bangsbo J: Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. Am J Physiol Regul Integr Comp Physiol. 2004, 286: R182-188.PubMedView ArticleGoogle Scholar
- Harris RC, Sale C: Beta-alanine supplementation in high-intensity exercise. Med Sport Sci. 2013, 59: 1-17.View ArticleGoogle Scholar
- Hoffman JR, Emerson NS, Stout JR: beta-Alanine supplementation. Curr Sports Med Rep. 2012, 11: 189-195.PubMedView ArticleGoogle Scholar
- Harris RC, Wise JA, Price KA, Kim HJ, Kim CK, Sale C: Determinants of muscle carnosine content. Amino Acids. 2012, 43: 5-12. 10.1007/s00726-012-1233-y.PubMed CentralPubMedView ArticleGoogle Scholar
- Culbertson JY, Kreider RB, Greenwood M, Cooke M: Effects of beta-alanine on muscle carnosine and exercise performance: a review of the current literature. Nutrients. 2010, 2: 75-98. 10.3390/nu2010075.PubMed CentralPubMedView ArticleGoogle Scholar
- Hobson RM, Saunders B, Ball G, Harris RC, Sale C: Effects of beta-alanine supplementation on exercise performance: a meta-analysis. Amino Acids. 2012, 43: 25-37. 10.1007/s00726-011-1200-z.PubMed CentralPubMedView ArticleGoogle Scholar
- Smith-Ryan AE, Fukuda DH, Stout JR, Kendall KL: High-velocity intermittent running: effects of beta-alanine supplementation. J Strength Cond Res. 2012, 26: 2798-2805. 10.1519/JSC.0b013e318267922b.PubMedView ArticleGoogle Scholar
- Saunders B, Sunderland C, Harris RC, Sale C: beta-alanine supplementation improves YoYo intermittent recovery test performance. J Int Soc Sports Nutr. 2012, 9: 39-10.1186/1550-2783-9-39.PubMed CentralPubMedView ArticleGoogle Scholar
- Jagim AR, Wright GA, Brice AG, Doberstein ST: Effects of beta-alanine supplementation on sprint endurance. J Strength Cond Res. 2012Google Scholar
- Sale C, Saunders B, Hudson S, Wise JA, Harris RC, Sunderland CD: Effect of beta-alanine plus sodium bicarbonate on high-intensity cycling capacity. Med Sci Sports Exerc. 2011, 43: 1972-1978.PubMedGoogle Scholar
- Kern BD, Robinson TL: Effects of beta-alanine supplementation on performance and body composition in collegiate wrestlers and football players. J Strength Cond Res. 2011, 25: 1804-1815. 10.1519/JSC.0b013e3181e741cf.PubMedView ArticleGoogle Scholar
- Walter AA, Smith AE, Kendall KL, Stout JR, Cramer JT: Six weeks of high-intensity interval training with and without beta-alanine supplementation for improving cardiovascular fitness in women. J Strength Cond Res. 2010, 24: 1199-1207. 10.1519/JSC.0b013e3181d82f8b.PubMedView ArticleGoogle Scholar
- Sweeney KM, Wright GA, Glenn Brice A, Doberstein ST: The effect of beta-alanine supplementation on power performance during repeated sprint activity. J Strength Cond Res. 2010, 24: 79-87. 10.1519/JSC.0b013e3181c63bd5.PubMedView ArticleGoogle Scholar
- Sale C, Saunders B, Harris RC: Effect of beta-alanine supplementation on muscle carnosine concentrations and exercise performance. Amino Acids. 2010, 39: 321-333. 10.1007/s00726-009-0443-4.PubMedView ArticleGoogle Scholar
- Van Thienen R, Van Proeyen K, Vanden Eynde B, Puype J, Lefere T, Hespel P: Beta-alanine improves sprint performance in endurance cycling. Med Sci Sports Exerc. 2009, 41: 898-903. 10.1249/MSS.0b013e31818db708.PubMedView ArticleGoogle Scholar
- Smith AE, Moon JR, Kendall KL, Graef JL, Lockwood CM, Walter AA, Beck TW, Cramer JT, Stout JR: The effects of beta-alanine supplementation and high-intensity interval training on neuromuscular fatigue and muscle function. Eur J Appl Physiol. 2009, 105: 357-363. 10.1007/s00421-008-0911-7.PubMedView ArticleGoogle Scholar
- Kendrick IP, Kim HJ, Harris RC, Kim CK, Dang VH, Lam TQ, Bui TT, Wise JA: The effect of 4 weeks beta-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres. Eur J Appl Physiol. 2009, 106: 131-138. 10.1007/s00421-009-0998-5.PubMedView ArticleGoogle Scholar
- Stout JR, Graves BS, Smith AE, Hartman MJ, Cramer JT, Beck TW, Harris RC: The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55-92 Years): a double-blind randomized study. J Int Soc Sports Nutr. 2008, 5: 21-10.1186/1550-2783-5-21.PubMed CentralPubMedView ArticleGoogle Scholar
- Hoffman JR, Ratamess NA, Faigenbaum AD, Ross R, Kang J, Stout JR, Wise JA: Short-duration beta-alanine supplementation increases training volume and reduces subjective feelings of fatigue in college football players. Nutr Res. 2008, 28: 31-35. 10.1016/j.nutres.2007.11.004.PubMedView ArticleGoogle Scholar
- Zoeller RF, Stout JR, O’Kroy JA, Torok DJ, Mielke M: Effects of 28 days of beta-alanine and creatine monohydrate supplementation on aerobic power, ventilatory and lactate thresholds, and time to exhaustion. Amino Acids. 2007, 33: 505-510. 10.1007/s00726-006-0399-6.PubMedView ArticleGoogle Scholar
- Einat H, Belmaker RH: The effects of inositol treatment in animal models of psychiatric disorders. J Affect Disord. 2001, 62: 113-121. 10.1016/S0165-0327(00)00355-4.PubMedView ArticleGoogle Scholar
- Sureda A, Pons A: Arginine and citrulline supplementation in sports and exercise: ergogenic nutrients?. Med Sport Sci. 2013, 59: 18-28.View ArticleGoogle Scholar
- Bescos R, Sureda A, Tur JA, Pons A: The effect of nitric-oxide-related supplements on human performance. Sports Med. 2012, 42: 99-117. 10.2165/11596860-000000000-00000.PubMedView ArticleGoogle Scholar
- Bendahan D, Mattei JP, Ghattas B, Confort-Gouny S, Le Guern ME, Cozzone PJ: Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. 2002, 36: 282-289. 10.1136/bjsm.36.4.282.PubMed CentralPubMedView ArticleGoogle Scholar
- Figueroa A, Trivino JA, Sanchez-Gonzalez MA, Vicil F: Oral L-citrulline supplementation attenuates blood pressure response to cold pressor test in young men. Am J Hypertens. 2010, 23: 12-16. 10.1038/ajh.2009.195.PubMedView ArticleGoogle Scholar
- Hickner RC, Tanner CJ, Evans CA, Clark PD, Haddock A, Fortune C, Geddis H, Waugh W, McCammon M: L-citrulline reduces time to exhaustion and insulin response to a graded exercise test. Med Sci Sports Exerc. 2006, 38: 660-666. 10.1249/01.mss.0000210197.02576.da.PubMedView ArticleGoogle Scholar
- Meneguello MO, Mendonca JR, Lancha AH, Costa Rosa LF: Effect of arginine, ornithine and citrulline supplementation upon performance and metabolism of trained rats. Cell Biochem Funct. 2003, 21: 85-91. 10.1002/cbf.1000.PubMedView ArticleGoogle Scholar
- Nagaya N, Uematsu M, Oya H, Sato N, Sakamaki F, Kyotani S, Ueno K, Nakanishi N, Yamagishi M, Miyatake K: Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med. 2001, 163: 887-891.PubMedView ArticleGoogle Scholar
- Perez-Guisado J, Jakeman PM: Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010, 24: 1215-1222. 10.1519/JSC.0b013e3181cb28e0.PubMedView ArticleGoogle Scholar
- Sureda A, Cordova A, Ferrer MD, Perez G, Tur JA, Pons A: L-citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol. 2010, 110: 341-351. 10.1007/s00421-010-1509-4.PubMedView ArticleGoogle Scholar
- Takeda K, Machida M, Kohara A, Omi N, Takemasa T: Effects of citrulline supplementation on fatigue and exercise performance in mice. J Nutr Sci Vitaminol (Tokyo). 2011, 57: 246-250. 10.3177/jnsv.57.246.View ArticleGoogle Scholar
- Kressler J, Millard-Stafford M, Warren GL: Quercetin and endurance exercise capacity: a systematic review and meta-analysis. Med Sci Sports Exerc. 2011, 43: 2396-2404. 10.1249/MSS.0b013e31822495a7.PubMedView ArticleGoogle Scholar
- Wu J, Gao W, Wei J, Yang J, Pu L, Guo C: Quercetin alters energy metabolism in swimming mice. Appl Physiol Nutr Metab. 2012, 37: 912-922. 10.1139/h2012-064.PubMedView ArticleGoogle Scholar
- Sharp MA, Hendrickson NR, Staab JS, McClung HL, Nindl BC, Michniak-Kohn BB: Effects of short-term quercetin supplementation on soldier performance. J Strength Cond Res. 2012, 26 (Suppl 2): S53-60.PubMedView ArticleGoogle Scholar
- O’Fallon KS, Kaushik D, Michniak-Kohn B, Dunne CP, Zambraski EJ, Clarkson PM: Quercetin does not attenuate changes in markers of muscle function or inflammation after eccentric exercise. Int J Sport Nutr Exerc Metab. 2012Google Scholar
- Konrad M, Nieman DC, Henson DA, Kennerly KM, Jin F, Wallner-Liebmann SJ: The acute effect of ingesting a quercetin-based supplement on exercise-induced inflammation and immune changes in runners. Int J Sport Nutr Exerc Metab. 2011, 21: 338-346.PubMedGoogle Scholar
- Abbey EL, Rankin JW: Effect of quercetin supplementation on repeated-sprint performance, xanthine oxidase activity, and inflammation. Int J Sport Nutr Exerc Metab. 2011, 21: 91-96.PubMedGoogle Scholar
- Nieman DC, Williams AS, Shanely RA, Jin F, McAnulty SR, Triplett NT, Austin MD, Henson DA: Quercetin’s influence on exercise performance and muscle mitochondrial biogenesis. Med Sci Sports Exerc. 2010, 42: 338-345.PubMedView ArticleGoogle Scholar
- Ganio MS, Armstrong LE, Johnson EC, Klau JF, Ballard KD, Michniak-Kohn B, Kaushik D, Maresh CM: Effect of quercetin supplementation on maximal oxygen uptake in men and women. J Sports Sci. 2010, 28: 201-208. 10.1080/02640410903428558.PubMedView ArticleGoogle Scholar
- Bigelman KA, Fan EH, Chapman DP, Freese EC, Trilk JL, Cureton KJ: Effects of six weeks of quercetin supplementation on physical performance in ROTC cadets. Mil Med. 2010, 175: 791-798.PubMedView ArticleGoogle Scholar
- Utter AC, Nieman DC, Kang J, Dumke CL, Quindry JC, McAnulty SR, McAnulty LS: Quercetin does not affect rating of perceived exertion in athletes during the Western States endurance run. Res Sports Med. 2009, 17: 71-83.PubMedView ArticleGoogle Scholar
- Dumke CL, Nieman DC, Utter AC, Rigby MD, Quindry JC, Triplett NT, McAnulty SR, McAnulty LS: Quercetin’s effect on cycling efficiency and substrate utilization. Appl Physiol Nutr Metab. 2009, 34: 993-1000. 10.1139/H09-099.PubMedView ArticleGoogle Scholar
- Davis JM, Murphy EA, Carmichael MD, Davis B: Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol. 2009, 296: R1071-1077. 10.1152/ajpregu.90925.2008.PubMedView ArticleGoogle Scholar
- Cureton KJ, Tomporowski PD, Singhal A, Pasley JD, Bigelman KA, Lambourne K, Trilk JL, McCully KK, Arnaud MJ, Zhao Q: Dietary quercetin supplementation is not ergogenic in untrained men. J Appl Physiol. 2009, 107: 1095-1104. 10.1152/japplphysiol.00234.2009.PubMedView ArticleGoogle Scholar
- Quindry JC, McAnulty SR, Hudson MB, Hosick P, Dumke C, McAnulty LS, Henson D, Morrow JD, Nieman D: Oral quercetin supplementation and blood oxidative capacity in response to ultramarathon competition. Int J Sport Nutr Exerc Metab. 2008, 18: 601-616.PubMedGoogle Scholar
- Henson D, Nieman D, Davis JM, Dumke C, Gross S, Murphy A, Carmichael M, Jenkins DP, Quindry J, McAnulty S, et al, et al.: Post-160-km race illness rates and decreases in granulocyte respiratory burst and salivary IgA output are not countered by quercetin ingestion. Int J Sports Med. 2008, 29: 856-863. 10.1055/s-2007-989424.PubMedView ArticleGoogle Scholar
- Nieman DC, Henson DA, Gross SJ, Jenkins DP, Davis JM, Murphy EA, Carmichael MD, Dumke CL, Utter AC, McAnulty SR, et al, et al.: Quercetin reduces illness but not immune perturbations after intensive exercise. Med Sci Sports Exerc. 2007, 39: 1561-1569. 10.1249/mss.0b013e318076b566.PubMedView ArticleGoogle Scholar
- Nieman DC, Henson DA, Davis JM, Angela Murphy E, Jenkins DP, Gross SJ, Carmichael MD, Quindry JC, Dumke CL, Utter AC, et al, et al.: Quercetin’s influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA. J Appl Physiol. 2007, 103: 1728-1735. 10.1152/japplphysiol.00707.2007.PubMedView ArticleGoogle Scholar
- Campbell B, Downing J, Kilpatrick M, La Bounty P, Elkins A, Williams S, dos Santos MG: The effects of a commercially available energy drink on resistance training and performance. Med Sci Sports Exerc. 2010, 42: S315-Google Scholar
- Forbes SC, Candow DG, Little JP, Magnus C, Chilibeck PD: Effect of Red Bull energy drink on repeated Wingate cycle performance and bench-press muscle endurance. Int J Sport Nutr Exerc Metab. 2007, 17: 433-444.PubMedGoogle Scholar
- Hoffman JR, Kang J, Ratamess NA, Hoffman MW, Tranchina CP, Faigenbaum AD: Examination of a pre-exercise, high energy supplement on exercise performance. J Int Soc Sports Nutr. 2009, 6: 2-10.1186/1550-2783-6-2.PubMed CentralPubMedView ArticleGoogle Scholar
- Candow DG, Kleisinger AK, Grenier S, Dorsch KD: Effect of sugar-free Red Bull energy drink on high-intensity run time-to-exhaustion in young adults. J Strength Cond Res. 2009, 23: 1271-1275. 10.1519/JSC.0b013e3181a026c2.PubMedView ArticleGoogle Scholar
- Cureton KJ, Warren GL, Millard-Stafford ML, Wingo JE, Trilk J, Buyckx M: Caffeinated sports drink: ergogenic effects and possible mechanisms. Int J Sport Nutr Exerc Metab. 2007, 17: 35-55.PubMedGoogle Scholar
- Alford C, Cox H, Wescott R: The effects of red bull energy drink on human performance and mood. Amino Acids. 2001, 21: 139-150. 10.1007/s007260170021.PubMedView ArticleGoogle Scholar
- Campbell B, Kilpatrick M, Wilborn C, La Bounty P, Parker B, Gomez B, Elkins A, Williams S, Dos Santos JA: A commercially available energy drink does not improve peak power on multiple 20-second Wingate tests. J Int Soc Sports Nutr. 2010, 7: P10-10.1186/1550-2783-7-S1-P10.PubMed CentralView ArticleGoogle Scholar
- Gonzalez AM, Walsh AL, Ratamess NA, Kang J, Hoffman JR: Effect of a pre-workout energy supplement on acute multi-joint resistance exercise. J Sports Sci Med. 2011, 10: 261-266.PubMed CentralPubMedGoogle Scholar
- Astorino TA, Matera AJ, Basinger J, Evans M, Schurman T, Marquez R: Effects of red bull energy drink on repeated sprint performance in women athletes. Amino Acids. 2012, 42: 1803-1808. 10.1007/s00726-011-0900-8.PubMedView ArticleGoogle Scholar
- Haff GG, Koch AJ, Potteiger JA, Kuphal KE, Magee LM, Green SB, Jakicic JJ: Carbohydrate supplementation attenuates muscle glycogen loss during acute bouts of resistance exercise. Int J Sport Nutr Exerc Metab. 2000, 10: 326-339.PubMedGoogle Scholar
- Kulik JR, Touchberry CD, Kawamori N, Blumert PA, Crum AJ, Haff GG: Supplemental carbohydrate ingestion does not improve performance of high-intensity resistance exercise. J Strength Cond Res. 2008, 22: 1101-1107. 10.1519/JSC.0b013e31816d679b.PubMedView ArticleGoogle Scholar
- Lambert CP, Flynn MG, Boone JB, Michaud TJ, Rodriguez-Zayas J: Effects of carbohydrate feeding on multiple bout resistance exercised. J Appl Sport Sci Res. 1991, 5: 192-197.Google Scholar
- Walsh AL, Gonzalez AM, Ratamess NA, Kang J, Hoffman JR: Improved time to exhaustion following ingestion of the energy drink Amino Impact. J Int Soc Sports Nutr. 2010, 7: 14-10.1186/1550-2783-7-14.PubMed CentralPubMedView ArticleGoogle Scholar
- Currell K, Jeukendrup AE: Validity, reliability and sensitivity of measures of sporting performance. Sports Med. 2008, 38: 297-316. 10.2165/00007256-200838040-00003.PubMedView ArticleGoogle Scholar
- Laursen PB, Francis GT, Abbiss CR, Newton MJ, Nosaka K: Reliability of time-to-exhaustion versus time-trial running tests in runners. Med Sci Sports Exerc. 2007, 39: 1374-1379. 10.1249/mss.0b013e31806010f5.PubMedView ArticleGoogle Scholar
- Scholey AB, Kennedy DO: Cognitive and physiological effects of an “energy drink”: an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions. Psychopharmacology (Berl). 2004, 176: 320-330. 10.1007/s00213-004-1935-2.View ArticleGoogle Scholar
- Smit HJ, Cotton JR, Hughes SC, Rogers PJ: Mood and cognitive performance effects of “energy” drink constituents: caffeine, glucose and carbonation. Nutr Neurosci. 2004, 7: 127-139. 10.1080/10284150400003041.PubMedView ArticleGoogle Scholar
- Rao A, Hu H, Nobre AC: The effects of combined caffeine and glucose drinks on attention in the human brain. Nutr Neurosci. 2005, 8: 141-153. 10.1080/10284150500096994.PubMedView ArticleGoogle Scholar
- Howard MA, Marczinski CA: Acute effects of a glucose energy drink on behavioral control. Exp Clin Psychopharmacol. 2010, 18: 553-561.PubMedView ArticleGoogle Scholar
- Pettitt RW, Niemeyer JD, Sexton PJ, Lipetzky A, Murray SR: Do the non-caffeine ingredients of energy drinks affect metabolic responses to heavy exercise?. J Strength Cond Res. 2012, [Epub ahead of print].Google Scholar
- Bloomer RJ, Fisher-Wellman KH, Hammond KG, Schilling BK, Weber AA, Cole BJ: Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men. J Int Soc Sports Nutr. 2009, 6: 4-10.1186/1550-2783-6-4.PubMed CentralPubMedView ArticleGoogle Scholar
- Dulloo AG, Geissler CA, Horton T, Collins A, Miller DS: Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. Am J Clin Nutr. 1989, 49: 44-50.PubMedGoogle Scholar
- Jitomir J, Nassar E, Culbertson J, Moreillon J, Buford T, Hudson G, Cooke M, Kreider R, Willoughby DS: The acute effects of the thermogenic supplement Meltdown on energy expenditure, fat oxidation, and hemodynamic responses in young, healthy males. J Int Soc Sports Nutr. 2008, 5: 23-10.1186/1550-2783-5-23.PubMed CentralPubMedView ArticleGoogle Scholar
- Mendel RW, Hofheins JE: Metabolic responses to the acute ingestion of two commercially available carbonated beverages: a pilot study. J Int Soc Sports Nutr. 2007, 4: 7-10.1186/1550-2783-4-7.PubMed CentralPubMedView ArticleGoogle Scholar
- Rudelle S, Ferruzzi MG, Cristiani I, Moulin J, Mace K, Acheson KJ, Tappy L: Effect of a thermogenic beverage on 24-hour energy metabolism in humans. Obesity (Silver Spring). 2007, 15: 349-355. 10.1038/oby.2007.529.View ArticleGoogle Scholar
- Taylor LW, Wilborn CD, Harvey T, Wismann J, Willoughby DS: Acute effects of ingesting Java Fittrade mark energy extreme functional coffee on resting energy expenditure and hemodynamic responses in male and female coffee drinkers. J Int Soc Sports Nutr. 2007, 4: 10-10.1186/1550-2783-4-10.PubMed CentralPubMedView ArticleGoogle Scholar
- Wilborn C, Taylor L, Poole C, Bushey B, Williams L, Foster C, Campbell B: Effects of ingesting a commercial thermogenic product on hemodynamic function and energy expenditure at rest in males and females. Appl Physiol Nutr Metab. 2009, 34: 1073-1078. 10.1139/H09-113.PubMedView ArticleGoogle Scholar
- Roberts MD, Dalbo VJ, Hassell SE, Stout JR, Kerksick CM: Efficacy and safety of a popular thermogenic drink after 28 days of ingestion. J Int Soc Sports Nutr. 2008, 5: 19-10.1186/1550-2783-5-19.PubMed CentralPubMedView ArticleGoogle Scholar
- Dalbo VJ, Roberts MD, Stout JR, Kerksick CM: Acute effects of ingesting a commercial thermogenic drink on changes in energy expenditure and markers of lipolysis. J Int Soc Sports Nutr. 2008, 5: 6-10.1186/1550-2783-5-6.PubMed CentralPubMedView ArticleGoogle Scholar
- Dalbo VJ, Roberts MD, Stout JR, Kerksick CM: Effect of gender on the metabolic impact of a commercially available thermogenic drink. J Strength Cond Res. 2010, 24: 1633-1642. 10.1519/JSC.0b013e3181db9bbd.PubMedView ArticleGoogle Scholar
- Rashti SL, Ratamess NA, Kang J, Faigenbaum AD, Chilakos A, Hoffman JR: Thermogenic effect of meltdown RTD energy drink in young healthy women: a double blind, cross-over design study. Lipids Health Dis. 2009, 8: 57-10.1186/1476-511X-8-57.PubMed CentralPubMedView ArticleGoogle Scholar
- Bloomer RJ, Canale RE, Blankenship MM, Hammond KG, Fisher-Wellman KH, Schilling BK: Effect of the dietary supplement Meltdown on catecholamine secretion, markers of lipolysis, and metabolic rate in men and women: a randomized, placebo controlled, cross-over study. Lipids Health Dis. 2009, 8: 32-10.1186/1476-511X-8-32.PubMed CentralPubMedView ArticleGoogle Scholar
- Stout J, Moon J, Tobkin S, Lockwood C, Smith A, Graef J, Kendall K, Beck T, Cramer J: Pre-workout consumption of Celsius(R) enhances the benefits of chronic exercise on body composition and cardiorespiratory fitness. J Int Soc Sports Nutr. 2008, 5: P8-10.1186/1550-2783-5-S1-P8.PubMed CentralView ArticleGoogle Scholar
- Higgins JP, Tuttle TD, Higgins CL: Energy beverages: content and safety. Mayo Clin Proc. 2010, 85: 1033-1041. 10.4065/mcp.2010.0381.PubMed CentralPubMedView ArticleGoogle Scholar
- Sepkowitz KA: Energy drinks and caffeine-related adverse effects. JAMA. 2012, 1-2. [Epub ahead of print]Google Scholar
- Torpy JM, Livingston EH: Energy drinks. JAMA. 2012, 1-1. [Epub ahead of print]Google Scholar
- Howland JRDJ: Risks of energy drinks mixed with alcohol. JAMA. 2012, 1-2. [Epub ahead of print]Google Scholar
- Clauson KA, Shields KM, McQueen CE, Persad N: Safety issues associated with commercially available energy drinks. J Am Pharm Assoc (2003). 2008, 48: e55-63. 10.1331/JAPhA.2008.07055. quiz e64-57View ArticleGoogle Scholar
- Duchan E, Patel ND, Feucht C: Energy drinks: a review of use and safety for athletes. Phys Sportsmed. 2010, 38: 171-179. 10.3810/psm.2010.06.1796.PubMedView ArticleGoogle Scholar
- Lockwood CM, Moon JR, Smith AE, Tobkin SE, Kendall KL, Graef JL, Cramer JT, Stout JR: Low-calorie energy drink improves physiological response to exercise in previously sedentary men: a placebo-controlled efficacy and safety study. J Strength Cond Res. 2010, 24: 2227-2238. 10.1519/JSC.0b013e3181aeb0cf.PubMedView ArticleGoogle Scholar
- Pennington N, Johnson M, Delaney E, Blankenship MB: Energy drinks: a new health hazard for adolescents. J Sch Nurs. 2010, 26: 352-359. 10.1177/1059840510374188.PubMedView ArticleGoogle Scholar
- Weiss EP, Arif H, Villareal DT, Marzetti E, Holloszy JO: Endothelial function after high-sugar-food ingestion improves with endurance exercise performed on the previous day. Am J Clin Nutr. 2008, 88: 51-57.PubMed CentralPubMedGoogle Scholar
- Petit A, Levy F, Lejoyeux M, Reynaud M, Karila L: Energy drinks: an unknown risk. Rev Prat. 2012, 62: 673-678.PubMedGoogle Scholar
- Why isn’t the amount of caffeine a product contains required of a food label?.http://www.fda.gov/AboutFDA/Transparency/Basics/ucm194317.htm,
- Health Canada’s proposed approach to managing caffeinated energy drinks.http://www.hc-sc.gc.ca/fn-an/legislation/pol/energy-drinks-boissons-energisantes-eng.php,
- McCusker RR, Goldberger BA, Cone EJ: Caffeine content of specialty coffees. J Anal Toxicol. 2003, 27: 520-522.PubMedView ArticleGoogle Scholar
- Jin KN, Chun EJ, Lee CH, Kim JA, Lee MS, Choi SI: Subclinical coronary atherosclerosis in young adults: prevalence, characteristics, predictors with coronary computed tomography angiography. Int J Cardiovasc Imaging. 2012, [Epub ahead of print]Google Scholar
- Thiene G, Carturan E, Corrado D, Basso C: Prevention of sudden cardiac death in the young and in athletes: dream or reality?. Cardiovasc Pathol. 2010, 19: 207-217. 10.1016/j.carpath.2009.04.001.PubMedView ArticleGoogle Scholar
- Radojevic N, Bjelogrlic B, Aleksic V, Rancic N, Samardzic M, Petkovic S, Savic S: Forensic aspects of water intoxication: four case reports and review of relevant literature. Forensic Sci Int. 2012, 220: 1-5. 10.1016/j.forsciint.2012.01.021.PubMedView ArticleGoogle Scholar
- Holmgren P, Norden-Pettersson L, Ahlner J: Caffeine fatalities–four case reports. Forensic Sci Int. 2004, 139: 71-73. 10.1016/j.forsciint.2003.09.019.PubMedView ArticleGoogle Scholar
- Kerrigan S, Lindsey T: Fatal caffeine overdose: two case reports. Forensic Sci Int. 2005, 153: 67-69. 10.1016/j.forsciint.2005.04.016.PubMedView ArticleGoogle Scholar
- Rudolph T, Knudsen K: A case of fatal caffeine poisoning. Acta Anaesthesiol Scand. 2010, 54: 521-523. 10.1111/j.1399-6576.2009.02201.x.PubMedView ArticleGoogle Scholar
- Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M: Effects of caffeine on human health. Food Addit Contam. 2003, 20: 1-30.PubMedView ArticleGoogle Scholar
- Higdon JV, Frei B: Coffee and health: a review of recent human research. Crit Rev Food Sci Nutr. 2006, 46: 101-123. 10.1080/10408390500400009.PubMedView ArticleGoogle Scholar
- Usman A, Jawaid A: Hypertension in a young boy: an energy drink effect. BMC Res Notes. 2012, 5: 591-10.1186/1756-0500-5-591.PubMed CentralPubMedView ArticleGoogle Scholar
- Worthley MI, Prabhu A, De Sciscio P, Schultz C, Sanders P, Willoughby SR: Detrimental effects of energy drink consumption on platelet and endothelial function. Am J Med. 2010, 123: 184-187. 10.1016/j.amjmed.2009.09.013.PubMedView ArticleGoogle Scholar
- Steinke L, Lanfear DE, Dhanapal V, Kalus JS: Effect of “energy drink” consumption on hemodynamic and electrocardiographic parameters in healthy young adults. Ann Pharmacother. 2009, 43: 596-602. 10.1345/aph.1L614.PubMedView ArticleGoogle Scholar
- Adverse event reporting for dietary supplements: an inadequate safety valve.https://oig.hhs.gov/oei/reports/oei-01-00-00180.pdf,
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.