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.