The energy drinks (ED) are caffeinated beverages that are popular among teenagers and young adults. They are aggressively marketed as providing alertness, energy and sex prowess. The EDs in addition to caffeine contain several plant stimulants and simple sugars, which increase their caloric content. The caffeine concentration in these drinks is high and their overconsumption could lead to insomnia, agitation, tremors and cardiovascular complications including sudden death. Alcohol is often mixed with EDs (AMEDs) in the wrong perception that the caffeine in the EDs will prevent the drowsiness and sleepiness from alcohol and allow the person to consume more alcohol. This false perception, could lead to alcohol intoxication and the taking of risky decisions, like driving under the influence of alcohol and the risk of serious physical harm to themselves and others. To prevent the problem of consumption of EDs and AMEDs, the caring physician could help by advising the parents and his young patients about the serious health risks from the consumption of these drinks. In order to grasp the extend of the problem of ED and AMED consumption, we did a Medline search of the English language literature from January 2010 to December 2013, using the terms EDs and alcohol-mixed EDs. All the findings from the recent studies regarding the cardiovascular complications from the consumption of EDs and AMEDs together with collateral literature will be discussed in this review.
Energy drinks (EDs) are beverages that are advertised as providing a burst of energy when consumed. They mainly contain caffeine in combination with different plant stimulants (guaranca, yerba), simple carbohydrates (glucose, fructose), amino acids (taurine, carnitine), herbs (ginko biloba, ginseng), and multivitamins. These drinks are aggressively marketed in college campuses and sports events using various catching names such as ‘Daredevil’, ‘WhoopAss’ and ‘Cocaine’ and emphasize that they increase endurance and sexual prowess.1, 2 Since the introduction in 1997 of ‘Red Bull’, the first ED in the beverage market, several more brands and formulations have been developed and marketed, with the Red Bull having the largest share of the market.3 Since their introduction, the EDs have become very popular among the young people. In 2005, US residents consumed an estimated 2.3 billion of EDs and this volume was increased to 9 billion drinks in 2010 (4). In 2011, the sales of EDs in the US accounted for $ 9 billion.4 However, the manufacturing and sale of these drinks are not regulated, although these drinks contain large amounts of caffeine, are often consumed together with alcohol and are frequently associated with several neuropsychological and cardiovascular effects including unexpected deaths among healthy persons.2, 5 To investigate all the possible adverse effects from the consumption of EDs, and especially those mixed with alcohol among young adults, a Medline search of the recent English literature was conducted between 2010 and 2013. The search terms used were EDs, alcohol mixed EDs, hypertension, cardiovascular disease and sudden death. From over 100 abstracts reviewed, 32 pertinent papers were selected and their findings together with collateral literature will be discussed in this review.
Adverse effects of caffeinated EDs
EDs are heavily caffeinated beverages that are marketed to young people to increase their alertness and to boost their energy. Upon ingestion of the drink, the caffeine is rapidly and completely absorbed from the intestinal tract and becomes completely bioavailable, achieving a Tmax within 30–45 min. Then, it is metabolized in the liver by the cytochrome P450 into three active metabolites paraxanthine, theobromine and theophylline.6 Their chemical structure is depicted in Figure 1. Of these three metabolites, paraxanthine is the most prevalent and accounts for most of the actions of caffeine. The widespread use of EDs created public concern owing to their caffeine content, and the Food and Drug Administration (FDA) investigated their caffeine content and proposed a reduction of the caffeine content to 0.02%, or 71 mg caffeine per 12 oz.7 The manufacturers complied initially, with the FDA regulations, but later they increased the caffeine content of EDs to 141 mg/8 oz can or bottle, or higher (7) as shown in Table 1. Although moderate caffeine consumption is considered fairly safe for adults, it may not be the same for the 12–17 year olds.8, 9 Caffeine consumption in this age group greater than 500 mg per day is considered toxic and this amount is not difficult to achieve from the consumption of certain EDs as shown in Table 1. The most common toxic effects of caffeine from the overconsumption of EDs include nervousness, anxiety, restlessness, insomnia, gastrointestinal complaints, tachycardia and cardiac arrhythmias and in rare cases death.10, 11, 12, 13 In addition, caffeine consumption by pregnant women between 200–300 mg per day is associated with decreased birth weight for the gestational age of the infant.14 The brain effects of caffeine, such as stimulation and wakefulness, are mediated through the antagonism of adenosine receptors A1 and A2A, as adenosine has the opposite effects, causing sedation and sleepiness. In addition, caffeine through the blockade of adenosine receptors induces the release of dopamine and facilitates its effects on neurotransmission.15 The A2A receptors are located in the basal ganglia, caudate putamen, tuberculum olfactorium, olfactory bulb, nucleus accumbens and the hippocambus, whereas the A1 receptors are present in almost all parts of the brain.15, 16 Stimulation of the A1 receptors induces sleep, whereas their blockade with caffeine induces wakefulness.15 Caffeine due to its strong hydrophobic properties is not affected by the blood–brain barrier and enters the brain within 45 min from its ingestion17 and achieves a plasma half-life of approximately 3–8 h. The caffeine’s half-life can be reduced by 30–50% with cigarette smoking,18 or doubled with oral contraceptives or drugs that interfere with the function of chromosome P450.
Blood pressure effects of ED consumption
The effects of EDs on blood pressure (BP) are attributed to their caffeine content. The acute hemodynamic effects of caffeine administration have been studied in two habitual coffee drinkers. In one study, 48 male subjects aged 20–39 years habitual coffee drinkers (500–700 mg caffeine per day) were studied in a cross-over design.19 Of these subjects, 24 were mildly hypertensive and 24 were normotensive. After an overnight’s coffee abstention, the study group received orally caffeine 3.3 mg kg−1 body weight in grapefruit juice, whereas the control group received only grapefruit juice. Compared with the control group, caffeine administration resulted in significant increase in systolic BP and diastolic BP both (P<0.001) and peripheral vascular resistance (P<0.01). The heart rate and cardiac output were not significantly affected by either caffeine or placebo. In a similar design study, the acute hemodynamic effects of caffeine were investigated in 35 normotensive men and 42 normotensive women habitual coffee drinkers (500–700 mg caffeine per day) ages 27–29 years.20 The study group received caffeine 3.3 mg kg−1 body weight in grapefruit juice, whereas the control group received only grapefruit juice. Compared with control group, caffeine administration resulted in significant increase in systolic BP, diastolic BP, cardiac output, heart rate and peripheral vascular resistance (P<0.05), with men demonstrating a slightly greater response than women. In both studies, the elevation of BP was attributed to the increase in systemic vascular resistance through the inhibition of the action of adenosine by caffeine and the facilitation of dopamine release. Besides these studies, other observational studies have shown elevations of BP after acute administration of caffeine of 100–300 mg in both men and women.8, 21, 22, 23 In a large review and meta-analysis,22 acute caffeine administration 200–300 mg was associated with elevations of systolic BP and diastolic BP lasting up to 48 h in treated or treatment-naïve hypertensive subjects (Table 2). These effects of caffeine appear to be only temporary, as several small studies and large reviews of studies have not shown an association of chronic coffee consumption with sustained hypertension in both men and women.22, 23, 24
Cardiovascular adverse effects of caffeinated EDs
Coronary heart disease
Older studies have suggested that coffee consumption is associated with increased incidence of myocardial infarction.25, 26 In contrast, two recent large prospective studies, which were analyzed for the presence of several cardiovascular risk factors, have shown an inverse association between chronic coffee drinking and cardiovascular disease or all-cause mortality.27, 28 In one such study, 20 179 Finnish men and women habitual coffee drinkers’ aged 30–59 years were followed for 10 years. The age-adjusted association of coffee drinking showed a J-shaped curve effect with coronary heart disease mortality and a U-shaped curve effect with all-cause mortality.27 In the other study, 229 119 men and 173 141 women aged 50–71 years were followed prospectively for 12 years. After adjusting for the presence of cardiovascular risk factors, coffee consumption was inversely associated with total and all-cause mortality.28 A lack of association between habitual coffee drinking and coronary heart disease and death was also, demonstrated in three prospective cohort studies29, 30, 31 and two large reviews and mete-analyses.22, 23 In the cohort studies, which included the Hypertension Detection and Follow-up Program (10 064 patients), the Nutrition Examination Survey Epidemiologic Follow-up Study (6594 subjects) and a cohort of 1354 older subjects from the Framingham Heart Study, there was either a protective effect or no association between chronic coffee drinking and sustained hypertension, cardiovascular disease, heart failure or sudden death after a long-term follow-up. In contrast, increased consumption of caffeinated EDs has been associated with serious or lethal cardiovascular complications, such as aortic dissection, ventricular arrhythmia, ST elevation, cardiac arrest and sudden death in young healthy persons.13, 32, 33 These serious cardiovascular complications from the consumption of EDs could be due to excessive caffeine consumption in combination with other stimulants contained in these drinks.
Congestive Heart Failure
The association of habitual coffee consumption and congestive heart failure has been investigated in several prospective studies included in a recent large meta-analysis involving 140 220 patients.34 This meta-analysis showed a J-shaped significant relationship between coffee consumption and congestive heart failure. Compared with no coffee drinking, a strong inverse association was observed in those consuming four cups of coffee per day, but a potentially higher risk for congestive heart failure was noted in those consuming larger quantities of coffee.34 This association could, also, be observed from high consumption of caffeinated EDs as was demonstrated by a recent case of reversible Takotsubo cardiomyopathy in a 24-year-old man after consuming several EDs containing high concentration of caffeine.35
Earlier, animal studies had indicated that caffeine administration appeared to cause arrhythmias in a canine model.36 In contrast, recent human studies have demonstrated that caffeine intake could have a protective effect against arrhythmia causation. In a large observational study from the Kaiser Permanente group in California, of 130 054 habitual coffee drinking subjects, there was an inverse relationship between hospitalizations for arrhythmias and coffee drinking.37 Of the 3137 patients hospitalized for arrhythmias over a period of 17.6 years, there was an inverse relationship between coffee intake and risk of arrhythmias irrespective of age, race or gender.37 Another study also showed, that caffeine administration (1 mg kg−1 body weight) in normal subjects did not affect the prevailing cardiac rhythm, and did not cause any clinically significant ventricular or supraventricular arrhythmia.38 Further, a prospective electrophysiologic study of 22 patients with a history of symptomatic non-sustained ventricular tachycardia, showed that administration of 275 mg of caffeine, did not significantly alter either the inducibility or the severity of arrhythmias.39 Similarly, another large epidemiologic study of 33 638 women older than 45 years, and free of cardiovascular disease or atrial fibrillation at baseline, followed for 14.4 years, did not show any association between coffee intake and atrial fibrillation.40
Adverse effects of alcohol mixed EDs
The consumption of alcohol mixed with EDs is quite prevalent among college students and young adults.1, 5, 41 Alcohol-mixed EDs (AMEDs) were also freely available for purchasing in the near past in a great variety. However, due to public concerns regarding their serious side effects, the FDA ordered the removal of alcohol content from the EDs. Consequently, many manufacturers of AMEDs either reformulated them, or discontinued their production altogether. Since 2010, only two brands of AMEDs are still available in the drink market, mate vesa (yerba mate beer) and 3 A.M. vodka (vodka, caffeine, taurine, guaranca). Despite the discontinuation or reformulation of AMEDs, alcohol is still being consumed together with EDs by students and young adults. In surveys of College students, as many as 39–57% have stated consuming EDs mixed with alcohol.38, 39, 40, 41 A possible reason for the consumption of AMEDs is the perception that the caffeine contained in AMEDs will antagonize the physical and cognitive impairment of alcohol. This concept of ingesting AMEDs will maintain a feeling of alertness will potentially, increase the risk of physical and social harm, because of the false perception of decreased intoxication.42, 43, 44, 45, 46 Several surveys have documented that this concept is being held among college students. A survey by Minauskas et al.,42 of 496 University students revealed that 65–67% used EDs to stay awake because of insufficient sleep and to increase energy, whereas 54% used AMEDs while partying. In another study, Peacock et al.,46 interviewed 403 young adults ⩾18 years. They found that the odds of enduring a physiological (heart palpitations, insomnia, agitation, tremors, crash episodes and increased speech speed) or psychological (irritability and tension), were significantly greater during AMED than alcohol consumption. In another study, Thombs et al.47 interviewed 802 randomly selected young adult patrons of college campus bars exiting between 2200 and 0300 hours and found that those consuming EDs mixed with alcohol were 3.32 times more likely to have high-breath alcohol level, and exited the bars later in the evening. Also, they drank for longer periods of time, consumed more total drinks and had higher levels of alcohol intoxication, compared with patrons who did not consume EDs mixed with alcohol. In addition, they were 4.26 times more likely intended to drive a vehicle after leaving the bar than those who consumed only alcohol.47 Another study by Mundt et al.,48 of 12 900 college students seeking routine medical care in five College clinics, 2090 who exceeded the at-risk alcohol use levels, participated in a face-to-face interview. Male students were 19% more likely to suffer an alcohol-related injury after consuming eight or more drinks, whereas female students were 10% more likely to sustain an injury after drinking five or more drinks.48 These findings have been replicated by more recent studies, which found that AMED consumption gives a false sense of intoxication and produces a precarious scenario of mental clarity.49, 50, 51, 52, 53, 54, 55, 56, 57 The findings from these studies are summarized in Table 3.
The data presented demonstrate that EDs are caffeinated beverages, which are aggressively marketed with innovative strategies to teenagers and young adults as providing mental alertness, energy, masculinity and sexual prowess.1, 2 Their popularity has skyrocketed since the introduction of ‘Red Bull’ in the United States in 1997.3 In 2005, an estimated 2.3 billion EDs were consumed in the United States and the volume increased to 9 billion in 2010.4 The caffeine content of these drinks is not closely regulated by the FDA, and some of them contain excessive amounts of caffeine (Table 1). Although chronic caffeine consumption in moderation (three cups coffee per day equivalent to 300 mg caffeine per day), is not associated with sustained hypertension or cardiovascular complications,22, 23, 24 large quantities of caffeine intake can cause serious cardiovascular complications and even death.13, 32, 33, 34, 35 In addition, acute caffeine ingestion can cause significant increases in BP and peripheral vascular resistance.19, 20 The mechanism for these hemodynamic changes has been attributed to the interference by caffeine of the action of adenosine through the blockade of its receptors A1 and A2A.15 Toxic levels of caffeine in the blood are not difficult to achieve by those consuming EDs due to high caffeine content of some of these drinks. The cardiovascular risks are even greater with the consumption of AMEDs. Fortunately, most of these premixed AMEDs have either been discontinued or modified with the removal of alcohol and are no longer available for purchasing, except two, mate vesa and 3 A.M. vodka. However, EDs are still being consumed mixed with alcohol and continue to be associated with serious physical and social harm.42, 43, 44, 45, 46 In addition, heavy AMED consumption has been associated with risky and unsafe sex practices with possible serious health consequences.53 Besides the young adults, AMEDs have become very popular among underage drinkers according to a recent survey. In this survey, the percentage of AMED consumption was 48.3% among the 13–15-year olds, 45.3% among the 16–18 year-olds and 58.4% among the 19–20 year-olds.58 Heavy consumption of AMEDs could lead to alcohol addiction, liver disease, obesity and diabetes from the high-caloric content of these drinks. The caffeine content of EDs increases the appetite for more alcohol consumption, which frequently leads to alcohol intoxication. Due to serious consequences from the consumption of EDs either alone or together with alcohol by healthy children and young adults, additional regulations should be instituted requiring the full disclosure of caffeine content of EDs. In this regard, the FDA and the Consumer Product Safety Commission should initiate regulatory steps regarding the manufacturing and marketing of the high energy EDs and in addition, medical vigilance is absolutely necessary and it will be the responsibility of the caring physician to advise his young patients and parents about the inherent risks associated with the consumption of EDs and AMEDs, especially by underage children in whom the risks of serious adverse events could be even higher.
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The authors declare no conflicts of interest.
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Chrysant, S., Chrysant, G. Cardiovascular complications from consumption of high energy drinks: recent evidence. J Hum Hypertens 29, 71–76 (2015). https://doi.org/10.1038/jhh.2014.47
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