One of the most rapidly growing sectors in the modern beverage market is that of the so-called “energy drinks”. Although varying in their individual composition, most energy drinks contain key ingredients such as caffeine, taurine, guarana or ginseng. This article reviews the basic pharmacology of these components; such pharmacological information is necessary to ensure the safety and effects of combinations of ingredients and the drinks containing them.

by Dr E. Duchan and N. Patel

The concept of energy drinks is loosely based on Asian “tonic drinks” containing taurine, vitamins and minerals that were popular in the Far East in the early 1980s. In 1987 the first mass-marketed energy drink was introduced in Austria under the name Red Bull, named after the original source of taurine, the bull. In addition to taurine, it also contained sugar and caffeine and was widely promoted to increase alertness and improve cognitive performance. Following success in the European market, Red Bull was introduced in the United States ten years later, where it was similarly popular [1]. Since then, the energy drink industry has experienced a sustained growth [2,3,4]. Beverage industry analysts report that over the last five years the average sales growth of energy drinks has been 14% per year and, in that period, the volume of energy drinks sold and consumed per person has almost doubled [5]. Currently the region with the most energy drink consumers is North America, followed by Asia Pacific and Western Europe [5].

Energy drinks are widely touted for their ability to increase energy levels and enhance cognitive performance and it has become increasingly popular to mix them with alcohol. A survey published in 2007 reported that more than half of college students consume at least one energy drink per month, primarily to compensate for insufficient sleep [6]. Of those who had consumed alcohol in the last 30 days, almost one-quarter reported doing so in combination with an energy drink, according to a survey published in 2008 [7]. Energy drinks have also become popular for their reported ability to improve athletic performance; among British cyclists, energy drinks were the most popular method of caffeine consumption [8-10].

Ingredients of energy drinks
The main active ingredient in most energy drinks is caffeine, although many also contain varying amounts of taurine, guarana and ginseng. Other ingredients, not discussed in this article as they are found only in select energy drinks, include carnitine, ginkgo biloba, royal jelly, bee pollen and inositol [11].

Caffeine
Caffeine (1,3,7-trimethylxanthine) is a naturally occurring central nervous system stimulant found in the seeds, fruits and leaves of more than 63 plant species. The three most commonly extracted sources are the Coffea arabica (coffee bean), Cola acuminate (kola nut) and Camellia sinensis (tea leaves) plants [12]. Coffee beans, the most common source of caffeine, contain 1-2% caffeine [12,13,14]. Caffeine is a lipid-soluble purine that is well absorbed following oral ingestion. The onset of action of caffeine is 15 to 45 minutes following ingestion, and the peak plasma concentration is obtained within one hour, regardless of the dose. Once ingested, 36% of the caffeine is protein-bound and is widely distributed throughout the body, with a volume of distribution of 0.6L/kg of body mass. The half-life of caffeine is 4-5 hours. Caffeine is metabolised in the liver by the isoenzyme CYP1A2 , primarily by demethylation of 1,3,7-trimethylxanthine to 1,7-dimethylxanthine (theophylline), but other active metabolites include theobromine and paraxanthine [15].

Energy drinks are generally available in 250, 330, or 500 mL cans that contain anywhere from 80 to more than 500 mg of caffeine. Some brands are also available as high-concentration energy shots: a 30 to 60 mL bottle that contains between 1 to 6 mg/mL of caffeine. Finally, the newest additions to the energy drink market are single-swallow ultra shots that are less than 30 mL in volume and provide between 3 and 80 mg/mL of caffeine [14]. Of note, a few energy drinks are caffeine free.

Some studies report that moderate amounts of caffeine have potential health benefits, including reducing the risk of type 2 diabetes, Parkinson’s disease, liver disease and colorectal cancer, as well as improving immune function; however the evidence is equivocal [12,15]. Caffeine is also reported to have ergogenic effects which can enhance athletic performance, however this claim has been contested [9,10].

Individual responses to caffeine vary widely. Some individuals are nonresponders while others experience significant side effects at similar doses. Adverse effects are numerous, including arrhythmias, psychomotor agitation, headache and irritability, but are generally not experienced at less than 3 mg/kg body weight [12,15]. Unfortunately, consuming more than 3 mg/kg body weight may be easily achieved, especially in adolescents or thin individuals. For example, a 100-kg person who drinks 150 mg of caffeine (approximately 240mL of drip coffee) obtains only 1.5mg/kg whereas a 50-kg person drinking the same amount of caffeine would of course have a per-weight concentration double this value. Serious adverse effects including hypertension, heart attack and seizures, are more likely in individuals who consume other foods or drinks containing caffeine as well as individuals with cardiovascular disease or those who smoke [2,3,12,15-21]. Caffeine toxicity is dose dependent and fatalities have been reported at very high dosages of greater than 150-200mg/kg.

Taurine
Taurine (2-aminoethane sulfonic acid) is a conditionally essential amino acid that is synthesised from cysteine and methioine in the liver and brain and is also found in a variety of dietary sources, including meat, fish and dairy products. A non-vegan diet typically supplies between 20-200 mg / day. Similar to caffeine, peak plasma concentration is reached in one hour. Within the body, taurine is stored primarily in skeletal muscle and myocardium but is also found in the retina and blood [3,22]. At physiologic levels, taurine is reported to function in bile acid conjugation, calcium regulation, carbohydrate metabolism, osmoregulation, platelet aggregation and retinal photoreceptor activity. Additionally, taurine is reported to have antioxidant effects [22].

The content of taurine in energy drinks is not always declared. However among energy drinks that do report this information, the content of taurine ranges from 300–4000 mg/L, with the majority of drinks reporting taurine content at the higher end [23].

 Although the health benefits of taurine have not been extensively studied, human clinical trials suggest taurine may be effective for managing alcohol withdrawal, congestive heart failure and cystic fibrosis. Taurine supplementation of 300mg to 2g / day has also been used in the management of diabetes, epilepsy, hypertension, cardiac arrhythmias, hepatitis, and anxiety despite the lack of supporting scientific evidence. While there is no established safe upper limit, the adverse effects of taurine are rare and include mild diarrhoea and constipation [22,23].

Guarana
Guarana, also known as Brazilian cocoa or zoom, is derived from the fruit seeds of the Paullina cupana and Paullinia sorbilis plants native to Brazil and other regions of the Amazon. The seeds are crushed and dissolved in water or juice to make a paste that can be added to beverages. Guarana contains between 3.6% to 5.8% caffeine, more than twice the amount found in coffee beans. Thus, the effects of guarana are primarily attributed to its caffeine content. However, the seeds of guarana also contain small amounts of theophylline, theobromine, tannins (primarily catechutannic acid and cetechol) and timbonine [24,25].

The guarana content of energy drinks varies widely, ranging from 1.4 to 400 mg of guarana per 240mL can [3,4,26]. While guarana’s side effects are related to its high caffeine content, it has also been shown to inhibit platelet aggregation [25]. Guarana is generally recognised as a safe food additive at the typical stimulant dose of 1 gram per day. However, guarana use can cause excessive nervousness and insomnia in individuals sensitive to caffeine or consuming caffeine from other sources, and if consumed in doses greater than 3 g/day, caffeine toxicity can result [24,25,27-29]. For these reasons, guarana should not be used by individuals who are pregnant or lactating, have anxiety disorders, hyperthyroidism, glaucoma, cardiovascular diseases or bleeding disorders [24,25].

Asian ginseng
Ginseng refers to several species of plants of the genus Panax, including the two primary species: American ginseng (Panax quinquefolius) and Asian ginseng (Panax ginseng) [30,31]. Dried ginseng roots are used to make ginseng supplements because the ginseng roots contain pharmacologically active saponins (ginsenosides or panoxosides). The amount of ginsenosides in the root of the ginseng plant varies based on the species of ginseng plant, the age of the root (ginsenosides are more concentrated in older plants), the season of harvest (autumn yields the most ginsenosides), and the method of preservation or curing. In addition to ginsenosides, ginseng root also contains variable amounts of methylxanthines, volatile oils, sterols, acetylenes, polysaccharides, starch, flavonoids, peptides, thiamine, riboflavin, vitamin B12, pantothenic acid, biotin, trace minerals, enzymes and choline [28,32]. Furthermore, following ingestion ginsenosides are metabolised by gastrointestinal microflora, resulting in pharmacologically active metabolites. These factors complicate the interpretation of research data and may explain the variability of the reported health benefits of ginseng.

The amount of ginseng in energy drinks is typically 25 to 100 mg per 250mL, which is below the typical recommended dietary supplement dosage. Although studies have not consistently shown definitive health benefits of ginseng [28,30-32], there are claims that 100 to 200 mg/day of ginseng can improve menopausal symptoms, cognitive abilities, mood, sexual function and immune function, and reduce the risk of certain cancers. Ginseng is usually considered safe when used for short periods of time, however side effects are more likely to occur if ginseng is consumed for more than three months. Adverse effects include palpitations, menstrual changes, headache, dizziness and oedema [24].

Future developments
As the popularity of energy drinks has increased, so has their variety. Now sold as beverages, concentrated shots and highly-concentrated single-swallow ultra shots, the options of available energy drinks are staggering. With this increased availability comes subsequent ease of unintentional caffeine overdose, further heightened by the addition of guarana and taurine in many energy drinks. Irrespective of this risk, the market for energy drinks continues to expand as consumer demand dictates. The addition of new ingredients could help new energy drinks stand out, however further research is needed to determine the safety and effects of combinations of these ingredients.

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The authors
Erin C. Duchan1, MD and Neil D. Patel2
1Department of Pediatrics
2Department of Emergency Medicine
Michigan State University Kalamazoo Center for Medical Studies
1000 Oakland Dr.
Kalamazoo, MI 49008, USA