Research Energy drinks: health risks and toxicity

Naren Gunja he new millennium has ush- MB BS, FACEM, Medical Abstract 1 ered in a wave of synthetic, Director and Toxicologist, Objectives: To describe the epidemiology and toxicity of caffeinated energy and Clinical Senior caffeinated high-energy 2 T drink exposures in Australia. Lecturer drinks targeted at the youth market. Design, setting and subjects: Retrospective observational study analysing data Jared A Brown Over the past 10 years, the consump- BPharm(Hons), MPH, from calls regarding energy drink exposures recorded in the database of an Senior Poisons Specialist tion of caffeinated beverages intended Australian poisons information centre over 7 years to 2010. (Research and Audit)1 to “energise” has increased signifi- Main outcome measures: Type of exposure; co-ingestants; symptoms cantly. Energy drinks were recently reported; and reported hospitalisations. 1 NSW Poisons Information shown to comprise 20% of the total Centre, The Children’s Results: Callers reported 297 exposures to energy drinks, which showed an Hospital at Westmead, convenience store beverage market, increasing annual trend from 12 in 2004 to 65 in 2010. Median age for the 217 Sydney, NSW. with “Red Bull” and “V” accounting subjects with recreational exposure was 17 years (interquartile ratio [IQR], 15–21; 2 Discipline of Emergency range, 11–60) and 57% were male. One hundred recreational users co-ingested Medicine, Sydney Medical for over 97% of sales in this multimil- 1 School, University of lion-dollar industry. Increasingly, other substances, predominantly alcohol (50) or other caffeinated products Sydney, Sydney, NSW. toxicity from caffeine overdose is (44). The number of energy drinks consumed in one session varied greatly (median, 5 units; IQR, 3–8; range, 1–80). Most subjects who reported naren.gunja@ being reported to hospitals and poi- sydney.edu.au recreational use reported experiencing symptoms (87%). The most common sons centres. symptoms were palpitations, agitation, tremor and gastrointestinal upset. The main active constituents of Twenty-one subjects had signs of serious cardiac or neurological toxicity, MJA 2012; 196: 46–49 energy drinks include varying amounts including hallucinations, seizures, arrhythmias or cardiac ischaemia. At least 128 doi: 10.5694/mja11.10838 of caffeine, guarana extract, taurine and subjects (57 with no co-ingestants) required hospitalisation. ginseng. Additional amino acids, vita- Conclusions: Reports of caffeine toxicity from energy drink consumption are mins and carbohydrates usually com- increasing, particularly among adolescents, warranting review and regulation of the labelling and sale of these drinks. Educating adolescents and increasing the plete the list of purportedly beneficial 2 community’s awareness of the hazards from energy drinks is of paramount ingredients. The intended effects of importance. energy drinks are to provide sustenance and improve performance, concentra- tion and endurance. Manufacturers on medical complications from energy in the 7-year period from January pitch their product to athletes, students drinks.8 Our study was undertaken to 2004 to December 2010. Our search and people in professions that require obtain an understanding of the scope strategy included “guarana”, “caf- sustained alertness. These drinks are of consumption-related issues and feine”, “ethanol”, “food additives”, also commonly consumed at dance toxicity from caffeinated energy “energy drink”, “alcohol: other/ parties, which require sustained energy drinks in Australia by analysing data unknown”, and “non-drug product: for prolonged activity into late hours. In from calls to the NSW Poisons Infor- other/unknown”. Due to the large this setting, they may also be combined mation Centre (NSWPIC) — the larg- number of “other/unknown” expo- with alcohol and recreational drugs est centre of its type in Australia, sures, a filter was applied to find such as ecstasy (MDMA; 3,4-methyl- taking about 110 000 calls per year, results with the name of any known enedioxymethamphetamine) or other which is 50% of all poisoning-related Australian marketed energy drink or amphetamines. Young adults and ado- calls in the country. “caffeine” or “energy” in the free-text The Medical Journallescents of Australiaare particularly ISSN: 0025- attracted to product name field. “Recreational” 729X 16 Januaryenergy 2012 196drinks 1 46-49 because of effective ingestion was defined as intentional ©The Medicalproduct Journal marketing, of Australia peer 2012influence and Methods ingestion for the purpose of gaining www.mja.com.aua lack of knowledge of the potential euphoria or other psychotropic effect. Research harmful effects.3-5 The high sugar con- We undertook a retrospective review “Accidental paediatric” ingestion was tent in caffeinated energy drinks is sim- at the NSWPIC. Data included calls defined as non-deliberate ingestion ilar to other soft drinks and is known to providing advice to the general public by a person under 18 years of age. contribute to obesity.6 and health professionals. Calls from Finally, all the cases found from this Adverse reactions and toxicity from New South Wales, Tasmania and the search were subjected to manual high-energy drinks stem primarily Australian Capital Territory are exclu- review for inclusion and subsequent from their caffeine content.7 The sym- sively handled by NSWPIC from 6 am coding and verification of the pathomimetic effects of high-dose to midnight; an after-hours call-shar- reported type of exposure, co-ingest- caffeine mostly explain the symptoms ing system is in place with interstate ants, symptoms, dose, brand of drink, and hospital presentations related to poisons centres. Ethics approval was and the subject’s age, sex and hospi- energy drinks. There is little published obtained from the human research talisation status. Symptoms and cod- literature on the extent and epidemi- ethics committee of the Children’s ing were reviewed separately by the ology of this problem. Indeed, a Hospital at Westmead. authors. Discrepancies were discussed recent literature review on the effects We searched the NSWPIC Micro- until agreement was achieved. of energy drinks in children and ado- soft Access database for calls relating We used mean and SD to describe lescents found only eight case reports to caffeinated energy drink ingestions normally distributed data, and

46 MJA 196 (1) · 16 January 2012 Research

1 Annual number of energy drink exposures reported to the NSW Poisons Information Centre, Jan 2004 – Dec 2010, by type of exposure

60

50

40

30 Recreational Accidental paediatric 20 Number of exposures

10

0 2004 2005 2006 2007 2008 2009 2010 median and interquartile range (IQR) amounts of energy drink consumption Year for non-parametric data. All statistical and were frequently reported with analyses were performed using SPSS, recreational use (87%; 188/217). The 2 Energy drinks accounting for most exposures reported to the version 19.0 for Windows (SPSS Inc, most commonly reported symptoms NSW Poisons Information Centre, Jan 2004 – Dec 2010 Chicago, Ill, USA). were related to gastrointestinal upset and sympathetic overdrive, as can be Main ingredients, dose/ Maximum Product 100 mL volume* (mL) No. of calls Results predicted for caffeine toxicity. Twenty- one callers reported signs of serious Red Bull Caffeine, 32 mg 500 126 Sugars, 11 g Over the 7-year period that we exam- toxicity such as hallucinations, sei- ined, data for 297 calls related to caf- zures, and cardiac ischaemia. At least V Caffeine, 32 mg 500 68 feinated energy drink exposures were 128 people required emergency Guarana extract, 120 mg recorded. Call numbers increased department (ED) attendance, 57 of Pulse Ethanol, 7 g 300 15 from 12 in 2004 to 65 in 2010 (Box 1). whom had not co-ingested another Caffeine, 7 mg The most common exposure type was substance. Of those attending an ED, Mother Caffeine, 32 mg 500 25 recreational (217); other exposures 79 had self-presented and 49 had Sugars, 10.5g were classified as accidental paediatric been referred by the NSWPIC for fur- RockStar Caffeine, 32 mg 473 5 (62), deliberate self-poisoning as part ther management based on the clini- Guarana extract, 10 mg of a polypharmacy overdose (16), cal significance of their symptoms. Ginseng extract, 20 mg allergic reaction (1) and paediatric lac- Sugars, 13 g Accidental paediatric ingestion tational exposure (1). The brands of Other/ ––58 energy drinks to which subjects were Sixty-two children were reported to unknown most commonly exposed and their have accidentally ingested energy Other caffeine-containing products (for comparison) active ingredients are listed in Box 2. drinks (mean age, 38 months; SD, 24 Cola drinks Caffeine, approximately – nd Sixty per cent of calls were received months; range, 7–120 months). Of 40 mg per can (11 mg per 100 mL) between 5 pm and 3 am. these, 14 had symptoms probably Coffee Caffeine, approximately –nd related to energy drink consumption 25–200 mg per cup Recreational use — most commonly hyperactivity (Box No-Doz/No- Caffeine, 100 mg/tablet – 545 Typically, recreational users were ado- 4) — and nine required assessment in Doz Plus (packs of 24 and 100) lescents or young adults. Median age hospital. nd = not determined. * Of individual serving sold. ◆ was 17 years (IQR, 15–21; range, 11– 60), and 57% were male. The number Discussion of drinks consumed in one session In 2009, the energy drink industry varied greatly (median, 5 units; IQR, Our study demonstrates the extent of spent nearly $15 million on marketing 3–8 units; range, 1–80 units). Co- the growing problem in Australia with alone in Australia. Value growth in the ingestion of other substances was energy drink consumption and toxi- convenience sector had increased by recorded for 46% of recreational users city, particularly among adolescents. 20% as compared with 10% for car- (Box 3). The most popular co-ingested Serious adverse effects and toxicity bonated beverages on the whole.9 The substances were alcohol and other are seen with energy drinks contain- target population for these types of caffeine-containing products. ing variable amounts of caffeine. The drinks clearly includes adolescents Commonly reported symptoms and phenomenon of mixing energy drinks and young adults, as well as profes- their frequency are listed in Box 4. with alcohol, stimulants and other co- sionals.10 Consumers are likely to be Symptoms were occasionally reported ingestants is clearly occurring and is a unaware of the variation in chemical even at manufacturer-recommended serious concern. composition and caffeine dosage in

MJA 196 (1) · 16 January 2012 47 Research

3 Recreational use of other substances 4 Frequency of the most commonly reported symptoms, by type of exposure and with energy drinks (n =217) co-ingestant use (n =202)

No. of Recreational ingestion (n =188) Co-ingestant subjects Alcohol or other Accidental None 117 No co-ingestants caffeinated paediatric ingestion One or more co-ingestant 100 Symptom (n =117) co-ingestant (n =71) (n =14) Alcohol 50 Palpitations/tachycardia 33 22 2 Caffeine tablets 34 Tremor/shaking 30 21 0 Ecstasy/amphetamines or 15 Agitation/restlessness 29 22 9 other illicit stimulants Gastrointestinal upset 29 29 4 Other caffeinated beverages 10 Chest pain/ischaemia 6 8 0 Other illicit substances 3 Dizziness/syncope 692 Other 12 Paraesthesia 6 3 0 Insomnia 53 1 energy drinks, and with little or no Respiratory distress 5 5 0 warnings on products, the potential Headache 43 1 for overdose and poisoning remains ever-present. arrhythmias and, potentially but ing of energy drinks with alcohol.3,23 A typical can of energy drink may rarely, death.15-20 In 2009, a caffeine- Young people, particularly adoles- contain up to 300 mg of caffeine, from related death from energy drinks was cents, appear to be least concerned added caffeine and natural sources reported.21 Electrocardiograms with this dangerous phenomenon.4,24 such as guarana.11 Guarana, an showed that the patient had acute This was evident in our results, in that extract from the plant Paullinia myocardial ischaemia that was proba- almost one-quarter of calls reporting cupana, contains caffeine, theobro- bly brought on by caffeine-induced recreational consumption involved mine and theophylline in varying coronary vasospasm. It has been pos- co-ingestion of alcohol. Nearly 30% quantities. Some studies have sug- tulated that the pathophysiology of of calls involved co-ingestion of caf- gested that the caffeine content of such coronary events involves feine tablets or other stimulants such guarana (40–80 mg per gram of increased platelet aggregation and as amphetamines. This suggests that extract) is not always declared in reduced endothelial functionality.22 knowledge of energy drink effects and packaging and is additional to the In our study, calls regarding toxicity toxicity is poor, and mixing of sub- listed caffeine content of energy from energy drinks fell into a bimodal stances is not seen as a problem in drinks.8 Hence, the caffeine dose may distribution: accidental ingestion in this cohort of adolescents and young be higher than that listed on the bev- young children, and recreational use adults. erage ingredients list. However, Aus- in adolescents. It is concerning that Data on caffeine-related toxicity tralian Food Standards Code 2.6.4 the trend of misuse and toxicity have been reported from poison cen- requires labelling of the total amount appears to be increasing among teen- tres in the United Kingdom and of caffeine from all sources, pure and agers and that the number of energy United States.17,25 We are not aware of naturally occurring.12 Guarana is cur- drink units ingested far exceeds rec- other studies specifically reporting rently thought to have no adverse ommended maximum levels. Some poison control centre data on toxicity effects other than potential caffeine manufacturers suggest 200 mg/day of from energy drinks. However, misuse toxicity.13 Similarly, taurine, an amino caffeine as a maximum, which by adolescents of caffeine in non- acid found in many energy drinks, is equates to roughly one and a quarter prescription medication as well as in purportedly inotropic, and considered 500 mL cans of energy drink. The energy drinks has been commonly to be non-toxic at typical doses. Gin- variety of symptoms reported in our reported to regional poison centres in seng, a herbal extract famous for its study was consistent with caffeine the US.26 Even more alarming is the purported stimulant and aphrodisiac overdose and, potentially, stimulant practice of combining caffeine misuse properties, is present in energy drinks misuse. Nearly 60% of calls reporting with other pharmaceuticals, which below common daily doses, and has recreational use came from EDs, sug- has been associated with admission to not been reported to be toxic. Gin- gesting that hospitalisation is war- hospital.27 A 1999 Australian survey of seng, however, has multiple and ranted in a significant proportion of NSW school children aged 8–18 years important drug interactions that may cases. Although it occurred in a found that energy drink consumption become clinically relevant depending minority of subjects, serious toxicity was more prevalent in boys and on the amount of ginseng ingested leading to cardiac complications (cor- increased with age in girls.28 and the dose and frequency of the onary ischaemia, arrhythmias) and Limitations of our retrospective drugs that might interact with it.14 neurological complications (halluci- analysis include the non-standardised Even as little as 50 mg of caffeine nations, psychosis, seizures) is of methods of telephone enquiry and can induce tachycardia and agitation. grave concern both to the community coding that are likely to have resulted In overdose, caffeine toxicity can and clinicians. in underreporting of exposures, co- mimic amphetamine poisoning and Studies among American college ingestants and symptoms. We did not lead to seizures, psychosis, cardiac students called attention to the mix- analyse outcomes for subjects who

48 MJA 196 (1) · 16 January 2012 Research were hospitalised. As the NSWPIC 1 AC Nielsen. Nielsen convenience report, 2008. 17 Shum S, Seale C, Hathaway D, et al. Acute http://au.nielsen.com/site/documents/ caffeine ingestion fatalities: management issues. takes roughly 50% of all poisons- ConvenienceReport2008-extob.pdf (accessed Vet Hum Toxicol 1997; 39: 228-230. related calls in Australia, our results Mar 2011). 18 Di Rocco JR, During A, Morelli PJ, et al. Atrial may only partially reflect national 2 Higgins JP, Tuttle TD, Higgins CL. Energy fibrillation in healthy adolescents after highly beverages: content and safety. Mayo Clin Proc caffeinated beverage consumption: two case trends. With increased call-load shar- 2010; 85: 1033-1041. reports. J Med Case Reports 2011; 5: 18. ing between the NSWPIC and other 3 Malinauskas BM, Aeby VG, Overton RF, et al. A 19 Cannon ME, Cooke CT, McCarthy JS. Caffeine- Australian poisons centres, the survey of energy drink consumption patterns induced cardiac arrhythmia: an unrecognised among college students. Nutr J 2007; 6: 35. danger of healthfood products. Med J Aust 2001; number of after-hours calls to the 4 Arria AM, Caldeira KM, Kasperski SJ, et al. Energy 174: 520-521. NSWPIC has decreased by roughly drink consumption and increased risk for alcohol 20 Menkes DB. Transient psychotic relapse 20% since 2009. This is also reflected dependence. Alcohol Clin Exp Res 2011; 35: 365- temporally related to ingestion of an “energy 375. drink” [letter]. Med J Aust 2011; 194: 206. in the drop in the number of calls 5 Attila S, Cakir B. Energy-drink consumption in 21 Berger AJ, Alford K. Cardiac arrest in a young man college students and associated factors. related to caffeinated energy drinks by following excess consumption of caffeinated Nutrition 2011; 27: 316-322. “energy drinks”. Med J Aust 2009; 190: 41-43. a similar percentage in 2010. 6 Riddell L, Keast RS. Is caffeine in soft drinks really Given the clear evidence of toxicity necessary [letter]? Med J Aust 2007; 187: 655. 22 Worthley MI, Prabhu A, De Sciscio P, et al. Detrimental effects of energy drink consumption 7 Reissig CJ, Strain EC, Griffiths RR. Caffeinated and the growing number of hospital- on platelet and endothelial function. Am J Med energy drinks — a growing problem. Drug Alcohol 2010; 123: 184-187. isations associated with consumption Depend 2009; 99: 1-10. 23 O’Brien MC, McCoy TP, Rhodes SD, et al. of energy drinks, particularly in a vul- 8 Seifert SM, Schaechter JL, Hershorin ER, et al. Caffeinated cocktails: energy drink consumption, Health effects of energy drinks on children, nerable adolescent population, health high-risk drinking, and alcohol-related adolescents, and young adults. Pediatrics 2011; authorities should increase awareness 127: 511-528. consequences among college students. Acad Emerg Med 2008; 15: 453-460. of the problem, improve package 9 AC Nielsen. Nielsen convenience and impulse report, 2010. http://au.nielsen.com/site/ 24 Kaminer Y. Problematic use of energy drinks by labelling and regulate caffeine con- documents/NielsenConvenience adolescents. Child Adolesc Psychiatr Clin N Am tent. We recommend that labelling ReportJune2010LR.pdf (accessed Mar 2011). 2010; 19: 643-650. and any marketing of these products 10 Red Bull Australia. Red bull products. http:// 25 Waring WS, Laing WJ, Good AM, et al. Acute www.redbull.com.au/cs/Satellite/en_AU/Red- caffeine ingestion: clinical features in patients should include appropriate health Bull-Australia/Products/011242758640967 attending the emergency department and warnings and the national poisons (accessed Feb 2011). Scottish poison centre enquiries between 2000 and 2008. Scott Med J 2009; 54: 3-6. hotline number (13 11 26 in Aus- 11 Pennay A, Lubman DI, Miller P. Combining energy drinks and alcohol — a recipe for trouble? Aust 26 Crouch BI, Caravati EM, Booth J. Trends in child tralia). Energy drinks are marketed for Fam Physician 2011; 40: 104-107. and teen nonprescription drug abuse reported to similar effects and should carry similar 12 Food Standards Australia New Zealand. Australia a regional poison control center. Am J Health Syst Pharm 2004; 61: 1252-1257. warning labels as non-prescription, New Zealand Food Standards Code — Standard 2.6.4 (2009): formulated caffeinated beverages. 27 McCarthy DM, Mycyk MB, DesLauriers CA. over-the-counter caffeine tablets. The http://www.comlaw.gov.au/Details/ Hospitalization for caffeine abuse is associated regulation of caffeinated energy F2009C00814 (accessed Nov 2011). with abuse of other pharmaceutical products. Am J Emerg Med 2008; 26: 799-802. drinks is currently under considera- 13 Duchan E, Patel ND, Feucht C. Energy drinks: a review of use and safety for athletes. Phys 28 O’Dea J, Rawstorne P. Consumption of dietary tion by the Australia and New Zea- Sportsmed 2010; 38: 171-179. supplements and energy drinks by school land Food Regulation Ministerial 14 Hu Z, Yang X, Ho PC, et al. Herb-drug interactions: children. Med J Aust 2000; 173: 389. a literature review. Drugs 2005; 65: 1239-1282. Council.29 This review and regulation 29 The Australia and New Zealand Food Regulation 15 McGee MB. Caffeine poisoning in a 19-year-old Ministerial Council. Food Ministers briefed on is timely and essential. female. J Forensic Sci 1980; 25: 29-32. progress of historic Food Labelling Review. http:/ Competing interests: No relevant disclosures. 16 Benowitz NL, Osterloh J, Goldschlager N, et al. /www.health.gov.au/internet/main/ Massive catecholamine release from caffeine publishing.nsf/Content/foodsecretariat- Received 4 Jul 2011, accepted 15 Nov 2011. poisoning. JAMA 1982; 248: 1097-1098. communiques-031210 (accessed Jun 2011). ❏

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