Energy drink and risk of arrhythmias: Recommendations for a safer use in young adolescents

Large epidemiologic studies have failed to find a connection between the amount of caffeine use and the development of arrhythmias. As such, it does not make sense to suggest that patients with palpitations, paroxysmal atrial fibrillation, or supraventricular tachycardia is produced from caffeine use. The main toxicity caused by caffeine is due to the increase in intracellular calcium concentration, which leads to a catecholamine surge that sensitizes dopamine receptors resulting in supraventricular or ventricular arrhythmias and death ultimately at very high doses [1-7]. Energy drinks (EDs) are a new corner on the beverage market, with 30-50% of young adults and teens using them regularly. EFSA (European Food Safety Authority) has published a report on a commissioned study that for the first time collates data on the consumption of EDs at European level for specific population groups, including children and adolescents. The study also estimates consumers [8] exposure, through both acute and chronic consumption, to some active ingredients found in EDs primarily caffeine, taurine and D-glucurono-lactone. The study found that, among respondents, the age group most likely to consume EDs was adolescents (68% of total respondents) and that EDs when consumed by children aged 3 to 10 years account for an estimated 43% of their total caffeine exposure. The key findings from the study are as follows: Adolescents (10-18 years): approximately 68% of those interviewed were consumers of EDs. Among these, about 12% were “high chronic” consumers, with an average consumption of 7 litres a month, and 12% were “high acute” consumers. Children (3-10 years): approximately 18% of those interviewed were consumers of EDs. Among these, around 16% were “high chronic” consumers, with average consumption of 0.95 litres a week (almost 4 litres per month). In our recent experience in young student of Naples the majority of users consumed one ED to treat most situations, although using three or more was a common practice to drink with alcohol while partying (53%) and before or during sport practice (68%) [9].


Introduction
Large epidemiologic studies have failed to find a connection between the amount of caffeine use and the development of arrhythmias. As such, it does not make sense to suggest that patients with palpitations, paroxysmal atrial fibrillation, or supraventricular tachycardia is produced from caffeine use. The main toxicity caused by caffeine is due to the increase in intracellular calcium concentration, which leads to a catecholamine surge that sensitizes dopamine receptors resulting in supraventricular or ventricular arrhythmias and death ultimately at very high doses [1][2][3][4][5][6][7]. Energy drinks (EDs) are a new corner on the beverage market, with 30-50% of young adults and teens using them regularly. EFSA (European Food Safety Authority) has published a report on a commissioned study that for the first time collates data on the consumption of EDs at European level for specific population groups, including children and adolescents. The study also estimates consumers [8] exposure, through both acute and chronic consumption, to some active ingredients found in EDs primarily caffeine, taurine and D-glucurono-lactone. The study found that, among respondents, the age group most likely to consume EDs was adolescents (68% of total respondents) and that EDs when consumed by children aged 3 to 10 years account for an estimated 43% of their total caffeine exposure.
The key findings from the study are as follows: Adolescents (10-18 years): approximately 68% of those interviewed were consumers of EDs. Among these, about 12% were "high chronic" consumers, with an average consumption of 7 litres a month, and 12% were "high acute" consumers. Children (3-10 years): approximately 18% of those interviewed were consumers of EDs. Among these, around 16% were "high chronic" consumers, with average consumption of 0.95 litres a week (almost 4 litres per month). In our recent experience in young student of Naples the majority of users consumed one ED to treat most situations, although using three or more was a common practice to drink with alcohol while partying (53%) and before or during sport practice (68%) [9].
EDs are loaded with caffeine, sugar, and other chemicals that can stimulate the cardiac system. There is an increasing body of mainly anecdotal case reports describing arrhythmias or even sudden death triggered by exercise plus using EDs. EDs contain a variety of substances, but caffeine is the main component. Safety has been the biggest concern associated with consuming EDs. Recently, ED-associated emergency visits have sharply increased [3]. They are often found in combination with other substances, such as alcohol and drugs of abuse, which further potentiates the effect of EDs [4]. EDs have been recognized to cause cardiovascular changes, particularly cardiac arrhythmias (Supraventricular arrhythmia, Ventricular arrhythmia) and elevated blood pressure, increased heart rate, increased QTc interval, Coronary artery spasm, Coronary artery thrombosis, Takotsubo cardiomyopathy, ST-Segment Elevation Myocardial Infarction (STEMI), Sudden cardiac death, Endothelial dysfunction [1]. It is unknown what makes some people more susceptible to arrhythmias. It may be that some individuals are genetically susceptible to the effects of EDs, resulting in arrhythmias or it may be the actual acute ingestion of EDs putting the patient at risk of arrhythmias [10][11][12][13][14][15][16][17][18][19][20].

Regulation of energy drinks
The FDA imposes a limit of 71 mg of caffeine per 12 fl oz of soda. EDs manufacturers may circumvent this limit by claiming that their drinks are "natural dietary supplements". Thus, safety determinations of energy drinks are made solely by the manufacturers, and there are no requirements for testing, warning labels, or restriction against sales or consumption by minors. In contrast, over-the-counter dedicated caffeine stimulants must list the minimum age for purchase (14 years), adverse effects, cautionary notes, recommended dose, and the total daily recommended dose of caffeine. In November 2009, the FDA asked manufacturers of non-alcoholic EDs to prove their safety [7]. The US Senate is considering a bill that would require supplement manufacturers to register annually with the FDA and allow FDA recalls of supplements suspected of being unsafe. Ingredients may also be restricted to those that have already been approved by the FDA. Regulatory controversies also extend internationally. When France banned Red Bull, the manufacturers challenged the ban through the European Commission, which determined that the caffeine and taurine concentrations in EDs had not been proven to health risks and ordered France to lift the ban; the European Food Safety Authority has encouraged international data-pooling to better assess risks in children, adolescents, and young adults.
Screening is especially important for athletes, children with highrisk behaviors, certain health conditions (eg, seizures, diabetes, hypertension, cardiac abnormalities) and in pregnant women. For most children, adolescents, and young adults, safe levels of consumption have not been established. Yet, heavy use may be harmful or interact with medications and cause untoward adverse effects. Health care providers should educate families and children at risk for the potential adverse effects of EDs. Routine high school athletic physicals do not identify everyone at risk for sudden cardiac death. Children and their parents with cardiac conditions should be counseled regarding the risks of caffeine-containing products, including irregular heart rhythms, syncope and sudden death. Community partners, including schools, athletic groups, and regulatory bodies, also need to promote risk awareness. This approach is essential for reducing morbidity and mortality, encouraging research, and supporting families of children and young adults at risk for EDs overdose, behavioral changes, and acute/chronic health consequences. The American Association of Poison Control Centers are the governmental agency responsible for collecting the information on all the ways people are poisoned each year [21]. They publish a very detailed annual report documenting reported cases during that given year. Looking at the above data, we can draw a few conclusions : Do not consume more than 1 can (250 mL) of an EDs per day; Avoid EDs consumption before or during sports practice; Individuals with diagnosed cardiovascular anomalies should consult cardiologists before drinking EDs; Do not combine ED consumption and alcohol or other drugs; Parents and Schools should provide continual advice against overconsumption/abuse of EDs.
Because caffeine is being put into products that are especially appealing to teens, teens can pretty quickly consume too much caffeine without realizing it. No one would argue that other substances are far more dangerous, but other drugs aren't specifically marketed to the younger demographic as EDs are. Pediatricians need to be aware of the possible effects of EDs in vulnerable populations and screen for consumption to educate families. Long-term research should aim to understand the effects in at-risk populations. Toxicity surveillance should be improved, and regulations of energy drink sales and consumption should be based on appropriate research. In 2013 the Canadian Journal of Cardiology [22] published a comprehensive study that looked at the incidences of cardiac events after EDs consumption among teens. They found that EDs abuse among teens did cause increased risk of cardiac events especially in those with underlying heart conditions and there were even some cases of EDs causing changes in heart rhythm among teens with healthy hearts. This risk increases when the child engages in sports or exercise. The researchers therefore have the following recommendations for safe use of EDs among this age group. In the 2014 the National Federation of State High School Associations (NFHS) Sports Medicine Advisory Committee (SMAC) published the Position Statement and Recommendations for the use of EDs by young athletes [23]. It strongly recommends that: EDs should not be consumed by athletes who are dehydrated; EDs should not be consumed without prior medical approval, by athletes taking over the counter or prescription medications. There are some clear instances where ED consumption by adults should be avoided; one notable example is a patient with underlying QTc prolongation or one using potentiating medications [14]. At the very least, providers should obtain a baseline electrocardiogram and inquire about ED consumption to evaluate the risk of QTc prolongation in patients before prescribing medications implicated in cardiac abnormalities. Health Canada used scientific data on the health hazard posed by caffeine to establish recommended maximum daily intake values for children (2.5 mg/kg bw/day), adults (6.0 mg/kg bw/day) and women of reproductive age (4.6 mg/kg bw/day) [24,25]. As a precautionary approach, adolescents can be considered to be as sensitive as children to caffeine. To date, for healthy adults FDA has cited 400 mg a day as a safe consumption limit; however, they have not set a level of safe consumption of caffeine for younger people. In 2013, the International Sport Society stated that EDs contain many ingredients which need further studies to demonstrate their safety and potential harmful effects. They therefore recommended that children and adolescents should not consume EDs without parental permission [26]. In 2013, Health Canada stipulated that the daily caffeine intake for younger children should not be greater than 2.5 mg/kg of body weight [22]. Thus, EDs are not recommended. In 2016 the European Parliament rejected the proposal of European Union Commision of promoting the Energy Drinks as a " human performances enhancer" because of potentially dangerous consequences of their inappropriate use. The label should state the following warning: "This product is not permitted for pregnant women, or women breast feeding, children under 16 years of age, persons susceptible to allergy by caffeine, or persons suffering from heart disease or athletes during sport practice". The Table 1 resumes the suggestions for EDs consumption respect to age and medical conditions.