Energy Drinks and Caffeine-Related Adverse Effects.......Risks of Energy Drinks Mixed With Alcohol
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Download the PDF here
Kent A. Sepkowitz, MD
JAMA. Dec 26 2012
"Most current soft drinks and coffees, as well as energy drinks, have about 100 mg of caffeine per serving. A few energy drinks have up to 250 mg per serving.....Caffeine is well-absorbed and achieves peak blood levels 15 to 45 minutes following ingestion. Caffeine is quickly metabolized by the liver into active stimulants such as theophylline and theobromine. Alcohol and other medications can prolong the 5-hour half-life of caffeine and contribute to its toxic effects......Of 5000 forensic autopsies performed in Sweden each year, 1% had caffeine levels exceeding 10 μg/mL. To place this in perspective, a single cup of standard brewed coffee results in blood caffeine levels of 1 to 2 μg/mL. In 16 years of autopsies, 20 cases had caffeine levels higher than 80 μg/mL, a dose considered potentially lethal.9 The cause of death for 12 of these patients (average age, 41 years) was caffeine intoxication, although several patients had other medications in their bloodstream.9 Arrhythmias were the most common cause of caffeine-related death......Caffeine and a number of medications are metabolized via the cytochrome P450 1A2 pathway.....Some people may have cardiac or liver diseases that could increase susceptibility to caffeine-related adverse effects, making a routinely consumed amount of caffeine more dangerous. Some ingredients in energy drinks may confer toxicity or promote drug-drug interactions."
In 1911, under authority granted by the recently enacted Food and Drug Act, US agents seized 40 kegs and 20 barrels of Coca-Cola syrup in Chattanooga, Tennessee.1- 2 The group, led by chief chemist Harvey Wiley, considered the caffeine in Coca-Cola to be a significant public health hazard (both cocaine and alcohol had been removed from the recipe in the previous decade). The case continued for years. Eventually Coca-Cola decreased the caffeine content in this product and legal action was dropped.3
In 2012, the Food and Drug Administration (FDA) is again investigating a caffeine-containing product, the "energy drink," because of safety concerns. Several types of these caffeinated drinks are linked to unexpected deaths in apparently healthy persons, raising calls for closer scrutiny and possible regulation. Drinks containing both caffeine and alcohol were considered unsafe by the FDA in 2010 because the caffeine obscured "some of the sensory cues individuals might normally rely on to determine their level of intoxication."4
The swift change in public perception of energy drinks from harmless mild stimulant to lethal, unregulated drug is unprecedented. Energy drinks were introduced in the United States in 1997. Since then their popularity has increased: US residents consumed an estimated 2.3 billion energy drinks in 2005 and 6 billion in 2010.5 About 6% of young men in the United States report consuming a daily energy drink. In a recent survey of US overseas troops, 45% reported daily use.6 Sales of energy drinks in the United States increased 16% in a single year to almost $9 billion in 2011.7
Product labels for most energy drinks do not list their caffeine content. Many energy drinks contain "natural" ingredients, such as ginkgo or milk thistle, allowing these drinks to be regulated as "dietary supplements" rather than as medications. The 1994 Dietary Supplement and Education Act classifies products containing herbs and other natural ingredients as supplements rather than drugs, allowing manufacturers to side-step disclosure of caffeine dose, even though some brands do provide the information.8 In contrast, caffeine-containing products such as No-Doz and Caffedrine, marketed as over-the-counter drugs, are required to provide dose.
The millions of persons consuming energy drinks seek more energy, alertness, or stamina yet may be unaware of the amount of caffeine they are ingesting. Consequently, unintentional caffeine overdoses have resulted in serious illness and rare deaths from caffeine poisoning.8- 9
Caffeine poisoning has only recently been characterized. Swedish researchers conducted an extensive analysis defining toxic doses of caffeine.9- 10 Of 5000 forensic autopsies performed in Sweden each year, 1% had caffeine levels exceeding 10 μg/mL. To place this in perspective, a single cup of standard brewed coffee results in blood caffeine levels of 1 to 2 μg/mL. In 16 years of autopsies, 20 cases had caffeine levels higher than 80 μg/mL, a dose considered potentially lethal.9 The cause of death for 12 of these patients (average age, 41 years) was caffeine intoxication, although several patients had other medications in their bloodstream.9 Arrhythmias were the most common cause of caffeine-related death.
Although blood levels of caffeine higher than 80 μg/mL have been described, the corresponding dose of caffeine needed to reach that level is not known. Ingestion over a brief time of 3 to 10 g of caffeine might be lethal.9- 10 Caffeine is well-absorbed and achieves peak blood levels 15 to 45 minutes following ingestion. Caffeine is quickly metabolized by the liver into active stimulants such as theophylline and theobromine. Alcohol and other medications can prolong the 5-hour half-life of caffeine and contribute to its toxic effects. Most current soft drinks and coffees, as well as energy drinks, have about 100 mg of caffeine per serving. A few energy drinks have up to 250 mg per serving (see the related table in the Patient Page).
To reach the possibly lethal dose of 3 g of caffeine, a person would need to ingest at least 12 of the highly caffeinated energy drinks within a few hours. It is not known how many energy drinks were ingested by patients thought to have energy drink-related deaths. A number of contributory factors require exploration. For example, drug-drug interactions relating to caffeine's toxic effects are incompletely understood. Caffeine and a number of medications are metabolized via the cytochrome P450 1A2 pathway. Some fatalities might have resulted from heightened and prolonged caffeine levels attributable to multiple drugs being metabolized by the same metabolic pathway. The rate of drug metabolism varies from person to person and depends on body size, age, sex, and genetic factors. Some people may have cardiac or liver diseases that could increase susceptibility to caffeine-related adverse effects, making a routinely consumed amount of caffeine more dangerous. Some ingredients in energy drinks may confer toxicity or promote drug-drug interactions.
Given the increasing popularity of these products, physicians should ask their patients about their use of energy drinks, particularly young men who are the heaviest users. In addition, information that defines the caffeine content of most commercially available products should be provided (see related table in the Patient Page). A ceiling of less than 500 mg of caffeine per day is generally considered a safe daily dose. A lower daily dose or no caffeine ingestion should be considered for patients with heart disease or liver disease.
The appropriate role of the FDA and other regulators in the oversight of energy drinks is yet to be defined. A logical first step might be to require placing the caffeine content of energy drinks on their label. In Sweden, restriction of caffeine tablet sales from 250 to 30 pills per customer appeared to decrease the rate of fatal caffeine overdoses, suggesting that deliberately restricting the sale of preparations with a high dose of caffeine might be an effective approach.9 Publicity about energy drink-related deaths should inform the public of the potential dangers of these products.
Risks of Energy Drinks Mixed With Alcohol
Jonathan Howland, PhD, MPH; Damaris J. Rohsenow, PhD
JAMA. Dec 26 2012
The energy drink market is a multibillion-dollar industry that uses aggressive and innovative marketing strategies to target teens and young adults. Consequently, 31% of young teens and 34% to 51% of 18- to 24-year-olds report regular consumption of these products.1
Energy drinks contain caffeine and often other substances such as guarana (containing guaranine, similar to caffeine), taurine (an amino acid), and sugar derivatives. The primary active ingredient is caffeine, usually with 80 to 141 mg of caffeine per 8 oz (equivalent to a 5-oz cup of coffee or 2 cans of soda).
The health effects of energy drinks have received attention from researchers and policy makers because there is limited knowledge about differential effects of caffeine on children and adults and the interaction of caffeine and alcohol. Alcohol mixed with energy drinks (AMED) has become increasingly popular, especially among adolescents and college students. In surveys of college students, as many as 56%2 report mixing energy drinks with alcohol in the past month. Alcohol mixed with energy drinks includes cocktails served at bars (eg, Red Bull and vodka), premixed caffeinated alcoholic beverages (eg, Four Loco), self-mixed beverages, and alcohol and energy drinks consumed separately but within the same drinking occasion.
POTENTIAL PUBLIC HEALTH CONSEQUENCES OF AMED
Hypotheses about the risks of AMED consumption are as follows. First, by offsetting the sedating effects of alcohol, the caffeine component of AMED reduces the sensation of intoxication. Second, reduced sensation of intoxication impairs judgment relative to risky behaviors (eg, drunken driving) because drinkers do not realize that they are intoxicated. Third, reduced sensation of intoxication induces more alcohol consumption, which further impairs judgment and neurocognitive functioning.
Although experimental evidence about the effects of AMED on perceived intoxication and sedation has been inconsistent, AMED use is correlated with increased risk for negative consequences of drinking. In a study of 802 bar patrons, the adjusted odds ratio for leaving the bar intoxicated (breath alcohol concentration >0.08 g/%) for those who consumed AMED, compared with those consuming alcohol without caffeine, was 2.99 (95% CI, 1.39-6.43; absolute risk difference, 9.5% vs 3.5%). For intending to drive after leaving the bar, the adjusted odds attributable to adding caffeine to alcohol was 4.26 (95% CI, 2.14-8.49; absolute risk, 12.3% vs 4.4%).3 Students who consumed AMED, relative to those who consumed alcohol without caffeine, were more likely to experience a variety of drinking-related negative consequences, including approximately double the risk of experiencing or committing sexual assault, riding with an intoxicated driver, having an alcohol-related motor vehicle crash, or requiring medical treatment.1
ASSESSING THE EVIDENCE
Some cross-sectional studies showing an association between AMED consumption and increased risk taking have used between-group analyses: behaviors for AMED users are compared with behaviors in people drinking alcohol without energy supplements. This study design leaves open the possibility that those who choose to use AMED are inherently more prone to risk-taking behaviors, and thus the relationship between AMED and risk taking could be spurious. It is possible that personality traits such as impulsivity and sensation seeking cause AMED consumption, rather than AMED causing risky behaviors. In one study, young people who frequently consumed energy drinks were more likely than their peers who consumed energy drinks less frequently to be heavy drinkers.4 In another study, college students who consumed AMED were more likely than those who consumed alcohol without caffeine to have drunk heavily, to have been drunk, and to have drunk more alcohol on a typical drinking occasion in the last 30 days.1
The way to control for this potential confounding is by comparing drinking and risk taking when the same individuals consume alcohol with and without caffeine. Studies using this within-participant approach have tended to find no association between AMED use and risky behaviors.5- 6
Most experimental studies found that caffeine reverses alcohol-related impairment on tests of reaction time, psychomotor speed, and simulated driving performance at moderate (but not high) alcohol levels but not on error rates.7 Thus, caffeine allowed moderately intoxicated individuals to respond as quickly as if not intoxicated, but their performance remained impaired. Caffeine antagonizes the effects of alcohol on response execution but not on inhibitory control, possibly increasing risk-taking behaviors while consuming AMED. Marketing of AMED to promote the belief that it reduces impairment and sedation is misleading. Social drinkers who believed that caffeine would counteract impairment from alcohol actually showed greater impairment.8 The extent to which AMED affects psychomotor impairment and sedation remains unclear.
PUBLIC HEALTH RESPONSE
In 2008, in response to the perceived public health threat posed by AMED, 13 state attorneys general and the San Francisco city attorney negotiated settlements by which 2 national breweries agreed to remove caffeine and all other stimulants from their products. In 2010, the US Food and Drug Administration (FDA) sent warning letters to 7 producers of premixed caffeinated alcoholic beverages, essentially halting their production and sale. The US Centers for Disease Control and Prevention has posted a fact sheet warning of dangers related to mixing alcohol and energy drinks. In 2012, when a number of students were treated for excessive consumption of Four Loco, a premixed, caffeinated, high-alcohol-content beverage, several states prohibited the sale of this product.
These initiatives may increase awareness and lead to reduced marketing of premixed AMED. However, most young people who consume AMED will mix alcohol and caffeine on their own. Thus, it is important that policy makers, parents, university administrators, health care professionals, and consumers of AMED have accurate information regarding AMED as a public health danger.
Brands of energy drinks continue to proliferate. The public needs more definitive information and education about the safety threshold for caffeine consumption and, in particular, the effects of caffeine on adolescent behavior and development. Policy makers should hold energy drink manufacturers accountable for claims regarding the health and psychosocial benefits of their products.
In the meantime, it is likely that young people will continue to mix alcohol with caffeine. Potential harms of AMED warrant additional rigorous experimental and survey research to examine 3 critical questions. Is the relationship between AMED consumption and risky behavior confounded by personality traits? Does AMED consumption distort perceptions of intoxication? Does AMED consumption increase alcohol consumption, relative to drinking alcohol alone?
For the present, however, consensus about these questions, and identification of gaps in knowledge, could be achieved by targeting research on this topic and by convening experts to assess existing evidence. Consensus panels might include participants from regulatory organizations, such as the FDA or the Consumer Product Safety Commission; research entities, such as the National Institutes of Health or the Institute of Medicine; and clinician organizations, such as the American Academy of Pediatrics. Such an effort could provide valuable guidance to emerging and future public health policy on AMED.
Janet M. Torpy, MD; Edward H. Livingston, MD
JAMA. Dec 26 2012
Beverages called energy drinks are popular, especially with teenagers and young adults. These energy drinks are advertised to give individuals a higher energy level, to make a person feel more awake, and to boost attention span.
Energy drinks are marketed in different serving sizes and have varying amounts of caffeine. Sodas (also known as pop, colas, or soft drinks) may contain sugar and caffeine, although most sodas contain less caffeine than energy drinks on an ounce-by-ounce basis. As a comparison, an 8-oz cup of coffee has about 100 mg of caffeine (see table at right, and expanded table online at www.jama.com). The January 16, 2013, issue of JAMA contains 2 articles discussing the harms associated with energy drinks.
COMMON INGREDIENTS IN ENERGY DRINKS
· Guarana (a plant with seeds that contain caffeine)
· B vitamins
· Herbs, including ginseng, licorice, and kola nut
HEALTH RISKS ASSOCIATED WITH ENERGY DRINKS
· Increased heart rate
· Irregular heart rate and palpitations
· Increased blood pressure
· Sleep disturbances, including insomnia
· Diuresis (increased urine production)
· Hyperglycemia (increased blood sugar) is related to all beverages with high sugar content. This can be harmful for individuals with diabetes or other metabolic health problems.
The American Academy of Pediatrics recommends that young children should not consume energy drinks. Caffeine may be especially harmful for children. Adolescents should not have more than 100 mg of caffeine each day. Parents should monitor how much soda or coffee (or other beverages containing caffeine, including energy drinks of any kind) their teenagers drink and help them understand the risks associated with taking in large amounts of caffeine.
Adults should limit their caffeine intake to 500 mg per day. Individuals who have heart problems, high blood pressure, or trouble sleeping or who are taking medications should be careful to limit the amount of caffeine they drink. Older persons may be more sensitive to the effects of caffeine.
Energy drinks are not regulated by the US Food and Drug Administration. However, the ingredients in energy drinks may be harmful to some individuals. It is important to read labels for any food or drink product that you consume. If you choose to use energy drinks, make sure you understand the ingredients and serving sizes listed on the label.