Caffeinated alcoholic beverages letter to the food and drug administration from scientists

Attorney General Richard Blumenthal Office of the Attorney General 55 Elm Street Hartford, CT 06106 Attorney General Mark Shurtleff Office of the Attorney General Utah State Capitol Complex 350 North State Street Suite 230 Salt Lake City, UT 84114-2320 Attorney General Alicia G. Limtiaco Office of the Attorney General 287 West O'Brien Drive Hagatna, Guam 96910 Re: The Use of Caffeine in Alcoholic Beverages Dear Generals Blumenthal, Shurtleff, and Limtiaco, This letter is written in response to the concerns raised by State law enforcement officials regarding the safety of caffeinated alcoholic beverages. Collectively, we have studied and conducted research in this area, and based on our findings and our comprehensive review of the scientific literature on this topic, we conclude that there is no evidence to support the claim that caffeine is "generally recognized as safe" ("GRAS") for use in alcoholic beverages. Caffeine is the most widely consumed central nervous system stimulant in the world. It is present naturally in the beans, leaves, and fruit of certain plants, including coffee, tea, cacao, kola, guarana, and yerba mate. Caffeine-containing foods or beverages are consumed regularly by approximately 90% of the United States population, including children (Frary, Johnson, & Wang, 2005). The combined use of caffeine and alcohol is increasing, with the reported prevalence among U.S. college students as high as 28% (Miller, 2008a; O'Brien et al., 2008; Malinauskas et al., 2007). Alcohol mixed with caffeine poses serious public health risks for several reasons. First, frequent consumers of caffeinated energy drinks drink greater quantities of alcohol than individuals who do not drink caffeinated energy drinks (Miller, 2008a; Oteri et al., 2007; Arria et al., in press). In fact, the consumption of caffeinated alcoholic beverages by college students is associated with significantly increased heavy episodic drinking and episodes of weekly drunkenness (O'Brien et al., 2008). Persons who consume caffeinated alcoholic beverages are much more likely to have alcohol-related problems (Miller, 2008b; O'Brien et al., 2008). This is a significant public health concern because many studies have shown that increased exposure to alcohol during the developmental periods of adolescence and young adulthood will increase the risk for alcohol dependence later in life (e.g., see Clark, Kirisci, & Tarter, 1998; Grant & Dawson, 1997). Moreover, there is emerging evidence that increased exposure to psychoactive drugs in general (including alcohol and caffeine) is associated with an increase in the risk for later drug dependence. Second, although a person’s subjective perception of alcohol intoxication (i.e., “feeling drunk”) may be reduced by the ingestion of caffeine, the impairments to judgment and reaction time associated with drunkenness are not (Ferreira et al., 2006; Marczinski & Fillmore, 2006). The advertising of caffeinated alcoholic beverages often suggests that they are “stimulating,” fueling the popular, but incorrect, notion that drunkenness may be ameliorated or altogether averted by mixing caffeine with alcohol, even when the amount of ingested alcohol is extreme. This particular consequence is a health and safety concern for many reasons. Being able to accurately perceive one’s level of intoxication is important; an inaccurate perception will, for example, increase the likelihood of driving while intoxicated or alcohol poisoning, or inflicting injury to oneself or another person. Expectancies regarding the palliative effects of caffeine may further exacerbate these risks by undermining compensatory adaptive responses to alcohol-induced impairment (Fillmore, Roach, & Rice, 2002). In addition, being wide awake and drunk at the same time increases the risk of engaging in several forms of violent or other high-risk physical behaviors that can cause injury. Even after adjusting for the amount of alcohol consumed, college students who consumed alcohol mixed with energy drinks had a significantly higher prevalence of serious alcohol-related consequences such as being taken advantage of sexually, taking advantage of someone else sexually, riding with a drunken driver, and being physically injured, compared to students who drank alcohol alone (O'Brien et al., 2008). Experimental studies conducted to date have not established the safety of co-ingestion of caffeine with high levels of alcohol. Experimental studies that have investigated the effects of co-ingestion of alcohol and caffeine have unanimously set the upper limit on the blood alcohol level achieved during the experiment to be the legal limit of 0.08 g/dL. Moreover, the amount of caffeine consumed in these experiments is moderate so as not to raise the risk of unintended cardiovascular and neurological consequences. The methodological limitations of these studies make extrapolation of the findings very difficult. In natural settings (e.g., bars, homes, etc.), young adults who drink alcoholic energy drinks routinely drink to excessive amounts where the legal limit of BAC is exceeded while simultaneously consuming high levels of caffeine. Finally, to our knowledge, only one recently published study investigated the possible arrhythmogenic effects associated with combining alcohol and caffeinated energy drinks (Wiklund et al., 2009). Their findings suggested that the risk of arrhythmias could be accentuated with the combined intake of energy drinks and alcohol, especially in predisposed individuals. In light of the foregoing health and safety issues, there has been growing international concern regarding the consumption of alcoholic energy drinks. The European Centre for Monitoring Alcohol Marketing (EUCAM), the Dutch National Foundation for Alcohol Prevention (STAP), the Food Safety Promotion Board of the Republic of Ireland (Safefood), Educ’alcool of Quebec, the French Minister of Health, and the governments of Australia and New Zealand have all issued warning statements about the physiological and safety risks associated with combining alcoholic beverages and energy drinks. 1 Regardless of the methodological limitations of experimental studies to extrapolate to “real world” settings, their findings have been mixed and generally inconclusive. Of the thirteen experimental studies we reviewed, two showed evidence that co-ingesting low doses of alcohol with caffeine in a laboratory setting was associated with impaired neuropsychological performance, three showed that caffeine can slightly reduce alcohol-related psychomotor impairment, three showed no significant effects, and five showed mixed results. The conflicting findings most likely stem from variation in the types of performance tests used as outcomes, timing of dose administration, individual variability in alcohol-tolerance and caffeine-sensitivity, and as pointed out by Fillmore et al. (2002), individual expectancies. 2 Our own recent work has documented that 65% of college students reached the level of getting drunk at least half the times they drank in the past month (Arria et al., in preparation). In summary, there is no general consensus among health professionals and the scientific research community that the use of caffeine in alcoholic beverages has been demonstrated to be safe. On the contrary, the consumption of caffeinated alcoholic beverages has been associated with increased risk of serious injury to oneself and to others, as the result of driving while intoxicated, sexual assault, and other dangerous behaviors. Sincerely,
Amelia M. Arria, Ph.D.

Mary Claire O’Brien, M.D.
Department of Social Science and Health Policy Wake Forest University School of Medicine Wake Forest University/ Baptist Medical Center Treatment Research Institute
600 Public Ledger Building
150 S. Independence Mall West
Philadelphia, PA 19106

Bruce A. Goldberger, Ph.D.
Professor and Director of Toxicology
University of Florida College of Medicine
Rocky Point Labs
4800 S.W. 35th Drive
Gainesville, FL 32608
Roland R. Griffiths, Ph.D.
Departments of Psychiatry and Neuroscience
Johns Hopkins University School of Medicine
5510 Nathan Shock Drive
Baltimore, MD 21224
Kathleen E. Miller, Ph.D.
Research Scientist
Research Institute on Addictions
State University of New York at Buffalo
University at Buffalo
1021 Main Street
Buffalo, NY 14203

References Cited (see attached in pdf file)
Arria, A. M., Caldeira, K. M., Kasperski, S. J., O’Grady, K. E., Vincent, K. B., Griffiths, R. R., & Wish,
E. D. (in press). Energy drink consumption, illicit drug use, and nonmedical use of prescription drugs among college students. Journal of Addiction Medicine. Arria, A. M., Caldeira, K. M., Vincent, K. B., & O’Grady, K. E. (in preparation). Longitudinal patterns of alcohol consumption among college students: Implications for early intervention with high-risk drinkers. Clark, D. B., Kirisci, L., & Tarter, R. E. (1998). Adolescent versus adult onset and the development of substance use disorders in males. Drug and Alcohol Dependence, 49, 115-121. Ferreira, S. E., de Mello, M. T., Pompeia, S., & de Souza-Formigoni, M. L. (2006). Effects of energy drink ingestion on alcohol intoxication. Alcoholism: Clinical and Experimental Research, 30(4), 598-605. Fillmore, K. M., Roach, E. L., & Rice, J. T. (2002). Does caffeine counteract alcohol-induced impairment? The ironic effects of expectancy. Journal of Studies on Alcohol, 63, 745-754. Frary, C. D., Johnson, R. K., & Wang, M. Q. (2005). Food sources and intakes of caffeine in the diets of persons in the United States. Journal of the American Dietetic Association, 105, 110-113. Grant, B. F., & Dawson, D. A. (1997). Age at onset of alcohol use and its association with DSM-IV alcohol abuse and dependence: results from the national longitudinal alcohol epidemiologic survey. Journal of Substance Abuse, 9, 103-110. Malinauskas, B. M., Aeby, V. G., Overton, R. F., Carpenter-Aeby, T., & Barber-Heidal, K. (2007). A survey of energy drink consumption patterns among college students. Nutrition Journal, 6, 35-41. Marczinski, C. A., & Fillmore, M. T. (2006). Clubgoers and their trendy cocktails: Implications of mixing caffeine into alcohol on information processing and subjective reports of intoxication. Experimental and Clinical Psychopharmacology, 14(4), 450-458. Miller, K. E. (2008a). Wired: Energy drinks, jock identity, masculine norms, and risk taking. Journal of American College Health, 56(5), 481-490. Miller, K. E. (2008b). Energy drinks, race, and problem behaviors among college students. Journal of Adolescent Health, 43(5), 490-497. O'Brien, M. C., McCoy, T. P., Rhodes, S. D., Wagoner, A., & Wolfson, M. (2008). Caffeinated cocktails: Energy drink consumption, high-risk drinking, and alcohol- related consequences among college students. Academic Emergency Medicine, 15(5), 453-460. Oteri, A., Salvo, F., Caputi, A. P., & Calapai, G. (2007). Intake of energy drinks in association with alcoholic beverages in a cohort of students of the school of medicine of the University of Messina. Alcoholism: Clinical & Experimental Research, 31(10), 1677-1680. Wiklund, U., Karlsson, M., Ostrom, M., & Messner, T. (2009). Influence of energy drinks and alcohol on post-exercise heart rate recovery and heart rate variability. Clinical Physiology and Functional Imaging, 29(1), 74-80.
Relevant Reviews of Literature (see attached pdf file)
Fudin, R., & Nicastro, R. (1988). Can caffeine antagonize alcohol-induced performance decrements in
humans? Perceptual and Motor Skills, 67(2), 375-391. Reissig, C. J., Strain, E. C., & Griffiths, R. R. (2009). Caffeinated energy drinks-A growing problem. Drug and Alcohol Dependence, 99(1-3), 1-10. Simon, M., & Mosher, J. (2007). Alcohol, energy drinks, and youth: A dangerous mix: Marin Institute. Additional Experimental Studies Reviewed (pdf file available upon request)
Azcona, O., Barbanoj, M. M., Torrent, J., & Jane, F. (1995). Evaluation of the central effects of alcohol
and caffeine interaction. British Journal of Clinical Pharmacology, 40(4), 393-400. Curry, K., & Stasio, M. J. (2009). The effects of energy drinks alone and with alcohol on neuropsychological functioning. Human Psychopharmacology, 24(6), 473-481. Fillmore, M. T. (2003). Alcohol tolerance in humans is enhanced by prior caffeine antagonism of alcohol-induced impairment. Experimental and Clinical Psychopharmacology, 11(1), 9-17. Fillmore, M. T., & Vogel-Sprott, M. (1995). Behavioral effects of combining alcohol and caffeine: Contribution of drug-related expectancies. Experimental and Clinical Psychopharmacology, 3(1), 33-38. Franks, H. M., Hagedorn, H., Hensley, V. R., Hensley, W. J., & Starmer, G. A. (1975). The effect of caffeine on human performance, alone and in combination with ethanol. Psychopharmacology, 45(177-181). Grattan-Miscio, K. E., & Vogel-Sprott, M. (2005). Alcohol, intentional control, and inappropriate behavior: Regulation by caffeine or an incentive. Experimental and Clinical Psychopharmacology, 13(1), 48-55. Hasenfratz, M., Bunge, B., Dal Pra, G., & Battig, K. (1993). Antagonistic effects of caffeine and alcohol on mental performance parameters. Pharmacology Biochemistry and Behavior, 46, 463-465. Kerr, J. S., Sherwood, N., & Hindmarch, I. (1991). Separate and combined effects of the social drugs on psychomotor performance. Psychopharmacology, 104, 113-119. Liguori, A., & Robinson, J. H. (2001). Caffeine antagonism of alcohol-induced driving impairment. Drug and Alcohol Dependence, 63(2), 123-129. Mackay, M., Tiplady, B., & Scholey, A. B. (2002). Interactions between alcohol and caffeine in relation to psychomotor speed and accuracy. Human Psychopharmacology: Clinical & Experimental, 17(3), 151-156. Martin, F. H., & Garfield, J. (2006). Combined effects of alcohol and caffeine on the late components of the event-related potential and on reaction time. Biological Psychology, 71(1), 63-73. Nuotto, E., Mattila, M. J., Seppala, T., & Konno, K. (1982). Coffee and caffeine and alcohol effects on psychomotor function. Clinical Pharmacology and Therapeutics, 31(1), 68-76.



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