Science and Law
3rd January 2013

DEFENDING CAFFEINE, ALCOHOL, AND ENERGY DRINKS

As the fastest-growing segment of the beverage industry, it is no surprise that energy drinks have come under increased scrutiny over the past year including the recent 5-hour Energy drink issue. This post provides a brief overview of the recent FDA regulatory history of the issue as well as a summary of some of the more recent science.

DEFENDING CAFFEINE, ALCOHOL, AND ENERGY DRINKS

As the fastest-growing segment of the beverage industry, it is no surprise that energy drinks have come under increased scrutiny over the past year including the recent 5-hour Energy drink issue. This post provides a brief overview of the recent FDA regulatory history of the issue as well as a summary of some of the more recent science.

After the death of a young Maryland girl who ingested two 24-ounce Monster energy drinks in a 24-hour period, Senator Dick Durbin called on the FDA to take regulatory action to enforce caffeine levels in energy drinks. The FDA replied to Senator Durbin’s letter, and noted that research by the Substance Abuse and Mental Health Services Administration (SAMHS) found levels of caffeine in energy drinks ranging from 160 – 500 mg per serving (while those for brewed coffee (16 oz) contain approximately 330 mg per serving).

The FDA’s general conclusion was that in healthy adults, caffeine intake up to 400 mg per day “is not associated with general toxicity, cardiovascular effects, effects on bone status and calcium balance (with consumption of adequate calcium), changes in adult behavior, incidence of cancer, or effects on male infertility” (FDA response). This has also been Health Canada’s stance: “For the rest of the general population of healthy adults, the long-standing advice still applies of no more than 400 mg of caffeine per day, the equivalent of about three 8-oz (237 ml) cups of brewed coffee” (Health Canada on Caffeine).

THE JAMA SERIES

The Journal of the American Medical Association (JAMA) recently published (the December 19, 2012 issue) a series of open-access commentaries on the risk of excess caffeine consumption in energy drinks, alone, or in combination with alcohol. A “Patient Page” was also published, which includes a listing of the caffeine content of beverages and other products, as well as a section on health risks associated with energy drinks (Patient Page). It is also interesting to note that the average caffeine value published for a 16-oz of brewed coffee was 170 mg in the Patient Page, whereas the SAMHS value was 330 mg per 16-oz, and Health Canada ~265 mg. Thus, depending on your source of information, the average level of caffeine in a 16-oz cup of coffee can range from 170 – 330 mg.

Overall, the two commentaries were very insightful, and a brief overview of them is provided below:

Energy Drinks and Caffeine-Related Adverse Effects

Kent A. Sepkowitz, MD

JAMA. 2012;1-2. doi:10.1001/jama.2012.173526.

In his commentary, Dr. Sepkowitz provides a short historical context of caffeine’s use in consumer products and the scrutiny that has ensued, including the most recent investigations on caffeinated energy drinks.

From a medical perspective, Dr. Sepkowitz digs down into the science of caffeine poisoning, noting that only recently has caffeine poisoning been characterized. In the report described by Dr. Sepkowitz, Swedish researchers reported that of 5,000 autopsies, 1% had caffeine levels exceeding 10 μg/mL, which is the equivalent of approximately five cups of standard brewed coffee. Over the period of 16 years in which the autopsies were conducted, 20 cases had caffeine levels higher than 80 ug/mL, a dose considered potentially lethal according to the investigators. The cause of death for 12 of these patients was caffeine intoxication (although several patients had other medications in their bloodstream). Sepkowitz notes that “arrhythmias were the most common cause of caffeine-related death.”

In conjunction with alcohol or some medications (especially those metabolized by the same pathway like the P450 1A2 pathway), Dr. Sepkowitz notes that caffeine’s 5-hour half-life can be prolonged, potentially increasing the stimulant’s effects, and “some fatalities might have resulted from heightened and prolonged caffeine levels attributable to multiple drugs being metabolized by the same metabolic pathway.”

Should the issue of caffeine intoxication become adjudicated in the courts, this leads to the interesting issue of specific causation – that is, an evaluation of whether it can be demonstrated that the exposure caused the adverse event or disease state in a specific individual. Sepkowitz states: “It is not known how many energy drinks were ingested by patients thought to have energy drink–related deaths.” Overall, a number of confounding factors could be involved including various medications, drug-drug interactions, cardiac or liver diseases, body size, sex, genetic factors, and the possible interaction of other ingredients in the energy drinks.

Overall, Sepkowitz recommendation to energy drink enthusiasts was to consult their physicians about energy drink use. He further suggested having caffeine content clearly listed on product labels could help users keep their intake of the stimulant below the safe level of 500 mg per day for people without heart or liver disease. In fact, he said while the role of regulators in energy drink oversight is undefined, requiring labeling of caffeine content on these drinks would be a good start. “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,” he said.

Sepkowitz article

Risks of Energy Drinks Mixed With Alcohol 

Jonathan Howland, PhD, MPH; Damaris J. Rohsenow, PhD

JAMA. 2012;1-2. doi:10.1001/jama.2012.187978.

Howland et al. discuss the increasing popularity amongst young people of alcohol mixed with energy drinks (AMED), and the potential public health consequences of AMED.

Citing a 2007 Nutrition Journal article that surveyed energy drink consumption patterns among college students. In that article, Malinauskas et al. found that 54% of college students mix energy drinks with alcohol while partying, and that using three or more energy drinks was a common practice to drink with alcohol while partying (49%) (Malinauskas article).

The hypothetical concern, as expressed by Howland and colleagues is that caffeine may offset the sedating effects of alcohol, and thus, reduce the sensation of intoxication. This reduced sensation of intoxication may then (theoretically) impair judgment related to risky behaviors, and even induce further alcohol consumption.

The authors summarize a number of scientific studies to support the notion that AMED has been correlated to “increased risk for negative consequences of drinking,” however they concede that studies on AMED’s health effects “on perceived intoxication and sedation [have] been inconsistent.”

According to their analysis, they identified a number of potential confounding variables in the studies, including certain study designs that “leave 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.”  Overall, it appears that from the available scientific evidence, a cause-and-effect determination would be difficult to support.

Of course, even if pre-mixed AMED ceased to exist, “most young people who consume AMED will mix alcohol and caffeine on their own.” Thus, Howland et al. conclude that the 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?”

Howland et al. article

As pressure mounts on the industry and regulatory bodies, changes may be in sight for setting upper limits on the level of caffeine per serving. Notably, Health Canada has just released a 180 mg per serving limit on energy drinks (about the same level found in an 8 oz cup of brewed coffee):

“Specific to caffeine, Health Canada’s scientific assessment supports the establishment of an initial maximum limit for total caffeine of 400 mg per litre with a maximum amount of caffeine not to exceed 180 mg per container presented as a single-serve container” (Health Canada Statement).

Overall, the potential toxicity to apparently healthy individuals from the ingestion of high levels of caffeine, with or without alcohol or other ingredients, is a complex issue. Reliable scientific studies either point to no effect, or are contradictory. Further, each reported case of toxicity is distinct, and determining causation will be difficult at best.

As always, a careful evaluation of the evidence will be critical so that we can understand the factors that are important and those that are incidental. There are so many aspects to this controversy and the evidence must be weighed carefully.

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