OVERVIEWIntroduction
Energy drinks are defined as over-the-counter commercial beverages with high caffeine content that are advertised as boosting energy including mental alertness and physical performance. More than 50 brands of energy drinks are available in grocery stores, nutrition centers, beverage shops and on the internet. Consumption of excess energy drinks has been linked to several instances of clinically apparent acute liver injury which can be severe and result in fatal or urgent liver transplantation. The components in energy drinks that account for the liver injury are not clear and caffeine by itself has not been linked to hepatic injury.
Background
Energy drinks are defined as beverages with high concentrations of caffeine that are purported to boost energy, physical and athletic performance and mental alertness. Energy drinks were first marketed in the late 1990s and have subsequently become popular and widely available. The commercial products vary greatly in concentration of caffeine as well as in other characteristics, such as carbonation, flavoring, sugar and sweeteners, vitamins, minerals, amino acids and botanical ingredients. Popular brands include Red Bull, Monster, Rockstar, NOS Energy, Xyience, Bang, Celsius, Zevia, Full Throttle and Kick Start. The caffeine content of these products varies from 5 to 40 mg per ounce, and a single serving (8 to 24 ounces; 235-710 mL) may contain up to 300 mg of caffeine. Caffeine is also present in regular soft drinks but generally in amounts similar to tea (2 to 5 mg/oz; and 24 to 60 mg per 12 oz can), although soft drink brands with extra caffeine have also become popular (Pepsi Max, Jolt Cola, Mountain Dew Energy). The average caffeine content in selected energy drinks and soft drinks is shown in the table below. Caffeine has been shown to have psychoactive properties and to increase alertness and wakefulness and improve physical and athletic performance, although to a minor degree and with considerable inter-individual variability. Caffeine in typical amounts is well tolerated and not associated with significant side effects or long term adverse outcomes. Adverse side effects of caffeine are generally dose related and can include nervousness, irritability, insomnia, headaches, rapid heartbeat, tremor, and gastrointestinal discomfort. In high doses, generally in excess of 1000 mg daily, caffeine can have severe toxicity, marked by confusion, excessive anxiety, mania, hallucinations, seizures, rhabdomyolysis, cardiorespiratory arrest and death.
Caffeine Content of Selected Soft Drinks and Energy Drinks Available in the United States
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Product NameCaffeine(mg/oz)Typical size(Can/Bottle)Caffeine(mg/Serving)Comments,Selected Other IngredientsSoft DrinksCoca-Cola2.912 oz23Pepsi3.212 oz38Dr Pepper3.412 oz41Mountain Dew4.512 oz54Diet Pepsi2.912 oz35Diet Dr Pepper3.412 oz41Diet Coke3.812 oz46Diet Mountain Dew4.512 oz54Sprite012 oz07-Up012 oz0Fortified Soft DrinksPepsi Max3.88 oz43Mountain Dew Kickstart5.816 oz92Coca-Cola Energy9.512 oz114AMP Energy916 oz142Energy DrinksRed Bull108 oz80Most commonly used energy drinkV8 Fusion108 oz8050% vegetable juiceZevia1012 oz120Stevia as sweetener, calorie-lessRockstar1016 oz160Taurine, ginseng, ginkgo, milk thistleNOS1016 oz160Taurine, acacia, B vitJolt Cola1016 oz160Xyience1116 oz176Ginseng, Guarana, vit, aa, minCelsius1216 oz200Green tea, guarana, ginger, vit, min5-Hour Energy1002 oz200Vit, aaSpike Shooter368 oz300Yohimbine, vit, aa “Spike S formula”Redline Xtreme408 oz316Green tea, yohimbe, yerba mate, aaOtherTypical Drip Coffee8-201 cup, 8 oz60-150Typical Black Tea2 to 51 cup, 8 oz15-35*
Concentrations and volumes are rounded off. Several of the commercial products have multiple formulations, flavors and special names. Abbreviations: aa, amino acids; min, minerals; vit, vitamins.
Hepatotoxicity
Caffeine containing energy drinks are widely used and generally well tolerated. Neverless, when taken in excessive amounts they can lead to caffeine toxicity with tremors, confusion, mania, stupor and coma and cardiac arrhythmias and cardiorespiratory failure. In addition, there have been several single case reports of liver injury linked to use of caffeine-rich energy drinks. These reports were often incompletely documented and not completely convincing. In several instances, the hepatic injury resembled acute hepatic necrosis or ischemic hepatitis (Case 1) that may have been due to a drug overdose or cardiac arrest. In other cases, other diagnoses were not completely ruled out (Case 2). Furthermore, it remains unclear whether the hepatic effects of the energy drinks were caused by caffeine per se or to other components included in their formulation, such as vitamins, herbs or other botanical products. The reports of caffeine overdose including cases with autopsies, hepatic injury has been absent or not mentioned. Thus, caffeine is unlikely to cause liver injury, but the various high caffeine energy drinks which are widely used may possibly cause liver injury when used to excess.
Likelihood score: C[H] (probable rare cause of clinically apparent liver injury when used in high amounts).
Mechanism of Injury
Caffeine is metabolized by the microsomal P450 drug metabolizing enzymes, predominantly CYP 1A2. Patients with advanced cirrhosis may have delayed metabolism of caffeine and experience caffeine side effects (nervousness, insomnia, headache) at levels of intake that are well tolerated by patients without liver disease.
Energy drinks typically have high concentrations of caffeine but also a myriad of other components including vitamins, minerals, amino acids, sugar and various herbal products, the concentration and purity of which are usually unknown.
Drug Class: CNS Stimulants, Xanthine Derivatives
See also Caffeine
CASE REPORTCase 1. Acute liver injury attributed to use of energy drinks.(1)
A 22 year old woman developed low grade fever, abdominal pain, nausea and vomiting and was found to have abnormal liver tests after having consumed 10 cans of energy drinks daily for 2 weeks. On examination in the emergency room, she had epigastric tenderness but no other findings and was sent home. The following day she developed jaundice and was admitted to the hospital. She denied alcohol or drug abuse and was not taking other medications. Laboratory tests showed marked elevations in ALT and AST (Table) but normal levels of bilirubin, alkaline phosphatase and GGT. The INR was 1.6. Acetaminophen levels were undetectable. There was no serologic evidence of acute hepatis A, B, C or E and tests for Epstein Barr virus and cytomegalovirus infection were negative. She was managed conservatively. She did not undergo liver biopsy or imaging studies. Serum aminotransferase levels decreased rapidly and she was discharged four days later. In follow up one month later, she was asymptomatic and serum ALT levels were normal.
Key Points
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Medication:Energy drinks (10 cans daily for 2 weeks)Pattern:Hepatocellular (R=~172)Severity:3+ (jaundice and Hospitalization)Latency:2 weeksRecovery:Within 1 monthOther medications:NoneLaboratory Values
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Time AfterStartingTime AfterStoppingALT(U/L)AST(U/L)Alk P(U/L)Bilirubin(mg/dL)Other2 weeks02161711.7Nausea, abdominal pain1 day75337709Normal3.5GGT 29, INR 1.65 days19472381.7Discharged1 month2226Normal ValuesNot given