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Table 1.  
Levels of Caffeine, Glucose, and Norepinephrine Before and After Energy Drink Consumption
Levels of Caffeine, Glucose, and Norepinephrine Before and After Energy Drink Consumption
Table 2.  
Changes in Hemodynamic Data Before and After Energy Drink Consumption (N = 24)
Changes in Hemodynamic Data Before and After Energy Drink Consumption (N = 24)
1.
Burrows  T, Pursey  K, Neve  M, Stanwell  P.  What are the health implications associated with the consumption of energy drinks? a systematic review. Nutr Rev. 2013;71(3):135-148.
PubMedArticle
2.
Goldfarb  M, Tellier  C, Thanassoulis  G.  Review of published cases of adverse cardiovascular events after ingestion of energy drinks. Am J Cardiol. 2014;113(1):168-172.
PubMedArticle
3.
Sepkowitz  KA.  Energy drinks and caffeine-related adverse effects. JAMA. 2013;309(3):243-244.
PubMedArticle
4.
Higgins  JP, Tuttle  TD, Higgins  CL.  Energy beverages: content and safety. Mayo Clin Proc. 2010;85(11):1033-1041.
PubMedArticle
5.
Jennings  JR, Kamarck  TW, Everson-Rose  SA, Kaplan  GA, Manuck  SB, Salonen  JT.  Exaggerated blood pressure responses during mental stress are prospectively related to enhanced carotid atherosclerosis in middle-aged Finnish men. Circulation. 2004;110(15):2198-2203.
PubMedArticle
6.
Flaa  A, Eide  IK, Kjeldsen  SE, Rostrup  M.  Sympathoadrenal stress reactivity is a predictor of future blood pressure: an 18-year follow-up study. Hypertension. 2008;52(2):336-341.
PubMedArticle
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Research Letter
November 17, 2015

A Randomized Trial of Cardiovascular Responses to Energy Drink Consumption in Healthy Adults

Author Affiliations
  • 1Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
JAMA. 2015;314(19):2079-2082. doi:10.1001/jama.2015.13744

Energy drink consumption has been associated with serious cardiovascular events,14 possibly related to caffeine and other stimulants. We hypothesized that drinking a commercially available energy drink compared with a placebo drink increases blood pressure and heart rate in healthy adults at rest and in response to mental and physical stress (primary outcomes). Furthermore, we hypothesized that these hemodynamic changes are associated with sympathetic activation, which could predispose to increased cardiovascular risk (secondary outcomes).

Methods

We conducted a randomized, double-blind, placebo-controlled, crossover pilot study. The trial protocol is available in the Supplement. Twenty-five healthy volunteers aged 18 years or older, who were nonsmokers, free of known disease, and not taking medications, were recruited by word-of-mouth from the local community. Each participant consumed a can (480 mL; 16 fl oz) of a commercially available energy drink (Rockstar; Rockstar Inc) and placebo drink within 5 minutes, in random order on 2 separate days, maximum 2 weeks apart. The placebo drink, selected to match the nutritional constituents of the energy drink, was similar in taste, texture, and color but lacked caffeine and other stimulants of the energy drink (240 mg of caffeine, 2000 mg of taurine, and extracts of guarana seed, ginseng root, and milk thistle).

The study was approved by the Mayo Clinic institutional review board. Informed written consent was obtained from participants. Data were collected at the Mayo Clinical Research Unit between August and November 2013.

Participants were fasting and abstained from caffeine and alcohol 24 hours prior to each study day. Serum levels of caffeine, plasma glucose, and norepinephrine were measured and blood pressure and heart rate were obtained at baseline and 30 minutes after drink ingestion. Hemodynamic measurements were also obtained during 2-minute physical, mental, and cold stressors performed in that order with 10-minute recovery times. Physical stress was performed by asking participants to sustain an isometric handgrip of one-third of maximum voluntary handgrip contraction, using a dynamometer. During mental stress, participants completed serial mathematical tasks as fast as possible. During the cold-pressor test, performed last because of its sustained effects, participants immersed 1 hand into ice water.

Randomization was computer-generated using a randomized block design, with a block size of 6. Results are reported as means and 95% confidence intervals. A 2 × 2 mixed-model analysis of variance was applied to continuous variables. Changes were compared between groups using a 2-sample t test and JMP version 10.0 software (SAS Institute Inc). Two-sided statistical significance was defined as P < .05.

Results

We studied 25 healthy participants (14 men) with a mean age of 29 years (95% CI, 26-31 years) and a mean body mass index of 25 (calculated as weight in kilograms divided by height in meters squared; 95% CI, 23-26). One participant did not complete 1 study day. Caffeine levels remained unchanged after the placebo drink, but increased significantly after energy drink consumption. Glucose levels increased similarly between the groups (Table 1).

Baseline blood pressure and heart rate were normal and similar for participants on both the energy drink and placebo study days. Consumption of the energy drink elicited a 6.2% (95% CI, 4.5% to 7.8%) increase in systolic blood pressure (from 108.4 mm Hg to 115.0 mm Hg) vs a 3.1% (95% CI, 1.5% to 4.7%) increase with the placebo drink (from 108.3 mm Hg to 111.6 mm Hg) (P = .01). Diastolic blood pressure increased by 6.8% (95% CI, 4.1% to 9.6%) vs 0% (95% CI, −2.8% to 2.8%) with placebo (P = .001). Mean blood pressure increased after consumption of the energy drink by 6.4% (95% CI, 4.3% to 8.6%) from 74.2 mm Hg to 78.9 mm Hg vs by 1.0% (95% CI, −1.2% to 3.2%) with the placebo drink (from 74.9 mm Hg to 75.4 mm Hg) (P < .001). There was no significant difference in heart rate increase between the 2 groups. The energy drink did not further potentiate hemodynamic responses to any stress stimuli (Table 2).

The mean norepinephrine level increased from 149.8 pg/mL (95% CI, 126.3-173.4 pg/mL) to 249.8 pg/mL (214.9-284.7 pg/mL) after consumption of the energy drink and from 139.9 pg/mL (95% CI, 116.3-163.5 pg/mL) to 178.6 (95% CI, 143.7-213.5 pg/mL) after placebo (change rate: 73.6% [95% CI, 53.9%-93.2%] vs 30.9% [95% CI, 11.3%-50.6%], respectively; P = .003; Table 1).

Discussion

In this pilot study, a commercially available energy drink significantly increased levels of blood pressure and catecholamines in young healthy adults. Physical, mental, or cold stress did not further accentuate the blood pressure increase. These acute hemodynamic and adrenergic changes may predispose to increased cardiovascular risk.5,6

Limitations of our study are the small sample size and only 1 energy drink being studied. Further research in larger studies is needed to assess whether the observed acute changes are likely to increase cardiovascular risk.

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Article Information
Section Editor: Jody W. Zylke, MD, Deputy Editor.

Corresponding Author: Anna Svatikova, MD, PhD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (svatikova.anna@mayo.edu).

Published Online: November 8, 2015. doi:10.1001/jama.2015.13744.

Author Contributions: Dr Svatikova had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Svatikova, KR Somers, KV Somers, Soucek, Kara, Bukartyk.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Svatikova.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Svatikova, Covassin, KV Somers.

Obtained funding: Svatikova.

Administrative, technical, or material support: Svatikova, KR Somers, Kara, Bukartyk.

Study supervision: Svatikova.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: This research was supported by grant M01-RR00585 from the Mayo Foundation and grant UL1 TR000135 from the National Center for Advancing Translational Sciences, National Institutes of Health.

Role of the Funder/Sponsor: The Mayo Foundation and the National Center for Advancing Translational Sciences had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The contents of this article are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health.

Trial Registration: clinicaltrials.gov Identifier: NCT01940822.

References
1.
Burrows  T, Pursey  K, Neve  M, Stanwell  P.  What are the health implications associated with the consumption of energy drinks? a systematic review. Nutr Rev. 2013;71(3):135-148.
PubMedArticle
2.
Goldfarb  M, Tellier  C, Thanassoulis  G.  Review of published cases of adverse cardiovascular events after ingestion of energy drinks. Am J Cardiol. 2014;113(1):168-172.
PubMedArticle
3.
Sepkowitz  KA.  Energy drinks and caffeine-related adverse effects. JAMA. 2013;309(3):243-244.
PubMedArticle
4.
Higgins  JP, Tuttle  TD, Higgins  CL.  Energy beverages: content and safety. Mayo Clin Proc. 2010;85(11):1033-1041.
PubMedArticle
5.
Jennings  JR, Kamarck  TW, Everson-Rose  SA, Kaplan  GA, Manuck  SB, Salonen  JT.  Exaggerated blood pressure responses during mental stress are prospectively related to enhanced carotid atherosclerosis in middle-aged Finnish men. Circulation. 2004;110(15):2198-2203.
PubMedArticle
6.
Flaa  A, Eide  IK, Kjeldsen  SE, Rostrup  M.  Sympathoadrenal stress reactivity is a predictor of future blood pressure: an 18-year follow-up study. Hypertension. 2008;52(2):336-341.
PubMedArticle
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