Major components of energy drinks (caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y cells by decreasing reactive oxygen species production

Oxid Med Cell Longev. 2013;2013:791795. doi: 10.1155/2013/791795. Epub 2013 May 22.


Scope: To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs).

Methods and results: On human neuronal SH-SY5Y cells, caffeine (0.125-2 mg/mL), taurine (1-16 mg/mL), and guarana (3.125-50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5-50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis.

Conclusion: Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or "antioxidative stress"), could be a cause of in vitro toxicity induced by these drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / metabolism
  • Caffeine / pharmacology*
  • Catalase / metabolism
  • Cell Count
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Energy Drinks*
  • Free Radical Scavengers / metabolism
  • Humans
  • Hydroxyl Radical / metabolism
  • Intracellular Space / metabolism
  • Lipid Metabolism / drug effects
  • Models, Biological
  • Nerve Degeneration / pathology
  • Neurites / drug effects
  • Neurites / metabolism
  • Neurites / pathology
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / metabolism*
  • Neurons / pathology*
  • Nitric Oxide / metabolism
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Paullinia / chemistry*
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / metabolism
  • Taurine / pharmacology*


  • Antioxidants
  • Free Radical Scavengers
  • Reactive Oxygen Species
  • Taurine
  • Nitric Oxide
  • Hydroxyl Radical
  • Caffeine
  • Catalase
  • Superoxide Dismutase