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The Consumption of Energy Drinks Induces Blood-Brain Barrier Dysfunction in Wild-Type Mice

Graneri L, Lam V, D'Alonzo Z, Nesbit M, Mamo J, Takechi R (2021) Frontiers in Nutrition doi:10.3389/fnut.2021.668514  

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Energy drinks containing significant quantities of caffeine and sugar are increasingly consumed, particularly by adolescents and young adults. Chronic ingestion of energy drinks may potentially regulate vascular risk factors.

This study investigated the effects of chronic ingestion of energy drinks on blood-brain barrier (BBB) integrity and neuroinflammation. Male C57BL/6J mice were maintained on water (control), MotherTM (ED), sugar-free MotherTM (sfED), or Coca ColaTM soft drink (SD) for 13 weeks. The BBB integrity and neuroinflammation were analyzed with semi-quantitative immunofluorescent microscopy. Blood pressure, plasma inflammatory cytokine levels and blood glucose were also considered.

Following 13 weeks of intervention, mice treated with ED, sfED, and SD showed significant disruption of BBB. However, marked neuroinflammation was observed only in sfED group mice. The consumption of ED and sfED significantly altered the blood pressure and plasma concentrations of inflammatory cytokines, TNF-a, IL-4, IL-6, and IL-10, and both increased plasma glucose. Correlation analyses showed significant associations between BBB dysfunction and hypotension, hyperglycaemia and cytokine dyshomeostasis.

The intake of energy drink, particularly the sugar free formulation, may compromise the integrity of BBB and induce neuroinflammation via hypotension, hyperglycaemia and inflammatory pathways.


The blood-brain barrier (BBB) describes the anatomical structure which surrounds the endothelial cells of cerebral capillaries (1). Its function is to serve as a selectively permeable barrier for brain parenchyme (2) and this is achieved ordinarily through highly regulated expression of endothelial tight junctions within the paracellular spaces.

A disruption in BBB integrity permits the cerebral extravasation of plasma-borne molecules, which may activate astrocytes and microglia and promote neuroinflammation (3). Chronically exaggerated astrocytosis and microgliosis lead to heightened oxidative stress, which consequently promotes degeneration of neurons (4). Indeed, BBB dysfunction is commonly observed in various neurodegenerative disorders such as Alzheimer's disease and multiple sclerosis, suggesting a causal association (5–8).

Energy drinks are highly caffeinated, carbonated beverages first marketed in Europe and Asia in the 1960's (9). The primary ingredients with popular energy drinks such as Red BullTM, MotherTM, and MonsterTM include caffeine/guarana [~160 mg per serving (375 ml)], remarkable abundance of taurine (~2,000 mg per serving), B6/B12 vitamins (1.0 mg/0.5 μg per serving, respectively), and in sugar-formulated energy drinks (~51 g sucrose per serving).

Recent population studies report significantly accelerating ingestion trends of energy drinks, particularly in young adults (10). Due to their complex formulations, both negative and positive effects on BBB integrity may be realized with regular, significant consumption of energy drinks. Evidence consistent with the latter are findings that energy drinks can have acute hypertensive effects on blood pressure, but paradoxically, hypotensive effects with chronic ingestion (11–17).

Chronic consumption of sugar-formulated energy drinks may also have secondary indirect neurovascular effects, exacerbating hyperglycaemia, insulin resistance (18–22) and neurovascular integrity and neuroinflammation (23–25).

To gain better insight into the potential effects of energy drinks on BBB integrity, in this pilot study, genetically unmanipulated wild-type mice were chronically provided with diluted energy drinks as their sole drinking solution. The putative effects of MotherTM, Sugar-free MotherTM, and Coca-ColaTM (which lacks taurine, B-group vitamins and has substantially less caffeine) were studied in the context of neurovascular integrity and neuroinflammation.



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