- doi: 10.1111/cts.12403
- Published online 2016 Jun 20
DR Krieger, 1 DS Kalman, 1 S Feldman, 1 L Arnillas, 1 D Goldberg, 1 O Gisbert, 1 and S Nader 1
Abstract
This double‐blind crossover clinical trial randomized 12 adult males to receive 200 mg of caffeine from a green coffee extract, a guayusa leaf extract, and a synthetic control to compare their safety, absorption, and effect on neurotransmitters. The results showed no statistically significant changes in blood pressure or heart rate from baseline to 120 min postdose of each natural source compared with changes from baseline in the control (0.094 < = P < = 0.910). The ratios of Cmax, AUC0‐4, and AUC0‐∞ of each natural source to the control were bioequivalent by US Food and Drug Administration standards (90% CI within 80–125%). The guayusa leaf extract stimulated a significantly lower increase in epinephrine compared with the control (+0.5 vs. +2.78 μg/gCr, P = 0.04), while the green coffee extract provoked an increase in epinephrine similar to the control (+3.21 vs. +2.78 μg/gCr, P = 0.569). Implications for future clinical research are discussed.
Study Highlights
WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
✓ The current research on this topic shows that natural sources of caffeine may have influences on the body similar to those of synthetic caffeine when absorbed in comparable doses.
WHAT QUESTION DID THIS STUDY ADDRESS?
✓ This study addressed the question of whether two natural sources of caffeine, green coffee extract and guayusa leaf extract, are safe to consume and what impact their consumption has on the body’s neurotransmitter system and vital signs compared with synthetic caffeine.
WHAT THIS STUDY ADDS TO OUR KNOWLEDGE?
✓ This study has several implications for future clinical research on the safety and neurological impact of natural caffeine sources. The findings suggest that the natural caffeine extracts behave like synthetic caffeine with respect to their effect on the cardiovascular system and their pharmacokinetic absorption profiles. However, the guayusa leaf extract may be less stimulating to the release of epinephrine compared with the green coffee extract and synthetic caffeine, which has implications for its therapeutic applications and safety.
HOW THIS MIGHT CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
✓ This study generates a hypothesis for the future study of clinical applications for natural caffeine sources—that tea‐leaf sourced caffeine may have differential impacts on excitatory neurotransmitters, particularly the adrenaline response, from the previously studied effects of synthetic caffeine. In addition, this study adds to the FDA’s investigation of caffeine metabolism in conjunction with food substances, since it shows that natural sources of caffeine plus carbohydrates are absorbed similarly to synthetic caffeine.
Caffeine is one of the most common stimulants consumed worldwide and can originate from both plant‐based and synthetic sources.1, 2 The average daily caffeine intake in the United States ranges between 210 and 238 mg per day, which can be consumed through a variety of dietary supplements, beverages, and food products.3 Although caffeine has historically not been regulated as a drug by government agencies, its diverse interactions with neurotransmitters in the brain have been shown to have both therapeutic and harmful effects. From a therapeutic perspective, caffeine’s role as an adenosine A2A antagonist has been linked to a lower risk of Parkinson’s disease and other neurodegenerative disorders such as Alzheimer’s disease.3, 4, 5 At the same time, caffeine’s stimulation of the body’s adrenaline response has been associated with acute increases in blood pressure and heart rate, although caffeine consumers seem to develop tolerance to these effects after prolonged regular consumption.6, 7
As caffeine continues to be added to a growing number of food products, it has become increasingly important for regulatory bodies to understand the clinical implications of caffeine’s effect on the brain and the body. In recognition of this, the US Food and Drug Administration (FDA) announced in May 2013 that it would begin a coordinated effort to investigate the safety of caffeine.8 This includes an investigation into plant‐based caffeine sources, which have identical chemical structures to synthetic caffeine, but also contain other ingredients that may differentiate some effects of plant‐based caffeine from those of synthetic caffeine.9 Substances other than caffeine in natural sources such as coffee and green tea have been proposed as a mechanism linking caffeine consumption to a variety of health outcomes, from reduced rate of metabolic syndrome through lowered serum triglyceride levels, to increased performance on memory and attention tasks.10, 11
In response to the need for more research on the safety and neurological mechanisms of natural caffeine sources, the current study investigated the safety, pharmacokinetics, and nervous system effects of two natural sources of caffeine compared with a synthetic control: a green coffee extract (JAVA.g) that was derived from 100% green C. arabica and/or C. robusta coffee, and a guayusa (Illex guayusa) tea‐leaf extract (AMATEA). These extracts are intended as replacements for synthetic caffeine in general circulation. Consumption of each extract in quantities comparable to synthetic caffeine has been generally recognized as safe (GRAS) by a panel of independent experts based on data available and the intended use of the product,9, 12 but there is no human clinical evidence to date examining the safety, pharmacokinetics, and nervous system effects of either caffeine source. This randomized, double‐blind, crossover clinical trial provides human clinical evidence of the safety, pharmacokinetics, and nervous system effects of a green coffee extract and a guayusa leaf extract in healthy adult males.
Guayusa – LIFE FORCE HEALTH CENTER
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