Heart Rate ↘, BP ↗ | Anxiety + Sleep Issues | Bitter Taste = Big Effect -- SuppVersity Caffeine Research Update June '17

This is not the coffee research update. That's important because coffee has a lot of health benefits that are unrelated or at least not directly related to its most famous ingredient, i.e. caffeine.
You may have seen it in the Facebook News, or on the SuppVersity Twitter Channel already: If you don't get your habitual quantity of coffee, your coffee cravings will ruin not just your day, but also your cognitive performance (learn more about the Palmer study). Palmer's caffeine craving study is yet not the only recent caffeine study that's (SuppVersity-)news-worthy.

Likewise worth mentioning are papers by Turley, et al. (2017), Distelberg et al. (2017), Soares et al. (2017) and Pool et al. (2017) - three studies that address the physiological (CNS, metabolism, etc.) response(s) to caffeine in various contexts.
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  • Caffeine = Blood pressure ↗, heart rate ↘ (Turley 2017) - A recent study in twenty-four 9- to 11-year-old boys participated in a double-blind, double-crossover, counterbalanced study. Children received in random order twice each, either a placebo (PL—drink only) or anhydrous caffeine (5 mg/kg) mixed in flavored Sprite®. Following a 60-minute absorption period, supine BP and HR were measured for 5 minutes then 10 minutes of HRV.
    Figure 1: Changes in diastolic + systolic BP and heart rate in boys receiving 5mg/kg caffeine (Turley 2017).
    The analysis of the results reveals a significant decrease in resting HR (77.9 ± 7.6 beats/min vs. 82.5 ± 8.6 beats/min), of which the scientists speculate that it was a way to compensate the significant increase in both, systolic (114.1 ± 7.5 mmHg vs. 110.6 ± 7.1 mmHg) and diastolic (64.3 ± 6.2 mmHg vs. 62.2 ± 6.2 mmHg) BP, in response to the comparatively high intake of caffeine in this study.
Systolic blood pressure increase in group S, sedentary non-habit. caffeine consumers; SC, sedentary habitual caffeine consumers; A, physically active non-habit. caffeine consumers; AC, physically active habitual caffeine consumers (Soares 2017).
The more active you are, the more your blood pressure will rise: It may sound odd, but a recent from the University of Calgary leaves no doubt that "[a]cute caffeine ingestion increases the SBP [=systolic blood pressure] in physically active nonhabitual caffeine consumers" (Soares 2017). As you can see in the figure to the left, though, the increase was not exorbitantly large and, maybe even more importantly, not statistically significant for active habitual caffeine consumers (AC).
  • More evidence in favor of caffeine's highly significant effect on vagal autonomic control were the changes in heart rate variability; more specifically, the high-frequency (HF) power (3359 ± 2632 ms vs. 2133 ± 1816 ms) and HF% (25.7% ± 6.3% vs. 21.1% ± 5.7%) were significantly higher in caffeine versus PL, respectively. The low-frequency percent (23.9% ± 4.8% vs. 27.0% ± 4.4%), on the other hand, was significantly lower in the caffeine trial.
  • Coffee, anxiety and your sleep - Overall negative effects in recent study (Distelberg 2017) -- While the effects are probably highly individual, the results of a recent study from the Loma Linda University in California clearly indicate that the average effect of caffeinated vs. decaf coffee on anxiety, sleep and - consequently - health-related quality of life (HRQL) is negative.

    In their randomized, double-blind, longitudinal study, forty-nine healthy participants between the ages of 18 and 45 consumed either regular of decaffeinated coffee for 5 days. To minimize the effects of habitual caffeine intake, all subjects had to abstain from caffeine during an initial 5-day washout period. Data were analyzed with repeated-measures analysis of covariance and ordinary least-squares mediational analysis.
    Figure 2: Rel. changes in study outcomes in response to caffeinated vs. decaf coffee (Distelberg 2017).
    The results of the analyses show significant direct effects on sleep, anxiety, and stress-based domains of HRQL in the caffeinated coffee group, as well as often opposing effects of decaf.
Caffeine in the AM can also affect your sleep: While more recent studies suggest that the degree of interference depends on your genes and other individual variables, the seminal paper by Landolt, et al. (1995) showed quite clearly that caffeine intake (200 mg) in the morning affects human sleep and EEG power spectra at night. More specifically, compared to placebo, sleep efficiency and total sleep time were significantly reduced and the EEG data suggested that the subject's REM sleep was impaired - and that despite the fact that the level of caffeine the scientists detected in the subjects' blood had declined from the maximum of 17 µmol/L to meager 3 µmol/l.
  • In view of a reduction in sleep quality and increased anxiety, it is not surprising, that the scientists' data analyses also revealed that global domains of HRQL were affected negatively in the caffeine group, while no significant changes were noted in the decaffeinated treatment group.
  • Figure 3: Who would have thought that we have bitter taste receptors on the pancreas, thymus or skeletal muscle?
    Caffeine tastes... well, how does it taste? "Bitter", Pool & Tordoff write in their latest review of what is known about caffeine as a bitter taste stimulus (Pool 2017) -- Basically, we know what caffeine directly activates T2Rs taste receptors. What we do not know, though is if there are other taste transduction mechanisms as well. Scientists suspect, though, that our taste response to caffeine may be modulated by other receptors caffeine interacts with, i.e. the adenosine receptors, GABA receptors and intracellular receptors and enzymes.

    Now, all that sounds hardly exciting, if you don't know that these targets, including the taste receptors T2Rs, "are expressed not only in taste tissue but also in diverse cell types throughout the digestive, endocrine, and reproductive systems" (Pool 2017). This obviously suggests that caffeine's bitter taste may well be involved in its far-reaching metabolic and CNS effects, as well... I assume we will see more research in this area being done in the years to come. After all, we do already know that receptors ‘taste’ the luminal content will "transmit signals that regulate nutrient transporter expression and nutrient uptake, and also the release of gut hormones and neurotransmitters involved in the regulation of energy and glucose homeostasis" (Depoortere 2013) - what if the same goes for non-luminal T2Rs throughout the body when they're activated by caffeine?
You don't necessarily have to bring fresh beans to the gym. A simple Nescafé instant coffee will serve the purpose, study shows. And it's going to work better than equal doses of straight caffeine | more.
Bottom line: I know the thing about caffeine messing with your sleep sounds scary. You shouldn't forget, though, that the 'latest and greatest' review from the University of Zurich says emphasizes that "the magnitude of caffeine's effects on sleep are modulated by individual differences related to age, sex, weight, genetic predisposition, and possibly other factors" (Clark 2017). Accordingly, it may make sense to revisit and cut your caffeine consumption if you have sleep problems, to stop drinking coffee if you don't have any sleep problems, however, doesn't make sense, as it would deprive you of the many previously outlined metabolic and anti-inflammatory effects of everyone's favorite beverage - ah... and never forget: that pre-workout coffee is more effective than your caffeinated pre-workout supplement | Comment!
  • Clark, Ian, and Hans Peter Landolt. "Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials." Sleep medicine reviews. 2017, 31: 70-78.
  • Depoortere, Inge. "Taste receptors of the gut: emerging roles in health and disease." Gut. 2013: gutjnl-2013.
  • Distelberg Brian J., Staack Andrea, Elsen K'dee D., and Sabaté Joan. Journal of Caffeine Research. June 2017, 7(2): 59-70. https://doi.org/10.1089/jcr.2016.0023
  • Landolt, Hans-Peter, et al. "Caffeine intake (200 mg) in the morning affects human sleep and EEG power spectra at night." Brain research 675.1 (1995): 67-74.
  • Palmer, Matthew A., et al. "Caffeine cravings impair memory and metacognition." Memory. June 2017: 1-10.
  • Poole Rachel L. and Tordoff Michael G.. Journal of Caffeine Research. June 2017, 7(2): 39-52. https://doi.org/10.1089/jcr.2016.0030
  • Soares Rogério Nogueira, Schneider Augusto, Valle Sandra Costa, and Schenkel Paulo Cavalheiro. Journal of Caffeine Research. June 2017, 7(2): 53-58. https://doi.org/10.1089/jcr.2016.0017
  • Turley Kenneth R., Rivas Joey D., Townsend Jeremy R., and Morton Aaron B.. Journal of Caffeine Research. June 2017, 7(2): 71-77. https://doi.org/10.1089/jcr.2016.0028

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