Sleepness Nights: Are Pre-Workouts and A Huge Cup of Coffee Messing With Your Sleep? Plus: 5h Half-Life & 15h Clearance Time Caffeine Stays

This couple probably didn't have a two huge cups of high-caffeine coffee with 400mg caffeine, each, before bed ;-)

The recent publications of a paper by Drake, Roehrs, Shambroom and Roth in the Journal of Clinical Sleep Medicine woke my interest in the quantitative and qualitative significance of the potential negative effects coffee / caffeine can or will have on sleep (Drake.2013).

In the experiment, Drake et al. describe in their latest paper, the researchers made (much to my surprise) a first attempt "to investigate the relative effects of a given dose of caffeine administered at different times of day on subsequent sleep." (Drake. 2013)

Fixed dose (400mg) + varied times

To do so, Drake and his colleagues from the Sleep Disorders & Research Center at the Henry Ford Hospital and the Department of Psychiatry and Behavioral Neurosciences at the Wayne State College of Medicine, in Detroit, as well as a scientist who worked for Zeo Inc in Newton, compared the potential sleep disruptive effects of a fixed dose of caffeine (400 mg) that was administered at 0, 3, and 6 hours prior to habitual bedtime.

Figure 1: Subjectively determined sleep latency (time it takes to fall asleep in min), total sleep (hrs) and wake time during sleep (min), sleep efficacy (%) and sleep quality (% of placebo) in 12 healthy men and women after the ingestion of a placebo or 400mg caffeine 0h, 3h or 6h before bed (Drake. 2013).

The study was blinded and the sleep duration and quality was assessed by questionnaires and data from the Zeo device all participants had to use (basically the Zeo is a device that measures your brain activity - unfortunately Zeo has gone out of business; cf. Orlin. 2013).

Figure 2: Objectively measured sleep latency (min), total sleep (hrs), wake time (min), sleep efficacy (%), stage 1 & stage 2 sleep (% of total sleep), slow wave and REM sleep times in minutes (Drake. 2013)

Based on this combination of subjective (Figure 1) and objective (Figure 2) data the researchers were able to confirm their hypothesis that 400mg of caffeine will provoke significant (p < 0.05 for all) sleep disturbances, regardless of whether the perfectly healthy subjects (n = 12; 50% women; mean age: 30y, BMI 25kg/m², 94.5% baseline sleep efficacy) consumed it at bedtime, 3 hours prior to bedtime, or 6 hours prior to bedtime. As Drake et al. point out, ...

"[t]he magnitude of reduction in total sleep time suggests that caffeine taken 6 hours before bedtime has important disruptive effects on sleep and provides empirical support for sleep hygiene recommendations to refrain from substantial caffeine use for a minimum of 6 hours prior to bedtime." (Drake. 2013)

For the PM-trainees and pre-workout fanatics among the SuppVersity readers this probably sounds scary. Stimulant-laden preworkout products are yet not the only offenders that could compromise your sleep hygiene.
With up to 500mg of caffeine in commercially available 16 oz servings of brewed coffee (McCusker. 2003), even an innocent (large) cup of coffee in the afternoon could have significant negative effects on the quality of the sleep you'll get, when you go to bed relatively early; and you wouldn't be the only one with that problem: Penalazzi et al. found that it is something 90% of the 18-58 year olds enjoy on an almost daily basis (Penalazzi. 2012).

"This must be a mistake. The must be an 'on the other hand' attached!"

You are right, the news are in fact so "bad" that I decided it may be worth digging a little further to see, if I, an outspoken coffee concessionaire, can't find a glitch in this or a conflict to another study that would put a relieving "?" behind the results of the study at hand:

• Statistical significance vs. real-world effects - While it is not a real glitch, it's certainly questionable how great real-world health consequences of the bordeline significant decrease in sleep efficacy and the significant 32% reduction in slow wave sleep actually are.
  With respect to the generic quantity "sleep quality", we could probably say that we give a damn. The loss of 15-22 minutes of slow wave sleep, of which scientists say that it is the time, when we consolidate new memories and our brain recovers from the daily activities, the 32% reduction in slow wave sleep does begin to sound scary. If we also take into account that Tasali et al. observed that ...
  

  "[...] all-night selective suppression of SWS, without any change in total sleep time, results in marked decreases in insulin sensitivity without adequate compensatory increase in insulin release, leading to reduced glucose tolerance and increased diabetes risk" (Tasali. 2013)

  in young, perfectly healthy subjects, I am not quite sure, if the overall beneficial metabolic and cognitive effects still outweigh the potential detriments that arise from the consumption of high amounts of caffeine shortly before going to bed.

• Figure 3: According to Blanchard et al. it can take up to 15h to get rid of 5mg/kg body weight caffeine.

  The "outlier hypothesis"- Unfortunately, the study at hand is not"just an outlier", the sleep disruptive effects of caffeine administration at bedtime are well documented and have even used to model insomnia (Bonnet. 1992).
  Previous dose-response studies, demonstrate that increasing doses of caffeine administered at or near bedtime are associated with significant sleep disturbance (Karacan. 1976; Lasagna. 1977; Yanik. 1987) and the recommendations to avoid caffeine close to bedtime is in every list of sleep hygiene practices. However, evidence is less clear regarding the consumption of caffeine at earlier time. 
• The "Ah, I am used to it hypothesis" - Being "used" as you may have gotten to the sleep disruptive effects of caffeine does not equate being "immune" to them. That's at least what the 36 healthy male and female habitual caffeine consumers in a 1998 study by Jack E. James had to realize, when they skipped on their beloved caffein for just one day and their sleep duration and quality increased significantly ().

Unlike the evidence for the sleep-disrupting effects of late-pm caffeine ingestion, the effects of coffee you drink earlier in the day are less conclusive. The underlying reason for these difference is probably the significant inter-individual difference in elimination half-lives of caffeine in healthy adults.

Coffee only in the AM!?

The time our bodies need to get rid of 50% of the caffeine we've consumed at T = 0 ranges from 2.7-9.9 hours (Blanchard. 1983a,b). According to Blanchard et al. 'the average' 22-year old needs ~15h to get rid of all the caffeine that made it into his / her bloodstream after the consumption of ca. 400mg caffeine. If you wanted to make perfectly sure that your coffee consumption does not compromise your sleep, it would thus appear advisable to drink your 3-4 cups of coffee in the morning.

In the absence of studies that have compared the sleep disruptive effects of caffeine given at different times before bed it does however remain unclear it remains unclear when exactly the 'coffee curfew' should begin.

References:

• Bonnet MH, Arand DL. Caffeine use as a model of acute and chronic insomnia. Sleep.
  1992;15:526-36
• Blanchard J, Sawers SJ. Comparative pharmacokinetics of caffeine in young and elderly
  men. J Pharmacokinet Biopharm. 1983a; 11:109-26. 
• Blanchard J, Sawers SJ. The absolute bioavailability of caffeine in man. Eur J Clin
  Pharmacol. 1983b; 24:93-8.
• Bryant Ludden A, Wolfson AR. Understanding adolescent caffeine use: connecting use
  patterns with expectancies, reasons, and sleep. Health Educ Behav. 2010; 37:330-42.
• Carskadon MA Sleep in adolescents: the perfect storm. Pediatr Clin North Am. 2011;58:637-47. 
• Drake C, Roehrs T, Shambroom J, Roth T. Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. J Clin Sleep Med 2013;9(11):1195-1200.
• James JE. Acute and chronic effects of caffeine on performance, mood, headache, and sleep. Neuropsychobiology. 1998;38(1):32-41.
• Karacan I, Thornby JI, Anch M, Booth GH, Williams RL, Salis PJ. Dose-related sleep
  disturbances induced by coffee and caffeine. Clin Pharmacol Ther. 1976; 20:682-9.
• Lasagna L. Dose-related sleep disturbances induced by coffee and caffeine. Clin
  Pharmacol Ther. 1977; 21:244. 
• McCusker RR, Goldberger BA, Cone EJ. Caffeine content of specialty coffees. J Anal
  Toxicol. 2003; 27:520-2. 
• Orlin, J. Sleep Tracking Startup Zeo Says Goodnight. theCrunch.com. May 22, 2013 < http://techcrunch.com/2013/05/22/sleep-tracking-startup-zeo-says-goodnight/ >
• Penolazzi B, Natale V, Leone L, Russo PM. Individual differences affecting caffeine
  intake. Analysis of consumption behaviours for different times of day and caffeine
  sources. Appetite. 2012; 58:971-7.  
• Roberts RE, Roberts CR, Xing Y. Restricted Sleep Among Adolescents: Prevalence,
  Incidence, Persistence, and Associated Factors. Behavioral Sleep Medicine. 2010; 9:18-30. 
• Tasali E, Leproult R, Ehrmann DA, Van Cauter E. Slow-wave sleep and the risk of type 2 diabetes in humans. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1044-9.
• Yanik G, Glaum S, Radulovacki M. The dose-response effects of caffeine on sleep in rats.
  Brain Res. 1987;403:177-80.