Sleepless 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.

"1kg Body Fat in 4 Weeks From < 2x Energy Drinks per Day!" | more

Young, sleepless and on caffeine: Recent scientific data appears to confirm that the increasing popularity of sugary, fattening (see link to the left), caffeinated energy drinks, and the high caffeine content of premium coffee are at least partly responsible for the surge in chronic sleep problems among young people (McCusker. 2003; Roberts. 2010; Carskadon. 2011). No wonder if >37% of them drink their first caffeine-containing beverage at 5 pm or later (Bryant Ludden. 2010).

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.

Learn to abUSE caffeine to modulate your circadian rhythm.

Bottom line: As unbearable as as it may sound for some of you, the currently available scientific evidence appears to suggest that (late) PM coffee consumption is a no-go for anyone for whom optimal sleep quality is more important than the rejuvenating pleasure of a huge cup of strong coffee.

On the other hand, a simple extrapolation from the data of the Blanchard study (see Figure 3)would  suggest that a small cup of coffee with only 100mg of caffeine at 4 o'clock pm is probably not so much of a problem - as long as you keep it 4h+ away from going to bed, your blood should be decaffeinated, when you hit the pillows ;-)

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. 

Fragmented Sleep Reduces 24h Fat Oxidation by > 50% - Not Getting a Good Night's Sleep Sets You Up For Obesity.

Image 1: It looks awkward, but sleep masks
and ear-plugs are effective, cheap and
save ways to improve sleep quality
(image from lackofsleepsymptoms)

I think you will be familiar with the idea that an insufficient amount of sleep has been found to correlate (! not induce !) with visceral obesity and other negative health markers (e.g. Strian. 2005). Now a study from a the Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM) at the University of Maastricht in the Netherlands found that not getting a good nights sleep or, in this particular case, waking up every hour, reduces the amount of fat you burn in a period of 24 hours by -52% (Hursel. 2011, cf. figure 1).

Other than in the initially mentioned epidemiological guesswork ... ah pardon, correlation studies, Hursel et al. had their 15 healthy male volunteers report to the laboratory twice (>2 weeks between the sessions of the randomized, single-blind cross-over study). During each visit, the subjects stayed for 48 h in a respiration chamber, where energy expenditure, physical activity (radar), and substrate oxidation were meticulously measured. On both occasions, the subjects had fixed bedtimes (lights out: 11:00pm; lights on: 7:40am) resulting in 8 h sleeping time per night. On one of the occasions, however, the scientists used induced sleep-fragmentation by the means of "approximately hourly wake-up calls" the subjects had to respond to by turning off their alarm after 2 min.

Figure 1: Relative differences in carbohydrate and fat oxidation, as well as respiratory quotient (higher quotient = more carbohydrate dependent) in 15 healthy men as a consequence of interrupted sleep (data calculated based on Hursel. 2011)

Diet-wise, the subjects who had been asked to abstain from strenuous exercise and to sleep for 8 h during the nights before their visit at the lab, were fed a standardized (protein:carbohydrate:fat ratio 12:55:33) diet consisting of "normal, everyday food products" two days before and in the course of their stay in a respiration chamber. The use of the latter, by the way, facilitated pretty exact measurements of the subjects energy expenditure and substrate oxidation (cf. figure 2).

Figure 2: Relative changes in total, resting (REE) and sleeping energy-expenditure (SEE), as well as absolute changes in activity induced energy expenditure (AEE) and overall caloric balance (data calculated based on Hursel. 2011)

As the data in figure 2 shows there was no statistically significant difference with respect to the overall calorie balances of the subjects (+0.41MJ/day to +0.41 MJ/day in the normal vs. the interrupted sleep group, respectively). While this appears counterintuitive as the recorded physical activity of the sleep-disturbed subjects had eventually increased, Hursel et al. point out that because of their study design, ...

we showed an initial increase in physical activity and AEE as an effect of sleep fragmentation, mainly because the subjects had to turn off their alarm clock 7 times during the night. However, the resulting increased exhaustion and sleepiness during the subsequent day might eventually counter-balance physical activity and AEE.

They go on to point out that the increased activity goes hand in hand with the increase in carbohydrate oxidation, the depletion of glycogen stores and the (this is my assumption) stress-related -52% decrease in fatty acid oxidation (cf. figure 1).

The real-world results of this unhealthy combination of non-regenerative sleep, daytime exhaustion and sleepiness and the accompanying abstract metabolic shifts are cognitive problems, a lack of motivation (esp. to work out or do any physical work), carb-cravings, snack-attacks & co... In your efforts to (re-)feed a body that is unable to access his well-stocked fat reserves, you end up overcompensate the initially increased energy expenditure, constantly provoking insulin spikes which totally blunt fat oxidation, trigger temporary hyperglycemia (if you are not already diabetic) and induce further snack-attacks. Thus, you are triggering a down-ward spiral that is especially hard to escape from, if your body does not get the chance to reset his insulin and stress levels in the course of a good nights sleep - keep that in mind before you place your cell-phone next to your pillow in order to "keep in touch" with your (facebook-)friends 24/7, as a very recent study published in the journal SLEEP showed that "mobile phone use for calling and for sending text messages after lights out was associated with sleep disturbances independent of covariates and independent of each other" (Munezawa. 2011).