When Timing Matters: When is the Best Time to Consume Caffeine Before a Workout? Is it 0, 5, 30, 60, 90 or 120 Min?

Timing matters with coffee / caffeine. But what's the optimal time?
I assume you believe that the statements in the "recommended usage" box on your pre-workout are science-based, right? Well, that's pretty naive. After all, 99% of the pre-workout formulas contain at least 3 ingredients that are just in there to be able to have more than just caffeine, creatine and beta alanine on the label. Against that background, it's only logical to question whether the recommendations on the label (usually "take 20-30 minutes before your workout") are valid or also just there , because "the others have it" ;-) And since caffeine is the main and in many case the only working stimulant in these products you don't want to use it in ways that doesn't allow caffeine to do its performance enhancing job optimally, right?

So let's see if we can put faith in recommendations that are not in line with the standard protocol in pertinent studies, in which caffeine is usually administered roughly 60 minutes before the workout.
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As Graham points out in his 2001 review "[t]his protocol has been selected because caffeine is rapidly absorbed and plasma concentrations approximate a maximum level in 1 hour" (Graham. 2001). Whether this is actually optimal, though, had never been questioned when Graham wrote his review; and it is, as Graham rightly points out "remarkable how rarely the investigators have measured the circulating concentration of the drug they are studying" (Graham. 2001). This did not prevent Nehlig et al. (1994) and Palmer et al. (1995) to write in their reviews of caffeine as an ergogenic that waiting 3 hours would be "optimal" because this is when the caffeine-induced lipolysis produces the highest free fatty acid levels, of which the authors believe that it would be ideal for (endurance) athletes.

As logical as Nehlig's and Palmer's advise may be, is was, when Graham, who questions the validity of their advise, wrote his review in 2002, based only on logical assumptions, not on scientific evidence. The latter was published only one year after Graham's paper by Bell and McLellan (2002). Their study which was conducted at Defence R&D Canada-Toronto and examined the duration of caffeine’s ergogenic effect on the longest time-scale of any of the hitherto published studies(see Figure 1 for an overview of the timing) clearly suggests that Nehlig's and Palmer's reasoning can stand the test of experimental science.
Figure 1: Time line for arriving, blood sampling, delivery of Gatorade, cereal bar, meal, and measurement of oxygen consumption (VO2) during the treatment trials. ER, exercise ride to exhaustion interval; 1, 3, and 6, 1-h trial, 3-h trial and 6-h trial, respectively. aProcedure was done at this time for all trials (Bell. 2002).
In Bell's and McLellan's study, twenty-one subjects (13 caffeine users and 8 nonusers) completed six randomized exercise rides to exhaustion at 80% of maximal oxygen consumption after ingesting either a placebo or 5 mg/kg of caffeine (for the 70kg light subjects that's "only" 350mg per trial). Exercise to exhaustion was completed once per week at either 1, 3, or 6 h after placebo or drug ingestion. A simple, yet effective study design with interesting results:
  • Figure 2: Time to exhaustion at 80% maximal V ˙ O2 in caffeine users and nonusers 1, 3, and 6 h after caffeine ingestion. *Nonusers users. Caffeine placebo (Bell. 2002).
    Firstly, the ergogenic effect, which was measured only as the time it took the subjects until full exertion, differed between users and nonusers - with the ergogenic effect being greater and lasting longer in nonusers. 
  • Secondly, the ergogenic effects of caffeine lasted for 6h only in the nonusers. In the caffeine users, the effects lasted for "only" 1-3 h - an observation that is in line with the previously established increase in caffeine clearance with regular consumption.
  • Third- and lastly, the non-significant advantage of working out 3h after the consumption of caffeine in the habitual consumers is interesting. It's not statistically significant, though.
So, 1-3h before your workout depending on whether you are a caffeine abstainer (1h) or habitual consumer (3h) it is, then? No, let's not jump to conclusions. If we look at the results of Edward J. Ryans' 2011 dissertation on "Caffeine timing and cycling performance" there's another parameter that may significantly influence the "optimal" timing: The route of administration.

Not so fast, it does always make sense to consider all the evidence

In his study, Ryan tested the effects of chewing gum with 300mg of caffeine on the performance of moderate (<300mg/day) caffeine users during a standardized time trial cycling exercise. 
Figure 3: Cycle time trial performance across experimental treatments (Ryan. 2011).
As you can see in Figure 3, the caffeine chewing gum is best taken according to the previously cited recommendation on the pre-workout products. After all, the only significant performance benefit was observed in the -5 minute trial which took place roughly 20 minutes before the time trial (the subjects started chewing the gum 5 minutes before a steady-state warm-up and thus 20 minutes before the time-trial Ryan used to test the effects).

What do we make of the contradictory evidence

In his study, Ryan also cites the previously discussed study by Bell and McLellan and states that the differences between his and Bell's results are probably related to the different routes of administration. While he used chewing gums , Bell and McLellan relied on classic caffeine capsules. Now, the questions we have to answer are: Which is more like a pre-workout? Pill or gum? And, more importantly, what's the optimal timing for pill, gum and pre-workout?
Figure 4: Peak value, half-life and the time it takes for the levels to peak differ significantly for caffeine capsules and caffeinated drinks like coffee and cola (and presumably pre-workout products). The respective times for the peak to occur are similar times for coffee (42 +/- 5 min) and cola (39 6 +/-5 min) but delayed for capsule (67 +/- 7 min | Ligouri. 1997).
Since the studies we'd need to answer this question are not available, we have to make some assumptions: Firstly, it is only logical to assume that the caffeine capsules Bell and McLellan used in their study will take longer to deliver the full load of caffeine than chewing gums or coffee. If we secondly assume that pre-workout powders you'd solve in water will have similar effects as caffeine and cola we can resort to the 1997 study by Ligouri et al. which (luckily) has all the data we need in one figure (Figure 4).

As you can see in Figure 4, cola and coffee had a very similar serum caffeine profile with a peak after 39-42 minutes. When caffeine was administered in capsule form, though, the caffeine levels peaked almost 30 minutes later and thus 67 minutes after the ingestion. If we take this as a reference and assume that caffeine may exert its neurological and performance enhancing effects even faster when it is administered as a chewing gum, we can state the following recommendations.
Adding the right amount of taurine to your caffeine pills or preworkout may make the caffeine even more effective, and ameliorate its negative side effects such as being all psyched up, feeling jittery, etc. Learn more about the "right amount" and how using too much or too little won't help or even hurt, here.
When do I take my caffeine? The answer to this question depends on how you are going to take it. Specifically, ...
  • if you want to use a caffeine chewing gum, take it ca. 20 minutes before the workout,
  • if you plan to drink it either in form of coffee, a pre-workout, cola or an energy drink, use it ca. 35 minutes before your workout,
  • if you rely on capsules or pills take them ca. 60 min before you need peak performance
to achieve "optimal" results. Since your habitual caffeine consumption, the type of exercise, nicotine and alcohol consumption, your liver health, menstruation and a dozen of not fully researched genetic polymorphisms will all influence the pharmacokinetics of caffeine (Smits. 1985; George. 1986; Joeres. 1988; Cheng. 1990; Kamimori. 1999), it may yet be worth experimenting with these recommendations.

Your personal optimum timing may well 50-100% earlier, i.e. 45-90 minutes before your workouts. On the other hand, it's very unlikely that anything less than 20 minutes will yield optimal results. Well, unless maybe you use caffeine brain injections ;-) | Comment on Facebook!
References:
  • Bell, Douglas G., and Tom M. McLellan. "Exercise endurance 1, 3, and 6 h after caffeine ingestion in caffeine users and nonusers." Journal of Applied Physiology 93.4 (2002): 1227-1234.
  • Cheng, Wendy SC, et al. "Dose‐dependent pharmacokinetics of caffeine in humans: Relevance as a test of quantitative liver function." Clinical Pharmacology & Therapeutics 47.4 (1990): 516-524.
  • George, J., et al. "Influence of alcohol and caffeine consumption on caffeine elimination." Clinical and experimental pharmacology and physiology 13.10 (1986): 731-736.
  • Graham, Terry E. "Caffeine and exercise." Sports medicine 31.11 (2001): 785-807.
  • Joeres, Rolf, et al. "Influence of smoking on caffeine elimination in healthy volunteers and in patients with alcoholic liver cirrhosis." Hepatology 8.3 (1988): 575-579.
  • Kamimori, G. H., et al. "The effect of the menstrual cycle on the pharmacokinetics of caffeine in normal, healthy eumenorrheic females." European journal of clinical pharmacology 55.6 (1999): 445-449.
  • Liguori, Anthony, John R. Hughes, and Jacob A. Grass. "Absorption and subjective effects of caffeine from coffee, cola and capsules." Pharmacology Biochemistry and Behavior 58.3 (1997): 721-726.
  • Ryan, Edward J. Caffeine timing and cycling performance. Diss. Kent State University, 2011.
  • Smits, Paul, Theo Thien, and Albert van't Laar. "Circulatory effects of coffee in relation to the pharmacokinetics of caffeine." The American journal of cardiology 56.15 (1985): 958-963.
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