Download Fitness Tools

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.
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

Figure 3: Cycle time trial performance across experimental treatments (Ryan. 2011).

From a physiological perspective NO is not primarily there to make you look vascular and pumped, boys.

If you've read the headline and are asking yourselves "Why on earth would I even want to spend money on cosmetic pump?", you probably need a reminder of the multiple important functions nitric oxide (NO) serves in your body: (1) With their ability to relax the musculature of your blood vessels to increase the blood flow through your veins, normal NO levels are required to guarantee optimal blood flow to every body part; (2) since this includes your sexual organs, normal NO levels are also a prerequisite for normal / optimal sexual function; (3) having enough NO is also required to keep your immune defenses up, because the white blood cells need it in their fight against intruders; and if heart disease, sexual dysfunction and immune health are all things you don't care about (4) you may be interested to hear that your brain and metabolic health critically depend on normal NO levels, as well.
Now that you've got the primer on "nitric oxide beyond the pump" you may be happy to hear that a very common NO supplement, i.e. citrulline, actually delivers. But there's more: In a very recent study, scientists from the Baylor University demonstrated for KYOWA HAKKO BIO CO (so this is sponsored research) that a combined treatment with citrulline and glutathione leads to significant increases in the levels of cGMP, nitrite, and NOx (nitric oxide metabolite) in cells, rodents and humans.

Figure 1: Overview of the design of the "human part" of the study (McKinley-Barnard. 2015).

In the latter part of the study (the human part), the researchers had sixty six participants randomly assigned (in a double-blind fashion) to one of four groups (n = 15 per group) involving 7 days of the oral ingestion of four capsules containing a total daily dose of either: cellulose placebo (2.52 g/day), L-citrulline (2 g/day), GSH (1 g/day), or L-citrulline (2 g/day) + GSH (200 mg/day). Supplementation compliance was monitored by participants returning empty containers of their supplement on day 7, and also by completing a supplement compliance questionnaire.
Each participant ingested all four capsules containing their respective daily supplement dose each evening for six consecutive days until at Visit 3 (Day 7), participants were provided the final daily dose of their respective supplement ingested one hour prior to performing a previously familiarized biceps training program consisting of  3 sets of 15 repetitions with as much weight as they could lift per set (typically 70–75 % of 1RM | 10s rest between sets, only) on a selectorized weight machine (Body Master, Rayne, LA).

Figure 2: Nitrate concentration and change in plasma NOx in rodents (NO metabolites | McKinley-Barnard. 2015).

Figure 2, which depicts data from the rodent study, already suggests that only citrulline or citrulline and glutathione would trigger significant increases in NO production in the 20-22 year-old healthy, well-trained (at least three resistance training sessions per week) participants, while GSH alone would trigger only a minor increases of the nitric oxide levels.

Figure 3: Changes in NO metabolites (NOx) and cGMP levels (McKinley-Barnard. 2015) in the human study.

The data in Figure 3 (left) which tells you that the increase in stable NO metabolites (NOx) in the blood of the subjects in the citrulline + GSH group was the highest. What may surprise you, though, is that the increase in nitric oxide that is obviously partly mediated by an increase in c-GMP (Figure 3, right) levels was not only maintained after the workout, the levels even kept increasing.
This is in contrast to your regular "pump" formula (using only citrulline), where the levels drop back to baseline ( and potentially even lower - after all only 30 min were monitored) after the workout.

Why is that important? Well, if you look back at the "nitric oxide beyond the pump" list from the introductory paragraph, you will notice that almost all of these "beyond the pump" effects are health-relevant during, but also and even more so after the workout.
References:

• Ghigo, D., et al. "Correlation between nitric oxide synthase activity and reduced glutathione level in human and murine endothelial cells." Amino acids 10.3 (1996): 277-281.
• Hofmann, Heinrich, and Harald HHW Schmidt. "Thiol dependence of nitric oxide synthase." Biochemistry 34.41 (1995): 13443-13452. 
• McKinley-Barnard, Sarah, et al. "Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis." Journal of the International Society of Sports Nutrition 12.1 (2015): 27.

As a waredownloadsoft reader you already know of the post-workout creatine advantage.

I am sure you will remember Jose Antonio's 2013 study on the effect of creatine timing in 19 male recreational bodybuilders (reread the waredownloadsoft article). The results indicated quite conclusively that taking creatine after the workout is a bit more effective than taking the same amount immediately before the workout.

In view of the fact that the effect did not reach statistical significance and an advantage was only "possible" or "likely", though, the debate about the importance or non-significance of creatine timing is far from being settled.
The latest evidence that creatine timing counts comes from the University of Regina, where Darren Candow, Emelie Vogt, Sarah Johannsmeyer, Scott Forbes, and Jonathan P. Farthing conducted a
double-blind study that involved older adults (50-71 yrs) who were randomized to one of three groups:

• Creatine-Before (CR-B: n=15; creatine [0.1g/kg] immediately before resistance training and placebo [0.1g∙kg-1 corn-starch maltodextrin] immediately after resistance training), 
• Creatine-After (CR-A: n=12; placebo immediately before resistance training and creatine immediately after resistance training) or 
• Placebo (PLA: n=12; placebo immediately before and immediately after resistance training)

The subjects remained on the respective protocol for 32 weeks. Prior to and following the study, body composition (lean tissue, fat mass; dual energy x-ray absorptiometry) and muscle strength (1-repetition maximum leg press and chest press) were assessed. The habitual dietary intake was evaluated by the means of 3-day dietary records during the first and final week of resistance training and supplementation, but significant and potentially relevant differences were not obeserved.

If you haven't already done so, review the results of J. Antonio's previous creatine timing study in "Creatine Before or After the Workout? Finally the Answer is Here! Study Says: Better Take it After for Mass & Strength" | read more

"Participants followed the same supervised whole-body resistance training program for 32 weeks in the same private laboratory. Training sessions were supervised as previous research has demonstrated greater gains compared to unsupervised training (Mazzetti et al. 2000). Prior to training sessions, but after the supplement was consumed, each participant performed a 5-minute stationary cycling warm-up at a self- selected intensity. Participants completed 3 sets of 10 repetitions to muscle fatigue with 1-2 minutes rest between sets for each exercise at an intensity corresponding to their 10- repetition maximum for each exercise. 

[...The machine-based program included the following exercises] leg press, chest press, lat pull-down, shoulder press, leg extension, leg curl, triceps extension, biceps curl, calf press, back extension and abdominal curl [all were performed in the given order]" (Candow. 2015). 

The participants had to maintain daily training logs where the load, number of sets and repetitions
were recorded. Resistance was increased by 2-10 kg once a participant could complete 3 sets of 10 repetitions to muscle fatigue for an exercise. Once the resistance was increased, participants maintained this load until a subsequent 3 sets of 10 repetitions to fatigue were completed.
References:

• Antonio J, Ciccone V. The effects of pre versus post workout supplementation of creatine monohydrate on body composition and strength. J Int Soc Sports Nutr. 2013 Aug 6;10(1):36. [Epub ahead of print]
• Candow, Darren, et al. "Strategic ingestion of creatine supplementation and resistance training in healthy older adults." Applied Physiology, Nutrition, and Metabolism ja.