Caffeine - 3mg, 6mg or 9mg/kg? What's the Optimal Dosage for Lifting & HIT Cycling and What About the Side Effects?

Wouldn't a single 200mg caffeine be enough to elicit the desired ergogenic effects without side effect like increased urination, headaches and muscle aches on the day after?
Caffeine is not only the world's #1 it is probably also the most (ab-)used ergogenic on the planet and whatever you may think about the longterm consequences of its use, there is not debating that it is part of those few "supplements" that actually work "no hype, no *bs*" ;-)

That being said, you may have noticed with yourself that its effect are dose dependent, but not linearly and that some things, such as an increase in mental focus at work require much lower doses of C8H10N4O2 aka 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione or 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione than the elucidation of a major buzz before an intense strength workout.

So what's the perfect dose, then?

Without wanting to hurt your feelings, you may imagine that you are not the only one who has come to this realization. In fact, the very same thought must have occurred to Jesús G. Pallarés and his colleagues from the University of Castilla-La Mancha and the Spanish Antidoping Agency, as well. With a whole host of technological equipment and the money to conduct a study with thirteen highly resistance train men (age 21.9 ± 2.9; 76.5 ± 8.5 kg, height 172.7 ± 5.4 cm, body fat 12.4 ± 2.7), the Spanish scientists are yet in a much better position to elucidate where exactly these sweet spots would be.
Figure 1: Illustration of the procedure on the testing days (Pallarés. 2013)
To this ends, Pallarés et al. had their volunteers undergo a battery of muscle strength and power tests, namely a  free-weight fullsquat (SQ) and bench press (BP) exercises against  4 incremental loads (25%, 50%, 75% and 90% 1RM), as well as a test in which their cycling peak power output (PPO) was measured using a 4s inertial load test in a randomized in a double-blind, cross over design.

On the four separate testing days, the subjects ingested either a placebo supplement (PLAC) or, caffeine at dosages of ...
  • 3mg/kg body weight (CAFF3mg), 
  • 6mg/kg body weight (CAFF6mg) and
  • 9mg/kg body weight (CAFF9mg)
The day before and during the seven days that the experiment lasted, the subjects lived at the sports performance center where they slept and ate all meals. They all consumed a diet of 2800-3000 kcal·day/day that had a macronutrient make-up where 55% energy intake came from carbohydrates, 25% from fat and 20% from protein. The energy intake was evenly distributed across three meals each day (breakfast at 7:00 a.m., lunch at 13:30 p.m. and dinner at 20:00 p.m.). Subjects refrained from physical activity other than that required by the experimental trials, and withdrew from alcohol, tobacco and any kind of caffeine intake 10 days before testing and while the experiment lasted.

On the actual testing day some baseline measurements, such as height, body fat %, as well as blood and urine samples were taken (PRE). Afterwards the subjects consumed a standardized "breakfast" consisting of a 330 mL of fruit milkshake (168 kcal) and a pastry (456 kcal; total energy for both 624 kcal; 68 g of carbohydrates) along with the their individualized randomized caffeine dose (3, 6 or 9 mg/kg) or placebo in capsule form. After this "delicious" *lol* breakfast, the participants performed
"[...] a standardized warm-up that consisted of 10 min of jogging at 10 km/h and 10 min of static stretches and joint mobilization exercises, the subjects entered the laboratory to start the neuromuscular test battery assessments under a paced schedule (see figure 1).  These tests consisted of the measurement of bar displacement velocity and muscle power output against 4 incremental loads (25%, 50%, 75% and 90% of 1RM) for upper and lower body musculature (BP and SQ).  Those step measures allowed a continuous representation of the load-velocity and load-power curves to study the interaction between load and caffeine dose on neuromuscular performance.  Cycling peak power output (PPO) was assessed next using a nonfatiguing inertial load test of 4 s duration.  Subjects remained blinded to the results during the whole experiment. Instructions prior to lifting were standardized and always delivered by the same experimenter.
The whole procedure took about 60min and upon completion of the test battery a second  urine  and  blood  sample  was  collected  (POST). Moreover, all participants were required to fill out an obligatory questionnaire (QUEST+0h) that was aimed to address whether side-effects of caffeine were present during the trial.

Caffeine a side effect free ergogenic? Not exactly, no...

As some of you may know from their own lingering experience things that work, usually don't do that without side effects and the study at hand confirmed that this is no different for caffeine. Somewhat surprisingly, though the side effects the subjects who had refrained from caffeine intake for at least 10 days before the the first test, reported "very similar side effects" for the medium and high dose caffeine trials:
  • a limited increase in the sensations of tachycardia and heart palpitations,
  • self-reported urine output and gastrointestinal problems (8% of the subjects)
At the same time, the subject’s perception of performance and vigor increased 5 to 7 times above PLAC during the CAFF 3mg and CAFF6mg trials (38% and 54% of the subjects, respectively), which would appear to be well worth the minor problems.

Figure 2: Overview over the number of participants reporting side effects / perceived ergogenic effects (Pallarés. 2013)
In the course of the 9mg trial (remember: this was a bolus of 693mg caffeine for the average study participant) the men did yet report a "drastic increase" of side-effects (Table 1), of which the researchers consider the reported increase in the estimates of urine output and gastrointestinal problems (62% and 31%, respectively) to be most important. So important, in fact that it is questionable whether that was worth the increased perception of performance and vigor or activeness of 62% and 54%.

On the subsequent day, participants in the CAFF6mg trials were complaining of increased muscle soreness, headaches and an increase in the estimates of urine output in comparison to the PLAC and CAFF3mgtreatments. Sleep problems and persistently increased vigor occurred only in the  CAFF6mg an CAFF9mg trials with a much higher incidence (23-54% vs. 8% in the high vs. medium dose trial).

What Pallarés et al. find particularly noteworthy is that "23% of participants reported tachycardia and anxiety or nervousness, 38% with gastrointestinal problems and 54% with insomnia or sleep disturbances" (Pallarés. 2013). This is also the main reason that the researchers recommend "administering the minimal ergogenic dose". But what exactly is this dosage?

What delivers the most bang with the least side effects?

In order to answer this question we will have to take a closer look at the performance measures and compare the increases in mean propulsive velocity and muscle power, as well as the cycling PPO and the likelihood and severity of side effects for all four dosing regimen (see figure 3)
Figure 3: Propulsive velocity during bench presses (left) and propulsive power during bench presses and squats (right) in the placebo, 3mg, 6mg and 9mg trials (Pallarés. 2013)
As the data in figure 3 goes to show you, caffeine produced ergogenic effects at all dosages. With the heaviest weights, however, the propulsive velocity during bench presses and the squat power required the side-effect laden 9mg dose of caffeine to reach statistical significance. The same goes for the cycling peak power output (not shown).

Suggested read: "Coffee - The Good, The Bad & The Interesting: 2-4 Cups of Coffee for Adiponectin. Roasted Filtered Coffee & High LDL!? The Optimal Caffeine / Taurine Ratios & the Buzz ". Could taking taurine ameliorate w/out compromising the benefits of caffeine (read more)?
Bottom line: The study at hand is actually a good example of the myriad of cases, where statistical significance and the real world collide. Let's take another look at the results in figure 3 and the side effects in figure 2. Assuming that you have not whacked your adrenal gland to an extend that you don't respond to caffeine any longer (in that case you better stop taking it all along, anyway), there clearly is no reason to even remotely consider taking caffeine in dosages of more than 6mg/kg body weight before a workout (personally I have found that anything beyond 200-300mg will - in the long run do more harm than good for me, but I guess this really depends on the individual).

Aside from the subjective side-effects the latter has also been shown to have profoundly detrimental effects on the cortisol to testosterone ratio after a workout (cf. "Revisited: Caffeine's Dose-Dependent Effects on the Testosterone to Cortisol Response to Exercise"; read more)...

... and yes, I know that the relevance of this ratio in terms of the "productivity" of your workouts is highly questionable, the latter has been proven for a normal, non-stimulant based increase in cortisol / testosterone, not for the exorbitant increase in cortisol Beavan et al. observed in their 2008 study. If you add the detrimental down-stream effects of messed up sleep, and the obvious dehydration that follows the increased urination observed in the study at hand - overdosing may thus well turn the "proven ergogenic" caffeine into a highly ergolytic agent.

References:
  • Beaven CM, Hopkins WG, Hansen KT, Wood MR, Cronin JB, Lowe TE. Dose effect of caffeine on testosterone and cortisol responses to resistance exercise. Int J Sport Nutr Exerc Metab. 2008 Apr;18(2):131-41. 
  •  Pallarés JG, Fernández-Elías VE, Ortega JF, Muñoz G, Muñoz-Guerra J, Mora-Rodríguez R. Neuromuscular Responses to Incremental Caffeine Doses: Performance and Side Effects. Med Sci Sports Exerc. 2013 May 10.
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