Revisiting Caffeine + Lactate - In Combination They May be Powerful Muscle Builders Which Boost Satellite Cell Activity + Anabolic Signalling And Trigger Muscle Hypertrophy - SuppVersity: Nutrition and Exercise Science for Everyone

Revisiting Caffeine + Lactate - In Combination They May be Powerful Muscle Builders Which Boost Satellite Cell Activity + Anabolic Signalling And Trigger Muscle Hypertroph

High intensity
training builds muscle and maximizes lactate build up. Caffeine helps
you to train at maximal intensities. Correct, but there appears to be a
more direct link between lactate accumulation, caffeine supplementation
and skeletal muscle hypertrophy.

No, you are not mistaken: The headline says and means that caffeine and
lactate are powerful agents that may promote skeletal muscle hypertrophy
by boosting satellite cell activity and anabolic signalling in favor of
muscle hypertrophy.



After a thorough review of the existing literature discussing the
individual effects of caffeine and lactate on skeletal muscle metabolism
and anabolism, Yoshimi Oishi and colleagues from the Ritsumeikan University
hypothesized that "a lactate-based supplement containing caffeine, an
activator of intracellular calcium signals, could elicit proliferation
and differentiation of satellite cells, activate anabolic signals in
skeletal muscle, and thereby increase muscle mass when combined with
low-intensity exercise training."



Study Indicates Cut the Volume Make the Gains! 



Well, you already know that they were able to proof their hypothesis,
right? Let's still take a look at how they did that - at least briefly:

"To assess this hypothesis, we initially examined whether lactate and/or
lactate-caffeine treatment could elicit proliferation and differentiation of satellite cells or
activate anabolic signals in C2C12 skeletal muscle cells. Furthermore, we examined
whether the administration of a mixed lactate and caffeine compound (LC compound),
concomitant with endurance exercise training, could effectively increase muscle mass
via activated satellite cells and/or anabolic signals in rat skeletal muscle" (Oishi. 2015)

I know, the human study is missing, but if you think about the
intensity dependent increase in lactate production it appears logical to
assume that increasing lactate levels which as previously been shown
to...

• upregulate the expression of MCT1 and genes coding for other
  components of the mitochondrial reticulum in skeletal muscle (Brooks.
  2009)
• increase myogenin (the satellite cell activator) mRNA in skeletal muscle cells in the petri dish (Hashimoto. 2007)

Now, this raises the question how calcium comes into play. According to
Oishi et al. its beneficial effects are related the ability of caffeine
supplements to increase the amount of intracellular calcium (Lu. 2007),
which activates
calcineurin, which will in turn induce slow and
fast fiber hypertrophy (Talmadge. 2008) - unfortunately, this effect
appears to favor type I (=endurance fiber) over type II hypetrophy, but
this may well depend on the trigger that's used, i.e. endurance training
as it was the case in a rodent study by Talmadge et al. or your
strength workouts.

Figure 1: Graphical illustration of the mechanism by which caffeine and lactate may increase your gains.

Too complicated? Well, check out my graphical summary in Figure 1.
I guess this should explain the basic mechanism: Lactate up = increase
satellite cell proliferation = hotbed for muscle hypertrophy + calcium
up = increased calcineurin = trigger for increased hypertrophy.

Bicarbonate
supplementation buffers the decline in muscle pH and allows for 15%
greater increases in lactate levels while still increasing training
performance on a high volume, high intensity leg workout | read more

High intensity = high lactate, high intensity + bicarbonate = even higher lactate: The study at hand used lactate + caffeine supplementation and low
intensity exercise. With high intensity exercise the increase the
usefulness of additional lactate supplements may be significantly
reduced, because higher intensity equals higher lactate accumulation
anyway. As a previously discussed study on high intensity high volume
leg training indicates, this effect can be augmented by sodium bicarbonate
supplementation which allows for increased lactate levels in the
absence of the debilitating effects of skeletal muscle acidosis (read more).

In the study at hand, the researchers quantified the effects on skeletal
muscle hypertrophy by weighing the gastrocnemius and tibialis muscle of
the rodents after 4 weeks of treadmill training and the effects on
muscle restructuring via incorporation of new muscle nuclei (learn more)
by measuring the increase in DNA content from exercise training alone
and exercise training in conjunction with lactate + caffeine
supplementation.

Figure 2:
Exercise and exercise + supplementation induced changes in muscle weight
and DNA content of skeletal muscle in mice exposed to four weeks of low
intensity treadmill running (Oishi. 2015).

As the data in Figure 2 indicates, both muscle hypertrophy and
the exercise induced increase in satellite cell activity were further
augmented by the addition of lactate and caffeine in dosages of 1g/kg
sodium-lactate and 36mg/kg caffeine.



In conjunction with the likewise observed increases in myogenin and
follistatin expression of the fast twitch (that's what you use for
lifting weights) gastrocnemius muscle relative to the exercise alone,
the results of the study at hand clearly warrant the scientists
conclusion that the administration of sodium lactate and caffeine "can
effectively increase muscle mass concomitant with elevated numbers of
myonuclei, even with low-intensity exercise training, via activated
satellite cells and anabolicsignals" (Oishi. 2015).

So, what does this mean in practice? Assuming the same effects
would occur in human beings the effective dosages of sodium lactate and
caffeine would be 81mg/kg and 2.9mg/kg, respectively. Practically
speaking you would have to take ~6.5g of sodium lactate and 232mg of
caffeine.

Remember? Study suggests, significant increases in mitochondrial builder PGC1-a with HIIT + sodium bicarbonate | read more

That's quite a reasonable amount and should not have nasty side effects.
Whether the sodium lactate offers additional benefits to trainees who
work out far beyond the lactate threshold (remember: the rodents did
only "light exercise"), remains questionable. The same goes for the
question whether the addition of sodium bicarbonate would elicit similar
beneficial effects on the lactate induced increase in satellite
activity. In view of the fact that previous studies show that it does
potentiate the beneficial effects on another albeit not directly related
marker of mitochondrial changes in muscle structure, namely PGC-alpha
(see previous SuppVersity article), I personally believe this would be worth investigating | Comment on Facebook!

References:

• Brooks, George A. "Cell–cell and intracellular lactate shuttles." The Journal of physiology 587.23 (2009): 5591-5600.
• Hashimoto, Takeshi, et al. "Lactate sensitive transcription factor
  network in L6 cells: activation of MCT1 and mitochondrial biogenesis."
  The FASEB Journal 21.10 (2007): 2602-2612.
• Lu, Ying-Mei, et al. "Imbalance between CaM kinase II and
  calcineurin activities impairs caffeine-induced calcium release in
  hypertrophic cardiomyocytes." Biochemical pharmacology 74.12 (2007):
  1727-1737. 
• Oishi, Yoshimi, et al. "Mixed lactate and caffeine compound
  increases satellite cell activity and anabolic signals for muscle
  hypertrophy." Journal of Applied Physiology (2015): jap-00054.
• Talmadge, Robert J., et al. "Calcineurin activation influences
  muscle phenotype in a muscle-specific fashion." BMC cell biology 5.1
  (2004): 28.