Two Weeks on 2.5g Betaine Increase Performance, IGF1 & Growth Hormone by Antagonizing Corticotropin-Releasing Hormone at the Hypothalamic Level

Image 1: You can probably get some cheap betaine (TMG) from your local fishing (not vitamin) shop.

Sometimes, the thing we have been looking for has been there all along. And, no, I am not talking about the love of your life, but the cheap, effective and side-effect free anti-catabolic ergogenic every hard training athlete and fitness fanatic could benefit from. It turns out, Betaine, or trimethyl-gylcine (TMG), the methylated version of the relatively unknown amino acid glycine could be just that: a readily available, cheap ergogenic with the ability to safely modulate your hormonal training response in a way that will actually translate into real world performance increments.

It is not without reason that I underline the importance of real world performance increments against impressive figures on a (oftentimes unrealiable) lab report. What's the use of the 40% increase in testosterone supplement X has been shown to provide, when the latter simply does not translate into practical performance, let alone muscle gains?

Figure 1: The decreases in cortisol and increases in IGF1 and GH compared to the control groups may not bee too impressive, yet they did produce statistically significant increases in two of the four measured markers of exercise performance (data calculated based on Apicella. 2011)

Compared to 40% more testosterone, the effects the supplementation of 1.25g betaine twice a day had on the IGF (+12.4%), GH (+4%) and cortisol (-4.7%) levels of the 12 male, previously resistance trained subjects (age, 19.7 years; height, 172.6 cm; weight, 84.27 kg; body fat, 18.7 %; BMI, 28.2 m²/kg) of the experiment in Jenna M. Appicella's Master thesis appear mediocre, at best, in contrast to the overwhelming majority of expensive "testosterone boosters" supplementation with N-N-N-methyl-glycine (the chemical name of betaine) delivered measurable real world results in form of increments in isometric squat force production and the number of boxes lifted during a box lift test (subjects had to lift as many 18.14 kg metal boxes onto a 1.32 m high platform in 10min, as possible).

Quinoa	630 mg
Spinach	577 mg
Wheat bran	360 mg
Lamb's quarters	332 mg
Beet	256 mg
Table 1: Amount of TMG in common foodstuff per 100g

Next to these immediate (14 days is a short time span) performance increments, both, the small, but measurable increase in total muscle Akt (+1% total Akt), a serine/threonine protein kinase that plays a key role in multiple cellular processes, as well as the compensation of training induced decreases in the phosphorylation of of Akt at S473 and p70 S6k at T389, both enzymes that are intricately involved in cell- and in this case muscle growth, it can be expected that long(er) term supplementation with betaine would also improve the hypertrophy response to resistance training.

With regard to the underlying mechanism of action, the author speculates that

since cortisol has been shown to inhibit GH release, specifically by blunting GH release
in response to GHRH [and] CRH [which is the hypothalamic messenger telling your body to release cortisol] has also been shown to inhibit GH release stimulated by GHRH [and] cortisol may increase somatostatin as another point of inhibition to GH [...] [i]t could be suggested that the decrease in cortisol during the post betaine supplementation trial would decrease the
inhibitory effects to allow the increase in GH release that was observed in our study.

In that, Appicella refers to the results of Yan et al. (2001; incomplete reference given, article not trackable) who observed that betaine deposition in the hypothalamus of pigs increased GHRH [growth hormone releasing hormone] gene transcription and thus elevated GH secrection and speculates

that the decrease in cortisol decreased somatostatin to allow the overall stimulus to the
anterior pituitary to be more positive and allow increased GH secretion.

Personally, I would be interested to see follow up studies with a) longer durations b) different dosing protocols and c) more sophisticated exercise regimens. In fact, Appicella is part of the Volek group from Department of Kinesiology at the University of Connecticut with whom she published her results in the March issue of the Journal of Strength and Conditioning Research, already and who have published similar findings on the effects of trimethylglycine on exercise performance (e.g. Lee. 2010) in the past.

Attention! There seems to be some confusion about betaine (tri-methyl-glycine, TMG) and betaine hcl, the former is the one used in the study, whereas the latter is what you would take (in smaller amounts!) if you had low stomach acid.

This means you can be pretty sure that we will hear more on this remarkable N-trimethylated amino acid and its potential application as an ergogenic, soon. And where is the place you will read about these news first? Correct! Right here at the SuppVersity ;-)