Taurine Mimics Effects of Insulin, Annihilates Appetite and Quadruples Hypothalamic mTOR Activity in Rodent Study.

Image 1: Bought in bulk, taurine is one of
the cheapest amino acids on the market.

If you listened to the third installment of the Amino Acids for Super Humans Series on Carl Lenore's Super Human Radio, you will know that I am a firm a believer in the power of the non-essential sulfur-amino acid taurine. You would have heard me talk about it's beneficial effects on diabetes, hepatic health, weight management and more.... a recent study (Solon. 2011) published in the influential journal Amino Acids does not only confirm all the beneficial effects, we already knew about, it also expands our current knowledge about taurine to its effects on the hypothalamic Akt/FOXO1, JAK2/STAT3 and mTOR/AMPK/ACC signaling cascades and the satiety signal neuropeptide Y (NPY).

Carina S. Solon and her colleagues from the University of Campinas in Brazil hypothesized that "some of the activity of taurine in the control of body fat would be exerted through direct action in the hypothalamus". To verify their hypothesis, the scientists injected an acute dose of taurine (1.0, 3.0 and 5.0mM) and/or insulin intracerebroventricularly into a cannula that had been placed in the lateral ventricle of the animals more than a week before. What they found was

that the intracerebroventricular injection of an acute dose of taurine reduces food intake and locomotor activity, and activates signal transduction through the Akt/FOXO1, JAK2/STAT3 and mTOR/AMPK/ACC signaling pathways. These effects are accompanied by the modulation of expression of NPY. In addition, taurine can enhance the anorexigenic action of insulin.

Even administered on its own (without insulin) the anorexic effect of taurine had a "similar magnitude to the effect produced by either insulin or leptin" that cannot be ascribed to the reduction in locomotor activity alone. Rather, the scientists argue that the latter is probably a direct result of the "increased primary satiety produced by taurine", which suppresses the well-known food-seeking behavior food-deprived rodents (and interestingly also anorexic human beings) display.

Figure 1: Changes in Akt, mTOR & AMPK expression after intracerebroventricular injection of insulin, taurine or a combination of both (calculated based on Solon. 2011)

At the hypthalamic level, taurine did in fact act similarly to insulin and activated the "Akt/FOXO1 and JAK2/STAT3 signaling pathways, while inhibiting the AMPK signaling pathway" without modulating systemic glucose or insulin levels. By selective inhibition of the JAK2 pathway and upregulation of the AMPK signaling cascade by AICAR infusion, the scientists were able to show that the upregulation of JAK2 and not the downregulation of AMPK were responsible for the appetite-suppressant effects of taurine.

Figure 2: Relative changes in food intake in rats vs. control after intracerebroventricular injection of taurine, AICAR or a combination of both (calculated based on Solon. 2011)

Taken together, these results suggest that the effects of taurine go well beyond its insulin-sensitizing effects on peripheral tissues (Wu. 2010). And while the exact mechanism by which taurine acts on the complex signaling cascade in the hypothalamus, as well as the respective downstream effects at the tissue level (eg. muscle, liver, pancreas, etc.) still have to be elucidated, it becomes increasingly evident that an amino acid, of which many people still believe that it was a somewhat esoteric, horse-sperm derived ingredient of energy drinks, could become a cornerstone in the ongoing battle against obesity.

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 ;-)