Friday, October 3, 2014

Low Dose GABA for Diabesity Treatment? Dose Dependent Conservation of Lean Muscle Mass & Reductions in Oxid. Stress + Weight Gain + Fasting Blood Glucose & Co.

GABA tea contains comparably low amounts of GABA (180mg/100g; Wang. 2006) and still or, as the results of the study at hand suggest, rather thus helps with sleep (Cheng. 2009).
As a SuppVersity reader you know that GABA has been used successfully to revive the pancreas of diabetic animals (Soltani. 2011). As a conspiracy theorist, you believe that it's the pharma business that's paying researchers not to follow up on the results of Soltani et al. and other researchers. And as a physical culturist, you are obviously attracted by the idea that GABA supplements may help you achieve a leaner and more muscular physique... right?

I don't care if everything or anything of what I wrote before is accurate. What I do care about, though, are the results Xie et al. present in their latest paper in the Journal of Animal Physiology and Animal Nutrition.
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The name of the journal gives it away: We are - again - dealing with animal data, but there is no reason to assume that the effect the researchers observed in obese mice would be completely irrelevant for human beings. The previously cited beneficial effects on the pancreas of diabetic animals have after all been confirmed in in vitro studies with human cells, already.

High amino acid levels in the blood of obese indiv. are not a result of their high protein intake, they're caused by low uptake and + high protein breakdown.
As Xie et al. point out the process of becoming obese goes hand in and with disturbances of the plasma free amino acids (pFAAs) pool. In fact, there is reason to believe that these disturbance are causally related to the increase in insulin resistance in obese patients and patients with diabetes mellitus and metabolic syndrome.

Now, contrary to what some "anti protein" gurus are going to tell you, the increased amounts of amino acids are not of dietary origin. Rather than that they are released as a consequence of the increase in protein breakdown - specifically muscle protein breakdown - in obese and diabetic individuals.
Beware of high dose GABA (>3g) supplementation on empty! Those 100mg of GABA are very unlikely to have any negative effects on your health. With higher amounts, on the other hand, specifically if they are taken on empty and thus rapidly absorbed, side effect can occur. Anxiety, slowed breathing, weakness, they all are probably caused by peripheral effects (not in the brain), but this does not make them desirable, either. So practically speaking this means that you best stick to low / divided doses and if you take more, take it with food.
Xie et al did now speculate that the previously cited ability fo gamma-aminobutyric acid (GABA) to reduce high-fat diet (HFD)-induced hyperglycaemia could be brought about by the effects GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system exerts on peripheral organ tissue, like skeletal muscle.

Figure 1: GABA ameliorates / reverses the HFD-induced increase in markers of ox. damage in skeletal muscle (Xie. 2014)
To elucidate, whether that's the case the scientists from the Jiangnan University randomly assigned one hundred male C57BL/6 mice to one out of the following five groups
  • CONTROL: rodents on control diet
  • HFD: rodents on high fat diet (high fat + high energy; HFD) 
  • GL: rodents on HFD supplied with 0.2%, 
  • GM: rodents on HFD supplied with 0.12%, and
  • GH: rodents on HFD supplied with 0.2% GABA in drinking water 
The animals remained on the respective diets for 20 weeks.
What else can GABA do for you? 80 mg of GABA reduce blood pressure in adults with mild hypertension (Matsubara. 2002). It can speed up the recovery of an alcohol intoxicated liver (Soh. 2003). And it will trigger an acute increase in growth hormone (with no proven benefit on muscle gains; Powers. 2013). The often-cited beneficial effects on sleep, on the other hand, are far from being confirmed - results of the study at hand suggest that this may be a result of the fact that you really have to hit the sweet spot to maximize specific effects and minimize the metabolism of GABA in the liver - taking high doses may thus trigger its excretion, while taking very low doses may not be enough get the GABA across the blood brain barrier (Kakee. 2001).
During and after the trial, the scientists observed significant increases in muscular oxidative stress (see Figure 1), protein oxidation, hyperglycaemia, as well as the previously cited plasma free amino acid disorders that included an augmented level of GABA in the blood
Figure 2: Body weight, rel. muscle weight and blood glucose expressed relative to control (Xie. 2014)
Interestingly, the provision of extra GABA was still able to restore normal fasting blood glucose levels and to dose-dependently inhibit body weight gains, muscular oxidation and protein degradation.
So what's the right dose, then? If we use the data from the study at hand and the regular HED calculations, the optimal, i.e. the medium dosage would be ~80mg per day, which is significantly less than most supplements provide and does not compare to the 5g of GABA that have been used by Cavagnini et al. in 1980 to elicit a growth hormone response GABA to which owes much of its fame in the bodybuilding community.
It's all about the right dosage! While medium and low doses of GABA mitigated HFD-induced pFAA disorders, the high dose of GABA deteriorated the pFAA disorders while reducing the level of GABA in the blood and increasing the activity of succinic semialdehyde dehydrogenase which is - you guessed it - responsible for the breakdown of GABA in the liver.

As Xie et al. point out, it is would thus be important to determine the optimal dose in human beings before any recommendations with respect to its use as an anti-diabesity supplement can be made. To do so, it would also be necessary to have a better grasp of its interactions with leptin of which Kahn & Minokoshi recently wrote that they me be interacting on a receptor level in the brain (Kahn. 2013) | Comment on Facebook.
  • Cavagnini, F., et al. "Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man." Acta endocrinologica 93.2 (1980): 149-154. 
  • Cheng, Tsun-Chi, and Jui-Feng Tsai. "GABA tea helps sleep." The Journal of Alternative and Complementary Medicine 15.7 (2009): 697-698.
  • Kahn, Barbara B., and Yasuhiko Minokoshi. "Leptin, GABA, and Glucose Control." Cell metabolism 18.3 (2013): 304-306.
  • Kakee, Atsuyuki, et al. "Efflux of a suppressive neurotransmitter, GABA, across the blood–brain barrier." Journal of neurochemistry 79.1 (2001): 110-118.
  • Matsubara, Futoshi, Et Al. "Effects Of Gaba Supplementation On Blood Pressure And Safety In Adults With Mild Hypertension." Japanese Pharmacology And Therapeutics 30.11 (2002): 963-972. 
  • Powers, Michael. "GABA supplementation and growth hormone response." (2012): 36-46.
  • Soh, Ju-Ryoun, Tokuo T. Yamamoto, And Youn-Soo Cha. "The Effects Of Carnitine And/Or Gamma-Aminobutyric Acid (Gaba) Supplementation On The Recovery Of Chronic Ethanol Administered Rats." Nutraceuticals And Food 8.2 (2003): 119-123.
  • Soltani, Nepton, et al. "GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes." Proceedings of the National Academy of Sciences 108.28 (2011): 11692-11697.
  • Wang, Hsueh Fang, et al. "Comparison of bioactive components in GABA tea and green tea produced in Taiwan." Food chemistry 96.4 (2006): 648-653. 
  • Xie, et al. "Effect of GABA on oxidative stress in the skeletal muscles and plasma free amino acids in mice fed high-fat diet." Journal of Animal Physiology and Animal Nutrition (2014).