3g Taurine Improve Post-Workout Glycogen Resynthesis, Protect the Testes of Doping Sinners & Battles Alzheimer's

Taurine - A useful supplement for chemical, natural athletes and even sedentary slobs who are afraid of diabetes.

Taurine, or 2-aminoethanesulfonic acid, as Wikipedia says, is an organic acid widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine, and accounts for up to 0.1% of total human body weight. That does not sound like much, but taurine has many fundamental biological roles, such as conjugation of bile acids, antioxidation, osmoregulation, membrane stabilization, and modulation of calcium signaling. It is essential for cardiovascular function, and development and function of skeletal muscle, the retina, and the central nervous system and you were thus probably not too surprised, when you've recently read on the SuppVersity Facebook Page that taurine may help with Alzheimer's disease.

You can learn more about taurine & other amino acids at the SuppVersity

Taurine Pumps Up Strength & Recovery?

Taurine Improves Insulin + Glucose Metabolism

Taurine ➲ 180% Testosterone Increase

Taurine + BCAA Work Hand in Hand

43% Reduced Performance W/ BCAAs

BCAA Neurotransmitter Depletion

In the corresponding paper that was published only recently in the ScientificReports on Nature.com Kim et al. report that orally administered taurine via drinking water rescued the cognitive deficits in a standard rodent model of Alzheimer's (APP/PS1 mice) and brought them back up to age-matching wild-type mice.

Figure 1: Improvement in spatial and hippocampal learning behaviours in taurine-treated transgenic mice. 7-month old wild-type (Wt) and agematched APP/PS1 transgenic (Tg) male mice were orally administered water or taurine (1,000 mg/kg/day) for 6 weeks (n 5 8–10 per group). After 6 weeks, behavioural tests were administered to the 8.5-month old mice. (Left) Y-maze. Average alternation (%) of each group of mice was calculated. (Right) Passive avoidance. Average latency time in seconds for each group of mice was measured (Kim. 2014).

That's unquestionably impressive, but what's more impressive is that this is by far not the first study to report that taurine exhibits a plethora of physiological functions in the central nervous system.

But taurine gives me diarrhea! If it does try taking it with a meal that will greatly reduce the risk of having to rush to the toilette and should not reduce the physiological benefits significantly. At least for the muscular effects its unlikely that it will matter at all. For the beneficial effects on the brain, it may be necessary to achieve higher serum peak levels. In view of the fact that the rodents in the aforementioned study by Menzie et al. received the taurine in the drinking water, even this is yet unlikely. If the taurine "goes right through", though, it's certainly not going to help you ;-)

In a recent review in the scientific journal Amino Acids review, Janet Menzie et al. describe the mode of action of taurine and its clinical application in the neurological diseases: Alzheimer’s disease, Parkinson’s disease and Huntington’s disease and conclude that taurine...

"[...] functions through multiple neuroprotective mechanisms: regulation of cellular osmolarity , anti-oxidant, neuromodulator of GABAergic transmission, maintenance of calcium homeostasis, inhibition of glutamate excitotoxicity, attenuation of endoplasmic reticulum stress, modulation of mitochondrial pore permeability, downregulation of a range of proapoptotic proteins while upregulating anti-apoptotic proteins and downregulation of inflammatory mediators." (Menzie. 2014)

Moroever, Menzie et al. believe that there is "strong evidence" of the existence of a specific taurine receptor, which is activated exclusively by taurine, but not by structurally similar amino acids such as glutamate, GABA and glycine and could be responsible for many of the beneficial effects taurine exerts in the context of central nervous system disorders. More specifically existing evidence clearly suggests protective effects in Alzheimer’s, Parkinson and Huntington diseases. Three pathologies that share a number of broad mechanisms: Oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium imbalance, inflammatory changes apoptosis - and *tadaa* a reduced level of (Arai. 1985; Alom. 1991; Molina. 1997).

Enough of the health stuff, what about the post-workout goodness?

I know, as long as we are healthy we don't really care about debilitating central nervous system disorders... well, ok. I will spare you my moral pointing finger and get straight to the similarly unsurprising results of a recent study from the University of Tokyo. A study which clearly indicates that the provision of taurine after workouts can lead to a significant enhancement of the already elevated glycogen synthesis after your workouts.

Figure 2: Muscle and liver glycogen and serum free fatty acids (FFA) before and after the workout (Takahashi. 2014).

In two rodent studies, the Japanese researchers tested whether the oral administered of taurine  at a dosage of 0.5 g/kg body weight (for human beings that's 0.04g/kg or approximately 3g total | the SuppVersity suggested dose from previous articles, by the way) immediately after treadmill running at 25 m/ min for 90 min would alter the metabolic response and glycogen synthesis after workouts when it was (A) administered alone or (B) as part of a glucose solution containing taurine and glucose at a ratio of 1:2 - in this case 0.5g/kg taurine and 1.0g/kg glucose.

Figure 3: AUC for glucose after for 60min and 120min after the ingestion of the taurine + glucose solution. As the data indicates taurine helped to "clear" the sugar from the blood stream (Takahashi. 2014).

As the scientists point out, their "results show that post-exercise taurine administration enhances glycogen repletion in skeletal muscle" (Takahashi. 2014). The underling cause, however, is still speculative. Takahashi et al. believe that it is triggered by

1. 

   Figure 4: Changes in general oxidative damage (TBARs), protein damage and exercise performance in response to taurine vs. placebo vs. bet alanine supplementation; expressed relative to untrained control (Dawson. 2002).

   an acceleration of glucose uptake, and
2. an increase in fat oxidation

of which the latter will have a carbohydrate sparing effect and will thus leave a higher amount of carbs for glycogen repletion. In conjunction with previously established benefits of taurine, such as

• the attenuation of exercise-induced DNA damage during workouts (young men | Zhang. 2004),
• the amelioration of cytotoxic (cell damaging) effects of exercise (rodents | Dawson. 2002),
• an increase in exercise performance (specifically endurance ex. | Dawson. 2002; Miyazaki. 2004),
• additional effects on the benefits of BCAA intake for the delayed-onset muscle soreness and muscle damage induced by high-intensity eccentric exercise (Ra. 2013),
• an improvement in osmoregulation (water balance) of the muscle (Cuisinier. 2002), and
• decreases in oxidative stress during eccentric exercises (Silva. 2011)

The optimal dosing for performance increments, by the way, is between 1.2-6.0g for 2 weeks (other timing has not been tested, so it's possible that one week will suffice, too). That's at least what the only hitherto published study that investigated the effects of different doses of taurine as a means to improve the endurance performance (Miyazaki. 2004). If you want the nutrient partitioning effects, though, you would have to consume CHO + taurine after the workout - 3g of taurine should suffice. Judged by the hitherto published studies this should automatically help you to increase your workout performance after 2 weeks (the beneficial effects will, just as it is the case for creatine, accumulate until the levels are saturated).

And there are more benefits - health benefits, for juicers and non-juicers

The former, i.e. the juicers will probably be happy to hear that taurine does not just have liver protective effects (Miyazaki. 2005), but will also reverse the nandrolone decanoate induced perturbations in sperm characteristics, normalize the serum testosterone level, and restore the activities of the key steroidogenic enzymes in rodents that are treated with nandrolone and taurine (at a dosage equivalent to only 1.3g/day | Ahmed. 2014).

In spite of the fact that the administration of taurine did also prevent the nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects, I would like to point out that this article is not intended as an incentive for nandrolone doping.

While taurine is not made from the sperm of Belgian Blues it may still boost your testosterone levels - whether that's going to be by 140% as in this study is questionable, though.

From performance to health doping: If you are not into "natural performance enhances" and don't care about the direct performance increases, reduced oxidative damage and increases in glycogen repletion during workouts. I would recommend you reread the previous SuppVersity article about the testosterone boosting effects of taurine, it's ability to improve your strength and recovery during and after resistance training sessions, as well as it's ability to improve your glucose metabolism (Franconi. 2006; Carneiro. 2009), to increase your glucose sensitivity (Han. 2004; Nakaya. 2000), to prevent insulin resistance in hyperglycemic states (Haber. 2003), to prevent the development of hypertension as a result of fructose overfeeding (Rahman. 2011), to prevent the cardiac damage due to iron overload (Oudit. 2004), to protect you from the kidney damaging assault of chemotherapy (Saad. 2010), and god knows which benefits I have simply forgotten in the aforementioned list | Comment of Facebook!

References:

• Ahmed, Maha AE. "Amelioration of Nandrolone Decanoate-Induced Testicular and Sperm Toxicity in Rats by Taurine: Effects on Steroidogenesis, Redox and Inflammatory Cascades, and Intrinsic Apoptotic Pathway." Toxicology and Applied Pharmacology (2014).
• Alom, J., et al. "Cerebrospinal fluid taurine in Alzheimer's disease." Annals of neurology 30.5 (1991): 735-735.
• Arai, Heii, et al. "A preliminary study of free amino acids in the postmorten temporal cortex from Alzheimer-type dementia patients." Neurobiology of aging 5.4 (1985): 319-321. 
• Carneiro, Everardo M., et al. "Taurine supplementation modulates glucose homeostasis and islet function." The Journal of nutritional biochemistry 20.7 (2009): 503-511.
• Cuisinier, Claire, et al. "Role of taurine in osmoregulation during endurance exercise." European journal of applied physiology 87.6 (2002): 489-495.
• Dawson Jr, R., et al. "The cytoprotective role of taurine in exercise-induced muscle injury." Amino acids 22.4 (2002): 309-324. 
• Franconi, Flavia, et al. "Taurine supplementation and diabetes mellitus." Current Opinion in Clinical Nutrition & Metabolic Care 9.1 (2006): 32-36.
• Haber, C. Andrew, et al. "N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress." American Journal of Physiology-Endocrinology and Metabolism 285.4 (2003): E744-E753.
• Han, Jin, et al. "Taurine increases glucose sensitivity of UCP2-overexpressing β-cells by ameliorating mitochondrial metabolism." American Journal of Physiology-Endocrinology and Metabolism 287.5 (2004): E1008-E1018. 
• Kim, Hye Yun, et al. "Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease." Scientific Reports 4 (2014).
• Menzie, Janet, et al. "Taurine and central nervous system disorders." Amino acids 46.1 (2014): 31-46.
• Miyazaki, T., et al. "Optimal and effective oral dose of taurine to prolong exercise performance in rat." Amino Acids 27.3-4 (2004): 291-298.
• Miyazaki, Teruo, et al. "Taurine inhibits oxidative damage and prevents fibrosis in carbon tetrachloride-induced hepatic fibrosis." Journal of hepatology 43.1 (2005): 117-125.
• Molina, José A., et al. "Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients with Parkinson's disease." Journal of the neurological sciences 150.2 (1997): 123-127.
• Nakaya, Yutaka, et al. "Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes." The American journal of clinical nutrition 71.1 (2000): 54-58.
• Oudit, Gavin Y., et al. "Taurine supplementation reduces oxidative stress and improves cardiovascular function in an iron-overload murine model." Circulation 109.15 (2004): 1877-1885.
• Rahman, Mizanur M., et al. "Taurine prevents hypertension and increases exercise capacity in rats with fructose-induced hypertension." American journal of hypertension 24.5 (2011): 574-581.
• Saad, Sherif Y., and Ammar C. Al-Rikabi. "Protection effects of taurine supplementation against cisplatin-induced nephrotoxicity in rats." Chemotherapy 48.1 (2010): 42-48.
• Silva, Luciano A., et al. "Taurine supplementation decreases oxidative stress in skeletal muscle after eccentric exercise." Cell biochemistry and function 29.1 (2011): 43-49. 
• Takahashi, Yumiko, et al. "Post-exercise taurine administration enhances glycogen repletion in tibialis anterior muscle." The Journal of Physical Fitness and Sports Medicine 3.5 (2014): 531-537.
• Zhang, M., et al. "Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men." Amino acids 26.2 (2004): 203-207.

Taurine + BCAAs - Scientists Identify Unkown Synergy of Branch-Chained and Sulfur-Amino Acids: Redutions in DOMS, Faster Recovery and Reduced DNA Damage

If this is true and sore is the new sexy, the combination of taurine + BCAA's may turn you into an ugly worm.

You know them and I would bet that >75% of you have already taken them: Branch-Chained Amino Acids (BCAAs) and the sulfur-amino acid taurine. Maybe you have taken the former for their beneficial effects on skeletal muscle protein synthesis and the latter for its anti-oxidant effects and the cascade of beneficial downstream effects I have written about quite extensively, here at the SuppVersity.

If I am asking you whether you have taken both in conjunction as a means to reduce post-workout delayed-onset muscle soreness and the expression of purported markers of muscle damage, on the other hand, I'd expect only few people to raise their hands... right?

Sometimes it's worth taking another look

The currently available literature on the beneficial effects of BCAAs on DOMS is pretty inconclusive. If you restrict your review of the literature to studies using resistance training as a trigger for muscular damage (Jackman et al. (2010), Howatson et al. 2012; etc.), it does yet appear warranted to say that the chronic ingestion of a high dose of BCAAs can ameliorate the peak in delayed muscle soreness after 24-48h.

You can learn more about taurine & BCAAs at the SuppVersity

Taurine Pumps Up Strength & Recovery?

Taurine Improves Insulin + Glucose Metabolism

Taurine = 180% Testosterone Increase

Leucine Only Tops Ergogenic Effects of BCAAs

43% Reduced Performance W/ BCAAs

BCAA Neurotransmitter Depletion

In the previously referenced 2012 study by Howatson et al. we are talking about a ~50% reduction after 24h and a 25% reduction after 48h. Both statistically and physiologically relevant, but if the decrease in maximal voluntary contraction had not been blunted, as well, it'd been another instance of much ado about nothing. Similar beneficial effects have been observed with taurine, as well:

• 

  Taurine & caffeine make another super-stack; but only at the right ratios | learn more

  Zhang et al. report that taurine can "attenuate exercise-induced DNA damage and enhance the capacity of exercise due to its cellular protective properties" in the musculature of healthy young men (Zhang. 2004)
• Silva et al. observed in a rodent model of skeletal muscle damage in response to eccentric exercise that taurine decreases the oxidative stress, in association with decreased superoxide radical production (Silva. 2011)
• learn more in previous SuppVersity articles about taurine

Against that background it was to be expected that the previously sedentary subjects of a very recent study from the University of Tsukuba in Japan was attenuated, irrespective of whether they were taking 3x3.5g of BCAAs or 3x2.0g of Taurine for 2 weeks before they performed a standardized eccentric exercise test:

"For the ECC protocol, subjects were seated on a bench with their arm positioned in front of their body and resting on a padded support, such that their shoulder was secured at a flexion angle of 0.79 rad (45°) and their forearm was maintained in the supinated position throughout the exercise. Subjects were repeatedly weight-loaded upon
dumbbell lowering to achieve a 90% MVC (34.3 ± 1.3 Nm). Subjects performed six sets of five repetitions of elbow extension from the flexed position at 90° to the fully extended position slowly over 5 s, while maintaining a constant speed of movement by following a verbal metronome provided by the investigator." (Ra. 2013)

What we could not necessarily be sure of is whether these effects would also add up in those 12 untrained male subjects (22.5 ± 3.8 years) who were assigned to the taurine + BCAA group.

Figure 1: Post workout muscle soreness, left; post workout arm circumference in response to cell swelling, right (area under the curve for the 96h after the eccentric exercise test; based on Ra. 2013)

Now that you've taken a glimpse at the data in Figure 1, it's probably pointless to ask you to make an educated guess. It's too obvious that the individual DOMS reducing effects of taurine and BCAAs add up. What's yet even more obvious is that only the combination of both leads to a rapid reduction in muscle swelling, the effect size of which goes far beyond what additive effects could achieve - this indirect marker of muscle damage would thus suggest that there is a special synergy between taurine and BCAAs, a synergy due to which a reduction of 35mm/96h + 45mm/96h (the individual changes for BCAAs and taurine) does not translate into a -80mm/96h, but into a 465mm/96h reduction of this commonly used indirect measure of skeletal muscle damage.

"Synergy" is the name of the game

If you take a parting look at the data in Figure 2, you should actually be able to understand why the combination of branch-chained amino acids and the sulfur amino acid taurine works so well: One excels where the other has only minor effects.

Figure 2: CK, left, and 8-hydroxydeoxyguanosine (8-OHdG), right (area under the curve for the 96h after the eccentric exercise test; based on Ra. 2013)

While the branch-chained amino acids have a more pronounced effect on the expression of CK and LDH (not shown in Figure 2), they do very little to protect the muscle from oxidative damage (as indicated by the quasi non-existent effect on the levels of 8-hydroxydeoxyguanosine (8-OHdG), a marker of DNA damage.

Suggested read: "Rats 'On' Taurine Can't Ever Get Enough... Exercise of Course! What Were You Thinking About? Mice Cover 50% More Distance W/ HED of 3-4G of Taurine Post Workout " | more

Bottom line: Actually there is very little I have to add to the researchers conclusion that "his study confirmed that a combination of 3.2 g BCAA and 2.0 g taurine, three times a day, two weeks prior to
and three days after exercise attenuates some subjective and objective markers of DOMS and muscle damage induced by high-intensity ECC, which could not have been influenced by BCAA or taurine supplementation alone." (Ra. 2013)

I am not 100% sure if they are also correct in their assessment that this supplement is particularly useful for beginners who would be more motivate to continue an exercise program, if it doesn't hurt so much, though. That it could help competitive athletes to train at higher intensities on the other hand, is something I would fully subscribe - whether that's necessarily going to be more productive, on the other hand, is question I would not want to answer without a follow up study ;-)

References:

• Jackman, S. R., Witard, O. C., Jeukendrup, A. E., & Tipton, K. D. (2010). Branched-chain amino acid ingestion can ameliorate soreness from eccentric exercise. Med Sci Sports Exerc, 42(5), 962-970.
• Ra, S. G., Miyazaki, T., Ishikura, K., Nagayama, H., Komine, S., Nakata, Y., ... & Ohmori, H. (2013). Combined effect of branched-chain amino acids and taurine supplementation on delayed onset muscle soreness and muscle damage in high-intensity eccentric exercise. Journal of the International Society of Sports Nutrition, 10(1), 51.
• Silva, L. A., Silveira, P. C., Ronsani, M. M., Souza, P. S., Scheffer, D., Vieira, L. C., ... & Pinho, R. A. (2011). Taurine supplementation decreases oxidative stress in skeletal muscle after eccentric exercise. Cell biochemistry and function, 29(1), 43-49.
• Zhang, M., Izumi, I., Kagamimori, S., Sokejima, S., Yamagami, T., Liu, Z., & Qi, B. (2004). Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men. Amino acids, 26(2), 203-207.

Grass-Fed Pork? Not Really. Still the Difference in Fatty Acid Composition & Micronutrient Content Are Profound & Not Accounted for by Food Databases - Let Alone Epidemiology

You often hear that pigs are pretty closely related to us humans, but "are all pigs created equal"? Or what may be a more appropriate question for the SuppVersity: Is all pork really created equal?

If you like databases like nutritiondata.com or the USDA's very own detailed nutrient database in order to evaluate whether your diet is actually delivering all the nutrients you need you are probably missing half of the picture. At least as far as the more sophisticated details go, a recent paper from the Instituto de Ingeniería de Alimentos para el Desarrollo at the Universidad Politécnica de Valencia clearly indicates that you would at least have to consider what the animals, in this case pork, were fed and from which muscle of the animal the piece of meat you are eating has been cut, in order to get an approximate idea of how much of unquestionably health relevant micronutrients, such as coQ10, carnosine, anserine, taurine, creatine glutamine or haem you get - and in some cases the differences can be way larger than 100%!

If pizza salami equals pork...

... in epidemiological studies, how can these studies on the fallacies and advantages of eating red meat, which usually get a hell lo of media attention, be accurate, given the fact that the amount of unquestionably beneficial coQ10, for example, would differ by 60 percent, even if you would only ignore the difference between loin that was cut from the trapezius (= high coQ10 content) and the longissimus dorsi (=low coQ10 content)?

Figure 1: Content of selected amino acids and micronutrients in cuts from different muscle; data expressed relative to respective mean (total value is given in mg/100g above the bars) of all tested muscle samples (data based on previous studies by the co-authors that have been compiled for Reig. 2012).

Moreover, if you take a look at the complete data in figure 1 it should be clear that coQ10 is only one of several micro-nutrients / amino acids that are highly dependent on which muscle your particular steak or whatever you are about to eat was cut from. Let's take taurine as yet another example. A prolonged low dietary intake of taurine has been observed to be linked to a number of disorders including retinal degeneration, retardation of growth and development, cardiovascular dysfunctions, CNS abnormalities, immune impairment and hepatic disorders (Abebe. 2011). If you eat meat (fish & other animal products) only occasionally and are therefore at risk of not getting adequate taurine in your diet, eating sausages from a butcher you trust would be a better choice than a piece of ham, since the former do include the high taurine meat from the masseter (cheeks) of the animals, while ham does not.

Let's get to the obvious: Grass-fed is... ah, wait a minute

"Grass fed is best" as you will people say about beef obviously won't be the case for pork, because pigs, just like humans, by the way, are omnivores. The simple formula, grass-fed = most beneficial fatty acid and micronutrient profile that may (in general) be valid for beef doesn't apply and we will have to take a closer look at the actual data first to decide what would be the "best" feed for pigs, if the goal was not a maximal yield of lean meat (in that case adding some clenbuterol, like the Chinese like to do it would be the least you should do; cf. The China Post. 2011), but rather to produce the meat with the most beneficial fatty acid  composition.

Figure 2: Fatty acid composition (primary axis) and omega-6 to omega-3 ratio of pork from pigs fed different diets (corrected version of data Reig et al. re-pupublished based on previous studies; spec. the figure for the n6:n3 ratio in the "standard feed" group that's based on Enser et al. was off - a ratio of 1.54 is obviously unrealistic)

I we define "most healthy" as having the lowest omega-6 to omega-3 ratio - a practice that seems appropriate given that 95% of the inhabitants of the so-called 'Westernized World' consumes way too much of the former and (comparably) way too little of the latter type of polyunsaturated fatty acids, the data in figure 2 clearly argues in favor of *surprise* the standard feed - at least if you define that by the feed the animals the meat of which (50 samples) Enser et al. bought in British supermarkets in 1996 (note: these values are still higher than for the conventional beef samples from the same study, which had a n-6:n-3 ratio of ~2.2; cf. Enser. 1996). There are however more intricate patterns that are not evident from the overview in figure 2, but could have implications as far as the direction into which "pork production" could or should head to in the future is concerned (summarized based on Reig. 2012):

Do you notice a pattern? I guess even based on the data in figure 2 you will already have noticed that the "grainier" the diet, or in other words, the more corn and soy there is in the diet of the swine the less favorable is the fatty acid composition of their meats going to be. Now, I am asking an outrageous question: If swine are such a good model for human metabolism, what do you believe your belly was going to be made of, if you copied the pigs' diets and lived on "healthy grains", their oils and the uber-healthy soy beans for the (probably pretty short) rest of your life?
• more food (yet no excess) can produce overall leaner muscle meat in the type II fibers, while the total body fat is increasing
• aside from local desaturation and elongination effects, the overall muscular fatty acid pattern does (much like in humans, by the way) mirror the dietary intake
• canola or linseed oils produce a substantial increase in the content of linolenic acid (C 18:3), and slightly increase the eicosapentaenoic (EPA, C 22:5) and docosahexaenoic (DHA, C 22:6) acid contents in pork mea
• soy, peanut, corn, and sunflower increase the content of linoleic acid (C 18:2; omega-6), increase the n-6:n-3 ratio and reduce the content of mono-unsaturated fats (MUFAs)
• fish oils or algae added to the feed substantially increases the content of EPA and DHA and thus reduce the n-6:n-3 ratio
• a high saturated fat content as in tallow (see figure 2) increases the levels of palmitic, palmitoleic, stearic and oleic acids in pork meat and reduces the PUFA:SFA ratio 
• CLA supplementation can increase the CLA content of the fatty portion of the meats (1% CLA results in 5.5 mg CLA/100g) and the adipose tissue (2% CLA yields 1,490mg CLA/100g fatty acids).

As you can see, the same rule applies for humans, pigs and, as you know from a previous SuppVersity post, mice who are fed inferior, since soy-fed salmon, as well: You are what you eat, folks!

Wallowing, roaming, routing: Work out like a pig

Since pigs make a pretty decent model of human metabolism and in view of the fact that - aside from our diets - the amount of exercise we get is one of the fundamental determinants of the total and relative levels of body fat, it should not be forgotten that "exercise" or rather the ability to range freely and be as active as any swine should be, is another determinant of the quality of the meat you are buying at the supermarket, grocery store, butcher or your local farmer. In this context, Reig et al. point out that

If you have no idea of the different cuts and location of the individual muscle, I suggest you download the "Meat Cuts Manual" from the website of the Canadian Food Agency. It's free and bilingual.

"[i]t has been reported that pigs maintained in free-range conditions in the Mediterranean forest had subcutaneous and intramuscular fats with higher monounsaturated fatty acids and lower saturated fatty acids than those pigs housed individually and receiving acorns as feed. The subcutaneous fat depth increases with exercise being 15.9 mm for exercised pigs in comparison to 11.5 mm depth for those kept in confinement. The same applies for the intramuscular fat content where 3.36% for extensive vs 1.44% for intensive raised pigs have been reported in the semimembranosus muscle." (Reig. 2012)

And if you really intend to overcomplicate things, you would also have to ask your butcher, whether the sausages you are about to buy were made of the meat of male of female pigs. After all, meat from barrows typically contain more fat and marbling and a thicker subcutaneous fat layer than meat from gilts (Armero. 1999). But let's face it: If you start stressing about things like this, the quality of your meat is probably your least problem.

If you want to know read more about epidemiological overgeneralization andthe effects of "pork" and red meat on your health (spec. the prostate) I suggest you go back to the Meat-Ology post.

So what's the bottom line, then: I guess the bottom line of the above insides is twofold. As far as you as an individual are concerned, it would be yet another argument for getting your meats (pork or whatever else) from a farm nearby, where you know what you are getting. It is yet also evidence of the fact that meticulous nutrient counting as I often see it in former calorie counters who have nor grasped the notion that "a calorie is not a calorie" is of little avail - at least if you expect to be able to calculate them as precisely as you can read them on the nutrition labels of the 90% artificial and 100% standardized convenient foods that's probably much more the answer to the question "Why are we fat?" than the non-descript statement "insulin".

In fact, the real significance of these results lies elsewhere. It concerns the way epidemiological studies are conducted (I may remind you of the metaphorical pizza salami being red meat or pork), their over-generalizing interpretations and the conclusions on what the optimal human diet should look like. So, once the next study is telling you "red meat" or "pork" is bad for you - you may want to remind yourself of some of the things you have learned in today's blogpost and ask yourself (and if you incidentally have the chance, the researchers as well): What kind of "pork" are we talking about?

References:

• Abebe W, Mozaffari MS. Role of taurine in the vasculature: an overview of experimental and human studies. Am J Cardiovasc Dis. 2011;1(3):293-311.
• Armero E,  Flores M,  Toldrá F,  Barbosa JA,  Olivet J,  Pla M,  Baselga M.Effects of pig sire types and sex on carcass traits, meat quality and sensory quality of dry-cured ham.  Journal of the  Science of  Food  and  Agriculture. 1999; 79:1147-1154.
• Enser M, Hallett K, Hewitt B, Fursey GA, Wood JD. Fatty acid content and composition of english beef, lamb and pork at retail. Meat Sci. 1996 Apr;42(4):443-56.
• Reig M, Aristoy MC, Toldra.Variability in the contents of pork meat nutrients and how it may affect food composition databases. Food Chemistry. 2012 [ahead of print]
• The China Post. Clenbuterol-tainted pork latest China food scandal. March 18, 2011. < http://www.chinapost.com.tw/china/national-news/2011/03/18/295146/Clenbuterol-tainted-pork.htm > retrieved Dec 06, 2012.

Rats "On" Taurine Can't Ever Get Enough... Exercise of Course! What Were You Thinking About? Mice Cover 50% More Distance W/ HED of 3-4G of Taurine Post Workout

On Taurine? If she was, she could run another marathon 6h later ;-)

Actually, the results a group of researchers report in a recent paper in the Journal of Sports Medicine and Physical Fitness are a bit surprising. After all, taurine is - as you all should know by now - a GABA agonist and should thus rather have had a calming effect on the mice, the scientists used in their experiment. What Yumiko Takahashi, Eiki Urushibata and Hideo Hatta from the Department of Sports Sciences at the University of Tokyo observed when they supplied their lab animals with 0.5 mg/g body weight immediately after they had them run on a treadmill at 25m/min for 90 min was yet quite the opposite of the laziness you would expect after having read about the calming and balancing effects of taurine Mure et al. (2003) observed, when they administered it either alone or in conjunction with caffeine (read pervious SuppVersity article).

Mice on taurine run more, because they can!?

Contrary to the saline-group in which the exhausting bout of exercise lead to a significant decrease in the amount of voluntary wheel running (compared to the non-exercised mice in the control group; p < 0.01), the rodents who had received a human equivalent of 3-4g taurine (that's what a human would have to take) did not exhibit any signs of exercise induced fatigue. On the contrary:

"Significant effects of post-exercise taurine administration on voluntary wheel running during 6 h were found (p < 0.05). The 30-min running distance was significantly higher in the taurine-treated group than in the saline-treated group at 1-1.5 h after treadmill exercise (p < 0.05)." (Takahashi. 2013)

This increase in voluntary endurance training occurred irrespective of similar blood glucose and liver and skeletal muscle glycogen concentrations in both, the supplemented and placebo treated rodents after the treadmill exercise.

Figure 1: Total running distance and running distance per food ingestion (left); liver and muscle glycogen content (right) at different time points before (baseline) immediately after 0 and 3-6h after the forced 90 min run (Takahashi. 2013)

The total food consumption during 6 h of voluntary wheel running was likewise identical, or as the scientists wrote, it "showed no difference between the two groups". This means that the ratio of total running distance to total food consumption was significantly higher in the taurine treated group - a clear advantage for anyone who wants to burn a few additional calories on the treadmill (you should yet always remember that 90% of the weight loss happens in the kitchen, i.e. by dieting, and "training to burn energy", only, is nothing but stupid!)

Now this clearly raises the question "what's going on here?"

SuppVersity Suggested Read: "Taurine Pumps Up Strength & Recovery in Response to Eccentric Curls. NAC Decreases Peformance & Boosts Fat Oxidation!?" | read more

Obviously you and me are not the only ones who are asking themselves this important question. What is it that makes the post-workout so effective? Actually the mere fact that taurine is effective, when it is administered after a workout and not chronic or pre-workout as in the majority of previous studies is already news.

Well, the scientists seem to believe that the effects must be directly mediated by improved post-exercise recovery. With identical blood, liver and skeletal muscle glucose, we do however have to discard the beneficial effects of taurine on glucose metabolism and a potentially faster restoration of muscle glycogen as a potential explanation (click here to learn more about taurine's beneficial effects on glucose metabolism) .

As Takahashi et al. point out, skeletal muscle loses various ions and other solutes including taurine during exercise to compensate for increases in many osmotically active molecules as a result of enhanced energy metabolism (Usher-Smith. 2009). They go on to explain that

"the restoration of [taurine] may no have direct beneficial effects on the contractile properties of skeletal muscle, including the release and uptake of Ca2+ by the sarcoplasmic reticulum in the excitation-contraction coupling process,  prevention of peroxidation of plasma membranes, and recovery from exercise-induced cellular membrane damage." (Takahashi. 2013)

Accordingly, rodents with a knockout of the taurine transporter (which means these rodents could not use the taurine) showed both reduced taurine concentration in skeletal  muscles and tissues and significantly lower endurance capacity (>80%) compared to wild-type mice.

---

Taurine could also help fatty oxidation; after all, a recent study by Piña-Zentella et al. observed that taurine treatment increased the catalytic activity of cAMP-activated protein kinase A in white adipocyte tissue cells (Piña-Zentella. 2012).

With this kinase being important for the activation of the lipolitic enzyme cascade in both adipocytes and skeletal muscle.

This may not just help you burn off more fat, but also provide you with the fuel you need during prolonged exercise.

Bottom line: While we still do not know for sure, if it is the increase / faster recovery of cellular osmolality or other aspects of skeletal muscle recovery that are promoted by the post-workout ingestion of 3-4g of taurine (that's what a human would take), the real world results in the study at hand appear to suggest that the usage of an amino acid most trainees usually think of as part of a pre-workout formula may make just as much, if not more sense after a workout. This is particularly true, if you are one of the many trainees who can't wait till he or she gets back to the gym.

In conjunction with the recently covered beneficial effects on insulin sensitivity and think of the importance of the latter with respect to the replenishment of glycogen stores, and the triggering of p-Akt and the nutrient-based increase in protein synthesis, it would therefore appear to make sense to get yourself a 250-500g bag of (dirt cheap) bulk taurine and start experimenting with it. As stated before, the effective dose in the study was 3-4g and the insulin sensitizing effects have been observed with dosages in the 6g range (spread evenly across the meals).

Don't go overboard, though, in susceptible individuals the chronic ingestion of high(er) amounts taurine could trigger an increase in anxiety and that despite the fact that it is actually an anxiolytic (=reduces anxiety; cf. Kong. 2006).

References:

• Kong WX, Chen SW, Li YL, Zhang YJ, Wang R, Min L, Mi X. Effects of taurine on rat behaviors in three anxiety models. Pharmacol Biochem Behav. 2006 Feb;83(2):271-6.
• Piña-Zentella G, de la Rosa-Cuevas G, Vázquez-Meza H, Piña E, de Piña MZ. Taurine in adipocytes prevents insulin-mediated H2O2 generation and activates Pka and lipolysis. Amino Acids. 2012 May;42(5):1927-35.
• Usher-Smith JA, Huang CL, Fraser JA. Control of cell volume in skeletal muscle. Biol Rev Camb Philos Soc. 2009 Feb;84(1):143-59.

Alpha Lipoic Acid, GABA, Taurine, Green Tea, Gooseberry & Fenugreek. Plus: Metformin the No.1 Drug? Supplements to Improve and Restore Insulin Sensitivity - Serving #1

Don't forget, those caps and pills are not worth a penny without you committing to the all the lifestyle changes I outlined in episode one of this series.

I am well aware that you had to wait for a full week for this 2nd part of the "Restore & Maintain Insulin Sensitivity" Series (read part I), so I am going to make no words about it and get straight to the annotated list of useful supplements.

Just a reminder for the lazy asses: Don't even think about starting any of the supplements on the list, if you have not already cut your carbs to a low, but not very low level, got rid of all plain sugar in your diet, started to work out frequently, get enough sleep, avoid stims and control (not totally eradicate) your linoleic acid (omega-6) intake.

Here we go, for serving #1

In order to give you at least some guidance on where you may want to start, I will classify the supplements in 4 very broad categories with

• [A] for supplements that are almost certainly useful,
• [B] for supplements that are potentially useful and definitely worth trying,
• [C] for supplements that are marginally useful and probably worth trying, and
• [D] for supplements that are simply bullocks and not even worth trying

Whenever I feel confident to do so, I will also suggest a concrete dosage - in some cases, such as GABA, I can however neither do the former, nor the latter, because there simply is too little quality research out there.

• Did you know that continuous use of metformin during pregnancy significantly reduced the rate of miscarriage, gestational diabetes requiring insulin treatment and fetal growth restriction in women with PCOS who have long been advised to stop metformin during pregnancy (cf. Nawaz. 2008)?
  Metformin [A]: Technically it is not a supplement, but let's be honest, who except for the FDA cares? Many supplements work as effectively as pharmacological drugs, but as far as real insulin sensitizers are concerned metformin still appears to have the edge on the rest of the pack (supplement or drug): It has an excellent safety profile (even in gestational diabetes, which has long been thought of being the one area of application, where metformin was not the first line intervention of choice; cf. Lautatzis. 2013). It works via a similar mechanisms as dieting and exercise does (→ AMPK; this is actually imho it's main advantage - an advantage it shares with lipoic acid btw.). And metformin has only recently been shown not to inhibit the benefits of exercise on glycaemic control or fitness (Boulé. 2013).
  
  Moreover, hundreds of studies support the preventive effects of metformin against the manifestation of tumors of pancreas, breast, colorectum, liver, endometrium and ovary. The prognosis of diabetic cancer patients on metformin therapy seems be better, than in diabetics without metformin treatment (Anděl. 2013).
  
  So, if you belong those people who have real issues and not just slightly elevated blood glucose levels, have your metformin prescription filled - it's unquestionable an [A] among the agents that can help you restore your insulin sensitivity [I don't have to tell you that this is not an agent you would use simply to stay insulin sensitive, right?].
  
  One thing you should keep in mind though, is that it may lower your B12 levels. While this could be a simply results of increased usage and more recent studies question previous reports according to which metformin radically depletes B12 levels have been questioned lately, it probably won't hurt to take 500-1,000mg of methylcobolamine alongside your metformin.
• Alpha lipoic acid (ALA) [A]: In a way lipoic acid, a naturally occuring organosulfur compound derived from octanoic acid, is a cousin of metformin. Unfortunately (for the future of alpha lipoic acid as an anti-diabetes agent and the diabetics who have ever since been treated with pro-obesogenic PPAR-agonists) the pharma industry realized that selling a natural and thus non-patentable anti-diabetes drug would not only generate a lower revenue, it would also hamper the sales of patentable and thus more profitable drugs.
  
  
  Don't take lipoic acid instead of working out. Why? Well, alpha lipoic acid has been shown to increase the arthesclerosis risk in a human trial by McNeilly et al. In the said study, 1g of alpha lipoic acid per day increased the cardiovascular disease risk, in 24 obese individuals with impaired glucose tolerance who participated in the experiment (McNeilly. 2012); the underlying mechanism was an increase in LDL oxidation that did albeit occur only in the "ALA only" but not the "ALA + exercise" group.
  Luckily, there are still more than enough animal and human studies (Jacob. 1999; Xiang. 2011; Porasuphatana. 2012) to support the beneficial effects lipoic acid will have on glucose management and hyperglycemic damage in (pre-)diabetics.
  
  In view of the fact that it could contribute to the development of heart disease precipitate hypoglycemic episodes (Khamaisi. 1990), has negative effects on appetite (which is the main mechanism by which it reduces weight gain in rodents) and appears to mess with lean mass gains - suggested reads ("You Could be Just as Lean, but More Muscular Without a Nutrient Repartitioner" (learn more); "Further Evidence Against Anti-Oxidant Supplementation: Vitamin E + Alpha Lipoic Acid Reduce Skeletal Muscle Mitochondrial Biogenesis" (read more) I would still not suggest you take high doses (>100-200mg) if you don't have problems with keeping your blood sugar levels in check.
  
  For those of you, who have established problems with managing their glucose levels, taking 2x250mg-600mg (with meals) would yet be a good point to start from (keep an eye on how it affects your glucose levels and adjust the dosage appropriately).
  
  With respect to the purported superiority of R-ALA vs. the regular (=racemic mixture) version of lipoic acid, I can only repeat that I am still waiting for someone to show me a study that would prove that R-ALA is more potent than regular the cheap racemic mixture that's been used in the vast majority of the currently available (mostly beneficial) studies.

• 

  Figure 1: GABA does effectively restore "almost" normal glucose levels in severly diabetic mice; the dosage is not mentioned in the FT or the supplemental material (Soltani. 2011)

  GABA [?]: No, the reason GABA (Gama-aminobutyric acid) is on the list is not that it will make you sleep better (although this may - for some(!) people, actually be the case). It's rather its direct protective and even restorative effect on pancreatic beta-cells (Soltani. 2011; Tian. 2013).
  
  Despite the fact that we have known about these effects for decades, up to now nobody seems to be interested to do or finance the research that would be necessary to make concrete and reliable dosage-recommendations. In fact, the evidence is still so scarce that we cannot even say: "Yes, GABA is definitely going to help" - if the prelminary evidence we have translates from the petri dish to the rodent cage and into the real world, it could however be the #1 agent on this list. Why? Well, this would basically mean that it could cure diabetes even when you have progressed from being insulin resistant to being a full-blown diabetic.
  
  The best evidence we have that this could in fact be the case does probably come from a 2011 study by Soltani, who have actually taken the important step from the petri dish to the rodent model and were able to show that  GABA restores β-cell mass and reverses diabetes in severely diabetic mice.
  
  
  Warning: Don't start out with 5g of GABA in one serving - esp. not on an empty stomach. This is not only going to give you parestesia (tingles), but could also have you gasp for air and have problems keeping on your feet, due to the profound actions on peripheral GABA receptors.
  Furthermore, human studies from the eighties have shown that 5g and 10g of GABA (consumed orally) exert direct insulinotropic effects (remember insulin resistance is not about too much insulin, but about the latter having no / too little effect on glucose uptake) and since oral GABA does not cross the blood-brain-barrier it's safe to be consumed by humans in relatively high doses (cf. Cavagnini. 1982). Still, as in the case of lipoic acid, GABA is not patentable and the stocks of the big players in the anti-diabetes drug business would certainly take a tumble, when someone actually proved that you could reverse diabetes by simply taking X grams of GABA everyday.
• Taurine [B]: You will remember that I mentioned Taurine only 2 days ago in the context of the anti-diabetic effects of whey protein (read more). You will probably also remember the numerous previous posts on the beneficial effects of taurine specifically for people with diabetes or pre-diabetes (learn more about taurine). I will therefore stick to a brief overview of the direct and indirect (protection against negative effects of high blood glucose) benefits taurine has to offer for people with insulin resistance and high glucose levels.

  • 

    Figure 2: The effects of taurine supplementation on glucose and insulin (top, left & right) 0, 6, and 12 weeks after beginning the taurine-supplemention in OLEFT rats (rodent model of diet induced diabesity), as well as the reaction to an insulin tolerance test and corresponding changes in insulin sensitivity (bottom, left & right; adapted from Kim. 2012).

    Taurine shows "independent of hypoglycemic effect in several animal model" (Ito. 2012)
  • It ameliorates both high glucose and lipid levels (Kim. 2012)
  • Taurine improves NO mediated blood glow in the corpus cavernosum (=battles erectile dysfunction) due to diabetes (Dalaklioglu. 2013)
  • Taurine exerts cardio-protective effects, partly via direct effects on the angiotensin II type2 receptor expression (Li. 2005)
  • It restores normal platelet aggregation in diabetics (Franconi. 1995)
  • Taurine protects the kidneys (Yao. 2009)
  • Taurine reduces mortality risk upon long-term administratio (rodent model; Franconi. 2004) 
  • It has a higher ability to reduce insulin resistance and stronger antioxidant properties than the diabetes drug glibenclamide (El Zahraa. 2012)
  • It protects the eye from diabetes induced damage (Hansen. 2001 Kim. 2007)
  • Taurine has protective effects against all components of the metablic syndrom (Hansen. 2001; Imae. 2012)
  • It increase the levels of conjugated tRNA, restore respiratory chain activity, and increase the synthesis of ATP at the expense of superoxide anion production (Schaffer. 2009)
  Beta alanine is the taurine antagonist #1: SuppVersity readers should know that (read more), but I guess I better repeat it: The "best" way to deplete taurine levels is the ingestion of copious amounts of beta alanine 24/7 (the side effects are similar to those of diabetes related taurine depletion, eg. Waterfield. 1993 → lowered protection against CCL induced liver damage). From a performance perspective there is as of now no evidence that you would need more than 2.5g of beta alanine per day, anyway. So why would you want to waste money and cellular taurine on additional beta alanine ;-)
  It should be mentioned thought that there are also studies which did not support the beneficial results reported above - they are not numerous, but may yield some insights into effective vs. uneffective dosage regimen.
  
  The 1.5g/day the overweight subjects with a predisposition for developing diabetes the subjects in a 2004 study by Brøns et al. received, may for example simply have been too little to exert any effects (Brøns. 2004). Based on the human equivalents of rodent studies, it appears most promising to distribute a daily taurine intake of 3g to max. 6g over your three main meals.
  
  Since taurine does also act as a gaba-ergic small molecule neurotransmitter (Albrecht. 2005), I would yet suggest you keep a close eye on (a) initial sedative effects and (b) longer term increases in anxiety - both of which have been reported in animal studies with allegedly higher and / or intracerebral administration of taurine.
  
  The effects on neurotransmitters, the diarrhea some users experience (esp. when they take it without food) and the fact that many, but by far not all studies confirmed direct inusulin sensitizing effects of taurine are the reason I'd still classify it as [B] level supplement - certainly one of the better ones, but still only "possibly beneficial".

• 

  Table 1: Within group changes in randomized controlled GTE supplementation study involving 20-65 year old type 2 diabetics with BMI > 25 kg/m² (Hsu. 2012)

  Green tea extract [C]: GTE can help with insulin sensitivity in two different ways. Firstly, it will help control the inflammatory processes that are (partly) responsible for the development of insulin resistance and it will secondly help you to "cut carbs" by simply blocking their digestion and assimilation (Forester. 2012; Williamson. 2013).
  
  And while the real world benefits of GTE supplementation in a 2012 study by Hsu et al. were not statistically significant, it may still be worth trialling a dose of 3x 200-500mg per day. That being said, unless you are specifically looking for the stimulant effects of GTE, you should consider using a decaffeinated extract because you do not really need the additional caffeine (cf. part I of this series). 
  
  The reason I still classified GTE as [C] as in "marginally useful" is that the study by Hsu is not the only human trial that did not find significant effects on insulin sensitivity. It is rather one of the few where you could actually argue that - though not significant - it may have had an independent effect on glucose management. In the majority of studies "green tea exhibited limited benefits in reducing FBS or HbA1c levels" and as Ruitang Deng puts it in his recent review: "Should not be recommended for managing hyperglycemia." (Deng. 2012) This does not mean that it cannot help ameliorate the side effects, but we are looking for agents that will actually help you lower your blood glucose levels and in this regard green tea extracts are only marginally useful.

• 

  Amla, gooseberry, or Emblica Officinalis call it whatever you want, but don't expect too much - it may work, but it's no comparison to the [A]-class supplements. Moreover, the results from the available human study could be distorted by additional ingredients in the supplement formulas the scientists used.

  Gooseberry (emblica officinalis) [C]: Studies by Mitra (2007), Faizal (2009), Iyer (2009) and Chen (2011) all provide evidence that the ingestion of extracts from Indian gooseberry (=Amla), an edible fruit from trees of the phyllanthaceae family can effectively improve blood glucose management.
  
  Due to the fact that the Gooseberry extract was administered in conjunction with other agents, it is however difficult to suggest an effective dosage, but it appears as if 100-150mg per day of gooseberry extract would be enough.
  
  In Iyer et al. even a single serving of fresh amla (~35g) got the job done, but the overall effect size is rather mediocre, thus Gooseberry is only "possibly useful" [C]. 
• Fenugreek [B]: Also known as trigonella foenum-graecum L., fenugreek belongs to the plant family fabaceae (or leguminosae).
  
  

  

  Figure 3: Relative changes in response to glucose challenge (glucose AUC, glucose half-life and metabolic clearance rate) in 5 non-insulin dependent diabetic patients after consuming a diet supplemented with 25 g fenugreek seeds daily for 15 days; the data is expressed relative to the values the scientists measured in five likewise diabetic control subjects (Raghuram. 1994)

  Fenugreek seeds and extracts from the leaves have a decent amount of studies to support its anti-hyperglycemic effects - including clinical studies with human volunteers showing that dosage of only 500 mg of seed or leaf extracts given once or twice daily either alone or in combination with standard, synthetic anti-diabetic drugs such as metformin and glipizide provided beneficial effects on controlling plasma glucose levels (Deng. 2012).
  
  The reason I'd still classify it as [B] are (a) the fact that it takes a huge amount of the seeds (e.g. 25g; see figure 3) to elicit significant effects and (b) the fact that studies using extracts yielded ambiguous results. Contrary to the whole seeds, of which it seems that they exert their beneficial effects by similar mechanisms as dietary fiber, leaf extracs appear to exert a direct insulin sensitizing effect.
  
  In a study by Abdel-Barry et al. from the year 2000, 40 mg/kg aqueous extract powder from fenugreek leaves(!) in 10 mL distilled water lowered the glucose levels of 20 healthy male volunteers aged 20-30 years by 13.4% 4h after ingestion. Unfortunately, the hunger, frequent urination and dizziness one third of the subjects complained about, was not the only side effect - the subjects also had significantly reduces serum potassium levels; an observation of which the researchers rightly state that it warrants further investigation to ensure the long-term safety of fenugreek leaf extracts.
  
  Bottom line? Well, once again "possibly useful", but only if you actually have problems with insulin resistance and high blood sugar.

"What? Where is there rest?" In case this is pretty much what you are thinking right now, I can calm you down, there will be at least another serving of pro-insulin sensitivity supplements. I simply don't have the time to write more today, but did not want to go back on my promise from last Sunday. So, be patient, there is going to be more: Promising supps such as cinnamon, vinegar, or grape seed extract, for example but also questionable stuff such as bitter melon or legume extracts.

References: 

• Abdel-Barry JA, Abdel-Hassan IA, Jawad AM, al-Hakiem MH. Hypoglycaemic effect of aqueous extract of the leaves of Trigonella foenum-graecum in healthy volunteers. East Mediterr Health J. 2000 Jan;6(1):83-8.
• Anděl M, Skrha P, Trnka J. [Metformin: the overlap of diabetology and oncology]. Vnitr Lek. 2013 Aug;59(8):738-42. 
• Boulé NG, Kenny GP, Larose J, Khandwala F, Kuzik N, Sigal RJ. Does metformin modify the effect on glycaemic control of aerobic exercise, resistance exercise or both? Diabetologia. 2013 Aug 23. 
• Brøns C, Spohr C, Storgaard H, Dyerberg J, Vaag A. Effect of taurine treatment on insulin secretion and action, and on serum lipid levels in overweight men with a genetic predisposition for type II diabetes mellitus. Eur J Clin Nutr. 2004 Sep;58(9):1239-47.
• Cavagnini F, et al. Effects of gamma aminobutyric acid (GABA) and muscimol on endocrine pancreatic function in man.Metabolism. 1982; 31:73–77. 
• Chen TS, Liou SY, Wu HC, Tsai FJ, Tsai CH, Huang CY, et al. Efficacy of epigallocatechin-3-gallate and amla (Emblica officinalis) extract for the treatment of diabetic-uremic patients. J Medicinal Food. 2011;14:718–23.
• Dalaklioglu S, Kuscu N, Celik-Ozenci C, Bayram Z, Nacitarhan C, Ozdem SS. Chronic treatment with taurine ameliorates diabetes-induced dysfunction of nitric oxide-mediated neurogenic and endothelium-dependent corpus cavernosum relaxation in rats. Fundam Clin Pharmacol. 2013 Jun 14. 
• Deng R. A review of the hypoglycemic effects of five commonly used herbal food supplements. Recent Pat Food Nutr Agric. 2012 Apr 1;4(1):50-60.
• El Zahraa Z El Ashry F, Mahmoud MF, El Maraghy NN, Ahmed AF. Effect of Cordyceps sinensis and taurine either alone or in combination on streptozotocin induced diabetes. Food Chem Toxicol. 2012 Mar;50(3-4):1159-65. 
• Faizal P, Suresh S, Satheesh Kumar R, Augusti KT. A study on the hypoglycemic and hypolipidemic effects of an ayurvedic drug Ra-janyamalakadi in diabetic patients. Indian J Clinical Biochem. 2009;24:82–7.
• Mitra A. Effects of a composite of tulsi leaves, amla bitter gourd, gurmur leaves, jamun fruit and seed in type 2 diabetic patients. J Clinical Diagnostic Research. 2007;6:511–20.
• Forester SC, Gu Y, Lambert JD. Inhibition of starch digestion by the green tea polyphenol, (-)-epigallocatechin-3-gallate. Mol Nutr Food Res. 2012 Nov;56(11):1647-54.
• Franconi F, Bennardini F, Mattana A, Miceli M, Ciuti M, Mian M, Gironi A, Anichini R, Seghieri G. Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation. Am J Clin Nutr. 1995 May;61(5):1115-9.
• Franconi F, Di Leo MA, Bennardini F, Ghirlanda G. Is taurine beneficial in reducing risk factors for diabetes mellitus? Neurochem Res. 2004 Jan;29(1):143-50.
• Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol Med. 1999 Aug;27(3-4):309-14.
• Hansen SH. The role of taurine in diabetes and the development of diabetic complications. Diabetes Metab Res Rev. 2001 Sep-Oct;17(5):330-46. 
• Hsu CH, Liao YL, Lin SC, Tsai TH, Huang CJ, Chou P. Does supplementation with green tea extract improve insulin resistance in obese type 2 diabetics? A randomized, double-blind, and placebo-controlled clinical trial. Altern Med Rev. 2011 Jun;16(2):157-63.
• Imae M, Asano T, Murakami S. Potential role of taurine in the prevention of diabetes and metabolic syndrome. Amino Acids. 2012 Dec 8.
• Ito T, Schaffer SW, Azuma J. The potential usefulness of taurine on diabetes mellitus and its complications. Amino Acids. 2012 May;42(5):1529-39. doi: 10.1007/s00726-011-0883-5. Epub 2011 Mar 25.
• Iyer U, Joshi A, Dhruv S. Impact of Amla (Embilica Officinalis) supplementation on the glycemic and lipidemic status of type 2 diabetic subjects. J Herbal Medicine and Toxicol. 2009;3:15–21.
• Khamaisi M, Rudich A, Potashnik R, Tritschler HJ, Gutman A, Bashan N. Lipoic acid acutely induces hypoglycemia in fasting nondiabetic and diabetic rats. Metabolism. 1999 Apr;48(4):504-10.
• Kim SJ, Ramesh C, Gupta H, Lee W. Taurine-diabetes interaction: from involvement to protection. J Biol Regul Homeost Agents. 2007;21(3-4):63-77.
• Kim KS, Oh da H, Kim JY, Lee BG, You JS, Chang KJ, Chung HJ, Yoo MC, Yang HI, Kang JH, Hwang YC, Ahn KJ, Chung HY, Jeong IK. Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes. Exp Mol Med. 2012 Nov 30;44(11):665-73.
• Lautatzis ME, Goulis DG, Vrontakis M. Efficacy and safety of metformin during pregnancy in women with gestational diabetes mellitus or polycystic ovary syndrome: A systematic review. Metabolism. 2013 Jul 22. 
• Li C, Cao L, Zeng Q, Liu X, Zhang Y, Dai T, Hu D, Huang K, Wang Y, Wang X, Li D, Chen Z, Zhang J, Li Y, Sharma R. Taurine may prevent diabetic rats from developing cardiomyopathy also by downregulating angiotensin II type2 receptor expression. Cardiovasc Drugs Ther. 2005 Mar;19(2):105-12.
• Mitra A. Effects of a composite of tulsi leaves, amla bitter gourd, gurmur leaves, jamun fruit and seed in type 2 diabetic patients. J Clinical Diagnostic Research. 2007;6:511–20.
• McNeilly AM, Davison GW, Murphy MH, Nadeem N, Trinick T, Duly E, Novials A, McEneny J. Effect of α-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance. Lipids Health Dis. 2011 Nov 22;10:217.
• Nawaz FH, Khalid R, Naru T, Rizvi J. Does continuous use of metformin throughout pregnancy improve pregnancy outcomes in women with polycystic ovarian syndrome? J Obstet Gynaecol Res. 2008 Oct;34(5):832-7. 
• Porasuphatana S, Suddee S, Nartnampong A, Konsil J, Harnwong B, Santaweesuk A. Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled study. Asia Pac J Clin Nutr. 2012;21(1):12-21. 
• Raghuram TC, Sharma RD, Sivakumar B, Sahay BK. Effect of fenugreek seeds on intravenous glucose disposition in non-insulin dependent diabetic patients. Phytotherapy Research. 1994;8:83–6.
• Schaffer SW, Azuma J, Mozaffari M. Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol. 2009 Feb;87(2):91-9.
• Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Li Y, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud'homme GJ, Wang Q. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11692-7.
• Tian J, Dang H, Chen Z, Guan A, Jin Y, Atkinson MA, Kaufman DL. GABA regulates both the survival and replication of human ss-cells. Diabetes. 2013 Aug 30. 
• Williamson G. Possible effects of dietary polyphenols on sugar absorption and digestion. Mol Nutr Food Res. 2013 Jan;57(1):48-57.
• Xiang G, Pu J, Yue L, Hou J, Sun H. α-lipoic acid can improve endothelial dysfunction in subjects with impaired fasting glucose. Metabolism. 2011 Apr;60(4):480-5.
• Yao HT, Lin P, Chang YW,Chen CT, Chiang MT, Chang L, Kuo YC, Tsai HT, Yeh TK. Effect of taurine supplementation on cytochrome P450 2E1 and oxidative stress in the liver and kidneys of rats with streptozotocin-induced diabetes. Food Chem Toxicol. 2009 Jul;47(7):1703-9

Confirmed: All Wheys, Not Just Hydro Whey Boost Glucose Uptake And Liver + Muscle Glycogen Supercompensation. Plus: How Could Taurine Be Involved in This Benefits?

Do it or don't? If the question is about consuming whey protein, the answer is clear: Do it! Use whey!

As a diligent student of the SuppVersity you will remember my previous article "The Glucose Repartioning Effects of Isoleucine: Falsely Underappreciated BCAA and Its Dipeptides Maximize GLUT-4 Expression and Ramp Up Muscular Glucose Uptake" (read more). If you don't let me briefly bring you up to speed in back in February, I told you about the beneficial effects of a class of isoleucine peptides in whey protein hydrosylate [as the study at hand goes to show you, this is important, see bottom line] on glucose transporter (GLUT-4) expression and thus glucose uptake in skeletal muscle.

Today I am pleased to be able to continue and expand on this discussion based on the results of the latest study from the same group of researchers from Sao Paulo, Brazil (Morato. 2013).

Whey, an anti-diabetic glycogen supercompensation tool

As Morato et al. point out, their own study is by no means the only one that supports the very special insulin sensitizing activity of whey proteins. In fact, whey is already touted as potential anti-diabetic. If the medical orthodoxy or rather it's "legislative" arm was not trapped by its own dogmas WPH [whey protein hydrolysate] would already be a central part of the dietary recommendation for type II diabetics. With the current study being the first to show that a whey protein based diet will lead to chronically increased GLUT-4 expression and thus help to lower blood glucose and improve glycogen storage, the study at hand is albeit similarly interesting for the average musclehead and his obese type II diabetic neighbor.

Figure 1: Effects of casein, whey and whey hydro(lysate) diets on GLUT-4 expression, baseline insulin, liver glycogen and muscle glycogen levels (g/100g tissue; Moreto. 2013)

Apropos obese neighbor. You should go and convince him to go to the gym with you. After all, the rodent data in figure 1 clearly shows that WPH leads its trumps only when it is combined with training - in this case treadmill running for 60 minutes at 15 m/min (the exercise took place 16 h before the sacrifice; so the increases are not in response to the exercise! they are just amplified by chronic endurance during).

Suggested read: "The Overlooked Glucose Repartioning Effects of Isoleucine" (read more)

While exercise alone is well known to boost GLUT-4 expression and subsequent glucose uptake significantly (Christ-Roberts. 2004; Kuo. 2004; note. GLUT-4 activity correlates with the degree of muscular clycogen depletion, so no "5 min rest, 2 sets all out and go home workouts!"), the addition of a whey protein hydrosylate with a pre-hydrolysation level of 12.5% (think of it as being enzymatically "pre-digested) as the sole protein component of the baseline diet (15% protein total, 7% fat from vegetable oil, 68% carbs from sugar and corn starches) of the 48 male Wistar rats in the experiment at hand did turn the +100% increase from exercise alone into a  +160% increase.

I have to admit, the increased GLUT-4 uptake per se may not be news, but this is in fact the first chronic feeding study where it was observed in conjunction with higher glycogen levels - ca. 90%, 70% and a whopping 400% in the heart, the musclulature and the liver in the sedentary state for both WPH and regular whey protein. That's certainly impressive, but you got to remember that this is a result of combining whey with a high carbohydrate diet (69% of the diet vs. 7% fat) which provides the necessary readily available substrate for optimal glycogen super-saturation (=packing in more glycogen than you usually could).

You will and can very well live with the insulin spike!

Though it may not look like it in figure 1, you got to be aware that the values were not taken right after the ingestion of a meal, let alone a protein shake. In other words, it is almost certain that the whey protein groups will have had higher insulin levels immediately after a meal (note: Casein is still way more insulinogenic than meat or eggs).

I've gone into quite some detail on why insulin spikes (in the presence of glucose) are not a problem, but rather a vital necessity in a previous post (read it)

"One of the primary means to increase the concentration of GLUT-4 in the plasma membrane is through insulin-regulated trafficking (Zorzano. 2005). However, in the present experiment, no increase was noted in serum insulin levels in the groups consuming WPH.

The experimental design of the study focused on the moment of greatest mobilization of glucose transporter-4, and the animals were sacrificed 2 h after consuming the meal; this was too long an interval to observe the maximum plasma insulin response." (Morato. 2013)

It is thus a given that the  GLUT-4 translocation was at least supported by profound and temporary (at least in the presence of an adequate carbohydrate intake, their temporary nature is what makes the whey induced insulin spikes physiologic and beneficial vs. pathological and detrimental as chronic elevations would be; learn more). According to Morato et al. this is however not the only way the ingestion of whey affected the translocation of GLUT-4 (upstream) and the subsequent uptake of glucose into the muscle and liver (downstream):

Translocation of GLUT-4 to the PM [plasma membrane] can also be stimulated in an insulinindependent manner. Carneiro et al. (2009) accomplished this through taurine activation of the insulin pathway, thus raising the GLUT-4 concentration in the plasma membrane independent of insulin. However, the molecular mechanism behind this effect has still not been elucidated (Carneiro. 2009).

There is actually evidence that would suggest that whey protein hydrolysate is not simply not superior, but actually inferior to regular whey proteins when it comes to improvements in body composition in athletes (read more)

In the exercised animals of the WP and WPH groups, the plasma concentrations of taurine (Table 1) were greater (p,0.05) than those in the control group consuming CAS. This could explain, at least in part, the greater translocation of GLUT-4 in the WP and WPH groups.

After investigating the amino acid composition of the WP and WPH, it was found they were rich in sulfur amino acids (Table 2), and methionine and cysteine are endogenous precursors of taurine. Thus, the consumption of WP or WPH provided a greater amount of substrate for the endogenous production of taurine than casein, and the presence of this amino acid may have facilitated activation of the insulin pathway and cell capture of glucose, as indicated in the literature." (Morato. 2013; my emphases)

That's quite a surprising insight, isn't it? I mean, as a SuppVersity reader you have long known about the anti-diabetic prowess of taurine, but who would have suspected that it could be #3 alongside the active isoleucine dipeptides and the insulin release among the mechanisms behind the profound beneficial effects whey has on glucose? I mean, there is basically no taurine in whey.

SuppVersity readers have known for years, that whey is far superior to an amino acid (AA) mixture with the same AA make-up (read more)

Bottom line: Yep, this is support for a previous advice I've gicen: You better never run out of whey protein for both, health and performance reasons. Personally, I am yet most fascinated by the potential involvement of endogenous (=your body's own) taurine synthesis. That 's certainly going to be a topic in Sunday's 2nd installment on supplements to improve and maintain insulin sensitivity (read part I on lifestlye modifications here).

Pratically speaking the most important and eventually less surprising message of the study at hand is however that it does not necessarily have to be whey protein hydrolysate. The regular whey protein did an outstanding job, as well, and the "real-world" = visible / noticeable differences are propably non-significant.

In this context, some of you may also remember the results from another recently published study by Lollo et al. (read it) which did in fact suggest that the muscle building and body recompositioning effects of whey hydrolysate are inferior and not superior to those of regular whey.

References:

• Carneiro EM, Latorraca MQ, Araujo E, Beltra M, Oliveras MJ, et al. Taurine supplementation modulates glucose homeostasis and islet function. J Nutr Biochem. 2009; 20: 503–511.
• Christ-Roberts CY, Mandarino LJ. Glycogen synthase: key effect of exercise on insulin action. Exerc Sport Sci Rev. 2004; 32: 90–94.
• Kuo CH, Hwang H, Lee MC, Castle AL, Ivy JL. Role of insulin on exercise-induced GLUT-4 protein expression and glycogen supercompensation in rat skeletal muscle. J Appl Physiol.  2004; 96: 621–627.
• Morato PN, Lollo PC, Moura CS, Batista TM, Carneiro EM, Amaya-Farfan J. A dipeptide and an amino acid present in whey protein hydrolysate increase translocation of GLUT-4 to the plasma membrane in Wistar rats. Food Chem. 2013 Aug 15;139(1-4):853-9.
• Zorzano A, Palacín M,Gumá A. Mechanisms regulating GLUT 4 glucose transporter expression and glucose transport in skeletal muscle. Acta Physiol Scand. 2006. 183: 43–58.