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Post-Workout High Isoleucine AA+CHO Decreases Glucose Spikes, But Impairs Musclular Glyocogen Resynthesis - Reason Enough to Skip Amino Acids?

If you put any faith into the promises of the supplement industry, amino acid supplements are the solution to all your problems - including those you havent even known about, yet. Against that background its always interesting if scientists study the real world effects of amino acid supplements in a realistic scenario like after strenuous exercise.

In their latest study Wang and colleagues from the University of Texas at Austin and the Shanghai Research Institute of Sports Science did just that: They studied the effects isoleucine and four additional amino acids, on blood glucose homeostasis and glycogen synthesis after strenuous exercise.
As the scientists point out, the results of their study "could provide a practical and safe means of increasing the rate of muscle glycogen synthesis after exercise and enhancing the rate of recovery" (Wang. 2015).

Table 1:  Subjects’ characteristics (Wang. 2015).

Ten healthy active adults volunteered for the study. All subjects were accustomed to cycling for prolonged periods of 3–5 h during an exercise session. The ,aximum oxygen uptake (VO2max) was measured in all subjects on a cycle ergometer by using a TrueOne 2400 metabolic measurement system (ParvoMedics, Sandy, Utah) to verify adequate aerobic fitness levels (results see Table 1).

Figure 1: Basically the AA supplement contained almost exclusively isoleucine. It was administered in the dosage shown above and at twice that amount in the LAA and HAA trials (Wang. 2015)

"Two to three days after the VO2max test, the subjects reported to the laboratory to perform a practice ride to familiarize them with the laboratory environment and the experimental protocol. The practice ride was also used to adjust and verify appropriate workloads for the experimental trials. The practice rides simulated the protocol ride but without blood samples or muscle biopsies being taken. The ride consisted of cycling at 70 % VO2max for 2 h, which was followed by five 1-min sprints at 85 % VO2max. The sprints were separated by 1 min cycling at 45 % VO2max. During the first 15 min of each hour, oxygen uptake was measured for 5 min to verify workload.

Water (250 mL) was provided every 20 min of exercise. Heart rate (HR) was monitored and ratings of perceived exertion (RPE) on a Borg-scale (ranging from 6 to 20) were collected every 30 min of exercise. The practice ride and each of the following three experimental trials were separated by a minimum of 7 days and maximum of 12 days" (Wang. 2015).

The actual tests consisted of cycling on an ergometer to deplete muscle glycogen. Blood sampling and a muscle biopsy were performed immediately on cessation of exercise. After the muscle biopsy, subjects were given the first of two supplement doses. More specifically they received either...

• 1.2 g carbohydrate/kg body weight (CHO), 1.2 g carbohydrate/kg body weight plus 6.5 g AA (CHO/LAA) or 
• the same carbohydrate supplement plus 6.5g (CHO/LAA) or 13 g AA (CHO/HAA) 

immediately after the first muscle biopsy and at 120 min of recovery. The carbohydrate base consisted of simple dextrose dissolved at a ratio of 100g/296 mL in an orange flavored drink (SUN-DEX, Fisher Healthcare, Houston, Texas). The additional amino acids contained 0.046 g cystine 2HCl, 0.023 g methionine, 0.045 g valine, 6.342 g Isoleucine, and 0.044 g leucine per person, or twice that amount in the CHO/HAA trial. The amino acids were simply added to the dextrose drink.

Why would you even believe that there may be benefits from AA supplementation?

As Wang et al. point out, "this amino acid mixture was selected as it was previously reported to be more effective in lowering the blood glucose response to a glucose challenge than isoleucine alone" (Wang. 2015) by Bernard et al. (2011).

Figure 2: Blood glucose AUC during the oral glucose tolerance test (OGTT). Sprague-Dawley rats were gavaged with either glucose (CHO), glucose plus a 5-amino acid mixture (CHO-AA-1), glucose plus a 5-amino acid mixture with increased leucine concentration (CHO-AA-2), or placebo (PLA). Blood was taken from the tail immediately before the gavage and 15, 30, 60, and 120 min afterward (Bernard. 2011).

The three test beverages were similar in color, taste, and texture to allow a double-blinded and counter-balanced study design. All test drinks were randomly assigned and dispensed by a laboratory technician who was not involved in the data collection.

Figure 3: Blood glucose postexercise and during the 4-h recovery. Treatments were with CHO (circle), CHO/LAA (triangle), and CHO/HAA (filled circle) supplements provided immediately after and 2 h after exercise. Values are mean ± SE. CHO/HAA vs. CHO (*p < 0.05). CHO/LAA vs. CHO (# p < 0.05) - left; Blood glucose area under the curve (AUC) during the 4-h recovery. Treatments were CHO, CHO/LAA, and CHO/HAA supplements provided immediately after and 2 h after exercise. AUC was calculated with baseline (pre). Values are mean ± SE. CHO/HAA vs. CHO (*p < 0.05). CHO/LAA vs. CHO (# p < 0.05) - right (Wang. 2015).

As the data in Figure 3 indicates,There was a similar effect in humans as it has previously been observed in rodents. An effect of which you as a SuppVersity reader know that it is probably mostly ascribable to isoleucine (see "The Glucose-Repartitioning Effects of Isoleucine" | more).

Figure 4: Total muscle glycogen storage in the vastus lateralis during the 4-h recovery from intense cycling. Treatments were CHO, CHO/LAA, and CHO/HAA supplements provided immediately after and 2 h after exercise. Values are mean ± SE. CHO/HAA vs. CHO (*p < 0.05 | Wang. 2015)

What is a bit disappointing is the fact that the decrease in blood glucose did not come with an increase in glycogen storage.

As the data in Figure 4 shows, the exact opposite was the case. After 4h of recovery the muscle glycogen levels were not higher, but lower in the amino acid supplemented trials.

For diabetics this wouldnt be a problem. For athletes its yet clearly a disadvantage that the 4-g recovery glycogen levels were lower and significantly lower in the low and high dose amino acid supplement trials.

Eventually this result is surprising because specifically in the high amino acid group (a) the insulin levels, (b) the AS160, a protein that controls insulin mediated glucose uptake, (c) the mTOR & p-AKT levels, (d) the "exercise hormon" levels of serum irisin  and (e) the levels of glycogen synthase which stores carbs in forms of glycogen in the high dose AA trials were significantly elevated.
References:

• Armstrong, Jane L., et al. "Regulation of glycogen synthesis by amino acids in cultured human muscle cells." Journal of biological Chemistry 276.2 (2001): 952-956.
• Bernard, Jeffrey R., et al. "An amino acid mixture improves glucose tolerance and insulin signaling in Sprague-Dawley rats." American Journal of Physiology-Endocrinology and Metabolism 300.4 (2011): E752-E760.
• Doi, Masako, et al. "Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes." Biochemical and biophysical research communications 312.4 (2003): 1111-1117. 
• Ivy, John L., et al. "Early postexercise muscle glycogen recovery is enhanced with a carbohydrate-protein supplement." Journal of Applied Physiology 93.4 (2002): 1337-1344.
• Ivy, J. L., et al. "Post exercise carbohydrate–protein supplementation: phosphorylation of muscle proteins involved in glycogen synthesis and protein translation." Amino acids 35.1 (2008): 89-97.
• Morifuji, Masashi, et al. "Dietary whey protein increases liver and skeletal muscle glycogen levels in exercise-trained rats." British journal of nutrition 93.04 (2005): 439-445.
• Morifuji, Masashi, et al. "Post-exercise carbohydrate plus whey protein hydrolysates supplementation increases skeletal muscle glycogen level in rats." Amino acids 38.4 (2010): 1109-1115.
• Wang, Bei, et al. "Amino acid mixture acutely improves the glucose tolerance of healthy overweight adults." Nutrition Research 32.1 (2012): 30-38.
• Zawadzki, K. M., B. B. Yaspelkis, and J. L. Ivy. "Carbohydrate-protein complex increases the rate of muscle glycogen storage after exercise." J Appl Physiol 72.5 (1992): 1854-9.

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 youve recently read on the SuppVersity Facebook Page that taurine may help with Alzheimers disease.
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 Alzheimers (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).

Thats unquestionably impressive, but whats 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.
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 dont 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 thats 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 its possible that one week will suffice, too). Thats 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.
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 Alzheimers 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 ?-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 Alzheimers 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 Parkinsons 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.