Tuesday, July 31, 2012

Up To 180% Increase in Testosterone w/ Taurine? Androgen Boost Just One of the "Side Effects" of Cysteine Derivative That Won't Benefit (Pre-)Diabetic Baby-Boomers, Only

Image 1: No, taurine is not made from the sperm of Belgian Blues and no it won't make you look like one overnight, either ;-)
After yesterday's allegedly pretty complicated post on the fallacious ups and downs in body weight from repetitive dieting and episodes of overeating, I decided it was about time to readdress one of your all-time favorites: supplemental testosterone boosting. Instead of the next best herb from the Brazilian jungle that has a "history as a potent aphrodisiac in traditional medice" or the shrub that can be found "only in a specific region of the remote [... insert whatever your marketing guy believes would increase sales here]", I decided to take another look at one of the established readily available and dirt cheap ways to give your natural androgen production, fertility, fatty acid and glucose metabolism a leg - taurine, or 2-aminoethanesulfonic acid (which is, by the way, not produced from bull semen, although its name, which has the greek word "tavros", or ταύρος for the wanna-be intellectuals out there, would suggest ;-)

Taurine doubles testosterone production in diabetic rats

The reason I am addressing this again is the recent publication of a study on the beneficial effects of supplemental taurine, administered at a dose of 500mg/kg (human equivalent: 80mg/kg, or 3-4g /day) on the following diabetes related ailments:
What's up with intraperitoneal administered drugs? When something is injected into the peritoneal cavity the cannot vomit whatever scientists would otherwise have to stuff down their pieholes or inject into their tiny veins back up. Unfortunately the bioavailability is usually higher than via the oral route with the differences varying profoundly between compounds. Melatonin, for example, has a bioavailability of 54% when administered orally and 74% for i.p. injections (based on 10mg/kg dose; cf. Yeleswaram. 1997).

  • wasting (loss of body weight),
  • testicular damage,
  • defect spermatogenesis,
  • systemic oxidative damage,
  • DNA damage,
  • loss of natural antioxidant defense,
  • low testosterone
in six-week-old male wistar rats. As the data in figure 1 goes to show, the non-essential amino acid, both humans and rodents (not so cats) can produce from dietary cysteine, was administered (as it is common practice in rodent studies) not orally, but via the peritoneal cavity had profound effects specially with regard to the oxidative damage and restoration of the natural antioxidant defense system.
Figure 1: Relative Body, testicular and epididymal weight (left); relative testicular & serum MDA, testicular catalase, serum testosterone and DNA damage (middle) and testicular damage (tissue samples) and Johnson score for spermatogenesis (right); all data except Johnson scores expressed relative to control (calculated based on Tsounapi. 2012)
Yet despite the fact that the serum malondialdehyde (CH2(CHO)2, marker of oxidative damage) decreased from 185% in the streptozotocin treated and consequently diabetic animals to 92% in the animals who received 500mg/kg of taurine for 4 weeks after the streptozotocin injection (50mg/kg intraperitoneally) and were thus lower than in the healthy control animals, the 7.5x increas in blood glucose which was not ameliorated by taurine was obviously too much for the testosterone levels to return into the normal range.

The average American is likely to benefit, as well

Figure 2 (Shin. 2012): Adjusted mean values of total testosterone according to fasting plasma glucose (FPG) - Q1 (65 - 88 mg/dL), Q2 (88 - 94 mg/dL), Q3 (94 mg/dL - 100 mg/dL), and Q4 (100 - 126 mg/dL; prediabetic according to American Diabetes Association)
With a 2x increase over the diabetic group the testosterone boosting effect in the Tsounapi study was yet still highly significant and could, in view of the results of Shin et al. who found that even high-normal (fasting blood-glucose levels ≥ 88 mg/dL) were associated with a decrease in testosterone levels in prediabetic and non-diabetic men (Shin. 2012; ,cf. figure 2), help one or another of the men among the estimated >79,000,000 American adults aged 20 years who are prediabetic (CDC. 2010) to bump their -25% reduced testosterone levels back into the normal range.

Adequate dosages are probably higher for diabetics

That would obviously require adequate dosing schemes which would, according to the Tsounapi study range from ~3-5g and are thus more than twice as high as the 1.5g /day Brøns et al. administered to overweight men with a genetic predisposition for type II diabetes mellitus without seeing the expected outcomes in terms of increased insulin sensitivity and glucose tolerance (Brøns. 2004). Especially in diabetics, whose ability to absorb taurine is decreased (-32%), while the amount of taurine they excrete is increased (+35%; cf. Merheb. 2007), dosages in the 5g+ range (like 3x2g per day with meals) could be very well indicated - not least because the previously calculated human equivalent dose did not account for the increased bioavailability from intraperitoneally injected vs. orally ingested taurine.

Taurine, women, pregnancy and healthy children

Likewise, low(-ered) serum levels of taurine have been identified as a correlate of gestational diabetes by Seghieri et al. According the researchers from Italy,
[...] plasma taurine was inversely related to previous gestational area-under-curve of glucose and directly related to post-gestational CP/glucose [CP: C-reactive protein, important marker of inflammation and correlate of cardiovascular disease and other ailments], as well to CP/glucose measured during pregnancy (p<0.05 for both). [Moreover, the] relative risk of altered glucose metabolism during previous pregnancies [impaired glucose tolerance and gestational diabetes] was higher as plasma taurine decreased, even after adjusting for age, time-lag from pregnancy, body mass index and family history of diabetes (OR: 0.980; CI 95%: 0.963-0.999, p=0.003)
Thus taurine is by no means a "man's amino acid" - despite the fact that its concentration is particularly high in "manly" foods, such as fish and meat. In this context, the results of Kim et al. appear noteworthy, as well.

Taurine an essential component of breast milk

Taurine has a whole host of additional beneficial effects related to the prevention of comorbidities of diabetes (Ito. 2012):
  • diabetic nephropathy
  • diabetic retinopathy
  • diabetic neuropathy
  • diabetic cardiomyopathy
The Korean researchers found that the taurine content (obviously a vitally important nutrient for infants, as well) is profoundly decreased in the breast milk even of lacto-ovovegetarian mothers, compared to their non-vegetarian counterparts (31.0-54.4 mg/L vs. 19.1-52.3 mg/L; Kim. 1996). That this could be a substantial risk factor for
  • diabetes, insulitis and pancreatic dysfunction (Arany. 2004)
  • cardiovascular disease (Kulthinee. 2010)
  • distortions of the renin-angiotensin system (Thaeomor. 2010)
  • high blood pressure (Roysommuti. 2009)
  • kidney problems (Roysommuti. 2010)
and all sorts of downstream complications, regardless of the obesity / glucose tolerance of the mother, is supported by a whole host of studies (see references above); and novel papers on related benefits appear on an almost monthly basis.

You don't have to be (pre-)diabetic, on the SAD diet or pregnant to benefit

Despite the fact that (pre-)diabetics, women in childbearing age and the notorious "average American" on his "standard American diet" (mostly this is identical to being prediabetic, as the previously cited data from the CDC goes to show; cf. CFC. 2010) already cover the majority of average Joes and Janes in the Westernized (or should I say super-sized?) world, this would not be the SuppVersity if today's post would not also have some merit for physical culturists.
Image 2: Those of you who listened to my dissertations in Episode III of the Amino Acids for Super Humans series on Super Human Radio, back in the day, will remember: Taurine ain't for obese pre-diabetics, only ;-)
Now, those of you who have been around for a while will probably remember the series of shows I did with my friend Carl Lanore, host, head, heart and soul of the Super Human Radio Network, on "Amino Acids for Super Humans" - and maybe, some of you have even read all the shownotes and will thus remember a study I mentioned both on the air, as well as in detailed notes on Episode III of the Amino Acids for Super Humans series.

T for T: Taurine for testosterone for athletes and beyond

The study I am talking about was conducted by Yang et al. in 2009 and compared the effects of taurine supplementation on male reproduction in rats of different ages. With ~1% taurine at a water the rodents received, which would be (assuming an average weight & water consumption) be equivalent to ~15g for an adult human being - or 3x5g per day (Note: I am emphasizing the split dosages for two reasons: (1) I think it is a mistake not to consider the intricacies of supplementation and chronic low dose vs. bolus does make a huge difference with other supplements, e.g. "Never(!) Sip Your Whey, If You Want to Kickstart Protein Synthesis", and (2) taurine is somewhat harsh on the stomach and taking 15g in one sitting is almost guaranteed to make you sprint to the toilette within no time ;-)
Figure 3: Serum testosterone levels (in mIU/ml) after 22 (baby) and 30 days (adult and aged rats) treatment with or without 1% taurine in drinking water (adapted from Yang. 2009)
As the data I have compiled in figure 3 goes to show, the chronic taurine administration lead to statistically significant increases in serum testosterone levels in rodents from all three age groups, i.e. baby rats (born to mothers who consumed the taurine enriched / control water during pregnancy), 10-week old adult rats, and 72-week old aged. Notwithstanding, the +46% increase in testosterone in the old rats, is probably still the most significant change as it would effectively restore the "old agers" testosterone levels to youthful heights, a change, the real-world significance of which cannot be underestimated in view of the effects "low" (as in "low" in lab standards, not as in low in bro-standards!) testosterone levels can have on your body composition as discussed in one of the installments of the "Intermittent Thoughts on Building Muscle" (specifically "Quantifying the Big T" > figure 2).

Image 3: Believe it or not, eggs contain sulfur and the raw materials to make taurine, but no taurine (cf. Zhao. 1998)
In conjunction with the improved antioxidant activity (SOD, ACP, GSH were all elevated), reduced oxidative damage and markers of muscle and liver damage, AST and ALT, as well as lipid oxidation, MDA, were all significantly reduced) and the increased expression of nitric oxide synthase and subsequent raise in nitric oxide production - by the way, the only parameter with statistical significance p<0.05 only in aged rats- it stands to reason that even people who have already found their way to physical culture are very likely to benefit from one or another gram of supplemental taurine. This is all the more true in view of the fact that even high taurine foods such as crustaceans and mollusks (300-800mg/kg), Albacore tuna (176mg/100g), lamb (110mg/100g), cod (108mg/100g), mackerel (78mg/100g), beef (77mg/100g), wild salmon (60mg/100g) and pork (40mg/100g) contain too little to get anywhere close to where the magic happens.
Implications: I guess based on the previous discussion it should be clear that of the numerous supplements that are marketed to gymrats and health-enthusiasts, alike, taurine unquestionably is one of the most promising ones (suggested dose non-diabetics start with 3x2g or 2x3g /day). Moreover, with the focus of today's post being on testosterone and glucose metabolism, I did not even mention all the proven and purported benefits of taurine, such as its ability to...
  • keep exercise induced oxidative stress at bay (Zhang. 2004; Silva. 2011)
  • prevent fructose induced hypertension (Rahman. 2011)
  • facilitate cell hydration (Lang. 2012)
  • increase skeletal muscle force production (EMS test, Goodman. 2009)
  • preserve function and exercise capacity in skeletal and heart muscle (Ito. 2010)
  • enhance the anorexic effects of insulin in the hyptohalamus (Solon .2012)
  • maintain the lipolytic activity in fat cells (Piña-Zentella. 2012)
  • increase fat oxidation while cycling (Rutherford. 2012; dosage 1.5g pre)
  • counter the obesogenic effects of MSG (Nardelli. 2012 + more on MSG & obesity)
  • increase stomach acid (Huang. 2011)
... and the list goes on and on and should theoretically be extended to all the benefits of TUDCA, I have written about only recently (cf. "Tauroursodeoxycholic Acid (TUDCA) - Research Overview"), because unless you don't have enough taurine all the cholesterol and bile in the world won't help your body to conjugate UDCA to taurine and make TUDCA from it ;-)

A word of caution
:
Since I know that you are just about to order a couple of bounds of taurine from your favorite bulk supplier, let me briefly mention a not-yet fully elucidated potential downside to excessive taurine supplementation (5g/day in divided doses does not seem to be a problem, though), which relates to its ability to act as a neurotransmitter in the brain: While Louzuda et al. point out that this can be an advantage and would render taurine a potential candidate for the treatment of Alzheimer's and other neurological disorders (Louzada. 2004), it's interactions with the GABA receptor in the brain and peripheral tissues (Hanretta. 1987; Albrecht. 2005; Jia. 2008) may be a problem for people with anxiety issues - whether it exerts anti- or pro-anxiety effects, is yet still a matter of constant debate and I am not even sure how reliable the rodent models are, by the means of which Chen et al., Kong et al. and Zhang et al. (Chen. 2004; Kong. 2006; Zhang. 2007) demonstrated anti-anxiety effects, El Idrissi et al. observed anti-anxiety effects after injection and pro-anxiety effect after chronic supplementation (El Idrissi. 2009), and Whirley et al. observed only "subtle" if not non-existant effects (Whirley. 2008).
References:
  • Albrecht J, Schousboe A. Taurine interaction with neurotransmitter receptors in the CNS: an update. Neurochem Res. 2005 Dec;30(12):1615-21. Review. 
  • Arany E, Strutt B, Romanus P, Remacle C, Reusens B, Hill DJ. Taurine supplement in early life altered islet morphology, decreased insulitis and delayed the onset of diabetes in non-obese diabetic mice. Diabetologia. 2004
  • 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.
  • CDC. Centers for Disease Control and Prevention. National diabetes fact  sheet: national estimates and general  information on diabetes and prediabetes  in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human  Services, Centers for Disease Control and  Prevention, 2011. 
  • Chen SW, Kong WX, Zhang YJ, Li YL, Mi XJ, Mu XS. Possible anxiolytic effects of taurine in the mouse elevated plus-maze. Life Sci. 2004 Aug 6;75(12):1503-11.   
  • El Idrissi A, Boukarrou L, Heany W, Malliaros G, Sangdee C, Neuwirth L. Effects of taurine on anxiety-like and locomotor behavior of mice. Adv Exp Med Biol. 2009;643:207-15.
  • Goodman CA, Horvath D, Stathis C, Mori T, Croft K, Murphy RM, Hayes A. Taurine supplementation increases skeletal muscle force production and protects muscle function during and after high-frequency in vitro stimulation. J Appl Physiol. 2009 Jul;107(1):144-54. Epub 2009 May 7.
  • Hanretta AT, Lombardini JB. Is taurine a hypothalamic neurotransmitter?: A model of the differential uptake and compartmentalization of taurine by neuronal  and glial cell particles from the rat  hypothalamus. Brain Res. 1987 May;434(2):167-201. Review.
  • Huang KH, Chang CC, Ho JD, Lu RH, Tsai LH. Role of taurine on acid secretion in the rat stomach. J Biomed Sci. 2011 Feb 5;18:11. 
  • Ito T, Oishi S, Takai M, Kimura Y, Uozumi Y, Fujio Y, Schaffer SW, Azuma J. Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice. J Biomed Sci. 2010 Aug 24;17 Suppl 1:S20. Review.
  • 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. 
  • Kim ES, Cho KH, Park MA, Lee KH, Moon J, Lee YN, Ro HK. Taurine intake of Korean breast-fed infants during lactation. Adv Exp Med Biol. 1996;403:571-7. 
  • 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.
  • Kulthinee S, Wyss JM, Jirakulsomchok D, Roysommuti S. High sugar intake exacerbates cardiac reperfusion injury in perinatal taurine depleted adult rats. J Biomed Sci. 2010 Aug 24;17 Suppl 1:S22. 
  • Lang F. Effect of cell hydration on metabolism. Nestle Nutr Inst Workshop Ser. 2011;69:115-26; discussion 126-30. Epub 2012 Jan 18.
  • Louzada PR, Paula Lima AC, Mendonca-Silva DL, Noël F, De Mello FG, Ferreira ST. Taurine prevents the neurotoxicity of beta-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer's disease and other neurological disorders. FASEB J. 2004 Mar;18(3):511-8.
  • Merheb M, Daher RT, Nasrallah M, Sabra R, Ziyadeh FN, Barada K. Taurine intestinal absorption and renal excretion test in diabetic patients: a pilot study. Diabetes Care. 2007 Oct;30(10):2652-4. 
  • Nardelli TR, Ribeiro RA, Balbo SL, Vanzela EC, Carneiro EM, Boschero AC, Bonfleur ML. Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamate-obese rats. Amino Acids. 2011 Oct;41(4):901-8.
  • 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.
  • Rahman MM, Park HM, Kim SJ, Go HK, Kim GB, Hong CU, Lee YU, Kim SZ, Kim JS, Kang HS. Taurine prevents hypertension and increases exercise capacity in rats with fructose-induced hypertension. Am J Hypertens. 2011 May;24(5):574-81.
  • Roysommuti S, Suwanich A, Jirakulsomchok D, Wyss JM. Perinatal taurine depletion increases susceptibility to adult sugar-induced hypertension in rats. Adv Exp Med Biol. 2009;643:123-33.
  • Roysommuti S, Malila P, Jirakulsomchok D, Wyss JM. Adult renal function is modified by perinatal taurine status in conscious male rats. J Biomed Sci. 2010 Aug 24;17 Suppl 1:S31.
  • Rutherford JA, Spriet LL, Stellingwerff T. The effect of acute taurine ingestion on endurance performance and metabolism in well-trained cyclists. Int J Sport Nutr Exerc Metab. 2010 Aug;20(4):322-9.
  • Seghieri G, Tesi F, Bianchi L, Loizzo A, Saccomanni G, Ghirlanda G, Anichini R, Franconi F. Taurine in women with a history of gestational diabetes. Diabetes Res Clin Pract. 2007 
  • Shin JY, Park EK, Park BJ, Shim JY, Lee HR. High-normal Glucose Levels in Non-diabetic and Pre-diabetic Men Are Associated with Decreased Testosterone Levels. Korean J Fam Med. 2012 May;33(3):152-6. 
  • Silva LA, Silveira PC, Ronsani MM, Souza PS, Scheffer D, Vieira LC, Benetti M, De Souza CT, Pinho RA. Taurine supplementation decreases oxidative stress in skeletal muscle after eccentric exercise. Cell Biochem Funct. 2011 Jan-Feb;29(1):43-9.
  • Solon CS, Franci D, Ignacio-Souza LM, Romanatto T, Roman EA, Arruda AP, Morari J, Torsoni AS, Carneiro EM, Velloso LA. Taurine enhances the anorexigenic effects of insulin in the hypothalamus of rats. Amino Acids. 2012 Jun;42(6):2403-10.
  • Thaeomor A, Wyss JM, Jirakulsomchok D, Roysommuti S. High sugar intake via the renin-angiotensin system blunts the baroreceptor reflex in adult rats that were perinatally depleted of taurine. J Biomed Sci. 2010 Aug 24;17 Suppl 1:S30.
  • Tsounapi P, Saito M, Dimitriadis F, Koukos S, Shimizu S, Satoh K, Takenaka A,  Sofikitis N. Antioxidant treatment with edaravone or taurine ameliorates diabetes-induced testicular dysfunction in the rat. Mol Cell Biochem. 2012 Jul 5.
  • Whirley BK, Einat H. Taurine trials in animal models offer no support for anxiolytic, antidepressant or stimulant effects. Isr J Psychiatry Relat Sci. 2008;45(1):11-8.
  • Yang J, Wu G, Feng Y, Lv Q, Lin S, Hu J. Effects of taurine on male reproduction in rats of different ages. J Biomed Sci. 2010 Aug 24;17 Suppl 1:S9.  
  • Yeleswaram K, McLaughlin LG, Knipe JO, Schabdach D. Pharmacokinetics and oral bioavailability of exogenous melatonin in preclinical animal models and clinical implications. J Pineal Res. 1997 Jan;22(1):45-51.
  • Zhang M, Izumi I, Kagamimori S, Sokejima S, Yamagami T, Liu Z, Qi B. Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men. Amino Acids. 2004 Mar;26(2):203-7.
  • Zhang CG, Kim SJ. Taurine induces anti-anxiety by activating strychnine-sensitive glycine receptor in vivo. Ann Nutr Metab. 2007;51(4):379-86. 
  • Zhao X, Jia J, Lin Y. Taurine content in Chinese food and daily intake of Chinese men. Adv Exp Med Biol. 1998;442:501-5.