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. 2013)

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. 2013): 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. 2013; ,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. 2013):

• 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. 2013) 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 .2013) maintain the lipolytic activity in fat cells (Piña-Zentella. 2013) increase fat oxidation while cycling (Rutherford. 2013; dosage 1.5g pre) counter the obesogenic effects of MSG (Nardelli. 2013 + 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. 2013 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 2013 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. 2013 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. 2013 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. 2013 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. 2013 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.

What's Worse: YoYo-Dieting or Constant Gluttony? What Happens During Weight Cycling? And Why Does Every Diet Make You Fatter? Lots of Questions, a Couple of Answers

Image 1: To eat or to diet, what's worse?

Despite the fact that the magazines are still full of "X pounds in Y weeks" diets, more and more people begin to realize that "diet hopping" and even "dieting" in the conventional sense, i.e. following a special, usually very strict and non-sustainable nutritional regimen for a very short amount of time, are futile. But can calling a halt before you blow up like a balloon from time to time actually be worse than letting yourself go all-day, everyday? According to the results of an experiment that has been conducted at the Institute of Biology of the State University of Rio de Janeiro, the results of which have just been published in the open access journal PLoSOne, the answer to this question must be: YES, it can! And that may be true, even when you are not starving yourself!

Even "healthy" weight cycling turns out to be profoundly unhealthy!

Now, the unfortunate news first: We are, as so often dealing with a rodent study - one that was done conducted with 80(!) 3-months old C57BL/6 mice. "Wow! 80 mice? That's plenty!" Yeah, initially it may sound like that, but in view of the fact that their number was decimated every 8 weeks, there would not have been the necessary 4x8 rodents left at the end of the 24-week study period for the final evaluation of the four experimental groups, which were

• standard chow (SC; 15kJ/g) - rodents in this group received the standard chow (76% energy from carbohydrates, 14% energy from protein, and 10% energy from fats) for the whole study period
• high fat diet (HF; 21kJ/g) - rodents in this group received a fattening hypercaloric diet (26% energy from carbohydrates, 14% energy from protein, 50% energy from animal lard and 10% energy from soy bean oil 
• SC ↔ HF - rodents in this group received standard chow for the first 8-week cycle, high fat diet for the 2nd 8-week cycle and standard chow for the third and last 8-week cycle
• HF ↔ SC - rodents in this group received high fat diet for the first 8-week cycle, standard chow for the 2nd 8-week cycle and high fat  for the third and last 8-week cycle 

If we go back to the initial question, the HF group would be our 24/7, 365 days a year eat everything the worst Western diet you can imagine has to offer, while the animals in the group SC ↔ HF and HF ↔ SC group would be representative of

• the high school football player who turns to a sedentary lifestyle and bad eating habits when he goes to college, is partying all night, bear pizza, etc. eventually, he realizes he got fat, and diets again (SC ↔ HF ↔ SC) and
• the obese kid who eventually turns to physical culture, works out, eats health and loses weight, when he starts college, to then fall back into his old bad habits and starts letting himself go, when he marries and has kids (HF ↔ SC ↔ HF)

I know this is a little far-fetched and as we are going to see later, mice are not exactly the best model to study things like that, but still, the way the weight of the rodents, who had free access to the respective chow they were on during the whole experimental period, developed is quite telling:

Figure 1: Despite intermediate fat loss the increased feed efficiency (=weight gain per kcal) that is especially pronounced in the HF phases of the weight cycling groups quashed the previous weight loss. If age effects had not become a problem this effect would have been more obvious in a 4th cycle.

And the message the data in figure 1 is sending is quite clear: Dieting, as in changing your eating habits only intermediately, is useless, at best! - "at best", because it becomes increasingly difficult to lose and constantly easier to gain weight or, as Barbosa-da-Silva et al. put it:

[...] after three consecutive WC [weight cycles], the reduction of BM is less marked during the SC cycle, as well as the increase of BM is more prominent during HF cycle (Barbosa-da-Silva. 2013).

Now, we probably would not have had to do a 24-week rodent study to know that, right? Right! Notwithstanding, though, the beauty of working with rodents - instead of Biggest Losers, for example - is that they usually don't complain much when you slaughter them, so that the scientist could not only measure the serum leptin (figure 2, left), triglycerides, cholesterol, insulin and glucose levels, but also count the number and measure the size of the adipocytes in their visceral fat pads.

Figure 2: Leptin expression and adipocyte density per area of adipose tissue mass after the 1st, 2nd and 3rd weight gain/loss cycle (data adapted from Barbosa-da-Silva. 2013)

And as you can see in figure 2 (right) the weight cycling induced quite profound effects on the adipose tissue morphology; effects that are similar to what we have seen in previous discussions on the underlying causes of the yoyo effect (see "Nasty Insights into the YoYo-Effect"). You have to keep in mind, though, that you would be comparing apples and oranges if you compare the two weight cycling groups with each other, as one group has always just lost weight, when the other has gained weight so that in one group the adipocytes will  be depleted, when they are filled to the seams in the other one. If there had been a fourth cycle in the course of which the fat cells of the SC ↔ HF group would have been repleted, we may thus safely assume that the absolute size-differences, which reached statistical significance only in the HF ↔ SC group after the third cycle (violette bar in figure 2, right), would have been similar or even more pronounced after 32 weeks and 4 cycles in the then HF dieting SC ↔ HF (note: one of the reasons the researchers did extend the experiment for another 4 weeks was that even now, age-related effects and obesity related morbidities would have reduced the significance of the data).

Adipocyte morphology, leptin expression, fat pad restructuring and body fat that sticks

Apropos significance, you ay remember from the "previously mentioned post" on this issue that one of the currently discussed hypothesis that could  (at least partly) explain why formerly obese people are not just having a really hard time to lose weight, but also, and often even more so, to keep that weight off, relates to what I have previously labeled "relative leptin defiency" (too little leptin production per adipose tissue mass) or, and this would be an alternative hypothesis, "leptin resistance" (more than enough leptin in the blood, but the signal transmission does not work).

The first thing we can say based on the data Barbosa-da-Silva acquired on the absolute fluctuations of leptin in the blood of the rodents (figure 2, left) ist that previously made conclusions about the effects of weight gain, weight loss and energy intake on leptin, like

1. weight loss and fasting are associated with reduced leptin levels, 
2. weight gain is associated with an increase in leptin concentration 
3. chronically increased leptin can lead to leptin resistance
4. meals and according to meal composition or short-term swings in energy balance such as fasting or overfeeding induce swings in systemic leptin levels

appear to be accurate. To check whether there is evidence for my "relative leptin deficiency" hypothesis, especially in weight cycling groups, I ploted the ratio of serum leptin to body fat in figure 3 (left):

Figure 3: Leptin levels in serum per body fat (left), leptin expression in adipose tissue (middle), and sectional area of adipocytes of the different groups (based on Barbosa-da-Silva. 2013)

And what is interesting is that in this calorically non-restricted scenario, the respective "relative leptin deficiency" occurs only in the SC ↔ HF group during the third and last cycle, when their relative leptin levels which should actually be identical to the SC group (we must compare them to the SC group, because the current diet will influence leptin expression as well) are 36% lower than they "should" be. In the same third cycle, the HF ↔ SC group (remember, those are our "formerly obese kids") have 21% more leptin in their blood than they "should" - given their current adipose tissue mass.

Some food for thought - Though not directly related to the topic, there is one thing pertaining to the heavily debated "CLA post" from last week (cf. "CLA Destroys Body Fat"), I want to mention. If we assume that the CLA-induced adipose tissue apoptosis Kim et al. observed in their recent study is as rodent-specific as the natural death and rejuvenation of adipose tissue Cinti et al. observed in the study I cite relating to the limited adipose tissue growth in rodents, this would not just indicate that taking copious amounts of CLA would not help to reverse the damage you may have done during previous "diets", but could also explain why conjugated linoleic acid supplements don't work in humans (or horses; see yesterday's news).

Now this segues directly into the allegedly somewhat counter-intuitive conclusion that anything that soothes the raging inflammation in your fat cells may ameliorate the downstream detrimental effects on glucose and lipid metabolism, but will, on the other hand, help your fat cells to survive or maybe even proliferate in amidst the TNF-alpha induced cytokine storm (Prins. 1997), which would otherwise kill them. Now with the current paradigm of "inflammation = bad" this may sound hilarious. In the the end, it does yet only echo the title of a 1999 paper by Hube and Hauner, "The role of TNF-alpha in human adipose tissue:  Prevention of weight gain at the expense of insulin resistance?" (Hube. 1999) and would provide us with a mechanistic explanation of several otherwise non-explicable phenomena such as the profound fat loss in rodents who lack the master antioxidant glutathion (see "Inflammation Is the True Fat Burner"),,, but as indicated: This is just some food for thought ;-)

In combination with the leptin overshoot (+153%) in the "former football players on their college binge", this data would suggest that we are not dealing with "relative deficiency" and "leptin resistance" but rather with a complex mixture of both, where the latter is probably a result of repeated overshoots like the one we see in the SC ↔ HF group after their first high fat feeding cycle (2nd cycle, 154% elevated leptin levels).

Relative leptin deficiency, systemic resistance and now local differences?

And as if things were nor already complicated enough, there are also potentially important differences between circulating leptin levels and local leptin expression in isolated fat pads figure 3 (middle; compare data to figure 2, left, 3rd cycle). Thus, the drop in leptin levels upon "fasting" in the (SC ↔ HF, 2nd cycle  and HF ↔ SC, 3nd cycle) is systemic, but does not reflect the expression of leptin in the intra-abdominal tissue. This stands in line with my previous dissertation on "relative leptin deficiency" and the differences between...

• intra-abdominal (easy to shed on a diet), and 
• subcutaneous (esp. in the lower body compartment difficult to shed on a diet)

...adipose tissue in "Nasty Insights into the YoYo-Effect" (a similar depot-specificity has been reported for pre-adipocytes, i.e. developing fat cells, as well - intriguingly only in 9 out of human subjects (=81%); cf. Niesler. 1998). Due to the fact that the expansion of adipose tissue in rodents appears to be limited and the cell-turnover high (contrary to humans, where you get the impression that obesity is only limited by death and the cell-turnover - if it exists at all - must be very slow), these effects are probably even more pronounced in humans than in mice. Consequently, it can be expected that the diet / feasting induced upward shifts of the body fat set point are more pronounced and their morphological reversal either more time-consuming (probably true for the visceral body fat) than in rodents or simply impossible (could be the case for parts of the subcutaneous body fat) in human beings.

Image 1 : Lose 20lbs now, gain 25 back and have 5 stick with every diet! We still don't understand exactly why, but by now it should be clear, diets like the "Kendra diet" are rather part of the problem than viable solutions

Implications: Despite the fact that we still don't really understand what's happening, when we are trying to shed the body fat we have acquired in times of gluttony, the few novel insights we have gained from the study at hand should make it even more obvious that "classic" dieting does not hold the answer to the obesity problem. Neither on an individual, nor on a societal level. Instead of "eat less, exercise more", the main message should read: "Don't ever think of dieting, again! Revamp your life, your activity profile and the way you eat and wait for things to fall in place." After all, the "formerly obese kids" in the HF ↔ SC group were not too bad off, when they had returned to a (for rodents!) healthy diet in the 2nd cycle. We may even speculate that the difference the rodents in the control group (SC) would not have been significant anymore, if the scientists had kept the HF ↔ SC rodents on standard chow for another 8 weeks.

The same group is however living (now dead ;-) proof that the notion that you could diet today, look better tomorrow and then return to what has gotten you into misery before is not just illusive, but outright life-threatening. Since caloric restrictions, which are still at the heart of 99% of the mainstream diets, will probably magnify the amplitude (i.e. the up and down) of the yoyo effect and its negative metabolic consequences, it appears reasonable to assume that the yoyo-dieter will eventually be worse off than the "happy fatso" who has been eating whatever he wanted for all his life and dropped dead morbidly obese with a heart attack at 45. After all, it seems likely that he (or she!) will not even live to the 45th year before he falls victim to the very same fate and that after not despite, but rather because of all the temporary austerities... now, this may be like choosing between pest and cholera, and the third option, i.e. following the path of physical culture would alway be my first choice, but honestly, if I had to choose, I'd rather be the fatso who enjoyed his 45 years of pizza, pasta and chocolate pie than the frustrated yoyo dieter.

References

• Barbosa-da-Silva S, Fraulob-Aquino JC, Lopes JR, Mandarim-de-Lacerda CA, Aguila MB. Weight Cycling Enhances Adipose Tissue Inflammatory Responses in Male Mice. PLoS ONE 2013; 7(7): e39837.
• Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46: 2347–2355.
• Hube F, Hauner H. The role of TNF-alpha in human adipose tissue: prevention of weight gain at the expense of insulin resistance? Horm Metab Res. 1999 Dec;31(12):626-31.
• Kim JH, Kim J, Park Y. trans-10,cis-12 Conjugated Linoleic Acid Enhances Endurance Capacity by Increasing Fatty Acid Oxidation and Reducing Glycogen Utilization in Mice. Lipids. 2013 Jul 11.
• Niesler CU, Siddle K, Prins JB. Human preadipocytes display a depot-specific susceptibility to apoptosis. Diabetes. 1998 Aug;47(8):1365-8.  
• Prins JB, Niesler CU, Winterford CM, Bright NA, Siddle K, O'Rahilly S, Walker NI, Cameron DP. Tumor necrosis factor-alpha induces apoptosis of human adipose cells. Diabetes. 1997 Dec;46(12):1939-44.
• Zhu. Ncb5or in Fatty Acid Desaturation and Metabolic Diseases. Zhu Diabetes Research Group. University of Kansas School of Health Professionals. < http://www.alliedhealth.kumc.edu/school/research/zhu/more_info.html > retrieved July 22, 2013

On Short Notice: Retinoic Acid vs. Lung Cancer / Metabolic Effect of Fats in Cerebral Fluid / Nucleotid Supplements Instead of Icepacks // Ibuprofen & Leaky Gut / Fish Oil Enema & Colitis / Fructose, Glut-5 & Obesity + More!

Image 1 (Coloribus): Unquestionably a great add, but the (Ex-)Marlboro man would be better off with a piece of liver than a carrot ;-)

Just as I promised I am pumping out another set of "short notice" items. To make sure not to be confused with what I have once heard someone call a "pubmed warrior", I did however spike today's episode with three longer items and saved a couple of mini-items for the next week. I hope you enjoy the ride and don't forget to copy "Fatfree" who asked for more in-depth info on TUDCA after reading last Saturday's installment of this series (see "Testosterone - 12% Drop With 75g Glucose? Low T3 Syndrome - Can TUDCA Help?"). If there is more information that would make a longer post worthwhile and I find the topic interesting enough to spent the time on doing the research, I am always willing to comply with wishes like this :-)

Retinoic acid (not beta carotene!) can protect smokers from lung cancer

In a paper that has just been published in the Journal of Food Sciences, Xue et al. report that the epigenetic switches retinoic acid (active, real vitamin A) triggers in cancer cells of lung cells in cigarette-smoke exposed rodents does effectively counter the upregulation of the 120 mostly cell-differentiation and proliferation related genes scientists believe to be a causative factor in the etiology of lung cancer. This is particularly interesting, because supplementation with larger amounts of the vitamin A precursor beta-carotene has been found to pose a serious health risk for smokers. With a passive smoke exposure equivalent to 80 nonfiltered commercial cigarettes the per day it is almost marvelous how effective the 10mg/kg bodyweight of all-trans retinoic acid were.

Figure 1: While all-trans-retinoic acid (left, bottom) appears to have potent anti-lung-cancer effects the β1-apocarotenoids our bodies produce from beta carotene could potentially negate these beneficial effects (see "Anti-Vitamin A Effects of Beta Carotene"); this would also explain why previous research has shown that beta-carotene supplements are potentially hazardous for for smokers (cf. Druesne-Pecollo. 2010)

I guess, the most studious among you will probably already know how the differing effects of vitamin A (real ATRA) and beta carotene come about, right? In my recent blogpost on the "Anti-Vitamin A Effects of Beta Carotene", I did actually provide a mechanistic explanation as the metabolic byproduct that arises from high dose beta carotene supplementation will block the retinoic acid receptor (similar to the way a SERM blocks the estrogen receptor) and thus inhibit the inhibitory effects of real vitamin A on the occurrence and progression of cancerous growth.

Image 2: Helicobacter pylori, ain't the reason you get lung cancer, but smoking will help him to prepare the breeding ground for gastric cancer.

Apropos lung cancer, a study by Koshiol et al. has recently refuted the claim that Helicobacter pylori (H. pylori) infections would increase the risk of lung cancer (Koshiol. 2013). Previous research from the German Center for Research of Ageing, on the other hand, found conclusive evidence that the combination of h. plyori and smoke increases the risk of gastric cancer by more than 600% (Brenner. 2002)! But don't worry, all-trans-retinoic acid can take care of that, as well. At least in the Petri dish, incubation of human gastric cancer cells with ATRA lead to immediate growth arrest (Zhang. 2005)... and did I mention it does the very same thing to pancreatic cancer, breast cancer and leukemia cells?

Implications: Regardless of whether you live with a chainsmoker, work in a bar or are stranded on a lonely island, where your campfire is the only source of smoke in your life, try to get your real vitamin A (=retinol) from fatty animal products and forget about beta carotene supplements (even if you brought some to your lonely island ;-). With fatty fish, a piece of liver every now and then, butter, eggs, etc. and large amounts of green leafy vegetables and a reasonable amount of whole fruits (no juices!) you are guaranteed not to fall short of any of these "vitamins A" (retinol and beta carotene) and the multitude of other potent carotenes that would be missing from your supplements anyway.

Type of fatty acids in cerebral fluid determine metabolic rate

Image 3: Assuming that the fatty acids you eat also float around in your brain peanut oil (1-2.5% C:24) is the worst edible oil for anyone who is concerned about his overnight energy expenditure.

A study that has just been published on PLos ONE provides astonishing insights into how long chain fatty acids (saturated fats) in your cerebral fluid could (we are dealing with observational human data from a metabolic ward study, here) slow down your fat loss or even make you gain weight by decreasing overnight energy expenditure. With correlations in the range of -0.6, lignoceric acid (C24:0, as in peanut oil) and Cerotic acid (C26:0; as in beeswax) are by far the worst offenders, as far as overnight energy expenditure are concerned; and though the design of the study did not allow for any conclusions on the underlying mechanisms, the fatty acid induced suppression of the nocturnal surge in growth hormone could be one potential and at least in my humble opinion not very far-fetched cause for this effect. Interestingly, things look completely different for the plasma levels of these fatty acids, which showed the exact opposite +0.6 correlation with 24h energy expenditure. Other noteworthy results were

• significant correlations of the mono-unsaturated fatty acids palmitoleic and oleic acid in the cerebrospinal fluid with higher rates of fatty acid oxidation (relative to carbs, not total) and 
• significant correlations of the omega-6 fatty acids linoleic (18:2n6), dihomo-g-linolenic acid (20:3n6) and arachidonic acid (20:4n6), the omega-3 fatty acids linolic acid and docosapentaenoic acid (DPA, C22:5n3) and the omega-9 fatty acid mead acid (C20:3n9) with better glucose clearance.

And no, the much-lauded fish-oil, i.e. the EPA and/or DHA content of the cerebrospinal fluid, had no significant effect on glucose tolerance. A result, by the way, which reminds me of another study I came across recently:  In their four day supplementation trial Miller et al. observed vast differences between the incorporation of EPA and DPA (docosapentaenoic acid, the one that did correlate - weaker than the omega-6s, though - with improved glucose tolerance) into plasma and red blood cell lipids subsequent to the oral provision of 8g/day of each to ten healthy women. Their observations and the respective alterations in EPA and DHA in the DPA supplementation group Miller and his colleagues concluded that DPA could serve as a reservoir of the major long-chain n-3 fatty acids (LC n-3 PUFA) in humans - exciting stuff and probably something you will read more about, here at the SuppVersity in the future.

Image 4: The data would support the use of MUFA and omega-6 laden olive and high MUFA macadamia oils, if we know how their consumption effects the fatty acid flux in our brains.

Implications: Due to our lack of knowledge about the ultimate determinants of cerebrospinal fluid fatty acid composition it is hard to say if these results do imply that you better focus on MUFAs in view of their beneficial effect on both glucose clearance and respiratory quotient - and still the usefulness of MUFA and omega-6 laden olive oils, which have time and again been shown to produce all sorts of favorable changes in glucose, fat and overall energy metabolism would support the notion that there is a direct or indirect downstream effect of higher intakes of the respective fats, their occurrence in our cerebrospinal fluid and their downstream metabolic effects.

Cooling trained muscles appears do decrease regeneration

Soon to be published in the Journal of Strength and Conditioning Research are the results of a randomized cross-over study into the effects 15 minutes of icing applied 0h, 3h, 24h, 48h and 72h after an intense eccentric arm workout with 6 sets of elbow extension performed at 85% maximum of the voluntary maximal load had on the subjective as well as measurable (inflammatory cytokines, creatine kinase (CK-MB), hemoglobin and oxygenation were assessed) regeneration of 11 young male college baseball players (Tseng. 2013).

Figure 2: Inflammatory cytokines, creatine kinase and visual analgue scale data on subjective perception of fatigue at different timepoints before and after the eccentric arm workout (data adaptedm from Treng. 2013)

As you can see from the data in figure 2 the icing did have a somewhat bizarre effect on the inflammatory and subjective indexes of muscular regeneration. While...

[...] significant change in the levels of IL-1β, IL-8, and IL-1 were observed following the muscle-damaging eccentric exercise in either the control or topical cooling conditions and no differences in these cytokines were found between the control and cooling trials throughout the 72 h observation period (data not shown in figure 2, Tseng. 2013).

The levels of the pro-anabolic cytokine IL-12 (Argile. 2001), TNF-α, and IL-6 were significantly lower 24h after the workout (see figure 2, left; p < 0.05). There were yet no significant differences at other time-points ant both the CK-MB, as well as the fatique score (figure 2, right) suggest that the overall regenerative capacity was compromised by the repeated cooling of the strained musculature.

Image 4: If you use a 41°C hot bath 48h before a workout to "pre-generate", you don't even need to ask yourself whether or not the results of the study at hand conclusively imply that icepacks are detrimental and their use after workouts has to be avoided at all costs.

Although I must admit that this is not a settled case for me, until we understand the unexpected dip in IL-12, TNF-α, and IL-6 after 24h and its relation to the obvious increase in muscle damage (CK) and corresponding fatigue levels, it would appear prudent not to make use of an icepack as your regenerative means of choice.

Instead, I would suggest you follow the example of the young lady on the left and take "pregenerative" measures by taking a 41°C hot bath 48h before a strenuous workout. As you will probably remember from my previous article on the Touchberry study (read full story based on Touchberry. 2013) this will not just keep the damage at bay, but may also help you on your quest to a more muscular physique. And if you want to do your immune system a favor, check out the on very short notice item about RNA + DNA precursor supplementation further down...

On Very Short Notice

• 

  Image 5: Adding ibuprofen on top of exercise will make your gut look like a riddle screen.

  Ibuprofen makes an exercise-induced leaky gut even leakier - The use of NSAIDs such as aspirin and ibuprofen has long been implicated in the etiology of all sorts of gastrointestinal problems ranging from benign gastroinstestinal distress, over gastrointestinal bleading, ulcers etc. to all sorts of cancers. Researchers from the Top Institute Food and Nutrition at the University of Maastricht in the Netherlands have now found that the way by which ibuprofen aggravates the exercise-induced small intestinal injury and induces an even more pronounced gut barrier dysfunction in healthy individuals than exercise alone, may not just contribute to the occurrence of the aforementioned pathologies, but also precipitate to systemic diseases. After all, it opens up the doors to pathogens and toxins, which would otherwise be blocked by an intact intestinal barrier (van Wijck. 2013).
  N-acetyl-L-cystein (NAC) a potent natural anti-inflammatory which has also  been shown to reduce exercise induced inflammation (see "NAC Improves Markers of Oxidative Stress Induced by High Intensity Exercise") and glutamine (in the dos Santos study a HED of "only" 3-5g/day), on the other hand, exert protective effects on the integrity of the intestinal barrier (Sun. 2002; dos Santos. 2010).
• Fish oil enema ameliorates colitis - When administered intra-rectally at a human equivalent dose of  ~13ml, fish oil effectively ameliorated the mucosal damage in experimentally induced ulcerative colitis in rat; flax oil and the corn oil control, on the other hand, did not prevent the increase in colonic weight / /length ratio and the associated histological changes 24h after Aisha Mohamed Dugani, Ahlam Elhelawi and Aisha Edrah had administered 1ml of 4% acetic acid to induce the colic (Mohamed Dugani. 2013). These results stand in line with general colon-protective effects of fish oil, observed in other studies and it's likely that they are a direct consequence of its non-negligible anti-inflammatory effect - which does not change my assessment that healthy physical culturists should not take more than max. 2g of supplemental fish oil per. The evidence supporting any beneficial effects on non-insulin-resistant, non-obese, non-hypertriglyceremic individuals is simply non-existent.

• 

  Image 6: No, this certainly does not look as if the conjugated linolic acid would work in horses as it does in mice ;-)

  Species specific effects of CLA: Horse don't lose weight, either - You will probably remember my recent post on the adipose tissue destroying effects of CLA (cf. "CLA Destroys Body Fat") in rodents, as well as my remarks that - if we discard potential underdosing as a contributing factor - it would appear that the beneficial effects of CLA we see in rodent studies is highly species specific. Now, Headley et al. have published the results of a study that investigated the effects of 0.05% CLA enriched chow on horses. Similar to what we see in humans, the conjugated linoleic acid had no effect on the body composition of the animals. Interestingly though, the mixture of three CLA isomers used in the study (cis-9, trans-11 + trans-10, cis-12 + and trans-9, trans-11; usually we have only the latter two in significant amounts) led to a statistically significant reduction of the potentially pro-inflammatory arachidonic acid in the blood of the horses. This spiked the interest of Headley et al. as it could turn out that this would render CLA (this specific isomer mix, I should say) as an agent that could have beneficial effects on the progression of joint disease, which is - in parts - driven by C20:4 (chemical name for arachidonic acid).
• Towards a better understanding of why fructose is making us fat - Using in-vitro studies and a genetically engineered Glut5 -/- mouse model (these mice lack the glut-5 receptor which is responsible for the uptake of fructose), Li Du and Anthony P. Heaney were able to show that the preferential expression of Glut5 in developing adipocytes and the corresponding adipogenic (=promoting the creating of new fat cells) effects of fructose could well explain why fructose, which can no longer be taken up by mature fat cells, has been shown time and again to be way more fattening than its pro-insulinogenic cousin glucose (Du. 2013). Put simply, you could say: Increased serum levels of fructose require a) the conversion of fructose to triglycerides of glucose in the liver or b) the proliferation of adipose tissue so that the developing new fat cells can take the superfluous fructose up. If you consume too much of so that your liver is already working overtime, it is no wonder that your healthy high-fructose corn-syrup fat-free breakfast cereals are making you fatter and fatter. 

• 

  Figure 3: Effects of incremental treadmill running on selected markers of immune activity before and after 2 weeks of sublingual treadmill running in 38 healthy young men nucleotid supplementation (Ostojic. 2013)

  Supplement with RNA and DNA building blocks protects from immune-suppressive effects of exercise - The effects Sergej M Ostojic and Milos Obrenovic observed in response to a 14-day sublingual nucleotide supplementation regimen were basically what common wisdom tells you, you should see as a result of glutamine supplementation (Ostojic. 2013): The RNA and DNA precursors did not just ameliorated the dreaded immune-suppressive effects of a standardized cardio workout on a treadmill, they effectively boosted natural killer cells count and cytotoxic activity as well as salivary immunoglobulins and lactoferrin (cf. figure 3); so profoundly, though, that I am not 100% sure this is a good thing - at least not for people with auto-immune issues.
• Don't stress yourself if you want to recover as fast as possible! That's the take home message of a recently published study by two researchers from the Nothern Illiniois University and the University of Texas at Austin, who correlated measures of perceived psychological stress with physical data on exercise recovery and found a surprisingly linear relationship between perceived stress, on the one hand, and phyical recovery as measured by maximal isometric force, on the other hand, in 31 undergraduate resistance training students (Stults-Kolehmainen. 2013). So, mark my words: Don't overstress about making everything right (this includes having the optimal workout and nutrition plan and thinking about whether or not you should add in another 0.5g BCAA pre-workout or not), if you don't want to sabotage your training success.

References

• Argilés JM, Meijsing SH, Pallarés-Trujillo J, Guirao X, López-Soriano FJ. Cancer cachexia: a therapeutic approach. Med Res Rev. 2001 Jan;21(1):83-101.
• Brenner H, Arndt V, Bode G, Stegmaier C, Ziegler H, Stümer T. Risk of gastric cancer among smokers infected with Helicobacter pylori. Int J Cancer. 2002 Mar 20;98(3):446-9.
• dos Santos RG, Viana ML, Generoso SV, Arantes RE, Davisson Correia MI, Cardoso VN. Glutamine supplementation decreases intestinal permeability and preserves gut mucosa integrity in an experimental mouse model. JPEN J Parenter Enteral Nutr. 2010 Jul-Aug;34(4):408-13.
• Druesne-Pecollo N, Latino-Martel P, Norat T, Barrandon E, Bertrais S, Galan P, Hercberg S. Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials. Int J Cancer. 2010 Jul 1;127(1):172-84.
• Du L, Heaney AP. Regulation of Adipose Differentiation by Fructose and GluT5. Mol Endocrinol. 2013 Jul 24.
• Headley S, Coverdale JA, Jenkins TC, Klein CM, Sharp JL, Vernon KL. Dietary supplementation of CLA in horses increases plasma CLA and decreases plasma arachidonic acid, but does not alter body fat. J Anim Sci. 2013 Jul 24.
• Jumpertz R, Guijarro A, Pratley RE, Mason CC, Piomelli , Krakoff J. Associations of Fatty Acids in Cerebrospinal Fluid with Peripheral Glucose Concentrations and Energy Metabolism. PLoS ONE 2013; 7(7): e41503.
• Koshiol J, Flores R, Lam TK, Taylor PR, Weinstein SJ, Virtamo J, Albanes D, Perez-Perez G, Caporaso NE, Blaser MJ. Helicobacter pylori seropositivity and risk of lung cancer. PLoS One. 2013;7(2):e32106.
• Miller E, Kaur G, Larsen A, Loh SP, Linderborg K, Weisinger HS, Turchini GM, Cameron-Smith D, Sinclair AJ. A short-term n-3 DPA supplementation study in humans. Eur J Nutr. 2013 Jun 23.
• Mohamed Dugani A, Elhelawi A, Edrah A. Comparative effect of flaxseed oil and fish oil in acetic acid induced colitis in rats. The Libyan Journal of Pharmacy and Clinical Pharmacology LJPCP. 2013;1.
• Ostojic SM, Obrenovic M. Sublingual nucleotides and immune response to exercise. Journal of the International Society of Sports Nutrition 2013, 9:31. 
• Stults-Kolehmainen MA, Bartholomew JB. Psychological Stress Impairs Short-Term
  Muscular Recovery From Resistance Exercise. Med Sci Sports Exerc. 2013 Jun 8.
• Sun Z, Lasson A, Olanders K, Deng X, Andersson R. Gut barrier permeability, reticuloendothelial system function and protease inhibitor levels following intestinal ischaemia and reperfusion--effects of pretreatment with N-acetyl-L-cysteine and indomethacin.
• Touchberry CD, Gupte AA, Bomhoff GL, Graham ZA, Geiger PC, Gallagher PM. Acute heat stress prior to downhill running may enhance skeletal muscle remodeling. Cell Stress Chaperones. 2013 May 17.
• van Wijck K, Lenaerts K, van Bijnen AA, Boonen B, van Loon LJ, Dejong CH, Buurman WA. Aggravation of Exercise-Induced Intestinal Injury by Ibuprofen in Athletes. Med Sci Sports Exerc. 2013 Jul 6.
• Xue Y, Meadors EP, Wang W, Baybutt RC. Microarray Analysis reveals that Dietary Retinoic Acid Suppresses Cancer Related Gene Expression of the Lungs of Cigarette Smoke-Exposed Rats. J Nutr Food Sci 2013, S2.
• Zhang JP, Chen XY, Li JS. Effects of all-trans-retinoic on human gastric cancer cells BGC-823. J Dig Dis. 2007 Feb;8(1):29-34.

On Short Notice: Insanity vs. TurboFire - What's the Best HIIT Regimen? Plus: USA vs. China, Chews vs. Raisins, Epi-Sesamine vs. Body Fat, Exercise vs. Neurotoxins & More

Figure 1: The latest medal prognosis for Olympia 2013 by researchers at the Department of Economics at the Ruhr-Universität Bochum in Germany (Otten. 2013) - I must admit I am curious how accurate this prognosis will be... what's your take? The US or China? Who's going to take the lead?

The Queen has officially opened the Olympic Games 2013 and the games have their first doping case - those of you who followed yesterday's advice to subscribe to the SuppVersity Facebook page are already in the know... anyways, this is not the place for one of my hypocrisy rants, but for the weekly installment of "On Short Notice". Still, in the "honor" of the Olympics *rofl* and the spirit of the SuppVersity - which is, as you all know, the place you will get the news first! - I have compiled the TOP15 from the latest medal prognosis by Sebastian Otten, the chair of the Department of Economics at the Ruhr-Universität Bochum in Germany, for you as an appetizer (figure 1). Moreover, I picked more sports and less health, weight-loss, supplementation and nutrition related topics from my ever-growing collection of "On Short Notice" items, which is by the way already so exuberant that there will be another episode of this series either tomorrow or early next week, mostly because otherwise the latest news would come in late... so, let's go for it!

Insanity vs. TurboFire Interval - What's the optimal HIIT regimen?

As part of her recently published master thesis, Sarah A. McGlinchy investigated the differential effects two commercial fitness programs had on the heart rate pulmonary O2 uptake, CO2 output, caloric expenditure and substrate utilization during exercise and recovery, as well as the subjective satisfaction and physical exertion of trained individuals (N=15, four males and 11 females, aged 22.3 ± 1.6 years McGlinchy. 2013).

• 

  Image 1: Insanity (top) vs. Turbo Fire (bottom) - My HIIT workouts look profoundly different, but this does not mean that those workouts cannot be effective; specifically if you enjoy stuff like this and don't do it alone in front of your TV, but with friends & new friends at the gym. And trust me, I don't even need a study to be able to tell you that a workout you enjoy will be more productive than the "objectively" best workout you hate

  Insanity® Interval Training Protocol - A plyometric cardio circuit workout that is performed after a 9 min warum-up and followed by a 5 min stretch. It revolves around different drills (performed at progressively increasing intensity) that are separated by 30s water breaks, the drills last about 1 min each - the total length of the workout is 41 minutes and 35 seconds (click here to watch a promo video on YouTube)
• Turbo Fire® Interval Training Protocol - The HIIT 30 variety of a series of DVDs that comes from the same company that sells the P90X DVDs includes a 3 min warm-up, a 3 min cool down with stretching and slow movements to get the heart rate back to normal and a series of five drills of which the first four are repeated twice and the last one three times. Drills last about 1 min and are supposed to be performed with maximum effort each is followed by one minute of active recovery (walking, jogging in place, etc.). Water breaks are allowed during the active recovery. The total length of the workout is 30 minutes and 36 seconds (click here to watch a private workout video on YouTube).

I don't know about you, but based on the part of the videos I saw, before I felt I had seen enough, I would probably prefer the Insanity (Ins) over the Turbo Fire (TF) protocol; not so the study participants, though: After having performed both workouts in a randomized order, their "positive engagement" was slightly more pronounced after the TF protocol (see figure 2, left). It should however be mentioned that neither the the pre- to post- nor the inter-workout differences were statistically significant (with a total number of subjects of N=15, the difference could well have been 7/8, had the subjects been asked to pick one or the other).

Figure 2: Physical exhaustion, tranquility and pos. engagement after workouts (left), respiratory exchange ratio at rest and from min. 5-60 (middle), and time (in s) during the workout, when the heart rate was within the given percentages of the calculated personal HR_max(data adapted from McGlinchy. 2013)

My gut tells me that the part of the preference for the TurboFire (TF) protocol could be due to from a) the shorter overall duration and b) the greater exhaustion the subjects in experienced during the Insanity trial -I mean "insanity"? What else do you expect???

Ignore fatty acid oxidation and total calorie expenditure - pick the one you like!

The significantly less pronounced at the end of the TurboFire Intervals stand in contrast to the total the subjects were working out in the 81-90% HR_max, though. With 1000 seconds (vs. 580s) the latter was significantly longer during the Turbo Fire session. Accordingly, the subjects' respiratory exchange ratio (RER), a measure for the relation of glucose to fatty acid oxidation was significantly higher, as well.

SuppTensity Workout Perform 3 cycles of these 5 drills, each drill lasts 1 min, 45s active recovery  between drills, 2 min between cycles

• Squats*
• Push ups
• Lunges**
• Clean & press*
• Rope skipping

use adequately loaded *barbell or **dumbbell

While the former was to be expected, it may appear somewhat odd at first, though, is the higher and longer-lasting post-exercise energy expenditure in the Insanity group (p < 0.05), which could yet be explained by an overall slightly more demanding (figure 1, left > exhaustion) workout, which - and this is just based on what I saw in the videos - appears to have more "complete" drills - or did you see things like push-ups in the Turbo Fire workout? Against the background that the minimal differences in intra- and post-workout energy expenditure and substrate utilization won't have any noticeable effect on the desired outcome variable, i.e. a leaner, still muscular physique, and in view of the fact that"EPOC comprises only 6-15% of the net total oxygen cost of the exercise" (LaForgia. 2006), anyway, I would fully subscribe to Sarah McGlinchy's recommendation to simply pick the workout you like - based on McGlinchy's interpration of her subjects' feedback that would be the ...

• Turbo Fire® for people who are "looking for more variety of movements with fun music"
• Insanity® for people for whom "music isn’t a priority", but who look for "intense motivation"

Before I conclude this pretty longish and therefore single "on short notice" item with the implications and go ahead to the promised truckload of "on very short notice" items, I would yet like to add one thing to this recommendation: You don't actually need to buy a DVD to do HIIT. It's actually pretty straight forward to compile your own personal HIIT 1min on, 30s off (alternatively 1min active rest) workout by handcrafting your drills from from simple sprints on the grass or beach, intense rope skipping, push-ups, pull-ups, squats, kettlebell swings, stair climbers and everything else you can think of - if you are at a loss now, check out my botchy sample workout on the upper right - took me ~1min to put that together and I know that each one of you can do better!

Image 2: I am not saying everyone needs one of those workout DVDs, but for those of you (or friends of yours) who are not already fed up with "motivational pics + statements" like the one above, which are handed around on facebook like the WWF cards 20y ago on my schoolyard, it my be worth looking into either of these.

Implications: I don't care whether you like it or not (I don't like those workouts either), but I am 2x more inclined to believe the numerous success stories the producers of these workout DVDs use to plaster the Internet than any of the reports on how great supplement X is working for Mr. Y on bodybuilding.com and the like.

Do I suggest you buy a DVD or hop around like a jackass in the gym, let alone in front of your TV, when you prefer going to the next best park or beach doing sprints and combine those with your regular strength training program in the gym? Certainly not! Would I rather see you, your friends or family perform any of these workouts than doing exclusively strength training (let alone ultra low volume 1-rep max style) or hours of steady state aerobics if your goal is to get jacked? Abs(!)olutely ;-)

On very short notice

• 

  Image 3: Not everything that's golden is good - the "golden" raisins for example have been treated with sulfur dioxide, to prevent them from darkening. At least in susceptible persons SO2 can lead to serious allergic reactions, 4-8% of asthmatics are (also) allergic to dietary sulfites and its general safety is still a matter of constant debate - commonly associated health effects are Urticaria, angioedema, and IgE-mediated anaphylaxis (Rangan. 2009).

  Commercial carbohydrate chews not better than plain raisins - I guess this one falls into the "Olympia tribute" category, aside from Albanian weightlifters, wo obviously prefer Stanozolol, most of the athletes probably use carbohydrate supplements in one form or another. Whether anybody relies on resins as is intra-competition carbohydrate supplement is yet questionable and that despite the fact that the dried grapes can easily compete with the far more expensive Cliff blocks carbohydrate chews. Aside from nonsignificantly faster time-trial performances, the fourteen healthy competitive runners from the University of California who consumed raisins instead of chews, also felt slightly less sore after and had lower insulin levels and greater fatty acid oxidation rates during the run.
  Reason enough for Brandon W Too and his colleagues to conclude "that consuming a natural CHO source (raisins) [..] is well tolerated and maintains blood glucose levels and running performance similar to a commercial CHO product (sport chews)" (Too. 2013). Did you hear that Michael Phelps?
• Epi-sesamine from Lindera obtusiloba could be novel source for potent anti-obesity drug - This is at least what a recently published study that was conducted by scientists from the German Charité Universitätsklinikum in Berlin would suggest (Freise. 2013). In their in-vitro tests the active ingredient of the Japanese spice bush, which has traditionally been used for treatment of inflammation and the prevention of liver damage in Oriental Medicine, did not just prevent the accumulation of lipid droplets, it also activated the pro-apoptotic enzymes caspases-3/-7, which initiated programmed cell-death in the treated fat cells. In view of my recent blogpost on the nasty persistence of lower body fat, the latter could turn out to be of extreme importance - especially for those of you who have already lost a significant amount of body fat and are now suffering from "relative leptin deficiency" (see "Nasty Insights into the Yo-Yo-Effect" for more on how this relates to the YoYo-Effect and weight loss plateaus).

• 

  Figure 3: Mild exercise (5x 30 min / week, treadmill) boosts brain 5a- reductase and neurogenesis (Okamoto. 2013)

  Mild exercise and the brain: Is DHT what builds new neurons? If there was one hormone that really has gotten a bad rep over the past 50 years, it certainly is DHT: All of you who've read the respective installment of the Intermittent Thoughts (cf. "DHT - The All Things Male Hormone") or the latest news on the DHEA <> DHT muscle generation connection will be aware that the myth of the dangerous, carcinogenic bigger brother of testosterone is at least overtly simplistic if not totally devoid any scientific bases.
  Recently published data from the Laboratory of Exercise Biochemistry and Neuroendocrinology at the University of Tsukuba, in Japan does now add another piece to the "DHT is not bad" puzzle - one even women could come to appreciate (Okamoto. 2013): According to Masahiro Okamoto and colleagues, the exercise induced increase in 5-alpha reductase activity (5-ar converts testosterone to dihydrotestosterone) and the subsequent rise in neuronal DHT appears to be the driving force of neurogenesis (the generation of new neuronal networks / brain tissue and wiring).

• 

  Image 4: Those of you who have made the transition to physical culture too late or have friends or relatives who missed the boat completely may be interested to hear that researchers from the RIKEN Center for Developmental Biology successfully used stem cells to replete Purkinje neurons two years ago, already (Maguruma. 2010)

  Chronic exercise renders Purkinje neurons bullet proof - In a way unquestionably related to the previous "On Very Short Notice" item are the findings from Huang et al. have just published in Journal of Applied Physiology. In their paper the researchers describe the 8-weeks of moderate treadmill running had on the toxin resistance of 6-week old rodents. Specifically, Huang et al. observed that the "exercised rats not only performed better in the rotarod task [skilled behavior test, see video] but also showed finer Purkinje cell structure (higher dendritic volume and spine density)" (Huang. 2013). And while this is unquestionably reminiscent of the aforementioned neuron-building effects of DHT (which is, as you should know increased with aerobic / volume training; cf. "Intermittent Thoughts on DHT"), the big news is that the neurons of the exercised rodents were also protected against the immunotoxin OX7-saporin.
  If these results translate (I personally believe that this is not a question of yes or no, but only one of the extend to which these results translate) to any of the bazillion other toxins we are exposed to on a daily basis, this would imply that regular exercise may not just protect us from the "classic" neurodegenerative diseases such as Alzheimer's or Parkinson, but also from autoimmune diseases which have a neuronal component and often involve damage to the very Purkinje neurons the researchers found to be "bullet proof" in the study at hand.
• Children of diabetic parents benefit most from hitting the weights - "The offspring" of type II diabetics that's the somewhat surprising result of a 9-week training + 9-week detraining experiment Katherine Schofield and her colleagues from New Zealand and Denmark conducted respond particularly favorable to resistance training programs (Schofield. 2013). At the end of the initial 9 week training period, the insulin response of the children with diabetic parents was still worse than thatof their peers in the control group, but with improvements of roughly 30% they were already approaching what you may call the "normal zone", when the detraining phase begun. Contrary to the kids in the control group, whose insulin sensitivity did not change over the 9 weeks of laziness, the children of type II diabetics lost all their previously achieved improvements. Now, you could certainly argue how those poor kids are at such a disadvantage, but unless you want to feed them metformin for the rest of their lives, I suggest we should rather think of ways to teach them how to resist the bad eating habits of their parents and stick to a workout routine that will make the diabetes medication obsolete - don't you agree?

• 

  Suggested reads for everyone interested in some background info on nitrates: (1) Ask Dr. Andro: Is Creatine Nitrate Worth it? (2) Nitrates Work! First NO2 Victim in ER

  Nitrate supplements don't work for athletes and could mess with blood pressure regulation - At least if you are a trained athlete who wants to improve his/her performance, the use of sodium nitrate is a waste of time and money - this is at least what the soon to be published results of a randomized, double-blind cross-over study by Spanish scientists would suggest. For their experiment, Bescós et al. recruited 13 trained athletes and had them perform a 40-min ergometer distance-trial test after a 3-day supplementation regimen with either sodium nitrate (10mg/kg body weight) or placebo (Bescós. 2013).
  Contrary to earlier trials in non-trained subjects, the athletes' performance did not benefit from the supplemental nitrate - despite statistically significant increases in plasma nitrate (+17%) and nitrite (+56%), by the way. Moreover, the concommitant increase in endothelin-1, a protein that constricts blood vessels, raises blood pressure and thus counters the vasodilating effects of the nitrates raises concerns regarding potential side effects that could occur once you drop the supplement.

• 

  Image 5: Mineral supplements are usually not necessary, as long as you pick the right foods and drinks! What's much more likely in the Western hemisphere than deficiencies, though, are imbalances - and weekend warriors and gymbros are even more likely than your average obese pre-diabetic to run into oftentimes self-inflicted problems... there is going to be a Super Human University seminar Carl Lanore and I are currently working on - and let me tell you this, this is a topic that is literally very dear to Carl's heart.

  Decrease your risk of heart disease by 5% with each mg/L of Magnesium in your drinking water! - I am certainly not among the magnesium enthusiast who propose supplementation with whichever form of oral mg supplement (let alone the scientifically hitherto not verified use of oils) as the latest panacea, but as you may have heard on Super Human Radio on Wednesday, July 25, 2013 (click here for the podcast), I do believe in the overlooked importance of getting your ratios straight; and that, i.e. having the right ratio of Ca:Mg begins at the most fundamental level - with the mineral ratios in your drinking water! Finish scientists who recorded the mineral intake of 14,495 male subjects (aged 35-74), for example, found that with a constant and roughly two times too high mean Ca / Mg ratio of 5.39 / 1 in the drinking water of the area, every additional milligram of magnesium per liter drinking water (e.g. from 2.61mg/L to 3.61mg/L), would help to reduce the risk of acute myocardial infarction by 4.9% (Kousa. 2006)!
  This is an impressive figure and yet, the real beauty of this study is that it emphasizes the need to re-evaluate your nutritional mineral intake, instead / before considering using dietary (let alone oily ;-) supplements!

References:

• Bescós R, Ferrer-Roca V, Galilea PA, Roig A, Drobnic F, Sureda A, Martorell M, Cordova A, Tur JA, Pons A. Sodium Nitrate Supplementation Does Not Enhance Performance of Endurance Athletes. Med Sci Sports Exerc. 2013 Jul 17.
• Freise C, Trowitzsch-Kienast W, Erben U, Seehofer D, Kim KY, Zeitz M, Ruehl M, Somasundaram R. (+)-Episesamin inhibits adipogenesis and exerts anti-inflammatory effects in 3T3-L1 (pre)adipocytes by sustained Wnt signaling, down-regulation of PPARγ and induction of iNOS. J Nutr Biochem. 2013 Jul 18.
• Huang TY, Lin LS, Cho KC, Chen SJ, Kuo YM, Yu L, Wu FS, Chuang JI, Chen HI, Jen CJ. Chronic treadmill exercise in rats delicately alters the Purkinje cell structure to improve motor performance and toxin-resistance in the cerebellum. J Appl Physiol. 2013 Jul 26.
• Kousa A, Havulinna AS, Moltchanova E, Taskinen O, Nikkarinen M, Eriksson J, Karvonen M. Calcium:magnesium ratio in local groundwater and incidence of acute myocardial infarction among males in rural Finland. Environ Health Perspect. 2006 May;114(5):730-4.
• LaForgia J, Withers RT, Gore CJ. Effects of exercise intensity and duration on the excess post-exercise oxygen consumption. J Sports Sci. 2006 Dec;24(12):1247-64.
• Muguruma K, Nishiyama A, Ono Y, Miyawaki H, Mizuhara E, Hori S, Kakizuka A, Obata K, Yanagawa Y, Hirano T, Sasai Y. Ontogeny-recapitulating generation and tissue integration of ES cell-derived Purkinje cells. Nat Neurosci. 2010 Oct;13(10):1171-80.
• McGlinchy SA. The Effect of Two High Intensity Interval Training Protocols on Heart Rate, Caloric Expenditure, and Substrate Utilization During Exercise and Recovery. University of Toledo - Submitted to the Graduate Faculty as partial fulfillment of the requirements for The Master of Science Degree in Exercise Science. 2013.
• Okamoto M, Hojo Y, Inoue K, Matsui T, Kawato S, McEwen BS, Soya H. Mild exercise increases dihydrotestosterone in hippocampus providing evidence for androgenic mediation of neurogenesis. Proc Natl Acad Sci U S A. 2013 Jul 17.
• Schofield KL, Rehrer NJ, Perry TL, Ross A, Andersen JL, Osborne H. Insulin and Fiber Type in Offspring of T2DM with Resistance Training and Detraining. Med Sci Sports Exerc. 2013 Jul 17.
• Rangan C, Barceloux DG. Food additives and sensitivities. Dis Mon. 2009 May;55(5):292-311.
• Too BW, Cicai S, Hockett KR, Applegate E, Davis BA, Casazza GA. Natural versus Commercial Carbohydrate Supplementation and Endurance Running Performance. J Int Soc Sports Nutr. 2013 Jun 15;9(1):27.