Eight HIIT Sessions on the Rowing Ergometer Cut Body Fat, Increase Adiponectin, VO2Max & Performance in National Level Rowers - Workmatched Classic "Cardio" Does Nothing

If you have hitherto ignored my previous advice (e.g. "Choosing Your Workout Style") to give the rowing machines a try, maybe the study at hand will rise your interest. Give it a try. It's an awesome whole body workout and highly effective, even if you just do 20min of steady state after lifting weights.

Yesterday you've learned that even the most idio... ah, I mean unconventional - not to say "experimental" in the literal sense - one-legged leg training routine is more likely to get you those six-pack abs, of which everyone appears to believe that it was a natural sign of outstanding health and a thing everybody must have (just like the new iPhone, you know ;-), than a bazillion of sit-ups. Today, you will see that a somewhat less "experimental" training regimen will not have you reach your goal faster and more efficiently, it will also have the welcome "side effect" of making you healthier and improving your conditioning. And you know what's the best about all that? It does not only work for sedentary baby-boomer, but also for highly trained athletes. 5 male and 2 female19(± 1.2)-year-old junior state and national level rowers from the Tasmanian Rowing Team (height: 1.77 ± 0.10 m, body mass: 74.0 ± 10.7 kg, body fat: 17.1%, VO2max 62.1 ± 7.0 mL·kg/min), to be precise (Shing. 2013).

Healthier, leaner, fitter - that's a HITTer ;-)

To evaluate the influence of two different training regimen, namely the traditional steady training (SST/LISS) on a rowing ergometer (a piece of equipment of which the regulars among you already know that I highly suggest you incorporate it into whatever cardio routine you may be doing), or a high intensity interval training (HIIT) variety of the latter the researchers from the School of Human Life Sciences at the University of Tasmania in Launceston, Australia put their participants, the aforementioned young national rowers, on two different workout protocols with matched cumulative energy expenditures (my emphases in Shing. 2013):

• SST: "The traditional training program involved rowers completing two ergometer sessions per week; one with a duration of 35 minutes and the other 40 minutes. [...] The intensity of each session
  was relatively low and more aerobic in nature when compared to the interval training protocol. The intensity of the traditional ergometer sessions was set to power outputs that corresponded to blood lactate concentrations of 2 and 3 mmol/l determined from the incremental exercise test."
• HIIT: "The interval training sessions consisted of eight 2.5 minute intervals at 90% of mean four-minute maximal power achieved during the incremental exercise test. Recovery between each interval was at an intensity of 40% of mean four-minute maximal power and the recovery duration was until heart rate returned to 70% of maximum heart rate, up to a maximum of five minutes."

The 2x four week experimental period (remember: we are dealing with a cross-over design, where all subjects participate in both protocols in random order) involved the incorporation of two ergometer sessions per week. Since all participants were part of the same squad the rest of their training regimen was identical, so that confounding factors - at least as far as the training is concerned - can be ruled out.

Body composition and adiponectin took a HIIT - a highly beneficial one that is ;-)

Performance tests were done and body fat mass (DXA), as well as a general blood profile and adiponectin values were taken at baseline and the end of both 4-week periods. Moreover, all participants had to keep a detailed training and diet log, so that the scientists could make absolutely sure that non of the effects they observed were due to unexpected changes in either activity levels or dietary habits.

Any potential influence of the randomized order, i.e. whether the rowers performed the classic training first and the HIIT sessions 2nd or vice versa was ruled out by statistical means before the scientists eventually analyzed their data sets and got the following results:

Figure 1: adiponectin levels before (pre) and after the respective workout at the beginning and end of the respective 4-week training period and body fat levels before and after 4 weeks of steady state (SST) or high intensity interval training (HIIT) in national level rowers (Shing. 2013)

I must admit, the changes are not earth-shattering, but there are changes - beneficial ones that is  - and they are statistically significant despite the small number of participants, and the fact that the subjects were already highly trained individuals and - I figure this may be the most convincing argument not to discard this effects - participated in no more than a total of only 8 HIIT sessions.

Bottom line: I guess, you could certainly argue that the novelty of the training stimulus was part of the reason, the HIIT regimen had so beneficial effects on the fitness, body composition and even the adiponectin levels of these already highly trained rowers (Adiponectin? That's the "new leptin", which promotes insulin sensitivity and exerts profound anti-inflammatory effects); but does this take away from the efficacy of this 4x2.5 min @90% max. + 5min active rest high intensity interval training regimen? I don't think so.

Click here to learn more about the "Iranian HIIT Solution" a minimalist program with maximal results

There is nonetheless one thing I want to add before I close the SuppVersity doors for today. The 4x2.5 minute protocol is certainly appropriate for trained athletes; in fact, previous studies even suggest that it requires those long(er) intervals in order to elicit gains in VO2max in highly trained (endurance) athletes (e.g. Franch. 1998; Laursen. 2002). The initially mentioned sedentary baby-boomer - obese or not - may however be better off, if they follows a different regimen, such as the one I outlined in the "Iranian HIIT Solution" (see image on the right) and incorporate that in a three-day split (e.g. A, B, hypertrophy, C strength) or a two-day full body circuit training.

The main message here is that starting out "low" (in terms of both volume and intensity) is not just possible, it's even advisable, so that there is still enough room to do more, and/or preferably up the intensity. I know I have been telling you that before, but I feel it's worth stating again: Real cardio training, i.e. the type of training that strengthens the cardiovascular system is progressive. If you do the same thing day in and day out the best you can hope for is to keep the status quo. Remember that before you start out way too high (esp. on the volume side of things) and either bunk directly, or end up without any room to make progress.

References:

• Franch J, Madsen K, Djurhuus MS, et al. Improved running economy following intensified training correlates with re-duced ventilatory demands. Med Sci Sports Exerc 1998; 30: 1250-6.
• Laursen PB, Jenkins DG. The scientific basis for high-intensity interval training: optimising training programmes and maximising performance in highly trained endurance athletes. Sports Med. 2002;32(1):53-73.
• Shing CM, Webb JJ, Driller MW, Williams AD, Fell JW. Circulating Adiponectin Concentration AND BODY composition ARE Altered in Response to High-Intensity Interval Training. J Strength Cond Res. 2013 Dec 4.

Chromium Picolinate Worsens Insulin Sensitivity in Healthy, Non-Diabetic, Non-Obese Individuals by Up to 25%

The more supplements you take the more likely you are to get way more than the 200mcg of chromium of which previous studies have shown that they are useless for healthy people, but at least not detrimental (cf. Lukaski 1996 & 2007; Vincent. 2007). Especially people who like the  'poly-supplementary' approach are yet at risk of getting so much of a this trace mineral that it will hamper not improve their insulin sensitivity.

I don't have to tell you that you would already be dead if you were following all the bro-scientific advice that's out there on the Internet and still I usually recognize a certain reluctance to give up on what X suggests and Y has tried an what has worked so well for Z. One of the instances, where I have hitherto been missing a 100% convincing argument to argue that this is just another instance where common wisdom would in fact be better called "common stupidity" is the "insulin mimetic" or "insulin sensitizer" (or whatever your favorite bro-expert may call it) chromium picolinate. With the recent publication of the result of a study on the effects of chromium supplementation in healthy individuals there is now finally a human study that confirms that chromium, which has never been an "insulin sensitizer", but rather an "insulin release amplifier" that reduced blood glucose in diabetics by simply having them produce even more insulin is not a supplement any healthy man or woman, let alone athlete should consider a staple of his or her regimen.

The long and short: Chromium hampers insulin sensitivity in normoglycemic individuals

For their experiment lead author Umesh Masharani and his colleagues from the UCSA recruited a group of 27 non-obese, non-diabetic, healthy subjects between the ages of 20 and 50 with a body mass index of less than 27 kg/m² and <24 kg/m² for subjects with Asian heritage (the cut-off limits were set so that they would be below a BMI that has not yet been shown to be an independent risk factor for insulin resistance; cf. Clausen. 1996; Newell-Morris. 1998).

To evaluate whether chromium picolinate (ChrPic) supplements, which contributed with $150,000,000 to the revenue of the supplement industry in 1996 (Nielsen. 1996), could come up to the claims that they would exert beneficial effects on glucose tolerance and insulin sensitivity, the study participants were randomized to take either a placebo or a high dose 500µg CrPic supplement twice daily for 4 months (the dosage was selected in view of previews studies reporting greater benefits of 1,000 vs. 200mcg of CrPic in - you already guessed it - diabetic subjects; cf. Morris. 2000).

Figure 1: Insulin sensitivity measured by euglycemic clamp before and after the 16 week intervention (left); change in insulin sensitivity of the individual subjects plotted against serum chromium levels at the end of the study (Masharani. 2013)

As the data in figure 1 goes to show, the results of the CrPic intervention were more or less the exact opposite of what the ~10 million US consumers of respective supplements probably expect from the pills many of them are taking almost religiously. Despite the fact that all subjects had very low chromium levels at the beginning of the study, the previously non-significant minimally benificial relation between both serum and urinary chromium, on the one hand, and insulin sensitivity (r = 0.24, p=0.1; r=0.08, p=0.79 respectively), on the other hand, had turned into a very significant negative correlation between high(er) urinary and serum chromium concentrations and lower insulin sensitivity at the end of the 16 week intervention period (figure 1, right).

"Due to the apparent variation in the degree of chromium absorption between subjects, we examined the relationship between serum chromium and change in insulin resistance. After controlling for baseline patient characteristics, results of a multiple regression analysis showed a strong association between serum chromium and worsening of insulin–mediated glucose disposal (β= -0.83, p<0.01), where subjects with the highest serum chromium had a decline in their insulin sensitivity. To further explore the association between chromium absorption and insulin resistance, patients within the chromium group were divided (based on  a medial split at 3.10 µg/L) into a high (n=6) and low (n=8) serum chromium group [...] There were no group differences at baseline; however, at post-assessment participants in the high serum chromium group (> 3.1  µg/L) were more insulin resistant than participants in the low serum chromium group (≤3.1  µg/L) or the placebo group (p=0.02, p=0.05 respectively) (Figure 3)." (my emphases in Masharani. 2013)

Due to the fact that the scientists did not observe any differences between the placebo and low serum  chromium groups (on a side note, contrary to many other studies insulin Masharani et al. measured the insulin sensitivity in a very reliable way with an euglycemic hyperinsulinemic clamp; cf. Defronzo. 1979), the scientists also conducted a post-hoc analysis to identify potential confounding factors that may have influenced the outcome of the trial. Neither changes in triglycerides levels LDL, BMI, or truncal fat were yet associated with the differences they observed between the supplemented and non-supplemented participants. Interactions that would reduce the significance of the observed correlations were likewise absent:

"Furthermore, when changes in triglycerides, LDL, BMI, and truncal fat were individually added to the model, none were independent significant predictors of change in insulin sensitivity, and chromium absorption remained a significant predictor of reduced insulin sensitivity in each model." (Masharani. 2013)

Against that background the scientists conclude that there must be a "direct effect of chromium on changes in insulin action". A mechanism, by the way, which is totally independent of classic markers of insulin resistance such as high serum lipids and abdominal / truncal adiposity .

Being healthy is a good predictor of increased chromium absorption and more pronounced negative effects, so if you are healthy and want to stay this way don't even think of taking high dose chromium supplements.

Despite the fact that the changes in insulin resistance did not depend on changes in serum lipids and other markers of metabolic health, Masharani and his colleagues were able to show that the increase in chromium levels in response to supplementation did. With the already mentioned statistically significant correlation between increases in serum chromium levels (higher response to supplementation = higher increase), on the one hand, and the worsening of insulin sensitivity, on the other hand, this means that the healthiest subjects, namely ...

"[...] subjects with lower triglycerides, and those with lower levels of homocysteine [who had] a greater likelihood of being in the high absorption group" (Masharani. 2013)

... were at the same time those who were at the greatest risk of the ill side-effects high dose chromium supplements exert on the insulin tolerance of healthy, non-diabetic, normal-weight individuals.

No matter if it may have helped you produce insulin back in your obese days, once you have accomplished this you better avoid high dose or multiple (hidden) sources of supplemental chromium like a plague - unless you can't afford new jeans, of course ;-)

Bottom line: Unless you are not a type II diabetic or feel the urgent desire to become one, you better steer clear of exuberant amounts of supplemental chromium the RDA is enough. This is particularly true, if you are already taking a multi (which is almost guaranteed to have 200mcg in it), or any BB-style supplements. After all, "broscience" wants it that chromium is in everything that's even remotely related to insulin / nutrient uptake or whatever. With the use of only one of these products and 200mcg of supplemental dietary chromium per day, you may still argue that it probably won't do much harm. When you add another 200mcg from your "nutrient partitioner" on top of the 200mcg you get from your multi and the 200mcg of which you probably did not even realize yet that they are part of your pre-workout supplement, however, you can hardly complain about simply not being able to tolerate carbohydrates - I mean, what's your body supposed to do if you are dumb enough to believe in the promises of fat loss and lean mass increases that have been debunked in the late 1990s, already (cf. Lukaski 1996 & 2007; Vincent. 2007), and simply chose to ignore the latest scientific evidence that chromium picolinate supplements are not just useless, but actually detrimental to your health?


References:

• Clausen JO, Borch-Johnsen K, Ibsen H, Bergman RN, Hougaard P, Winther K, Pedersen O. Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of  the impact of gender, body fat, physical fitness, and life-style factors.  J Clin Invest. 1996;  98(5):1195– 1209.
• Defronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979; 237:E214–E223. 
• Lukaski HC, Bolonchuk WW, Siders WA, Milne DB. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr. 1996 Jun;63(6):954-65.
• Lukaski HC, Siders WA, Penland JG.  Chromium picolinate supplementation in women: effects on body weight, composition, and iron status. Nutrition. 2007; 23(3):187– 195.
• Masharani U, Gjerde C, McCoy S, Maddux BA, Hessler D, Goldfine ID, Youngren JF. Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity. BMC Endocr Disord. 2013 Nov 30;12(1):31.
• Morris BW, Kouta S, Robinson R, MacNeil S, Heller S. Chromium supplementation improves insulin resistance in patients with Type 2 diabetes mellitus.  DiabetMed. 2000; 17(9):684–685.
• Newell-Morris LL, Treder RP, Shuman WP, Fujimoto WY. Fatness, fat distribution, and glucose tolerance in second-generation Japanese-American (Nisei) men. Am J Clin Nutr. 1989; 50(1):9–18.
• Nielsen FH. Controversial Chromium: Does the superstar minearal of the mountebanks receive appropriate attention from clinicians and nutritionists?  Nutr Today. 1996; 31(6):226–233.
• Vincent JB: The nutritional biochemistry of chromium (III). Amsterdam, Boston: Elsevier. 2007.

Stevia - More Than Super Sweet: More Scientific Evidence, More Potential Implications for Weight Loss & -Maintenance, Anti-Diabetic & -Autoimmune and Even Pro-Anabolic Effects

Image 1: Stevia is sweeter than sugar, healthier than sugar and could even help reverse some of the damage sugar may already have done to your pancreas.

I know that a few of you were almost furious, when I had the audacity to mention the case-report on the pro-cortisol effects of stevia in the On Short Notice post on Saturday, August 18, 2013; and though I did emphasize that this was most likely something like an allergic reaction and/or an issue with solvents, heavy metals (click here for data on heavy metals in stevia leaves; based on Das. 2013), or whatever else may have been in the specific stevia product the lady used; I suspect that you will like today's blogpost which is basically an update on the beneficial effects stevia could have on your overall and metabolic health, much better.

So what's the latest about stevia, then?

Previous studies have already hinted at the fact that the benefits of the use of stevia go well beyond a mere reduction in energy intake and the overall glucose load the average sweet tooth is exposing her- / himself to. Against that background, the results of a recent publication from the School of Pharmacy in Madhya  Pradesh in India are actually not really surprising.

Figure 1: Blood glucose response (mg/ml) to oral glucose load (left) and superoxide dismutase (SOD) levels in mice treated with 250mg/kg (HED: 20mg/kg; ~1.4-2.0g) stevia extract/day (right; data based on Sharma. 2013)

With most previous studies being conducted on isolated pancreatic islet cells in the petri dish, this is however one of the few studies, which in which the scientists were able to observe a robust in-vivo effect from the administration of no more than 250mg/kg of stevia extract (Herbocal) to alloxan-diabetic (this is a model of type II diabetes that is induced by the injection of the drug Alloxan aka 2,4,5,6-pyrimidinetetrone, an oxygenated pyrimidine derivative) and healthy rodents for 28days - with benefits for both, the sick (normalization of blood glucose and restoration of endogenous antioxidants) and the healthy animals (no drop of blood glucose to hypoglycemic levels and increases in SOD above baseline!)

Could stevia not just ameliorate, but actually "heal" diabetes?

Figure 2: It takes it's time but stevia appears to (fully?) restore pancreatic function!

What's also intriguing are the time-course and general trend of the beneficial effects on blood glucose levels in the diabetic group. If you take a closer look at the data in figure 2 you could even speculate that another four weeks later the blood glucose levels would have totally normalized! And if that were the case, this would mean that the steviosides and rebaudiosides, the active molecules in stevia extracts, could actually have the ability to restore or repair the pancreatic beta cells that have been destroyed by either years of high blood glucose (normal type II diabetics) or the assault of the toxic sugar equivalent alloxan (in the study at hand). and protect healthy individuals against future damage by increasing the endogenous antioxidant system (as can be seen by the allegedly non-significant, but probably still physiologically relevant increase in SOD in figure 1, right)

"But this won't work in humans, will it?"

The above is certainly a good question, but in view of the fact that the short term benefits (e.g. +40% increase in insulin response in type II diabetic with -18% reduced postprandial glucose AUV with 1g of stevia in Gregersen et al. 2004), of which the Hermansen group at the Aarhus University Hospital in Aarhus, Denmark, argues that they are based on the interaction of rebaudioside A (cf. table 1) with the ATP-sensitive K-channels of the pancreatic cells in healthy and its glucagon (and thus gluconeogenesis) inihibiting effects in diabetic individual (Abdula 2004 & 2008; Jeppesen. 2007), have already been reproduced in human trials, I would say that it is more than likely that we will see similar effects in humans, as well, once the correct dosing has been established

Note: especially if you use those combination products of stevia + sugar alcohol you are very unlikely to get sufficient amounts of stevia to elicit those restorative effects; this does not mean that this is a better alternative than aspartame or cyclamate, but in those tiny amounts stevia is a sweetener, not a substance with almost drug-like effects.

Table 1: What's in stevia leaves?
(based on Yadav. 2013)

The latter is by the way all the more likely in view of the fact that Maryam Mohammadi-Sichani and her colleagues from the Falavarjan Branch-Islamic Azad University and the Esfahan University of Medical Sciences in Iran found that stevia extracts will also kill S. mutans, a common bacteria in your mouth that has its share in the development of dental caries and shows, irrespective of generally lower caries rates in type I diabetics, a hitherto not fully explained correlation with (poorly controlled) type I diabetes (Siudikiene. 2006).

Your gut starts in your mouth: The stevia - bacteria connection

These observations stand in line with previous results, of a whole host of peer-reviewed studies Yadav & Guleria summarize in a 2013 review that's about to be published in the November edition of Critical Revision of Food Science, as follows :

Image 2 (20th Century Fox): You better feed your gut bacteria right, otherwise they will disbehave just like the Alien in Ellen Ripley in Alien 3  - read more about the "Gut Type Diet" and how what you eat influences the bacterial composition of your gut on the SuppVersity

"[...] Different extracts showed differential inhibitory activity against various microbes. This experimentation confirmed the antibacterial as well as antifungal potential of Stevia leaf extract and documented that Stevia might be a source of new non-antibiotic antibacterial and antifungal agent. Its antifungal activity was estimated to be higher than the standard fungicide usually used against plant pathogens. Such extraordinary antimicrobial activity of Stevia has presented it as a potent non-antibiotic pharmaceutical and an efficient food preservative. Stevioside alone has been observed to significantly reduce the amount of inflammation mediators and activate cytotoxic cells of the host. These activities suggested that stevioside might play a synergistic role with the innate immunity of the host. Thus stevioside is antibacterial, antifungal, anti-inflammatory, anti-tumorous, and safe for use. While at the same time rebaudioside A has been reported to be clinically insignificant." (Yadav. 2013; my emphases)

In other words, stevia could exert part of it's beneficial effects via the immune-modulatory effects it exerts due to it's impact on the human gut microbiome, the contribution of which to the etiology of both diet-induced type II, but also auto-immune type I diabetes is getting more and more attention among researchers, as of late:

"[...] the autoimmune microbiome for T1D may be distinctly different from that found in healthy children. These data also suggest bacterial markers for the early diagnosis of T1D. In addition, bacteria that negatively correlated with the autoimmune state may prove to be useful in the prevention of autoimmunity development in high-risk children." (Giongo. 2011; my emphases)

And even if the whole "bacteria theory" of autoimmune disease and inflammation turns out to be yet another sidetrack - you will always have the

• beneficial effects on skeletal muscle insulin sensitivity and glucose uptake that has been established by Lailerd et al. in insulin sensitive and resistant mice and the 
• hopefully physiologically relevant increase in satellite cell activity, Bunprajun et al. observed earlier this year in response to lower NF kappa-beta activity (=modulation of inflammation) in an in-vitro model (Lailerd. 2004; Bunprajun. 2013) 

as additional* arguments to satisfy your sweet tooth with stevia instead of sugar or artificial alternatives (*in addition to being able to avoid the "alternatives").

And as long as you keep an eye on the overall amount of food you consume, instead of simply stuffing yourself until you feel like there was no tomorrow, the previously discussed effects any sweetener - natural, artificial, or whatever else the future may hold - could have on your ability to sense the energy density of your foods should not be all too much of a problem problem (cf. "Sweeter Than Your Tongue Allows").

References:

• Abudula R, Jeppesen PB, Rolfsen SE, Xiao J, Hermansen K. Rebaudioside A potently stimulates insulin secretion from isolated mouse islets: studies on the dose-, glucose-, and calcium-dependency. Metabolism. 2004 Oct;53(10):1378-81.
• Abudula R, Matchkov VV, Jeppesen PB, Nilsson H, Aalkjaer C, Hermansen K. Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels. Diabetes Obes Metab. 2008 Nov;10(11):1074-85. Epub 2008 Apr 22.
• Das, K., R. Dang, L. Hegde and A.S. Tripathi. Assessment of heavy metals in dried stevia leaves by Atomic Absorption Spectrophotometer grown under various soil conditions. Middle–East J. Sci. Res. 2011; 8: 107-113.
• Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, Drew JC, Ilonen J, Knip M, Hyöty H, Veijola R, Simell T, Simell O, Neu J, Wasserfall CH, Schatz D, Atkinson MA, Triplett EW. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 2011 Jan;5(1):82-91.
• Gregersen S, Jeppesen PB, Holst JJ, Hermansen K. Antihyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism. 2004 Jan;53(1):73-6.
• Jeppesen PB, Dyrskog SE, Agger A, Gregersen S, Colombo M, Xiao J, Hermansen K. Can stevioside in combination with a soy-based dietary supplement be a new useful treatment of type 2 diabetes? An in vivo study in the diabetic goto-kakizaki rat. Rev Diabet Stud. 2006 Winter;3(4):189-99. Epub 2007 Feb 10.
• Sharma R, Yadav R, Manivannan E. Study of effect of Stevia rebaudiana bertoni on oxidative stress in type-2 diabetic rat models Biomedicine & Aging Pathology. 2013 August 28.
• Siudikiene J, Machiulskiene V, Nyvad B, Tenovuo J, Nedzelskiene I. Dental caries and salivary status in children with type 1 diabetes mellitus, related to the metabolic control of the disease. Eur J Oral Sci. 2006 Feb;114(1):8-14.
• Yadav SK, Guleria P. Steviol Glycosides from Stevia: Biosynthesis Pathway Review and their Application in Foods and Medicine. Crit Rev Food Sci Nutr. 2013 Nov;52(11):988-98. 

The Iranian HIIT Solution: Three 200m Sprint Sessions per Week Double Insulin Sensitivity & Normalize Leptin Levels

Image 1 (iransportspress): Maryam Tousi Iran's first female Iranian athlete to compete in the IAAF World Championships in South Korea in 2011 was certainly not one of the 30 overweight study participants.

You will certainly remember the HIIT training video study, I mentioned in last Saturday's installment of the On Short Notice series, right (cf. "Insanity vs. TurboFire")? Now, despite the fact that at least some women seem to prefer hopping around like crazy with a bunch of other crazy "bunnies" in a gym and I will always stick to the recommendation that you will have to pick a type of exercise you actually enjoy doing in order not to fall off the wagon, when the initial success begins to slow down, a recently published study from the Islamic Azad University in Tehran, Iran, clearly suggest that "cheerleading" is not the only way and probably not even the most effective way to HIIT your metabolic syndrome with full intensity.

The Iranian success formula: 12 weeks, constant progression, 1,600 - 3,200m, thrice weekly

Sohaily Shahram and her colleagues from the Department of Physical Education and Sport Science at the University of Teheran handpicked  30 female overweight volunteer students from the university campus, who did not have any confounding health issues aside from their weight and ensuing metabolic problems and randomly assigned 15 of them to the HIIT exercise group.

Figure 1: Outline of progressive HIIT protocol that was used in the Shahram study (based on Shahram. 2013)

While the subjects in the control group did do nothing but continue on their regular, lazy lifestyle, the young women in the HIIT group performed the above HIIT sprint workout (cf figure 1) three times per week, with a work to rest ratio of 1:3 and a 10min warm-up (incl. light stretching) + 5 min cool down.

Would you really prefer taking medication and keeping your insulin sensitivity from further deteriorating over 21-42min of sprinting per week to increase your insulin sensitivity by 100%?

If we assume for simplicity that the women needed ~45s for the 200m (average for 8th graders is ~25-27s, but we don't want rise the bar too high, do we ;-) this would yield a total workout time (including warm up and cool-down) of 39-63min, increasing from week 1 to week 12, respectively.

Figure 2: BMI, body fat percentage, VO2Max (marker for cardiorespiratory fitness), insulin, glucose and leptin levels, as well as insulin resistance index  (calculated via HOMA model) after 12-weeks on the HIIT protocol from figure 1; data expressed relative to baseline (calculated based on Sharam. 2013)

If you take a look at the results in figure 2, you will obviously see right away that those two to three hours on the track per week had an immensely beneficial effect on the overall metabolic health of the subjects, who were, just as their sedentary peers advised to follow their "regular eating habits" over the course of the 12-week intervention.

Obesity and the Westernization of the East

Image 2: According to Esteghamati et al. the risk to become obese has increased from 13.6% to 22.3% for normal weight and from 32.2% to 36.3% from 1999 - 2007, alone (Esteghamati.2010). Yet despite the rise in overall and childhood obesity, Iran is still the country with the slimmest children (14%) in the Middle East, where Bahrain is the inglorious  leader with childhood obesity rates of 35% among the girls and 21% among the boys (Mirmiran. 2010)

Against that background it is not unusual and by no means lamentable that their weight stabilized (which probably is what not so educated physical culturists as you are would immediately have complained about). Rather than making a fuss about the minor loss of body weight (-2.29kg on average), the women should rather celebrate that they lost a total of 2% body fat (equiv. to a -9% reduction in body fat percentage, see figure 2) and primed their bodies to actually be able and willing to lose fat in the future by

• improving their aerobic workout capacity by 26% and thus lying the foundation for more intense fat loss workouts on a future diet
• improving their glucose metabolism and reducing their insulin resistance by >50% and thus being able to fuel their future workouts with the necessary amount of carbohydrates without totally negating their weight loss efforts while dieting

The one thing that would be missing now was a ~20% reduction in caloric intake and a switch away from energetically dense convenient and fast food, which has lead to a drastic incline in obesity in Iran over the last two decades (see caption of image 2) and towards a healthier more "oriental diet". The latter is, just like the infamous "Mediterranean diet", which has countless times being mislabeled as a "low fat diet", particularly rich in MUFAs (oils with 70%+ MUFA content: olive oil, macadamia oil, avocado oil) - and as you are going to learn in tomorrow's installment of On Short Notice these monounsaturated fatty acids have only recently been shown to be just as, if not more effective in keeping diet induced weight gain in check via their epigenetic effects on the expression of the growth hormone stimulating "hunger hormone" ghrelin as fish oils (Saidpour. 2013).

A word of caution The 16 x 200m variety of these HIIT workouts is nothing you'd perform after a strength workout. These workouts are about as taxing a leg workout and will require their own training day. If your current routine has three ore more strength days, don't do more than one of the long HIIT workouts per week. Depending on your goals you can incorporate max. 8x200m sprints after shorter workouts, or do HIIT (8x200m) in the AM and weights in the PM. Check out the Step By Step to Your Own Workout Guide to learn how set up your own workout routine and how to combine weights, HIIT & LISS.

Implications: Aside from the protocol, itself, which is unquestionably equally (I'd say even more) suitable for advanced trainees (women and men), the Shahram study has two major take home messages:

• Change and challenge have more in common than the initial three letters - If you don't challenge your body you cannot expect change to happen; just like your muscles won't grow if you always train with the same weight, HIIT workouts at least when are they supposed to increase your cardiorespiratory fitness need progression (the HRMax programing will automatize that, as you will simply have to work out harder to get your heart rate up, when your fitness has improved)
• Workouts prime your metabolism for fat loss, diets pull the trigger - If you have been lying on the couch for the last two or three years, your body will change even without any dietary intervention, but to really transform your physique you must make appropriate changes to your diet.

I guess, you could say that it's funny how many scientists (and certain science writers), usually with a bias to one or the other, still propagate that diet and exercise would be different means to one and the same end, if their messages would not lead millions of "dieters" and "1h-per-day-on-the-treadmill-walkers" into disaster ... you see, on their own, both can in fact become means to the same disastrous end.

Image 3: Leave the cheerleading to the boys, ladies and HIIT it hard! Fast paced and glycolytic sports will reduce / minimize your need to "diet" and help to avoid the dreaded YoYo Effect

Can you lose weight by simply eating less? Yes, you can. Can you lose weight by working out like a mad(wo-)man? Yes you can! ... but did you even notice that the word "lose" was in each of this questions? You don't want to join the Biggest Losers, do you? So lets start with a better question, then!

Can you improve your health, extend your life and look like a cover model? Yes, you can! All you got to do is build your success on both, not just one pillar of physical culture: Diet and exercise, exercise and diet!

So what are you waiting for? All you'll need is your daily dose of SuppVersity news and a pair of running shoes!

And eventually, even the shoes are obsolete. If you sprint on the beach you will get a greater training effect, anyways: Binnie et al. report 4% faster 3-km running times, when subjects performed their conditioning workouts on the beach (Binnie. 2013)

References:

• Binnie MJ, Peeling P, Pinnington H, Landers G, Dawson B. Effect of training surface on acute physiological responses following interval training. J Strength Cond Res. 2013 Jun 26.
• Esteghamati A, Khalilzadeh O, Mohammad K, Meysamie A, Rashidi A, Kamgar M, Abbasi M, Asgari F, Haghazali M. Metabolic Syndrome and Related Disorders. June 2010, 8(3): 209-213. 
• Mirmiran P, Sherafat-Kazemzadeh R, Jalali-Farahani S, Azizi F. Childhood obesity in the Middle East: a review. East Mediterr Health J. 2010 Sep;16(9):1009-17. Review. 
• Saidpour A, Kimiagar M, Zahediasl S, Ghasemi A, Vafa M, Abadi A, Daneshpour M, Zarkesh M. The modifying effects of fish oil on fasting ghrelin mRNA expression in weaned rats. Gene. 2013 Jul 25.
• Shahram S, Elham Y, Heshmatolah P, Abdolali Baneifar. The effect of intermittent aerobic exercise on serum leptin and insulin resistance index in overweight female students.Annals of Biological Research, 2013, 3 (6):2636-2641

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.

Tauroursodeoxycholic Acid (TUDCA) - Research Overview: Newly Appreciated Liver Protectant, Potential Antidiabetic, Thyroid Booster and a Heart- and Neuroprotective Agent!?

Image 1: If you decide to start your own TUDCA import/export company, make sure you get your supply from chemical sources in the Far East and not from a bear farm like this in the northern province of Quang Ninh, Vietnam, where bear bile is "harvested" and sold to tourists for $500+/20cc (TalkVietnam. 2013)

Last week's "On Very Short Notice" item on the ability of TUDCA, i.e. tauroursodeoxycholic acid to stimulate the conversion of the "inactive" thyroid hormone T4 to its active counterpart T3 has caused quite a stir and instigated questions related to appropriate dosages and other potential benefits of a previously largely overlooked bile acid. With the recent interest from "using" muscle heads looking to protect their liver and overall health, however, the demand for TUDCA appears to be so high that whichever source Nutraplanet, the only major retailer I know of that has been selling bulk TUDCA at a reasonable price, must have gotten overwhelmed. This and Fatfree's personal request are reason enough for me to compile a brief write-up that may provide you with some clues on whether or not it may be worth to look for alternative sources on the web or even start your own little TUDCA import/export business.

What is tauroursodeoxycholic acid aka TUDCA ?

Tauroursodeoxycholic acid is a bile acid also known as TUDCA formed in the liver by conjugation of deoxycholate with taurine, usually as the sodium salt. While Western medicine has only gotten wind of the anti-apoptotic effects and its ability to protect mitochondria from cellular elements that would otherwise interfere with energy production within the past 20 years, or so, bear bile - you guessed it, a natural source of TUDCA - has an over 3,000 yearlong history of being used to treat visual disorders (Boatright. 2006), if which we know today that many of them can be treated and prevented by the administration of TUDCA and other bile-acids or bile-acid precursors, such as taurine (click here to read all about taurine).

So what's the suggested dose? That's actually quite a tricky question, because the number of human studies can be counted on the fingers of one hand (and this is still an exaggeration) and the available rodent data is mostly based on studies where the TUDCA was injected into the peritoneal cavity, which - depending on the compound that is used - will usually yield a bioavailabilty that's higher than what you will see with oral ingestion of the compound, yet lower than from intravenous injections
All of the following values are calculated for an 80kg human using the standard HED formula and are based on rodent studies showing benefits for the respective organ:

• Heart - 650mg
• Diabetes - 975mg
• Liver - 400-3,200mg
• Alzheimer's - 4,000mg*
• Parkinson's - 350mg
• Pancreas -  3,250mg

* This is the only value that's based on oral administration for the others I simply assumed 1:1 bioavailability which is probably already an overestimation for the liver and certainly for other tissues, since part of the TUDCA probably won't survive the first pass through the liver.

The distinction between different bile acids is difficile and beyond the scope of this mini-overview. What all of them have in common is that they are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol, which makes them the ideal partner for both "water" and "fat soluble" molecules and allows them to do their job as major modulators of lipid secretion, bile flow and the absorption of dietary fats and vitamins. Aside from these long-established functions their role as regulators of key enzymes involved not only in cholesterol homeostasis, but also whole energy homeostasis has attracted more and more interest over the last years. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients.

No effect without "side effect"!

Yet despite their metabolic utility bile acids have potent toxic properties and can - at high dosages - actually disrupt the very membranes they help to protext when they are administered at lower doses, therefore their accumulation in the blood and tissue is usually tightly regulated. And while Martinez-Diez et al. have shown that conjugated.bile acids have a very high toxicity threshold compared to their unconjugated cousins (Martinez-Diez. 2000), we are most probably still dealing with one of those classic U-shaped dose-response curves for TUDCA (with no effects at very low, beneficial effects at medium levels and toxicity issues at high levels) which are so ubiquitous in nature and still so difficult to understand for someone acculturated to the typical Western "more is more" mentality (Zinc would be another example, by the way; cf. "Zinc: 15mg is Plenty!").

A non-exhaustive list of proven benefits

• With its modulatory effects on the cell cylce regulator c-Jun N-terminal kinase (JNK), the generation and scavenging of radical oxigen specimen  and glutathione S-transferase (GST) activity, which is necessary for the masteroxidant glutathione to do its job, TUDCA effectively prevented / reduced neurodegenation in rodent model of Parkinson's disease (Castro-Caldas. 2013). It has also been shown to reduce the amyloid beta-induced synaptic toxicity that is so characteristic of Alzheimer's disease (Nunes. 2013; Ramalho. 2013)

• 

  Figure 1: Anti-inflammatory effect of TUDCA on FFA treated adipocytes; reduction in TNF-alpha and IL-6 (also vs. baseline; directly from Jia. 2011))

  Similar to taurine TUDCA appears to play an important role in cell osmolity, and has been shown to inhibit endoplasmic reticulum stress (ER) in embryonic development and ventricular contractile dsyfunction (malfunction of the heart) due to type II diabetes, fatty acid accumulation in the heart (Hua. 2010) and preserve cone density in the eye (Kim. 2013; Takada. 2013; Zhang. 2013a,b). 
• The same anti-ER mechanism also protects the insulin releasing pancreatic beta cells of Wistar rats (Lee. 2010; Tang. 2013) and the kidney (Gao. 2013) from damage due to increased blood glucose.  And Rivard et al. were even able to show that 400mg/kg of TUDCA, when they were administered intravenously were able to reduce apoptosis (death of hear cells) following myocardial infarction in rats (Rivard. 2007).
• TUDCA has also been shown to ameliorat insulin resistance in hypertrophic adipocytes (fat cells that burst from the seams; Jiao. 2011, Yoshizaki. 2013), to keep the expression of the adiponectine up (Zhou. 2010) and the inflammatory induced neovascularization in type II diabetes in check (Amin. 2013).  
• Despite the fact that TUDCA is also effective against endoplasmic rectilium stress in the liver and in skeletal muscle it cannot save a methionine and choline deficient liver from getting clogged with fat (Henkel. 2013), or a palmitate (a saturated fatty acid) treated myotube from becoming insulin resistant, (Rieusse. 2013). 
• What it can do, however is protect liver from apoptosis induced by natural or synthetic PPAR-gamma ligands (see "TTA + Fish Oil - Fat Burning Superfats or Hepatoxic Pro-Oxidants?" and "TTA + Fish Oil Revisited - Increased Intramuscular Omega-3 Levels Compromise Heart and Skeletal Muscle Performance"; cf. Nonaka. 2008) and ethanol-feeding (Colell. 2011)

• 

  Figure 2: Western blot analysis of influenza NP, NS1, and M1 proteins with corresponding densitometry displayed as averages with S.E. Proteins - reduced expression indicate a reduced replication rate (adapted from Hassan. 2011)

  Interestingly the same anti-ER effects that protect the heart, the pancreas, the kidneys and, in the presence of adequate choline and methionine, also the liver, will also inhibit influenza A viral replication (Hassan. 2013; in-vitro data)
• TUDCA has also been found to have antibacterial effects, or rather to prevent the cytotoxic effects of  Clostridium sordellii lethal toxin (CSLT) from virulent strains of Clostridium sordellii (Schulz. 2009) 

• Only when it's conjugated to taurine UDCA (then T + UDCA = TUDCA ;-) will promote hydrocholeresis or, put simply, the output of bile acid (Úriz. 2011; intravenous administration). In view of the emerging importance of bile acids in overall energy expenditure and thyroid function (Ockenga. 2013).
  This observation could well-explain the effects TUDCA has on the conversion of T4 => T3, which spiked your interest in the last installment of "On Short Notice", here at the SuppVersity (see "On Short Notice July 21, 2013").
• In this context it may also be wort mentioning that Nathanson et al. observed a direct stimulative effect of UDCA, the taurine devoid cousin of TUDCA on hepatic ATP secretion (Nathanson. 2001) and Drack et al. report that subcutaneous injections of 500 mg/kg in 0.15 M NaHCO₃ to obesity prone mice reduced their weight gain by -22%; a significant effects on "normal" mice could was yet not observed in the study (Drack. 2013). 

And what about humans?

As mentioned earlier, the number of studies in which TUDCA was actually administered to human beings is negligible and of actual relevance in the current context are probably on these two:

Figure 3: Effect of placebo or TUDCA on skeletal muscle insulin receptor substrate (IRS), Akt and JNK levels (Kars. 2010)

• Improved liver & muscle, but not adipose tissue insulin sensitivity in obese men and women (Kars. 2010) The main finding of this randomized double-blind study in which 20 obese subjects ([means +/- SD] aged 48 +/- 11 years, BMI 37 kg/m²) were assigned to receive either TUDCA at a dose of 1,750 mg/day or a placebo was a highly significant increase in insulin sensitivity (~30%; p < 0.05), which was - and this is would actually not be a bad thing for a physical culturist - liver and muscle specific!
  In combination with it's effect on the muscular and hepatic expression of p-AKT, this could make TUDCA the nutrient repartitioner (R-)ALA is not (cf. "Lean & Muscular with Alpha Lipoic Acid?"), if those effects would translate to individuals with normal insulin sensitivity (they do translate into human muscle cells in the Petri dish, which are protected against glucosamine induced decreases in GLUT-4 activity, when enough TUDCA was present in the incubation media; cf. Raciti. 2010).
• Surprisingly ineffective adjuvant after liver transplantation (Angelico. 1999) While you would expect that something that is good for liver health would also help as an adjuvant to the treatment of patients who received a liver transplant, the 16 subjects who were randomized to the active 2x250mg TUDCA treatment arm of the study did not see any statistically significant benefit in terms of one-year actuarial survival.

Although the latter of these studies may actually be somewhat disappointing, its results are actually quite educative - after all, they put another emphasis on something I have touched upon in numerous previous blogposts, already: Even in cases as the one at hand, where the presence of statistically reduced serum cholesterol levels (p < 0.02) and less exuberant cholestasis confirm that a certain compound, in  this case TUDCA, worked in vivo similarly to what it did in vitro, this does by no means implicate that it will also yield the real world results you would expect.

Image 2: Like the SuppVersity on Facebook and make sure you always get the latest news; this includes updates, links and comments on interesting articles around the web many of which are not even mentioned on the website - you don't want to miss those, do you?

Implications: The "negative" or rather NULL outcome of the study by Angelico et al. should have reminded you that you better display a healthy degree of skepticism towards all the previously presented "scientifically established" benefits of TUDCA. Neither I, nor any of the researchers (not even Kars et al.) should have the hubris to tell you that taking X amounts of tauroursodeoxycholic acid will save your liver from the toxic effects of oral anabolic steroids, will help you in your battle against diabesity or make a powerful ally in your quest for a leaner, more muscular physique. And still, this mini-review of the literature should have shown you that TUDCA has a lot of potential, future studies will yet have to confirm, for whom these potentials can actually be realized and what dosages of a hitherto pretty pricey supplement will be necessary to produce the desired results... Needless to say that the SuppVersity is going to be the place wheer you will read about these studies first- right?

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