Saturday, July 21, 2012

On Short Notice: Testosterone - 12% Drop /W 75g Glucose? Fat Loss - Adzuki, Leucine + B6 or HiMaize? Thyroid - T3↓ + rT3↑, Is Blood Sugar to Blame and Can TUDCA Help? +More!

Image 1: It's quite funny, I am piling up so many of these interesting mini-news that I actually had to drop a few or postpone them to next week to keep the size of this post manageable without a direct brain transmission device like the one you see in this picture ;-)
"On short notice" is the name of the new 'saturdaily' SuppVersity column and therefore I will try to make it short: After all, you've got a hell lot to learn today and unless you have just crawled out from beneath your sheets, your testestorone levels and with it your cognitive abilities will aready have declined - that's not you? Well I guess you have the hubris of a boxer, then, or you did simply sleep so little that even your increased energy consumption could not make up for the memory dysfuction that's been brought about by the sleep deficit. Let's just hope that your cell mass is at least so high that your basal energy expenditure is sufficient to burn those serotonergic carb binges off, because I am pretty sure that the leucine + B6 combo from NuSirt Science won't do that for you... what? You don't understand a word? Don't worry, you will, once you are done with today's installment of "On Short Notice"...

Adzuki bean extract - just another fat binder or more?

Image 2: Those Adzuki beans look pretty much like kidney beans, don't they? Ah, btw. you did know that kidney beans contain a "carb blocker" (a molecule that hampers carbohydrate digestion; cf. Mosa. 2008) - did you?
I am really no a fan of those "anti-fat absorption agents", as most of them will have immediate or long-term consequences on your supply of fat soluble nutrients which could in fact be worse for your overall health than the few additional lbs of body fat you may be carrying around. That being said, you may still be interested in the latest results from Tomoko Kitano-Okada and his colleagues from the Department of Food Science, Obihiro University of Agriculture and Veterinary Medicine in Inadacho, Obihiro, Hokkaido, Japan. In a combined in-vivo (rodent) and in-vitro study, the researchers found that control and high fat diets with 1% adzuki bean extract, despite having only non-significant effects on the high fat diet (HFF) induced weight gain, did not just ameliorate the HFD induced deteriorations in serum low-density lipoprotein (LDL) and triglyceride (TRIG) levels, but lead to marked improvements in LDL and TRIG in the rodents on the standard diet (55% cornstarch + 10% succrose, 20% casein, 5% soybean oil), as well.

Figure 1: Absolute total cholesterol and triglyceride levels, as well relative (expressed in percent of respective values for animals on control diet) liver and faecal matter weight and lipid content in male Fischer rats after 4 weeks on control (high carb) or high fat diets (data based on Kitano-Okada. 2012)
This is interesting as it appears to confirm the hypothesis that the Adzuki beans do not work their anti-hyperlipidemic (=cholesterol and triglyceride lowering) effects solely via their ability to increase the fat content of the excrements, but also via other mechanisms of which Kitano-Okada et al. identified the reduction of inflammatory cytokines (e.g. 24–51% IL-6 reduction following treatment with Adzuki bean extract containing polymerised polyphenols) and the likewise dose-dependent profound reduction in glycerol-3-phosphate dehydrogenase, an enzyme that is necessary to generate glycerol (fatty acids) from carbohydrates, in in-vitro cell studies with human adipocytes by up to -50%!
Implications: Just in case you are now interested in popping some of those beans you should be aware that the product that was used in the study contained 16% polyphenols (including 470 mg anthocyanidins, 20.7 mg catechins, 2.33 mg caffeic acid, 2.62 mg ferulic acid, 44.5 mg quercetin, and 102 mg protocatechuic acid), that the human dose equivalent would ~5-6g /day and that you should try to get an extract with polymerized (=interconnected) phenols, as those were roughly 2x more active in the in-vitro essays (although it is questionably if this translates into better real world results).

Marathon running is for the metabolically efficient!

Image 3: Marathoners have nothing to lose!
Just in case you have ever wondered what makes a good marathon runner a very good marathon runner, the results of a study that was published in the latest issue of Sport Sciences for Health could hold the answer: Marathon champions have a surprisingly high metabolic efficiency (Andreoli. 2012), or put more simply, they are carrying little to no (for their goals!) useless ballast like profane fast-twitch muscle fibers and only so much fat as it takes to optimally protect their organs (in percentages this is yet still way more than the guys with the "profane" fast-twitch fibers are carrying around)

As the data in figure 2 goes to show, their body cell mass (BCM), a more accurate measure of the amount of metabolically active tissue in their body than "lean mass" (Moore. 1963), is about equal to the one of division 1 football players (data compiled from Andreoli. 2003 and Andreoli. 2012), but their lean mass is much lower (as mentioned before they have no use for heavy type I and type IIX muscle fibers).
Figure 2: Body composition data (fat free  mass, body cell mass, body fat percentage) in different athletes and control (left), as well as correlation between BCMI (BCM / height) with marathon running time (right; data compiled from Andreoli. 2003 and Andreoli. 2012)
In conjunction with higher metabolic rates, of which Andreoli et al. found that they are the 2nd best predictor of marathon times (correlation r = -0.69 vs. BCMI = BCM / height with r = -0.73), a high amount of "oxygen-exchanging, potassium-rich, glucose-oxidizing, work-performing cells" (=what the BCM measures ;-) and correspondingly high resting energy expenditures (r = 0.77) do thus make the difference between victory and defeat.

Sounds strange, when you come to think about it - right? "People with higher energy expenditures make good marathon runners?" Well, I guess you better think of it differently: Bigger engines need more fuel and as we have seen yesterday, a very welcome side effect of "mitochondrial biogenesis that's induced by Chitooligosaccharide supplementaton" was an increase in endurance - that those big engines have to be fueled adequately, by the way, does also explain why people like Michael Phelps do in fact have to eat like a horse - that he really needs 12,000-15,000 calories per day is yet probably just another of those urban legends.
Implications: Interestingly enough, the necessity of having a "big engine" (=huge metabolically active cell mass) does also implicate that the formerly obese, who appear to flock around marathon or at least endurance running, with their slabs of metabolically unactive tissue and suppressed metabolic rates due to months or years of undereating and overtraining have little to no chance of ever winning a marathon race, which  - and this may be the most surprising finding of the study - is not the prerogative of the person who "burns the less fuel"  - at least not as long as nobody takes away their 30 bananas a day and the highly concentrated energy gels marathoners use on their 42-km run, I guess ;-)

Can 75g of Glucose Reduce Testosterone by 10% Within Minutes?

In a recently conducted trial, Lisa M. Caronia and her colleagues from the Massachusetts General Hospital in Boston observed an astonishing -12% drop in total testosterone within 30 min of the ingestion of an 75g of glucose - the same amount you would ingest in every regular oral glucose tolerance test (OGTT) and even less than some hilarious "expert suggestions" will tell you would need to optimally replenishing your allegedly depleted glycogen stores after an intense workout.
Figure 3: Glucose, insulin, SHBG, lepin, LH and testosterone levels in response to the oral ingestion of 75g glucose in 74 young men; data expressed relative to baseline (data adapted from Caroni. 2012)
If you take a closer look at the exact data in figure 3 you will probably be as startled with respect to the underlying mechanism behind this reduction as the researchers were. Aside from the drop in testosterone, the only statistically significant changes (indicated by * in figure 3) the scientists observed, were a profound drop in leptin and the explosive increase in glucose and insulin - both of which, the decrease in leptin and the increase in insulin, have yet been shown to augment testosterone production in previous studies (Adashi. 1982; Giovambattista. 2003). At least with respect to the drop in leptin, Caronia et al. do yet point out, that it could be a mere conseqence of "circadian fluctuations in leptin that are unrelated to glucose administration" (Caronia. 2012; those fluctuations, by the way, have been observed by e.g. Panarotto. 1999)

Symptoms of low Testosterone
  • Lean muscle loss, agitation/motor dyskinesia, decreased appetite
  • Depression, guilt, low-self esteem, anhedonia, decreased cognitive capacity
  • Increased stress, general fatigue, sleep disturbances
  • Decreased libido, decreased spontaneous erections, decreased ejaculate, erection dysfunction, decreased sexual fantasies, anorgasmia
Furthermore, neither cortisol (not shown in figure 3), a potential suppressor of testicular testosterone production, nor luteinizing hormone (LH), which stimulates testicular testosterone production and should actually increase in response to the drop in testosterone, did budge in the course of the 120 min after the 74 men (age range: 19-74 years, mean: 51.4 ± 1.4) who reported to the lab after a 12-hour overnight fast had ingested the 75g of glucose.

As Caronia et al. point out, the non-existent response of the luteinizing hormone (LH) levels to the reduced testosterone levels, is probably the only clue we have as far as the underlying mechanism of allegedly glucose-induced reduction in testosterone levels is concerned, because "one would anticipate that the decreased negative feedback of T would lead to increased LH levels" (Caronia. 2012). And though Caronia et al. are certainly right that this and the fact that this was not the case and that the effect occured in healthy, in insulin resistant and in diabetic subjects (where it was slightly more pronounced, though; data not shown), clearly "suggests an additional central component", the latter should actually, as it was observed by  Iranmanesh et al. only recently involve a drop in luteinizing hormone (Iranmanesh. 2012).

After thinking about that for a couple of minutes I was just about to write in the implications that this would be another good reason not to go overboard on fast carbs, when I remembered my previous research on all things testosterone for the "Intermittent Thoughts on Building Muscle" Series and what the scientists themselves had said about the declining leptin levels - well, let's take a look at what the testosterone levels of both young and old men do between 8:00am and 12:00pm, i.e. during the exact time the subjects in the Caronia study ingested their allegedly anti-androgenic bolus of 75g of glucose:
Figure 4: An analysis of the natural diurnal testosterone rhythm in young men (dotted line in graph in the background; Diver. 2003) reveals that the "drop" in testosterone in response to the OGT is likely only a consequence of the pronounced diurnal rhythmicity of the total testosterone levels - in older men we see the exact same phenomenon, but the effect is about 50% less pronounced.
The data from the Diver study in figure 4 does not leave a slight doubt that the OGTT, or rather the 75g of glucose the subject had to consume probably had no independent effect on the level of testosterone and that the decline Caronia et al. observed is simple a result of the natural diurnal rhythm. This does not exclude that the latter is per se connected to food intake as the availability / influx of energy is, beside light, probably, the most important setscrew for our clock-genes.
Image 4: Conclusions are rarely 100% conclusive.
Implications: There are actually two important take home messages from this study and "carbs are so bad for you" is not one of them:
  1. draw your own conclusions, and don't trust those of others blindly regardless of their "credentials"
  2. make sure that you don't ignore the diurnal rhythmicity of testosterone, and are thus fooled to believe that short term changes in the +/- 50% range would make you build or lose muscle, let alone your virility
The second take home message is also of great importance when you test your own testosterone levels and/or read about the testosterne boosting magic of the latest supplement scam (aka "natural testosterone booster"). As you can see, you can easily achieve a  70-80% increase or decrease in testosterone by simply measuring at different points in the day.

On Very Short Notice

  • Figure 5: Changes in fatty acid metabolism (top) and inflammatory markers (bottom) in response to 4 weeks of thrice daily NuFit (250mg leucine + 30mg vitamin B6) supplementation to 20 obese men and women (based on Zemel. 2012)
    Astonishing improvements in RQ & fatty acid oxidation from 2g of leucine and 30mg vitamin B6 - Although you need to be somewhat cautious with a study that was financed by NuSirt Sciences the producer of the 750mg leucine + 10mg pyridoxin supplement under scrutiny (Zemel. 2012), the effect the ingestion of those caps had on the fatty acid metabolism and moreover the expression of inflammatory markers in 20 overweight or obese subjects was literally marvelous (I leave the interpreation of this term up to you ;-). A decrease in respiratory quotient (=greater fatty acid, lower glucose oxidation), an increase in total fatty oxidation per day and more importantly and probably causally the decreases in TNF-alpha and CRP are changes I would not have expected to see within 4 weeks on 2.25g of leucine and 30mg of vitamin B6. After all,  you should see similar effects with almost every cheap (or expensive) BCAA supplement on the market - aside from even greater amounts of leucine most of them contain at least 10mg of additional B6.
  • Fat burning machines can't have orange juice for breakfast - The additional 210kcal the subjects of a 2012 trial by scientists from the Children’s Hospital Oakland Research Institute consumed in form of "healthy" orange juice were not just more or less empty calories, they also reduced the postprandial fatty acid oxidation by whopping 25%. This lead Stookey et al. conclude that "independent of a state of energy excess, [drinking] a caloric beverage instead of drinking water with a meal [will decrease] the amount of fat consumed in the meal before their next meal." (Stookey, 2012) If you want to become / stay a fat burning machine (and in my humble opinion even if you just want to stay lean and healthy) you better eat your fruit and never drink it (let alone other caloric beverages, see "Fat content per Energy Drink 0g, Fat Gain Per Energy Drink 16g").
  • Image 5: The first hit on google says HiMaize will cost 8$/340mg; mimicking the dosage used in the study would thus be ~1$ per day; relatively cheap if you consider that it is not necessary a supplement, but can also be used for baking & co
    Resistant starch could stop and reverse developing diabetes - scientists from the University of Surrey and the venerable Imperial College in London were able to show that their 12 overweight (BMI 28.2±0.4 kg/m2) prodiabetic subjects' first-phase insulin secretion, which is the one that determines whether you do or don't go hyperglycemic right after the ingestion of a meal, by improved by ~35% after only 4 weeks of consuming a mildly resistant (60% resistant / 40% digestible) maize starch. Probably as a direct result of this early pro-insulinogenic effect, the HiMaize260 RS2 starch produced a -10% reduction in fasting blood glucose, compared to a regular tapioca starch of which the subjects in the control group consumed only 27g to assure that they would ingest equal amounts of glucose (Bodinham. 2012).
    Despite the fact that WM HDP is an artificial restistant starch, of which even less will be digested and absorbed as glucose in the small intestine, these results do confirm what we have already seen in the WM HDP studies and what some of the latest blogposts bordering on dietary fiber have hinted at, as well (e.g."Weightloss Threesome"): The effects of these not, or only partially digestible fibers and carbohydrates go way beyond simply filling you up or being non-insulinogenic (=not causing an insulin spike as even the low GI starches do). There is however, as Carolin L. Bodinham and her colleagues rightly point out, need for "further studies [...] to confirm these findings and to elucidate the mechanisms" and, as I would add, to identify whether or not this could work for people who have already developed type II diabetes, as well.
  • Counter-intuitive effects of high glucose-dependent insulinotropic polypeptide (GIP) levels in form of increased insulin and reduced obesity: While the hitherto published studies on WM HDP (see previous bullet point) clearly suggest that part of its fatburning effect is mediated by a reduced, even almost non-existant GIP (and subsequently insulin response), a recent study from Canada clearly suggest that whenever you do consume regular starch a more pronounced incretin response will not just avoid hyperglycemia (due to the more pronounced release of insulin from the pancreas), but also improve / prevent adipose tissue inflammation, hepatic steatosis (non-alcoholic fatty liver disease) and even weight gain - remember: we are talking about higher insulin responses, here (Kim. 2012)! Unfortunately, the anti-obesity effect Su-Jin Kim and his colleagues observed in their experiments with GIP-overexpressing rodents, were mostly a direct consequence of reduced energy intakes and that those hardly ever translate into the real world is something I believe I don't have to tell you, right?
  • Figure 6: If your body does not convert T4 into T3 adequately taking levothyroxin (T4) may even worsen many of the symptoms of hypothyroidism due to increased conversion to r-T3 and an even more sluggish metabolism that certainly won't help to get blood glucose back under control (see also "Natural Thyroid Treatment with food")
    Low T3 syndrome (pseudo-hypothyroidism) or diabetes? This is an "oldie, but goldie", i.e. a study I happen on while doing research on this and that... in this case I do not even really know how this study appeared on my radar, but according to Kabadi et al. high blood sugar in type II diabetes does reduce the conversion of the "inactive" form of thyroid hormone, T4, to its active cousin, T3 and increases the conversion of T4 to rT3 (reverse T3). The latter is believed to act similar to a receptor blocker, which hinders T3 do to its metabollically activating job. The statistically highly significant (p < 0.0001) correlation (r = 0.611) the scientists observed between rT3 and fasting blood glucose would suggest that improper blood glucose management could be the root course of the heavily lamented high rT3 levels of thousands of posters on various bulletin boards all across the Internet (Kabadi. 1982). Now, the good news is that the researcher found that by controlling blood glucose levels you can return your rT3 and T3 levels back into the normal zone. 
  • Tauroursodeoxycholic (TUDCA) and 4-phenylbutyric (4-PBA) increase T4 to T3 conversion - The chemical chaperones TUDCA and 4-PBA, of which the former has as of late been hailed as the new "milk thistle", i.e. the go-to-supplement for liver health among athletes who use oral anabolic steroids, could turn out to be a valuable tool not just to escape from the aforementioned vicious circle of low T3 and high rT3 levels, but also as a means to kickstart your metabolism. Although this hypothesis is based on data from a combined in-vitro + in-vivo rodent study (da-Silva. 2011), the shift away from glucose and towards fatty acid oxidation, as well as the doubled activity of the fat burning brown fat and the profound improvements in glucose tolerance, da-Silva et al. observed in their high-fat fed rodents certainly won't harm your physique.
  • Figure 7: Narcicistic personality traits of kickboxers, freestyle and  Greek Roman wrestlers, Boxers and Weightlifters (based on Tazegül . 2012)
    Weight lifters and boxer are the most narcissistic athletes - At least among the five groups the Turkish scientist Ünsal Tazegül analyzed for his recently published paper, the 17-19-year old male boxers and weight lifters had the most pronounced narcissistic character traits. While the boxers were the most exhibitionists and pretentious, the weight lifters were the most rebellious, inadaptable, spiteful, disrespecting (subsumed under exploitation) and ambitious, power-thirsty and spiteful among the subjects who participated in this study. Interestingly enough, the freestyle wrestlers appeared to be the guys with whom you would probably get along best. So what does that tell you? Nothing... and that's why this study is only on very short notice ;-)
  • If you don't sleep yourself smart, you got to binge yourself half-smart: Just in case you have already forgotten what you read a few paragraphs above, the reason could be sleep deprivation. And while cognitive deficits due to sleep deprivation is nothing essentially new, another thing, namely the effectivity of increased daytime energy intake to recover your mental capacity, is something a recent study by Nina Herzog et al. has investigated for the first time (Herzog. 2012). Unfortunately, binging rescues only the procedural part of your memory (where you store how to brush your teeth before you go to bed ;-), it will not compensate for the detrimental effects a lack of adequate sleep will have on your declarative memory. If you also  take into account that it is going to make you fat and sick, I would thus suggest you go to bed now, after all you havale already done the single most important thing of the day - you've gotten your daily dose of SuppVersity news! And let's be honest, you don't want to forget any of these valuable lessons, do you ;-)
  1. Adashi EY, Fabics C, Hsueh AJ. Insulin augmentation of testosterone production in a primary culture of rat testicular cells. Biol Reprod. 1982 Mar;26(2):270-80.
  2. Andreoli A, Melchiorri G, Brozzi M, Di Marco A, Volpe SL, Garofano P, Di Daniele N, De Lorenzo A. Effect of different sports on body cell mass in highly trained athletes. Acta Diabetol. 2003 Oct;40 Suppl 1:S122-5.
  3. Andreoli A, Marfe G, Manzi V, Sinibaldi-Salimei P. Is body cell mass a predictive index of performance in male recreational long-distance runners? Sport Sci Health. 2012; 8:47–50
  4. Bodinham CL, Smith L, Wright J, Frost GS, Robertson MD (2012) Dietary Fibre Improves First-phase Insulin Secretion in Overweight Individuals. PLoS ONE 7(7): e40834.
  5. Diver MJ, Imtiaz KE, Ahmad AM, Vora JP, Fraser WD. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol (Oxf). 2003 Jun;58(6):710-7.
  6. Giovambattista A, Suescun MO, Nessralla CC, França LR, Spinedi E, Calandra RS. Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats. Neuroendocrinology. 2003 Nov;78(5):270-9.
  7. Herzog N, Friedrich A, Fujita N, Gais S, Jauch-Chara K, et al. (2012) Effects of Daytime Food Intake on Memory Consolidation during Sleep or Sleep Deprivation. PLoS ONE 7(6): e40298.
  8. Iranmanesh A, Lawson D, Veldhuis JD. Glucose ingestion acutely lowers pulsatile LH and basal testosterone secretion in men. Am J Physiol Endocrinol Metab. 2012 Mar;302(6):E724-30.
  9. Kabadi UM, Premachandra BN, Maayan M. Low serum 3, 5, 3'-triiodothyronine (T3) and raised 3, 3', 5'-triidothyronine (reverse T3 or RT3) in diabetes mellitus: normalization on improvement in hyperglycemia. Acta Diabetol Lat. 1982 Jul-Sep;19(3):233-42.
  10. Kim S-J, Nian C, Karunakaran S, Clee SM, Isales CM, et al. (2012) GIP-Overexpressing Mice Demonstrate Reduced Diet-Induced Obesity and Steatosis, and Improved Glucose Homeostasis. PLoS ONE 7(7): e40156.
  11. Kitano-Okada T, Ito A, Koide A, Nakamura Y, Han KH, Shimada K, Sasaki K, Ohba K, Sibayama S, Fukushima M. Anti-obesity role of adzuki bean extract containing polyphenols: in vivo and in vitro effects. J Sci Food Agric. 2012 Apr 11.
  12. Moore FD, Olesen KH, McMurray JD. The body cell mass and its supporting environment. WB Saunders, Philadelphia, 1963.
  13. Mosca M, Boniglia C, Carratù B, Giammarioli S, Nera V, Sanzini E. Determination of alpha-amylase inhibitor activity of phaseolamin from kidney bean (Phaseolus vulgaris) in dietary supplements by HPAEC-PAD. Anal Chim Acta. 2008 Jun 9;617(1-2):192-5. Epub 2008 Feb 1. 
  14. Panarotto D, Maheux P. Reduction of plasma leptin during a short-term fast, an oral glucose tolerance or a meal test can be a misleading bias in clinical studies. Diabetologia. 1999 May;42(5):634.
  15. da-Silva WS, Ribich S, Arrojo e Drigo R, Castillo M, Patti ME, Bianco AC. The chemical chaperones tauroursodeoxycholic and 4-phenylbutyric acid accelerate thyroid hormone activation and energy expenditure. FEBS Lett. 2011 Feb 4;585(3):539-44.
  16. Stookey JD, Hamer J, Espinoza G, Higa A, Ng Vivian, Tinjero-Deck L, Havel PJ, King JC. Supplement: 2nd Forum on Child Obesity Interventions: Orange Juice Limits Postprandial Fat Oxidation after Breakfast in Normal-Weight Adolescents and Adults Adv Nutr July 2012.
  17. Tazegül, Ü. Comparison of narcissims in some branches of athletes. International Journal of Sport Studies 2011, 1 (4), 168-179.
  18. Zemel, M.B.; Bruckbauer, A. Effects of a Leucine and Pyridoxine-Containing Nutraceutical on Fat Oxidation, and Oxidative and Inflammatory Stress in Overweight and Obese Subjects. Nutrients 2012, 4, 529-541.