Broccoli No Superfood? Female Orgasm, What's It Good For? Can Piperine Make You Lean? Skinfold Thickness, An Exact Indicator of Insulin Sensitivity? Exercise, Cortisol, BDNF, Fatigue, IGF, Pollution, NOPE, EGCG & More!

Alberto Contador almost certainly wouldn't benefit from the use of a nitrate supplement.

17 seconds and 5 watts! Those are the SuppVersity figures of the week and the performance "increases" which were associated with the consumption of either 0.5 L nitrate-boosting beetroot (BR) juice over a 0.5 L placebo (PLA) drink with blackcurrant juice during time trials and repeated maximal sprints, respectively, in 10 male elite cyclists who are competing at the highest domestic level in a study that was conducted by P. M. Christensen, M. Nyberg and J. Bangsbo from the University of Copenhagen in Denmark (Christensen. 2013).

What does sound as if it could make the difference between victory and defeat, was however statistically non-significant and is further evidence of the fact that things that work in rookies are not necessarily advantageous for highly trained athletes (for nitrates benefits have been reported in untrained or recreationally active individuals by e.g. Bailey or Vanhatalo in 2010, and Lansley in 2011).

As a SuppVersity student the specificity of the ergogenic effects of dietary supplements is yet not really news for you, but I would hope at least some of the following items of today's installment of On Short Notice are...

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Next to broccoli blueberries got an "unhonorable mention" in the Kingston University press release, as well.

Is broccoli really no superfood? Usually this is not the place to discuss mainstream popular science "articles", mostly because 99% of them are simple "copy and paste" jobs of press releases. However, since just that, i.e. copying and pasting is what all the major "science website" have been doing with a recently published press release from the Kingston University College in London about their smartest scientists "debunking" the myths about superfoods, I felt impelled to check what all the fuss was actually about.

Let's start with the most important message first: There is no such thing as a "superfood" which will ward off all diseases and make you live forever, as long as you simply eat as much as you can and then, when your tummy is ready to explode, top that off with respective extracts and related dietary supplements. So, in this regard, there is no debating that Dr Jones, Deputy Dean at the University's Faculty of Science, Engineering and Computing, is right: Broccoli is no superfood!  It stands to reason that the same goes for blueberries, acai berries, parsley, rosemary, sage, thyme and the bazillion of other items on an ever-growing list of superfoods, which, by one way or another, continuously fails to to enlist dairy, meat, eggs and all the other "bad" foods of which you could easily argue that they are likewise "superfoods".

Figure 2: Why do we need Caco 2 cells in the petri dish, when we do already have numerous studies on "superfoods" showing the actual rate of appearance of the purportedly active substances in the blood of both healthy human beings (top, cacao catechins; based on Hanlon. 2008) and rodents (bottom; for the purported anti-cancer molecule in sulforaphane from - you guessed it, the "unhonorable mention" from the press release, Broccoli; Mullen. 2009) after oral consumption? So, while the researchers criticism of the hilarious TEAC essays based on which snake oil vendors identify "superfood" after "superfood", may be right, their own approach appears likewise questionable and is by no means without alternatives.

It is also correct that the researchers observed in a previous study (Chohan. 2013) that raw, cooked and cooked + pre-digested parsley, rosemary, sage and thyme exert different (much more pronounced!) anti-inflammatory effects on peripheral blood lymphocytes (PBLs) and those Caco-2 cells, of which Dr. Opara, a colleague of Dr. Jones (likewise correctly) states:

"The Caco-2 is a single layer of cells grown in a laboratory environment that develops the characteristics and functions of the micro-villi, the tiny hair-like projections that aid efficient absorption found mainly in the small intestine.

[...] This allows us to look at what nutrients pass through into the body and could be used to test food supplements, drugs and foodstuffs. We found that while some compounds may have a local effect in the gut itself, in terms of the rest of the body the impact could be negligible." (Kingston. 2013)

What does yet not appear to be either logical or correct is the assumption that the absence of anti-inflammatory effects in the Caco-2 cells implies that systemic benefits can be ruled out. What's downright unwarranted, however is the way in which the press release generalizes these findings in the absence of experimental evidence to all polyphenols and (even more) the potential beneficial effects of whole foods, of which I hope that you, as a regular SuppVersity reader have meanwhile understood that they go well beyond those of the  individual nutrients you can extract and fill into caps, powders, tablets or gels.

Moreover, this approach also neglects potential effects of metabolites of the polyphenols that are formed in the body’s tissues or by the colonic microflora (see Scalbert. 2000; Rechner. 2002), as well as the existing real (not cell-line, petri dish, in vitro) data on the bioavailability of many of the beneficial polyphenols, catechins, flavonoids & co from both, rodent and human studies (Manach. 2005). What on earth would be the benefit then of reviving an early 1980s technique that has been developed by the US cancer research institute, which will never be able to capture the complex interactions that are taking place during the digestion absorption and subsequent metabolism of these molecules?

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Exercise, cortisol, stress, IGF-1, BDNF, depression and cognitive impairment Sounds pretty damn complicated, right? If you add one and two together, or, in this case, very recent studies from the University of Hong Kong, the Vrije Universiteit in Brussel (Belgium) and the University of Heidelberg in Germany, the picture that emerges is actually pretty straight forward.

Figure 1: The difference between acute (~7days) and chronic (>21days) stress (in form of exogenous cortisol) does also reflect in the voluntary running distance. The initial motivating / ergogenic effects of cortisol begin to show their ugly face after roughly 3 weeks, though and it is likely that a continuation of the study would have put the rodents in a state similar to what is commonly labeled as "chronic fatigue" (based on Yau. 2013)

In their study, the results of which have just been published in the October issue of Neuroscience, the Chinese researchers report that acute (5-days) exposure to stress (here in the form of daily cortisol injections) exerts beneficial effects on both, the expression of the brain-derived neurotropic factor, as well as corresponding improvements in spatial learning, without altered cell proliferation compared to vehicle treatment. Chronic exposure to cortisol for 28 days in a row, however, decreased circulating and hippocampal BDNF and IGF-1 levels and lead to significant reductions in spatial learning, which were ameliorated, when the rodents had free access to running wheels.

In that it's noteworthy that the distance the animals covered also reflects the diametrically opposed (i.e. empowering vs. draining) effects of stress with initially higher (acute cortisol phase) activity rates and a profound lack of drive towards the end of the 27day study period.

That said, it appears likely that the protective effects of exercise would also begin to wear off with longer periods of chronic stress exposure; a hypothesis, by the way, which should remind you of the last installments of the (Female) Athletes Triad Series and the "vicious circle of overtraining, overdieting and overstressing".

As sarcastic as it may sound (and actually is), China would be the ideal place to study the long- and short-term consequences of air pollution on brain and overall health from childhood to (premature?) death

Now lastly, the Belgian study by Bos et al. adds yet another factor to the BDNF <=> cognition <=> exercise equation that may not be relevant for rodents, but could provide another incentive for you to incorporate regular, yet not overly taxing exercise and physical activity in general into your everyday life: Air pollution!

It has already been established that healthy children and young adults who have been exposed to particle matter from polluted air, show deposits of ultra-fine particles (UFP) in the olfactory bulb neurons. These depositions are accompanied by neuroinflammation, the disruption of the blood–brain barrier (read more about the latter in the SuppVersity Facebook News), and an early accumulation of amyloid β42 and α-synuclein (Calderón-Garcidueñas. 2008 & 20012).

Similar associations between living in a polluted environment with high particle matter concentrations and cognitive decline have been reported by other scientists, as well (Chen and Schwartz. 2009; Ranft. 2009; Suglia. 2008). Now the novel result in Bos et al.'s experiment is that even under those conditions, exercise can increase the otherwise successively suppressed hippocampal expression of BDNF and thus antagonize, or at least ameliarate some of the negative effects of environmental pollution (Bos. 2013)

You have read about the somewhat questionable use of colostrum as a muscle building IGF-1 booster before, but intranasal IGF-1 as a means to treat depression? That's news, right?

To finally come full circle, we do now only have to link these negative effects of air pollution on BDNF, the counter-intuitive circle of stress, cognitive abilities, exercise, the (female) athlete triad, BDNF and air pollution with the high correlation of daily emergency department visits for depression and air pollution Szyskowicz et al. observed in 2009 (Szyszkowicz. 2009) and the recently proposed necessity of adequate IGF-1 levels (as you know those are rock bottom in people suffering from the athlete triad) for BDNF to be able to exert its antidepressive effects, properly, and their suggestion to simply bump those up, with intranasal IGF-I so that you would have a novel, "plausible and promising treatment option of depression" (Paslakis. 2013).

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Figure 3: The effects 0.05% piperine had on the fatty acid metabolism and storage of the HFD group was so pronounced that they ended up with a better visceral fat / body weight ratio than their peers in the control group (Jwa. 2013)

Piperine will get you lean This does not simply rhyme, according to a very recent study from the Yonsei University in Seoul, it could also be true (Jwa. 2013). At least in the rodent study Jwa et al. conducted in order to check, whether their promising in-vitro data would translate from the petri dish into the "real world" of a rodent cage, the addtion of 0.05% piperine to the chow of mice that were kept on a hypercaloric high fat diet did not just "markedly decrease LXRα mRNA expression and its lipogenic target genes (i.e., SREBP1c, ChREBPα, FAS, and CD36)" (check out figure 1 for the real world consequences of these epigenetic changes), it also lead to statistically highly significant reductions in plasma insulin and glucose concentrations, while concomitantly increasing the insulin sensitivity of the rodents.

"In addition, piperine downregulated the expression of genes involved in ER stress, including GRP78, activating transcription factor 6, and eukaryotic translation initiation factor 2α, and upregulated GLUT2 translocation from the cytosol to the plasma membrane in the livers of PSD mice." (Jwa. 2013)

In conjunction with the aforementioned epigenetic reprogramming of genes that are involved in the oxidation (upregulated) and formation (downregulated) of lipids, piperine's modulatory effect on the liver X receptor α  (LXRα) expression does thus entail a bi-variate anti obesity / metabolic syndrome effect that counters both of the two hall-mark features of diet-induced metabolic derangements: high blood glucose levels and lipid accumulation.

That I would still like to see human data on the efficacy and safety of this approach is yet not the least related to previous research which suggests that piperine does not just mess around with the cytochrome P450 enzymatic cascade (among others with the enzyme that is also responsible to clear estrogen from the body), which is by the way also the most likely explanation that bioperine "improves the bioavailability" of all sorts of supplements - it simply hampers their metabolism and subsequent excretion (Najar. 2011)

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In the minutes up to the orgasm "excitement" spreads in a chain reaction from the genital sensory cortex all over the brain (img whatsonxiamen)

Female orgasm? What's it good for, I mean "biologically" ;-) Probably some of you will have heard the SuppVersity Science News Round Up which broached the issue of anorgasmia (=inability to get an orgasm) in women. Now, while it is pretty much indisputable and straight forward that those women who are affected by this condition are missing out with respect to the literal climax of sexual intercourse, the potential biological consequences are actually less obvious.

In a recent article in The Science in Society Review, Claire Wilson points out that due to the complexity and the fact that it cannot be empirically measured, scientists have always been wondering, why the female orgasm even exists, "as its evolutionary significance is unclear compared with the male orgasm’s explicit connection to reproduction." Among the more prominent theories are among others:

• the evolutionary / physiological "byproduct" theory
• the socio(-evolutionary) "cryptic choice" theory and 
• the (bio-)mechanistic "sperm upsuck" theory

From a mere mechanistic perspective, the latter, i.e. the proposal that the "uterine contractions may cause the cervix to lower into the seminal pool, resolving the obstacles against sperm transport posed by vaginal tenting" certainly appears to be most straight forward, as the actual orgasm is in fact accompanied by powerful striated muscles that surround the vagina producing rhythmic contractions in 0.8s intervals.

Video 1: Meg Ryan aka Sally in When Harry Meets Sally is not just an example of an evolutionary nonsensical orgasm. The popularity of the scene is also testimony of how exciting (all puns intended) the topic.

What's problematic about this theory is that according to Meston et al. some women report having experienced an orgasm when no contractions were observed (Meston. 2004). Moreover,

"non-genital stimulation, dreams, hypnosis, and even mental concentration have all been shown to produce orgasm in certain women, highlighting the critical role of the brain and psychology in female sexual response." (Wilson. 2013)

These observations would also speak against the "byproduct" theory according to which the female orgasm is just an unnecessary remnant or evolutionary "byproduct" of both sexes developing from the same embryological structure, much like how males develop nipples without any gender-specific need for them (Wallen. 2008).

In a way likewise of evolutionary (though more socially than biologically) origin is the "cryptic choice" theory, according which regards the "females’ greater difficulty in achieving orgasm" as an incentive "for taking multiple mates among pre-human ancestors" thus promoting the confusion over their offspring’s biological sires and consequently entrusting their care to the whole of the society (Thornhill. 1996). Others argue that unreliable orgasms may bond females to those males capable of eliciting

"Many 'cryptic choice' theorists furthermore believe that the inconspicuous nature of the female orgasm may aid in selecting which partners’ sperm make it to the egg. For instance, one study found that males’ body symmetry - a trait indicative of stable genes - predicted frequency of orgasm in their female partners." (Wilson. 2013)

"I think women rule the world and that no man has ever done anything that a woman either hasn't allowed him to do or encouraged him to do."

-Bob Dylan

Yet whatever the exact "reason" (if you can even talk about that in this context) of the female orgasm may be, in the end, it is just as Claire Wilson states: "The male sex drive may have played the major role in ensuring that future generations exist, female psychology may have had a major role in deciding what they are like." (Wilson. 2013) Why does that sound to me much like what Bob Dylan once said about the relation between men and women (see box on the right)?

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Video 2: TAFE NSW video tutorial on how to measure the sub-scapular skinfold thickness. I guess it is obvious that you can hardly do that without the help of someone else ;-)

What skinfold thickness tells you about insulin resistance in adolescents was at the center of the statistical analysis O.Yaw Addo, Mark A. Pereira and John Hime ran on a subset of the cross-sectional data of 1496 adolescents (age 12.0–17.99y) from the US national health and nutrition examination survey (NHANES) cycles 2001–04.

According to their results, simply measuring the subscapular skinfold thickness (SF technique; see video 2 for how it's done) could provide an as reliable indicator of high risk of being / developing insulin resistance as an expensive X-ray absorptiometry (DXA) based body fat analysis (DTF technique):

"When the top quintiles of predicted HOMA-IR values from the SF and DTF models were
crosstabulated to identify adolescents at highest risk of insulin resistance, the exact agreement (efficiency) exceeded 92% in both sexes. Therefore, both in terms of estimating fatness-related contributions to measured HOMA and also in identifying those at most risk of insulin resistance, subscapular and triceps skinfold thickness compared well with DXA total body fat as estimators of insulin resistance in adolescents." (Addo. 2013)

While statistically non-significant, the skinfold method was even more precise than the DXA scans in view of it's prognostic value as a tool for estimating continuous HOMA IR with adiposity measures.

Compared to the group average, each 1 millimeter increase in subscapular skinfold thickness was associated with a ~1.5% increase in HOMA-IR in boys and girls.

Another interesting side-finding of the study was that after a transient rise during puberty the average HOMA-IR (by the way a measure of long-term blood sugar levels) returned to pre-pubescent in many of the adolescents. The effect was most pronounced in boys and showed a high interaction with the pubertal increase in body height.

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NOPE + EGCG for practical diet help instead of overhyped fat burner!? I know that sticking to a diet and simply giving it time to do its magic does not sound half as sexy as taking the blue, red, yellow or whatever pill and shedding 4kg of pure fat within two weeks while you simply continue to eat the same junk that has made you obese in the first place, but the reality is - there is no such pill on the market and the one non-OTC "pill" I could think of that could do just that is toxic, has been used to produce ammunition in the first world war and will literally have you melt away.

NOPE, no idea what that is? The acronym stands for N- oleoyl- phophatidyl-ethanolamine, a naturally occurring phospholipid found in animal (fish) and vegetable (cereals, soy) food that is hydrolyzed into N-oleyl-ethanolamide (NOE) and phosphatidic acid when during the digestive process. The former of these, i.e. NOE has an inhibitory effect on the expression of the endocannbinoid anandamide (N- arachidonyl- ethanolamine). The latter leads to an increase in appetite and, consequently, an intake of food (Fu. 2003). In rats, an intra-peritoneal injection of NOE has been shown to promote an anorexic effect through the activation of several intestinal receptors, which signal the brain center to reduce food intake (Broccalli. 2005).

With N-oleoyl-phophatidyl-ethanolamine which occurs naturally in various animal and vegetable foods, and EGCG, of which I guess that all of you know that it stands for the unpronounceable green tea constiutent epigallocatechin gallate, Chemi Nutra, the manufacturer of PhosphoLean™ promises to have found a natural alternative that will help you by making it easier for you to stick to your diet.

And in fact, if we assume that the  40 mg of NOPE, 35 mg of EGCG and 25 mg of mixed phospholipids each serving of those pills contains, will have the same effect on you, as it had on the 50 healthy, but obese adults (35 female, 15 male; 32.7 ± 13.7 years; BMI = 33.4 ± 6.2; 43.2 ± 7.2% Body Fat), you will feel

• more relaxed instead of more tense*,
• happier instead of more depressed,
• less angry instead of angrier,
• much more vigorous instead of exhausted*, and
• less confused instead of jazzed

while you are dieting. Unfortunately, those inter-group differences, which were evaluated by questionnaires were statistically significant only for those parameters I marked with an asterisk (*). Moreover, the purported psychological edge translated directly into a higher compliance, for the first four weeks only. It is therefore not very surprising that the overall changes in body composition in response to 8 weeks of -500 kcal or 30% (maximum of 1000 kcal) reduction in caloric intake and voluntary exercise (subjects were "encouraged to exercise 30 minutes per day, three times per week") were not significantly different.

The fact that there was a trend towards greater improvements in body composition in the placebo group, however, is surprising. So surprising, in fact, that it made me take a look at the funding of the study: "This study was supported by a grant from Chemi Nutra, White Bear Lake, MN" (Mangine. 2013) - must be coincidence that the researchers didn't mention this trend, right?

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That's it for today, at least as far as the "On Short Notice" news here at the SuppVersity are concerned. If you want more, I suggest you take a closer look at the SuppVersity Facebook Wall, as well, where you will find (among a lot of other news) infobits on ...

• a novel Anti-Alzheimer's drug that's based on a substance those of you who have been faithfully listening to Super Human Radio, even before the SuppVersity Science Round Up  was born will be familiar with, methylene blue,
• even more on BDNF and its role in morphine addiction, including some insightful comments by Kamal Patal, the brain behind the PAINDatabase,
• Pycnogenol(R) not delivering on all of the promises the producers of respective products are making, but does exert somewhat unexpected protective effects against hexavalent chromium induced spermatotoxicity, and lastly
• CAD assisted insights into the endocrine side effects of the evil metabolic byproducts of bisphenol A and the association of BPA exposure with thyroid hormone abnormalities in mothers to be and their offspring

... as well as the handful of additional items I am probably going to post in the course of the next 24h before the third installment of the SuppVersity Athletes Triad Series will provide you with novel reading material ;-)


References:

• Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol 2009: 107: 1144–1155.
• Bos I, De Boever P, Int Panis L, Sarre S, Meeusen R. Negative effects of ultrafine particle exposure during forced exercise on the expression of Brain-Derived Neurotrophic Factor in the hippocampus of rats. Neuroscience. 2013 Oct 25;223:131-9.
• Broccali GBM, Pistolesi E, Cestaro B: N-oleoylphosphatidylethanolamine reduces food intake and body weight of dietary obese rats ameliorating their antioxidant status. Gazzeta Medica Italiana Archivo Per Le Scienze Mediche 2005, 164:101–107.
• Calderón-Garcidueñas L, Solt AC, Henríquez-Roldán C, Torres-Jardón R, Nuse B, Herritt L, Villarreal-Calderón R, Osnaya N, Stone I, García R, Brooks DM, González-Maciel A, Reynoso-Robles R, Delgado-Chávez R, Reed W. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults. Toxicol Pathol. 2008 Feb;36(2):289-310.
• Calderón-Garcidueñas L, Kavanaugh M, Block M, D'Angiulli A, Delgado-Chávez R, Torres-Jardón R, González-Maciel A, Reynoso-Robles R, Osnaya N, Villarreal-Calderon R, Guo R, Hua Z, Zhu H, Perry G, Diaz P. Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults. J Alzheimers Dis. 2013;28(1):93-107.
• Chen JC, Schwartz J. Neurobehavioral effects of ambient air pollution on cognitive performance in US adults. Neurotoxicology. 2009 Mar;30(2):231-9. Epub 2008 Dec 30.
• Chohan M, Naughton DP, Jones L, Opara EI. An investigation of the relationship between the anti-inflammatory activity, polyphenolic content, and antioxidant activities of cooked and in vitro digested culinary herbs. Oxid Med Cell Longev. 2013;2013:627843.
• Christensen PM, Nyberg M, Bangsbo J. Influence of nitrate supplementation on VO(2) kinetics and endurance of elite cyclists. Scand J Med Sci Sports. 2013 Oct 1.
• Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodriguez De Fonseca F, Rosengarth A, Luecke H, Di Giacomo B, Tarzia G, Piomelli D: Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 2003, 425:90–93.
• Hanlon N, Coldham N, Gielbert A, Kuhnert N, Sauer MJ, King LJ, Ioannides C. Absolute bioavailability and dose-dependent pharmacokinetic behaviour of dietary doses of the chemopreventive isothiocyanate sulforaphane in rat. Br J Nutr. 2008 Mar;99(3):559-64.
• Jwa H, Choi Y, Park UH, Um SJ, Yoon SK, Park T. Piperine, an LXRα antagonist, protects against hepatic steatosis and improves insulin signaling in mice fed a high-fat diet. Biochem Pharmacol. 2013 Sep 20. pii: S0006-2952(12)00640-5.  
• Kingston University London. Press Release: Researchers challenge super food claims. October 01, 2013 < http://www.kingston.ac.uk/pressoffice/news/461/01-10-2013-researchers-challenge-super-food-claims.html > last accessed on October 03, 2013.
• Lansley KE, Winyard PG, Fulford J, Vanhatalo A, Bailey SJ, Blackwell JR, Dimenna FJ, Gilchrist M, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study. J Appl Physiol 2011: 110: 591–600.
• Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 2005 Jan;81(1 Suppl):230S-242S.
• Mangine GT, Gonzalez AM, Wells AJ, McCormack WP, Fragala MS, Stout JR, Hoffman JR. The effect of a dietary supplement (N-oleyl-phosphatidyl-ethanolamine and epigallocatechin gallate) on dietary compliance and body fat loss in adults who are overweight: A double-blind, randomized control trial. Lipids Health Dis. 2013 Oct 4;11(1):127.
• Meston CM, Levin RJ, Sipski ML, Hull EM, Heiman JR (2004). Women’s orgasm. Annual Review of Sex Research, 2004;15:173-257.
• Mullen W, Borges G, Donovan JL, et al. Milk decreases urinary excretion but not plasma pharmacokinetics of cocoa flavan-3-ol metabolites in humans. Am J Clin Nutr. 2009; 89:1784–1791.
• Najar IA, Sharma SC, Singh GD, Koul S, Gupta PN, Javed S, Johri RK. Involvement of P-glycoprotein and CYP 3A4 in the enhancement of etoposide bioavailability by a piperine analogue. Chem Biol Interact. 2011 Apr 25;190(2-3):84-90. 
• Paslakis G, Blum WF, Deuschle M. Intranasal insulin-like growth factor I (IGF-I) as a plausible future treatment of depression. Med Hypotheses. 2013 Aug;79(2):222-5. Epub 2013 May 23.
• Ranft U, Schikowski T, Sugiri D, Krutmann J, Krämer U. Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly. Environ Res. 2009 Nov;109(8):1004-11.
• Rechner AR, Kuhnle G, Bremner P, Hubbard GP, Moore KP, Rice-Evans CA. The metabolic fate of dietary polyphenols in humans. Free Radic Biol Med. 2002 Jul 15;33(2):220-35.
• Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. J Nutr. 2000 Aug;130(8S Suppl):2073S-85S.
• Suglia SF, Gryparis A, Wright RO, Schwartz J, Wright RJ. Association of black carbon with cognition among children in a prospective birth cohort study. Am J Epidemiol. 2008 Feb 1;167(3):280-6.
• Szyszkowicz M, Rowe BH, Colman I. Air pollution and daily emergency department visits for depression. Int J Occup Med Environ Health. 2009;22(4):355-62.
• Thornhill R, Gangestad SW. Human female copulatory orgasm: a human adaptation or phylogenetic holdover. Animal Behaviour, 1996;52(4):853–855. 
• Vanhatalo A, Bailey SJ, Blackwell JR, Dimenna FJ, Pavey TG, Wilkerson DP, Benjamin N, Winyard PG, Jones AM. Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am J Physiol Regul Integr Comp Physiol 2010: 299: R1121–R1131.
• Wallen K, Lloyd, EA. Clitoral variability compared with penile variability supports nonadaptation of female orgasm. Evolution & Development, 2008;10(1):1-2.
• Wilson, C. The Mysterious Function of the Female Orgasm. The Triple Helix - A Global Forum For Science In Society. 2013; 17.
• Yau SY, Lau BW, Zhang ED, Lee JC, Li A, Lee TM, Ching YP, Xu AM, So KF. Effects of voluntary running on plasma levels of neurotrophins, hippocampal cell proliferation and learning and memory in stressed rats. Neuroscience. 2013 Oct 11;222:289-301.

6x Bananas a Day!? Meta-Analysis: Lower Glucose, Insulin and HbA1c Levels From 'Catalytic' Dose of 36g Fructose

Figure 1: At least according to the USDA data, the average US citizen did never in the last 40 years get even close to the "catalytic" dose of fructose - at least not if we go by his / her daily HFCS consumption.

I usually don't start these articles with a disclaimer, but in this case I want to make sure that this post is not misinterpreted as a corn-refiners advertisement (and contrary to one of the authors of the Sievenpiper study, Coca Cola has unfortunately as of yet never covered my travel expenses ;-)... anyways, whenever the word "fructose" is used in the following lines it to the simple monosaccharide found as part of a complex nutrient matrix in many plants and their fruits (who would have expected that?). It is not used to denote the controversial results of a three-step enzymatic isolation process (Cornstarch → alpha-amylase → oligosaccharides + glucoamylase →  glucose + xylose isomerase →  42% fructose + 50–52% glucose + other sugar; cf. Wikipedia. "High Fructose Corn Syrup") that's at the heart of a very emotional debate about who would be to blame for the current obesity epidemic, now that the bad fats are no longer bad enough to be the scapegoat and ultima ratio for why we get fat.

Junk food is more than HFCS and fruit is more than fructose!

Fortunately, you, as a "whole food eating" SuppVersity reader, don't really have to care about the whole HFCS business. With your minimal intake of processed foods, your exposure to high fructose corn syrup should ideally be identical to the one of the parents and grandparents of America's obese children in the flower power seventies (~0.1-1g, see figure 1); a time, when your parents would not tell you to "beware of high fructose corn syrup", but to stay away from "those hairy, drug-addicted, reprobate hippies next door". Against that background, today's SuppVersity article is to be understood as an incentive to rethink, whether or not it is really necessary, let alone beneficial to deprive yourself of a whole class of vitamin and micronutrient-laden foods, simply because they contain a small number of molecules of which you are told that they "must not to be eaten, if you want to stay lean & healthy".

To help your thought process along, I have compiled the data from a recently published meta-analysis (that's a study, the results of which are based on data from multiple previous trials, which was weighed and compiled to come up with "new" data with a larger empirical foundation and thus greater significance). And I am honestly curious whether or not the evidence Sievenpiper and his colleagues presented in favor of the existence of a"catalytic dose" of  ≤36g/day of fructose that's been shown to improve, not compromise, blood glucose, insulin and HBA1C, when it is consumed instead of 36g of carbs from other sources (the studies in the review used either starches or simple sugars with almost identical beneficial results, by the way) will have catalytic effects on your opinion making process ;-)

Figure 2:  Effect of isoenergetic exchange of "catalytic" fructose doses (≤36g/d) for other carbohydrates (starches or simple sugars) on glycaemic endpoints: HbA1c, fasting blood glucose and fasting blood insulin, data calculated based on analysis of the scarce literature that is currently available (adapted from Sievenpiper. 2013)

The improvements in HbA1C, which is still the gold standard for evaluating long-term blood sugar level, in fasting blood glucose and insulin levels were across the board statistically significant, regardless of whether or not you apply the quality criteria, Sievenpiper and his colleagues used to weigh the results of the individual studies (cf. figure 2). Accordingly, the authors are right, when they point out that

[...] this small meta-analysis of controlled feeding trials supports earlier13C NMR spectroscopy investigations and acute feeding studies showing that ‘catalytic’ doses (≤36g/d) of fructose may improve glycaemic control [and that this] benefit is seen without the adverse cardiometabolic effects reported when fructose is fed at high doses or as excessenergy. (Sievenpiper. 2013)

Based on the data in figure 1, which clearly shows that the "average American" does not and never did pass this "catalytic threshold level" it may - at first sight appear odd that 42% of your countrymen and -women are supposed to be obese by the year 2030 (Hellmich. 2013)... at least for so long until you realize that for every American who follows your lead and consumes virtually no HFCS, there must be another one who consumes this person's 43.3g of HFCS on top of his own 43.3g of HFCS on a daily basis and would thus easily surpass the "scientifically proven" catalytic threshold levels which was (and I leave it up to you to decide whether this is coincidence or not) in none of the studies achieved from HFCS intake, by the way (I guess I don't have to tell you that my calculation is of mere illustrative nature, despite the fact that the 43.3g /day HFCS intake are actually from the USDA dataset for 2010).

Bad news for the guy who eats / drinks your daily share of 43.3g of high fructose corn syrup, ...

...but what does that mean for you? As long as your only significant fructose source are whole fruits and the few vegetables that contain more than trace amounts of fructose, you can answer this question by taking a look at the data in figure 3. The small figures on top of the bars will tell you how many 100g servings of apples, dates, pears or tomatoes you can consume until you hit the catalytic limit*uhuhhh...*: 3.9x 100g servings, of apples, for examples, or 5x 100g servings of bananas, or a whopping 32.7x 100g servings of lemons... sounds plenty? Well, I don't know, but certainly plenty enough to finally stop worrying when Adelfo Cerame would not ruin his health, let alone his physique, when he eats a banana along with his postworkout shake, wouldn't you agree?

Figure 3: Number of 100g servings of various common fruits to get to the more or less arbitrary  ≤36g/day threshold.

Notwithstanding, this ≤36g/day limit does certainly appears more or less arbitrary. This is all the more true in face of previous results by Livesey & Taylor, who could not find evidence that such a thing as a "threshold dosage" for the Hb1AC improving effects of fructose even exists (Livesey. 2008) or the fact that a "low-GI fruit intake [and not the number of servings of fiber-laden cereals!] was the strongest independent predictor of [lowered] HbA1c" in a 2011 6-months low-GI diet experiment by Jenkins et al. who compared Kellog's... ah, pardon me, I meant the medical orthodoxy's gold standard, the high-cereal fiber diet in 152 participants with type 2 diabetes with a simple low-GI diet (Jenkins. 2011).

Can ≤35g of fructose per day really be the answer to everything?

Though the main reason for the arbitrariness of the 36g limit certainly is the scarcity of valid experimental data from well-controlled human trials, Sievenpieper et al. claim that their reference for the "catalytic range" was in accordance with "an emerging literature" that "has shown that low-dose fructose (≤10g/meal) may benefit glycaemic control".

Now, those of you who have read my "Carbohydrate Shortage in Paleo Land" post from back in June 2011, will probably remember that from a mere physiological point of view every healthy (=nondiabetic and with an intact liver) human being, including the tiniest woman, should be able to handle a minimum of ~100g of carbohydrates on a daily basis. If we now take the 2:1 glucose to fructose ratio, of which Walliset al. found that it is just as effective in repleting muscle gylcogen stores after a workout as the same amount (90g) of pure glucose, and apply it to the 36g fructose threshold this yields a "total carbohydrate threshold" of 108g - coincidence or physiological necessity?

And even when you didn't replace some of the starches or other simple sugars for your daily dose of 2kg of apples (another example of exclusively illustrative nature), you would maybe get fatter, but according to the results of Silbernagel et al. not a single gram fatter than from the same amounts of calories from glucose from fructose or glucose conducted with healthy young men; cf. Silbernagel. 2011).

You can have another apple today and will still (or rather hence?) live tomorrow ;-)

Image 3 (edited in response to anon & JP, thx!): Certainly impressive what lifelong caloric restriction did to the 27.6 year-old ape on the right, if you take a look at his wrinkled age-mate on the left, no? Suggested read: "Health and Longevity Effects of Intermittent Fasting"

Overall it does therefore seem more than unlikely that a healthy, non-sedentary or even athletic individual has to worry about eating another apple, when he or she already reached their purported catalytic limit of 36g with the pound of blackberries, two bananas and a huge grapefruit this person could have eaten earlier in the day.

Moreover, skipping on the apple would also mean that you would miss out on its recently confirmed life-extending effects (+130% in yeast; Palermo. 2013), of which Vanessa Palermo and her colleagues from the Dept. of  Biology and Biotechnology “Charles Darwin” have shown that they are the prerogative of the whole fruit and not a result of the high antioxidant or polyphenol content of apples, as they occurred only, when the yeast is treated with a handcrafted extract that had approximately 26.7 g/100ml of fresh apple in it... and guess what, that apple, Golden Delicicious, happens to be one of my personal favorites, taste-wise, or course ;-)

Bottom line: I know it is more than questionable to which extend (1:20, 1:100, not at all?) the lastly cited life-prolonging effects of whole apples can be extrapolated to human beings, but that does neither diminish the perplexing results of Sivenpiper's meta-analysis nor long-established cancer protective effects of fruits in general and apples in particular (eg.  Veeriah. 2006;  McCann. 2007; Yoon, 2007; Gerhauser. 2008; Zessner. 2008; Jedrychowsk. 2009; Liu. 2010; Reagan-Shaw. 2010) and should therefore suffice to put more than a non-legible font-size "1" questionmark behind any previously taken decision of yours that it would be better to deprive yourself of these delicious superfoods (=fruits) than trust on your livers ability to to what she has evolved to do and turn the slow influx of relatively low amounts of fructose and glucose into energy and deliver the rest of the vitamins, polyphenols, and other micronutrients via the bloodstream to other organs.

References:

• Gerhauser C. Cancer chemopreventive potential of apples, apple juice, and apple components. Planta Med. 2008 Oct;74(13):1608-24. Epub 2008 Oct 14. Review. 
• Hellmich J. Obesity could affect 42% of Americans by 2030. USA TODAY. Aug 05, 2013 < http://www.usatoday.com/news/health/story/2013-05-07/obesity-projections-adults/54791430/1 > accessed Aug 07, 2013
• Jandrain BJ, Pallikarakis N, Normand S, Pirnay F, Lacroix M, Mosora F, Pachiaudi C, Gautier JF, Scheen AJ, Riou JP, et al. Fructose utilization during exercise in men: rapid conversion of ingested fructose to circulating glucose. J Appl Physiol. 1993 May;74(5):2146-54.
• Jedrychowski W, Maugeri U. An apple a day may hold colorectal cancer at bay: recent evidence from a case-control study. Rev Environ Health. 2009
• Jenkins DJ, Srichaikul K, Kendall CW, Sievenpiper JL, Abdulnour S, Mirrahimi A, Meneses C, Nishi S, He X, Lee S, So YT, Esfahani A, Mitchell S, Parker TL, Vidgen E, Josse RG, Leiter LA. The relation of low glycaemic index fruit consumption to glycaemic control and risk factors for coronary heart disease in type 2 diabetes. Diabetologia. 2011 Feb;54(2):271-9. 
• Livesey G, Taylor R. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am J Clin Nutr. 2008; 88, 1419–1437. 
• Liu L, Li YH, Niu YB, Sun Y, Guo ZJ, Li Q, Li C, Feng J, Cao SS, Mei QB. An  apple oligogalactan prevents against inflammation and carcinogenesis by targeting LPS/TLR4/NF-κB pathway in a mouse model of colitis-associated colon cancer. Carcinogenesis. 2010 Oct;31(10):1822-32. 
• McCann MJ, Gill CI, O' Brien G, Rao JR, McRoberts WC, Hughes P, McEntee R,  Rowland IR. Anti-cancer properties of phenolics from apple waste on colon carcinogenesis in vitro. Food Chem Toxicol. 2007 Jul;45(7):1224-30. 
• Reagan-Shaw S, Eggert D, Mukhtar H, Ahmad N. Antiproliferative effects of apple peel extract against cancer cells. Nutr Cancer. 2010;62(4):517-24. 
• Palermo V, Mattiv, F, Silvestri R, La  Regina G, Falcone CM. Oxidative Medicine and Cellular Longevity. 2013 [Article in press]
• Sievenpiper JL, Chiavaroli L, de Souza RJ, Mirrahimi A, Cozma AI, Ha V, Wang DD, Yu ME, Carleton AJ, Beyene J, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ. 'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials. Br J Nutr. 2013 Aug;108(3):418-23.
• Silbernagel G, Machann J, Unmuth S, Schick F, Stefan N, Häring HU, Fritsche A.Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Br J Nutr. 2011 Jul;106(1):79-86. 
• Veeriah S, Kautenburger T, Habermann N, Sauer J, Dietrich H, Will F, Pool-Zobel BL. Apple flavonoids inhibit growth of HT29 human colon cancer cells and modulate expression of genes involved in the biotransformation of xenobiotics. Mol Carcinog. 2006 Mar;45(3):164-74. 
• Wallis GA, Hulston CJ, Mann CH, Roper HP, Tipton KD, Jeukendrup AE. Postexercise muscle glycogen synthesis with combined glucose and fructose ingestion. Med Sci Sports Exerc. 2008 Oct;40(10):1789-94.
• Wikipedia contributors, "High-fructose corn syrup," Wikipedia, The Free Encyclopedia, < http://en.wikipedia.org/w/index.php?title=High-fructose_corn_syrup&oldid=505539604 > accessed August 7, 2013. 
• Yoon H, Liu RH. Effect of selected phytochemicals and apple extracts on  NF-kappaB activation in human breast cancer MCF-7 cells. J Agric Food Chem. 2007  Apr 18;55(8):3167-73. Epub 2007 Mar 21.
• Zessner H, Pan L, Will F, Klimo K, Knauft J, Niewöhner R, Hümmer W, Owen R,  Richling E, Frank N, Schreier P, Becker H, Gerhauser C. Fractionation of polyphenol-enriched apple juice extracts to identify constituents with cancer chemopreventive potential. Mol Nutr Food Res. 2008 Jun;52 Suppl 1:S28-44.

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. 2013)

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. 2013), 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. 2013), 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. 2013)

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. 2013)

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. 2013; 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. 2013). 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. 2013).

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. 2013)

  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. 2013), 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 2013 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, 2013) 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. 2013).
  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. 2013)! 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 T3 to T4 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 . 2013)

  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. 2013). 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 ;-)

References:

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