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. 2012).

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. 2012) 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. 2012)

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. 2012)

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. 2012)

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. 2012).

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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. 2012)

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. 2012). 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. 2012)

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. 2012)

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. 2012)

"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. 2012) 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. 2012)

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. 2012) - 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. 2012 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. 2012;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. 2012;2012:627843.
• Christensen PM, Nyberg M, Bangsbo J. Influence of nitrate supplementation on VO(2) kinetics and endurance of elite cyclists. Scand J Med Sci Sports. 2012 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. 2012 Sep 20. pii: S0006-2952(12)00640-5.  
• Kingston University London. Press Release: Researchers challenge super food claims. October 01, 2012 < http://www.kingston.ac.uk/pressoffice/news/461/01-10-2012-researchers-challenge-super-food-claims.html > last accessed on October 03, 2012.
• 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. 2012 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. 2012 Aug;79(2):222-5. Epub 2012 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. 2012; 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. 2012 Oct 11;222:289-301.

6 + 1 Convincing Reasons You Should Not Subscribe to the "Chocolate is Good For You" Hype Indiscriminately. Plus: Which Chocolate is the Healthiest? Organic, Baking, Dark?

Your hedonic response usually isn't a good food guide

I have never been a great chocolate eater, and the soothing and misleading news about research that would show that chocolate consumption was good for your heart, your brain and your belly have not yet changed this.

For a good reason, as I should say. Being written for the average inhabitant of the Western Obesity Belt, the authors of these articles willingly accept that their readers will (mis-)understand them as a soothing incentive not just to maintain their overtly hedonistic lifestyle, but to top it off with an extra portion of super-sized chocolate cookies... I mean, it's "chocolate", right? So it's good for you, even the latest science says so, right? And not just that, even the NY Times writes chocolate is a "health food" (NY Times. 2009)

Right, science says: Chocolate is good for you! But when we look closer, the chocolate that is good for you has little to no resemblance to the candy bars the lady in the photo is savoring. What scientific research really says is that small amounts of real chocolate and somewhat larger amounts of artificially pimped high polyphenol chocolate are good for you; and it goes without saying that this constraint excludes 99% of the chocolate and allegedly "chocolate" containing foods that are sold at supermarkets and even health food stores.

Most of the "chocolate" on the market makes you fat, diabetic, hypertensive, and forgetful

Yes, you hear me right. Regular (milk) chocolate with a phenol content of <5 gallic acid equivalents (that's the unit you use to measure the total amount of polyphenols in a given product), and the average dark chocolate with a phenol content of <15 gallic acid equivalents have the same pro-obesogenic effect as the low-polyphenol chocolate in a recent study by Farahat et al. (2014).

Figure 1: The unfortunate truth is, for most people "bad things" happen, when they eat more chocolate.

As you can see in Figure 1, consuming only 20g/day (=one bar) of the low-polyphenol chocolate for 4 weeks had the already overweight and obese subjects of Farhat's study gain ~500g of what certainly wasn't "muscle weight". Over the course of one year this would be 6kg of extra weight - 6kg of which a 1997 study by Ford et al., the results of which are based on data from the National Health and Nutrition Examination Survey (NHANES), shows that they would increase your type II diabetes risk by a whopping 19%!

You can learn more about chocolate at the SuppVersity

Chocolicious Statin 4 Women

Real Cacao Delicious + More

The Female Chocolate Diet

Fattening Effects of Zero Fat Drinks

Tomaotorade(R) Intra-Workout

Too much ado about protein?

Those 6kg of extra weight will also more than double your risk of hypertension (Stevens. 2002) and thus increase your risk of stroke, heart & kidney disease and dementia (Chobanian. 2003).

Real chocolate, on the other hand, will nor make you fat, improve your blood lipids, ...

I guess before I will give away the actual three reasons, why eating real chocolate (in moderation), may be a good idea, it's worth defining the word "real" which, in this case, refers to the chocolate and polyphenol content of the brownish bars and powders you can buy in the supermarket, grocery and specialty stores.

And as the tabular overview of the polypenol content and total antioxidant activity in Table 1 goes to show you, the latter, i.e. the specialty store, may not even always be the best choice. With a total phenol content of 26-29 gallic acid equivalents, the cheap baking chocolate is after all a viable alternative to the expensive organic cacao powder, of which I don't have to tell you that it will be hard to "eat", anyway (click here to see the brands | the scientists say it's not the same order as in Table 1):

Table 1: Analysis of Selected U.S. Cocoa-Containing and Chocolate Products; CP, cocoa powder; BC, baking chocolate; DC, dark chocolate; SSC, semisweet chocolate chips; MC, milk chocolate; CS, chocolate syrup. b - VCEAC units expressed as vitamin C equivalents(mg/g), c - total polyphenols expressed as gallic acid equivalents (Miller. 2009)

The data in Table 1 does yet also show you that "dark chocolate", which is probably what most people who have at least some brains left in spite of a life of SAD dieting, is not really much healthier than conventional milk chocolate. Yes, it has twice as much polyphenols in that's still more than 50% less than you would get from baking chocolate and thus probably eventually so low that it's questionable whether the often-cited health benefits will eventually be realized.

Table 1: Study Examples - Cocoa and Cardiovascular Risk Factors (Minor. 2014). Impressive as they may be, all these beneficial effects were observed when "real" chocolate was tested against "regular" chocolate.

In the end, this may also depend on whether the chocolate is eaten instead of the common SAD junk-food diet or on top of it. The overall beneficial health effects on blood pressure Hensen and Deborah S. Minor summarized in their latest paper in the Journal of Clinical Hypertension, for example, were all observed in trials where a flavenol / polyphenol rich chocolate was compared to a regular milk or low polyphenol dark chocolate.

Impressive as they may be, there is little doubt that the increases in HDL, flow-mediated dilitation (FMD), insulin sensitivity, and beta cell function, and the corresponding decreases in total cholesterol, LDL, blood pressure & co (see Table 1) will not occur in the average press release reader who picks up the next best super-size pack of chocolate at the supermarket after reading how healthy chocolate eventually is for him / her.

Against that background it's even more important to raise the awareness of often-voiced, but rarely published concerns and reservations respectable scientists have advanced with respect to the constant pimping of chocolate as a health food. Six of them have been aptly compiled by F. Willford Germino in a 2013 comment on the previously referenced article by Minor & Minor (2013):

• Publication bias. Positive results of studies get published while negative results are relegated to the back of the file cabinet, never to see the light of day or word in print. This is particularly an issue with studies that may be investigator-generated and not registered.
• Limited enrollment. Generally, only small numbers of patients were included in the study populations, with enrollees usually numbering in the low double digits. The largest study included in this review comprised only 152 patients, perhaps enough to suggest some statistical benefit, but insufficient to convince most.
• Short duration. The studies are typically short-term, lasting hours to days, with the longest study period lasting 18 weeks. Recommendations regarding long-term therapy require longer-term studies to demonstrate that efficacy continues with extended usage.
• Soft endpoints. The studies often incorporated surrogate soft endpoints (effects on nitric oxide, flow-mediated dilation, and platelet aggregation), with the assumptions that there may be a correlation with hard cardiovascular endpoints. These studies, although provocative, have often failed to demonstrate universal clinical correlation. Even modest BP reductions, when found and reported, have been seen in only a small number of patients for short periods. Additionally, the only metric used to determine BP were readings performed in the office.
• Double-blind issues. Challenges exist in the investigation of chocolate to achieve a true double-blind test. Chocolates have various tastes, colorations, and textures and any attempt to investigate the properties of one vs another must control for this. The value of single-blind studies needs to be proven.
• Translation. Flavanols are the putative active compound in chocolate that results in possible health benefit, but chocolate formulations are more varied than coffee. Broadly speaking, dark chocolates, bitter and less creamy and smooth, are of far greater benefit that the more pleasing to the American palate milk chocolate. Yet, patients will often attribute possible benefit of one to the other. Additionally, there is little in the way of standardization among chocolates to know the actual content of active compound in each sold product.

Even as a SuppVersity reader it's possible that you have not heard about all of these objections before. No wonder, there is after all, as Minor & Minor point out, certainly not the same degree of interest among patients as to whether or not 8 daily Brussels sprouts might provide similar cardiovascular protection as chocolate.

Already available brussel sprout chocolate.

"Chocolate is often associated with special occasions, holidays, and festivities. It is often displayed in boxes, wrapped, and meant to be something special, and, as such, evoke warm feelings in many, harkening back to earlier, happy times as a comfort food.

Certainly this bears little resemblance to the 'charms' of Brussels sprouts." (Minor. 2013)

Well, if only they knew that you can already buy "brussel-sprout chocolate" ... ok, agreed, I doubt it will offer the allure of pure chocolate, the satisfaction as the melting of the fats and cocoa on the tongue release the full flavor upon the taste buds and send a message of satisfaction to the brain... and then: the blatant taste of brussel sprouts? *shocker*

So, it it really any wonder that press releases with titles such as "Why dark chocolate is good for your heart", "Key chocolate ingredients could help prevent obesity", "Chocolate may help keep brain healthy",  or "Regular chocolate eaters are thinner, evidence suggests" drives people to hope that chocolate may provide health benefits far beyond the satisfaction we derive with its consumption. A satisfaction neither brussel sprouts, nor real cacao have to offer.

Figure 2: Mean scores (mm) on visual analogue scale for hedonic and other perceptual responses to chocolate puddings varying in sugar and fat content; 100 = extremely pleasant (Geiselmann. 1998)

It is, after all. the perception of sweetness of chocolate that determines the hedonic and other perceptual responses we are looking for in this and other "comfort" foods (Geiselman. 1998). Which is why I am not sure, if consuming"organic cacao powder" and "baking chocolate" instead of milk chocolate and he accompanying decrease your diabetes and heart disease risk is actually going to make you happy.

Eating Frequency, not amount, is what counts! Well, that's at least what a recent study from the University of California, San Diego, would suggest. Unlike the frequency of chocolate consumption, which is inversely associated with BMI, "the amount of chocolate eaten was not related to BMI, favorably or adversely (eg, per medium chocolate serving or 1 oz [28 g], =0.00057 [P=.97] in an age- and sexadjusted model" (Golomb. 2012).

Beware of the being lied to: If you look closer, there is absolutely zero reliable evidence that eating more of the brown stuff, of which most people assume it was chocolote, entails any health benefits. It has become an unfortunate practice among press-release writers and even reviewers to overlook the experimental design (regular chocolate or other sweets vs. extremely high polyphenol chocolate) to make sure their pamphlet sends the previously cited message, we all want to hear: "Doing what you love to do, in this case eating chocolate is not bad for you."

As the previous elaborations should have made clear, though, this statement lacks an asterisk and a dagger, to inform readers that (*) this statement is only valid if you are eating high polyphenol (="real") chocolate instead of other sweet, and that (†) even if it's "real" chocolate it will make you fat and sick, when it's eaten in excess. In moderation, on the other hand, chocolate can but certainly doesn't have to be a part of everyone's diet from Biggest Loser to Olympian athlete.

References:

• Chobanian, Aram V., et al. "The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report." Jama 289.19 (2003): 2560-2571.
• Farhat, Grace, et al. "Dark chocolate low in polyphenols increases BMI in normal weight and overweight adults (121.3)." The FASEB Journal 28.1 Supplement (2014): 121-3.
• Ford, Earl S., David F. Williamson, and Simin Liu. "Weight change and diabetes incidence: findings from a national cohort of US adults." American journal of epidemiology 146.3 (1997): 214-222.
• Geiselman, Paula J., et al. "Perception of sweetness intensity determines women's hedonic and other perceptual responsiveness to chocolate food." Appetite 31.1 (1998): 37-48.
• Germino, F. Willford. "Chocolate Is Good for Me, Right?." The Journal of Clinical Hypertension (2013). 
• Golomb, Beatrice A., Sabrina Koperski, and Halbert L. White. "Association between more frequent chocolate consumption and lower body mass index." Archives of internal medicine 172.6 (2012): 519-521.
• Latham, Laura S., Zeb K. Hensen, and Deborah S. Minor. "Chocolate—Guilty Pleasure or Healthy Supplement?." The Journal of Clinical Hypertension (2013). 
• Miller, Kenneth B., et al. "Survey of commercially available chocolate-and cocoa-containing products in the United States. 2. Comparison of flavan-3-ol content with nonfat cocoa solids, total polyphenols, and percent cacao." Journal of agricultural and food chemistry 57.19 (2009): 9169-9180.
• Stevens, J., et al. "Associations between weight gain and incident hypertension in a bi-ethnic cohort: the Atherosclerosis Risk in Communities Study." International Journal of Obesity & Related Metabolic Disorders 26.1 (2002).