Saturday, October 6, 2012

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...





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?





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).





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)





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)?




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.




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?





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.