Yohimbine & Berberine Protect From Death Due to LPS Intoxication; BCAAs Inhibit Serotonin Metabolism & Cause Anxiety, Tryptophan but not SSRIs Help; Sweet Tea Leaves Are PPAR-G Antagonists & Battle High Lipid + Leptin Levels

Skip the fireworks invest the money in some quality ingredients for a fondue or whatever you like and invest the (often non-negligible) rest of the money in a gym membership for the next year.

Actually my figure of the week is 115,000,000 EUR (~152,000,000 US Dollar), which is the sum my fellow country men and women are about to waste on pyrotechnics this year. And a scientifically unconfirmed addition based on my personal observation: 90% of the worst offenders as far as spending money for fireworks goes are at least overweight. Would be interesting to see, if the use of pyrotechnics on New Years Eve is directly associated with fat mass...

I mean, it could be that they spent so much money on their fireworks that they feel they can only afford the junkfood of which everybody and his/her mama still tend to believe that it would be cheaper than buying fresh products and preparing your own food from those.

Ah, I am ranting. That's usually Carl Lanore's task, so I will better go on with the items I have compiled for the today's last installment of On Short Notice in the year 2012:
 

• Berberine + yohimbine - a synergistic duo to prevent LPS toxicity (Li. 2012) -- With all the recent hoopla about the gut microbiome, I suppose that I don't have to tell you what the acronym LPS stands for, right? Hmm... just to make sure it stands for lipopolysaccharide endotoxins which are produced by gram negative bacteria in your gut and are so "toxic" (in fact they cause profound inflammation) that they can be lethal at higher doses.
  
  

  

  Figure 1: Survival rates (%) after ALB/c mice LPS injection (Li. 2012)

  A group of Chinese scientists have now found that aside from berberine the anti-inflammatory effects of which have been known for quite some time now, yohimbine administered in a daily dose of 2mg/kg (human equivalent 0.16mg/kg) does add to the survival rate of berberine treated rodents (human equivalent 4mg/kg) that were injected intragastrically (so not directly into the blood) with a potentially lethal dosage of 20mg/kg LPS. What's more, taken on its own yohimbine is even more potent than the alkaloid that's found in such plants as Berberis aquifolium, Oregon grape, Berberis vulgaris, Berberis aristata, Hydrastis canadensis (goldenseal), Phellodendron amurense, Coptis chinensis and Tinospora cordifolia.
  
  The mechanism is mediated by the prevention of liver injury, an upregulating of IL-10 production (an anti-inflammatory cytokine), and related anti-inflammatory effects resulting from the suppression of phosphorylation of IkBa, JNK, ERK and IRF3 in macrophages.

• Chronic 9-week high BCAA diet impairs brain tryptophan levels and causes anxiety (Coppola. 2012) -- Scientists from the Duke University took another look at the BCAA-tryptophan depression connection, you may have read about in the context of my "Sugar Addicted or Just Stressed Out?" post from January 3, 2012.
  
  According to the results Anna Coppola and her colleagues are about to publish in the American Journal of Physiology  - Endocrinololgy and Metabolism the provision of a BCAA-enriched diet for 9 weeks leads to both reductions in brain tryptophan levels and an increased turnover of serotonin (5-HT) in rodent brains:
  

  

  Figure 2: Composition of low fat  (LF) and high fat (HF) diets with or without added BCAAs (left); effects on the ratio of tryptophan  to the molar sum of large neutral amino acids with and without supplemental  tryptophan in the drinking water and 5HT turnover in the brain (no supplemental trp, right; Coppola. 2012)

  Both groups (BCAA and non-BCAA) consumed about identical amounts of food as the rodents in the complementary (LF or HF) groups, which confirms that the BCAA content did not modify the taste of the chow or rendered it unpalatable (cannot have been cheap bulk powder then ;-). The reduction in both the availability of tryptophan as well as the increase in serotonin (5-HT) turnover in the brain must in fact have been a consequence of the added BCAAs and are most likely the root of the disrupted transport of tryptophan across the BBB in rats, leading to reduced exploratory behavior of rats in EPM testing, a sign of increased anxiety.

  "Recent studies demonstrating a strong  association between BCAA levels, obesity, and obesity-related metabolic disorders, when linked to the findings reported here, may help to explain the strong association between obesity and behavioral abnormalities, including depression and anxiety." (Coppola. 2012)

  

  As the slight differences between the high an low carb diets show, other nutrients can influence serotonin as well (read more)

  In this regard it is important to point out that these negative side effects were mostly reversible by the provision of 15 mg/100 ml tryptophan in the drinking water of the rodents, but were not alleviated by  the administration of the common serotonine reuptake inhibitor fluoxetine (at 10 mg/kg/day for four weeks).
  
  Bottom line: Isolation is not what you want if what your body has been build for is complex food. And while the single serving of BCAAs you may gulp down during or right before a workout, on the other hand, probably isn't going to harm you. The "I need BCAAs every 30min" approach to gaining muscle mass, may well turn you into a psychotic wrack if you follow it day in and day out for months or years - at least without chronically adding some l-tryptophan to the equation.

• Sweet tea leaves protect against obesity: Once more via PPAR-gamma blockade (Zhou. 2012) -- Actually this is probably not news to anyone out there with a degree in Traditional Chinese medicine. After all, Lithocarpus polystachyus Rehd.(Sweet Tea) is Chinese folkloric medicine that has always been used to treat obesity, diabetes, and hypertension in South China:
  

  "Previous experiments revealed that it contains plentiful bioactive flavonoids and polyphenolic compounds, e.g. phlorizin, trilobatin, 3-hydroxy-phlorizin, etc. These components have extensive pharmacological activities, such as anti-diabetes, memory improvement, anti-aging, inhibition of lipid peroxidation and the growth of human colon cancer cells, and so on." (Zhang. 2012)

  From a "scientific" perspective, however, the efficacy of this herbal medicine as an obesity treatment had still to be elucidated.

  

  Figure 4: Effects of oral gavage of 75 mg, 150 mg and 300 mg/kg of body weight/day of sweet tea extract or placebo (DIO) in conjunction with the 8 weeks on a obesogenic diet (Zhang. 2012)

  In this context it is yet worth mentioning that this study demonstrated for the first time that the aqueous dry leaves extract of Lithocarpus polystachyus Rehd. can potently reduce the worst metabolic side effects of obesity, such as the hypolipidemia, hypoleptinaemia and the degree of insulin resistance (FINS, HOMA-IR, cf. figure 3) what it does not answer, however, is whether the decline in PPAR-gamma is tissue specific, what exactly is behind the profound decline in leptin levels and whether or not lean rodents, let alone humans, who don't consume an obesogenic diet will see anywhere similar benefits.
  
  In other words, this is research in progress, but I suppose something you are going to hear more about at the Supppversity in 2013.

* * * * * *

Apropos hearing or rather reading more, I guess you will realize that you have reached the end of today's installment of On Short Notice which means that you will have to progress to the SuppVersity Facebook Wall if you want a second serving of news on...

• The history of vitamin A as a light sensor and beyond - actually a free full-text I guess those of you who like to "think paleo" may enjoy (read more)
• A paper on "good" and "bad" inflammation, where the author points out that soothing inflammation too much can lead to a reduction in energy expenditure and may therefore not be the king's road to getting rid of the last blubber (read more)
• The food-hitlist of young Americans - Featuring sugar, sugary drinks, sugary bakery, sugary ... as their main energy and carbohydrate sources... (read more)
• Problems with synthroid and generics that have surfaced in a recent study on their efficacy in the treatment of congenital hypothyrodism (read more)

as well as a handful of other news, which are already there or are going to be posted within the next hours. Have a great weekend, everyone! 

References

• Coppola A, Wenner BR, Ilkayeva O, Stevens RD, Maggioni M, Slotkin TA, Levin ED, Newgard CB. Branched-chain amino acids alter neurobehavioral function in rats. Am J Physiol Endocrinol Metab. 2012 Dec 18.
• Li H, Wang Y, Zhang H, Jia B, Wang D, et al. Yohimbine Enhances Protection of Berberine against LPS-Induced Mouse Lethality through Multiple Mechanisms. PLoS ONE. 2012; 7(12): e52863. 
• Zhou CJ, Huang S, Liu JQ, Qiu SQ, Xie FY, Song HP, Li YS, Hou SZ, Lai XP. Sweet tea leaves extract improves leptin resistance in diet-induced obese rats. J Ethnopharmacol. 2013 Jan 9;145(1):386-92.

Beyond Warding Off Holiday Weight Gain: 250-1000mg of Freeze-Dried Ginger Reduce Visceral Fat Even When Rodents Are Fed an Obesogenic "High Fat" Diet.

Image 1: If ginger works only half as good in humans as it does in rodents, you can drink your way to a leaner and healthier you with Alisa Profumo's delicious low-carb "Healthy REAL Ginger Ale".

Zingiber officinale, or, in plain English, Ginger, is unquestionably one of the most remarkable plant rhizomes that is known to mankind. It has been used in various cultures for treating common colds or fever, to aid digestion, treat stomach upset, diarrhoea or nausea, to alleviate rheumatic disorders, gastrointestinal complications and dizziness, and, as of late, it has received quite some attention as a possible adjuvant to treatment modalities of cancer (Peirara. 2011). In a pretty recent study, the administration of 500 mg/kg zinigiber officinale to streptozotocin-induced diabetic rats (cf. related study in CLnA, the Omega-3 Variety of CLA), was able to partly restore the deteriorated glucose metabolism (Abdulrazaq. 2011), and a 2010 study was able to show that 6-Dehydrogingerdione, an active constituent of dietary ginger stopped the growth of breast cancer cells in the petri dish. "That is all very well", you may now be thinking, "but what does that all have to do with warding off the holiday weight gain?" Well, the answer lies in the results of a very recent study, which have just been published in the International Journal of Pharmacology (Malik. 2011).

Ginger reverses diet-induced visceral obesity and restores blood lipids to normal

Z.A. Malik and P.L. Sharma, two researchers from the Department of Pharmacology at the ISF College of Pharmacy in Moga, India, investigated whether the administration of 0.25-1g/kg body weight of dietary ginger (freeze dried powder that was made from fresh ginger juice; human equivalent would be 40-160mg/kg) would have any beneficial effect on the high-fat diet induced deteriorations in body composition, energy, lipid and glucose metabolism of male Wistar rats. For eight weeks, the scientists fed the rodents a diet that consisted of 33% normal rat chow, 33% Nestlé milk powder, 7% sucrose, and 27% tap water.

Figure 1: This is probably the lowest fat "high fat diet", I've seen in some time (data adapted from Malik. 2011) - ridiculous, but hey, if the diet had really been "high fat", who knows if the rodents would have gotten obese, anyway ;-)

If you take a look a the macronutrient breakdown of the "high fat" and the "normal diet" in figure 1, it is quite obvious that the former is - if anything - higher in fat than the latter, but by no means what any sane individual would consider a "high fat diet" (I really have to check myself not to start ranting against the "high fat diet induced whatever" in rodent models, again ;-) But be that as it may, ... the data in figure 2 shows that the milk powder and the sucrose were obviously enough to really fatten the rats up, profoundly:

Figure 2: Relative increases in body weight (BW), white adipose tissue weight (WAT), visceral fat weight and brown fat in rats on the "high fat diet" (data adapted from Malik. 2011).

With a whopping +417% increase in the total white adipose tissue weight, the poor rodents became profoundly obese. Their visceral fat depots (mesenteric, epididymal  and retroperitoneal) more than doubled (on average +150%), whereas the weight of their metabolically active brown adipose tissue increased by "only" 107%.

Figure 3: Relative changes in body weight (BW), white adipose tissue weight (WAT), visceral fat weight and brown fat in rats on the "high fat diet" who were supplemented with 250, 500 or 1000mg/kg ginger (data adapted from Malik. 2011).

The addition of 250mg/kg, 500mg/kg and 1g/kg body weight of the freeze-dried ginger juice (now obviously in powdered form) to the chow dose-dependently ameliorated the weight gain and reduced the weight of both the visceral, as well as the brown fat to level that were below those of the rats on the "normal" diet (cf. figure 3). Intriguingly, the "low" dose of 250mg/kg body weight turns out to be the most effective one, when it comes to the reduction of the epididymal, retroperitoneal and mesenteric visceral fat pads.

Figure 4: Relative changes in triglycerides (TG), total cholesterol (TC), HDL and total cholesterol to HDL radio in rats on the "high fat diet" and rats who were fed the HFD with 250, 500 or 1000mg/kg ginger (data adapted from Malik. 2011).

The addition of ginger to the diet also kept the blood lipids in check (cf. figure 4) and normalized the glucose response to an oral blood glucose tolerance test in the "high-fat" fed rodents. Other than the scientists had speculated, it had no effect on energy intake and did not increase the fecal fat content. The two markers of hepatic health, AST and ALT, which were measured in the study, remained almost unchanged - in the 250mg group there was even a -17% and -13% reductions in the respective transaminases (I am thusly amazed why the study has the words "anomalies after chronic administration" in its title).

How does it work and how effective is it?

Let's finally have a brief look at a) the potential mechanism by which ginger exhibits its fat-burning magic and b) how effective ginger would be, as compared to other, better known, "tools" to ward off weight gain or induce weight loss. To check whether the mechanism of action involves increased beta-oxidation, Malik and Sharmaa mixed an additional 30mg/kg of the beta-blocker propranolol into the high fat, ginger-supplemented diets of the animals - and as you can see in figure 5, the addition of the beta-blocker led to a profound reduction in the ameliorative / fat burning effects of the freeze-dried ginger powder.

Figure 5: Relative increases (vs. control on normal diet) in body weight (BW), white adipose tissue weight (WAT), visceral fat weight and brown fat in rats on the "high fat diet" supplemented with ginger, ginger + propanolol, or sibutramine (data adapted from Malik. 2011).

And as far as its effectiveness is concerned, ginger stands the comparison to the (in-)famous weight-loss drug Sibutramine, of which you will probably have heard that Chinese manufacturers of otherwise ineffective herbal weight-loss remedies like to mix it into their products (obviously without mentioning this banned ingredient on the label).

So, if we assume that these amazing results translate to humans, the addition of a few ginger rhizomes to your holiday diet could be a very effective tweak to ward off unwanted weight gain. And if your plans for 2012 include getting rid of the nasty love-handles you have acquired in the course of the past 12 months, you better get accustomed to the spicy, yet fruity flavor of the rhizomes of this perennial reed-like plant. You could, for example start out by following Alisa Profumo's delicious low-carb "Healthy REAL Ginger Ale in Minutes"-recipe on the Super Human Radio webpage (cf. image 1). And just in case you are too lazy to juice and / or freeze-dry some fresh ginger rhizomes yourself, you may want to consider buying a bag of Carl Lanore's  standardized ginger extract, which is also available on the Super Human Radio website.

Complete Meals & GI (Non-)Sense, Glutamine & GLP-1, Low Thyroid & High Trigs, N-3 vs. N-6 Interactions, Optimal DHA Dosage in Kids W/ NAFLD, Selenium vs. Aluminum Toxicity

While this is not the exact combination of chicken breast, mashed potatoes and salad in the first one of today's news items, it's more than likely that the predicted GI (and thus probably what you would find if you looked it up in a table) overestimates the postprandial glucose response to this meal by ~50% and says absolutely nothing about the insulin response. It looks like complex meals and over-simplified theories, don't mix well, at all ;-)

78% that's the SuppVersity Figure of the Week and actually part of the additional information I provided on one of today's On Short Notice items. It's the increase in coronary heart disease risk women with subclinical hypothyroidism have compared to their peers with spot on TSH levels of 0.5-1.5mU/L (Asvold. 2012). In conjunction with other more or less recent studies, such as Mitchel's, Hsu's and Sahai's paper confirming the previously often talked about but not well-established 2-fold increase in congenital hypothyroidism from the early 1990s to the first years of the new millennium (Mitchel 2011), the predictive value of high TSH levels in the first trimester (early pregnancy hypothyroidism) for adverse pregnancy outcomes (Schneuer. 2012), the 30% risk increase in all-cause mortality in both women and men with subclinical hypothyroidism Tseng et al. reported in their paper earlier this year or the impairment of spatial working memory (Yin. 2012), Asvold's results only add to the evidence that the potential pitfalls of an increasingly prevalent metabolic dysfunction may have been ignored way too long.

• More GI lovin' - On the menu today: Mashed potaoes with chicken, rapeseed oil or both (Hätönen. 2011) - I thought a mini-follow-up on Friday's post on the GI would be nice, 'cause some of you have not without reason been complaining that not everyone would eat pure white bread, like my students do.
  
  

  

  Figure 1: The real (=measured) GI of a meal does differ significantly from the theoretical prediction. So, even if the concept was worth bothering, the GIs of complete meals simply wrong, if they are not measured (Hötönen. 2011).

  Moreover, the mere fact that the scientists from the Department of Lifestyles and Participation at the National Institute for Health and Welfare in Helsinki, Finland, found that the addition of chicken breast, rapeseed oil and a salad, individually and in combination, had the GI of a meal containing six mashed potatoes (this was the parameter that was held constant) induced more than twofold changes in GI, with the addition of chicken breast having the greatest deviation from the predicted value in this group of 11 (initially 12) healthy subjects, three men and nine women, aged 36.2 (SD 14.1) years with a BMI of 21.3 (SD 1.7) kg/m² and normal glucose tolerance (see figure 1).
  
  Now given the fact that most data on the GI of complete meals has never been measured, but is actually based on the same predictions the scientists used, it stands to reason that...
  

  [...] this highlights the problems encountered when predicting the GI values of mixed meals. The protein com-ponent of the mixed meal evoked the largest insulinaemic responses and markedly increased the II of the mixed meal containing protein. However, introducing fat into the meal decreased the effect of protein on the insulinaemic responses (Hätönen. 2011)

  So, this does not simply bust the idea that you could calculate the GI, it does likewise show you that people who are still overtly scared of insulin (which is hillarious as long as you are insulin sensitive) are doing he exact wrong thing, when they make food-choices based on GI: Whey protein would in that case be in as much a no-go as simply eating a chicken breast with your mashed potatoes would be, because other than what most people believe, it does increase the insulin spike and thus reduce the glycemic index by allowing your body to clear the glucose more efficiently from the circulation.
  
  Suggested reads: The red box in the "Whey is More Insulinogenic than White Bread" post on the partitioning effects of BCAAs and yesterday's Facebook post on the anti-Alzheimer's effects of insulin.

• 

  Suggested read: Amino Acids for Super Humans the purported ergogenic effects of l-glutamine

  30g of oral glutamine have similar effects on GLP-1 as 75g of glucose (Greenfield. 2008) - Still a follow up on the GI discussion, I think you may be interested in. If you are someone who follows the questionable practice of ingesting large boluses of glutamine in the futile believe that this would increase your gains or speed up recovery, you may be pleased to hear that only 30g of oral l-glutamine produced an increase in the "Fat Burning Satiety Hormone GLP-1" (read more on GLP-1) that's on a gram to gram basis more pronounced than in response to insulin (0.41pmol/L per gram glucose vs. 0.75pmol/L per gram of glutamine; in 8 healthy subjects).
  
  Before you go and buy tons of glutamine, you should however consider that GIP, the pro-insulinogenic peptide and glucagon (ramps up gluconeogenesis in the liver) were likewise increased by the ingestion of this bolus of glutamine. It is therefore no wonder that glutamine has never been shown to be a "fat burner". Nonetheless, a 1999 study by Bowtell et al. would suggest that it may come handy to replenish liver and muscle glycogen after a workout (8g alone did increase glucose storage after a workout to a similar degree as a 18.5% glucose polymer solution and additional 25% glucose storage mostly in the liver, when both were coingested; cf. Bowtell. 1999). And if you don't care about that - your gut integrity could also be a reason to consider supplementation in the vicinity of particular strenuous or length workouts (see "Shedding Some Light on the Leaky Gut <> Exercise Connection") 

• Practical relevance? Based on data from a 12-year longitudinal study, even women with subclinical hypothyroidism have 76% risk for coronary heart disease (p = 0.005), than women with spot on TSH levels of 0.5-1.5mU/L (Asvold. 2012). And even women well within in the "normal range" (TSH of 1.5-2.4mU/l) have a 41% higher risk of heart disease, although this is only borderline significant (p = 0.08). For men the TSH level alone had not predictive value. Spec. w/ regards to T3, there are also reports of increased incidence of ventricular disfuntion (Cassetti. 2009), increased cardiac death in CVD patients (Iervasi. 2003) and impaired recovery after a stroke (Alevizaki. 2007). We do yet have to be cautious, here as "low T3" syndrome could as well be the consequence of overall inflammation and the association does not tell us anything about what's the chicken and the egg.
  Low thyroid, high triglyceride (Hashimoto. 2012) -- If you are wondering why on earth your trigs won't come down, it may well be that it's the absence of sufficient amounts of thyroid hormone. I a soon-to-be-published paper in Endocrinology scientists from the Gunma University in Maebashi, Gunma, Japan, report that thyroid hormone regulates the expression of a Stearoyl-CoA desaturase-1 (SCD-1) which controls the production of trigs from carbohydrates.
  
  Surprisingly the 75% increase due to hypothyroidism and the 75% decrease in SCD-1 mRNA expression (both compared to a euthyroid state) the scientists observed in rodents in response to the administration of T3 were not mediated by receptor binding, but simply as a down-stream effect of direct modifications of the SCD-1 gene promoter between -124 and -92 bp by T3.
  
  On a related side note: It is actually the last mentioned mechanism which is the major new finding in the study at hand and not the fact that T3 can reduce the conversion of carbohydrates to triglicerides that is the actual news here. After all, the latter is something scientist should know, but obviously like to forget about ever since the late 1999s (Waters. 1997)

• Omega-6 intake and not low omega-3 intake is the problem (Liou. 2007) -- Another older study, but one I am posting in response to a discussion some of you are having about omega-3 (ALA) intake in the post about safflower oil and DHT, because I simply feel that it's necessary to shed some light  on the erroneous assumption that by simply upping your intake of omega-3s or fish oil intake you could get away without decreasing your omega-6 intake, which in and out of itself will already increase the amount of anti-inflammatory omega-3 fatty acids (supplementation of DHA can still be advisable, specifically if you are a vegetarian).
  
  

  

  Figure 2: Effect of 4 weeks of high (red) vs. 4 weeks of low (green) linoleic acid (n-6) intake on short and long-chain omega-3 plasma phospholipid content in healthy men (Liou. 2007)

  In 2007, already Liu et al. conducted a very interesting experiment in the course of which they fed healthy men diets with identical amounts of omega-3 fatty acids (1% of the total energy intake), but two different amounts of linoleic acid (omega-6) and found that the high omega-6 intake (10.1% vs. 3.8% of the total energy intake) alone decreased the total amount of EPA among the plasma phospholipids (the major long-chain omega-3 fatty acid in fish oil), not just the ratio of omega-3 to omega-6, in the blood of their 29-45 year-old subjects by more than 25% (see figure 2). The paradoxical effect on DHA, on the other hand, would warrant further investigation, and underlines how reliant we are - if anything on the intake of pure DHA, which dropped in consequence to the test diet, which was devoid of fatty fish, while the original diet of the non-vegetarian subjects had fish in it.
  
  In this context, I would also like to point out that DHA is exactly where real fish is far superior to fish oil caps, because it has a way more favorable EPA:DHA ratio than fish oil caps. Salmon fillets for example have - depending on the fatty acid source in the diet 8.5g : 13.8g, 4.4g : 7.8g and 1.5g : 2.9g (all values per 100g) when the feed contains fish oil, fish and rapeseed and fish + rapeseed and rapeseed, only.
  
  And while the ratios are similar regardless of the chow, the data from the Seierstad et al. clearly shows that the fatty acid content of the diets can induce almost 5-fold differences in terms of the total DHA content and the omega-3 to omega 6 ratio (fish oil diet: 6.5, fish oil + rapeseed: 1.7, rapeseed: 0.6) of salmon fillets (Seierstad. 2003). 

• It does not take much: 500mg DHA not more effective than 250mg  (Nobili. 2012) -- At least if it comes to its beneficial effects against liver steatosis in children  (mean age 11 years; BMI 26.6kg/m² and 24.4kg/m², in the low and high dose groups respectively with with NAFLD, the amount of DHA does not appear to be so important. According to the results of their 2-year registered controlled trial, both 250mg and 500mg of Docosahexaenoic acid lead to identical and profound reductions in the odds ratio of developing more severe steatosis during the study period.
  
  

  

  Figure 3: Odds ratio (comparing DHA supplement vs. placebo) of more severe vs. less severe liver steatosis determined every 6 months during the 24-month study period (Nobili. 2012)

  If you take a closer look at the data in figure 3, you will even have to concede that the lower dosage did a better job - while the mean odds ratios were only marginally lower in the 250mg DHA group, the extremely high standard deviations in the 500mg DHA would suggest that the 250mg dose appears to be more reliable. In this regard it may be interesting that the increase in serum DHA did mirror the dosages. With a 0.65% and 1.15% increase in DHA those were about 2x higher in the 20 boys and girls in the high dose group compared to the 20 kids in the control group who received a 290 mg linoleic acid germ oil supplement "placebo" (by the way, a monosaturated fatty acid placebo would have been more of a placebo than 290mg of omega-6)
  
  In view of the fact that the changes in triglycerides, ALT, HOMA-IR and BMI (which was not even different from the placebo group) were likewise identical, it does not appear as if anything that goes beyond the amount you will find in 2x cheap fish oil caps, or 10g even of the cheapest salmon fillet (see last paragraph of previous item) would be necessary to ellicit the anti-steatosis effect of fish oil - since those kids weight on average 55kg, an adult may want to add in another fish oil cap to get up to 360mg DHA per day or simply eat his fatty fish once or twice a week.

• Selenium ameliorates aluminum toxicity (Viezeliene. 2012) -- With the whole upheaval about the potential negative side effects of the aluminum in vaccines, the formerly overlooked yet well-known neurotoxic (Exley. 1992; Gupta. 2005), hepatotoxic (Abubakar. 2003; Perez. 2005) and nephrotoxic metal (Geyikoglu. 2012) has all of a sudden returned to the center of public interest.
  
  Therefore I thought that you will be interested in the results of a study that's going to be published in the next issue of the Journal of Trace Elements in Medicine and Biology - irrespective of whether you believe, like Tomljenovic and Shaw that
  

  "the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community"(Tomljenovic. 2011)

  After all, vaccines are not the only potential source of aluminum in our environment, so that the ameliorative effects (all values remained normal in the aluminum exposed group, while there were 30%, 55% and 42% increases in GSH in the animals who received only the selenium injection) the co-administration of supplemental selenium had on the GSH reductions in liver, kidney and brain of Balb/c mice weighing 20–25g who were exposed (by i.p. injection)to AlCl3 (25 mg Al(3+)/kg body mass) for 16h could be important, regardless of whether you do or don't intend to get vaccinated.
  
  

  

  There is more about selenium at the SuppVersity, for example on its pro-fertility effects, and its anti-corrosive effects in the brain.

  That said, the dosage requirements necessary to maintain healthy GSH levels are probably much lower than the hillarious (for a healthy individual) in the study at hand 1,250µg/kg body weight of sodium selenite (Na2SeO3). Considering the elemental selenium content in Na2SeO3, the latter would equal to ~3,650µg - unquestionably WAY too much (remember this was a one-time dosage that was specifically co-administered w/ the aluminum). Even the 'no observed adverse effect' level for a 70kg man of intake which is ~1000µg/d (Whanger. 1999) appears unnecessarily high, so that the consumption of a handful of brazil nuts once or twice a week and/or other high selenium foods such as tuna, cod, oysters, shrimp, but also eggs, meats, poultry, mushroom and onions on a regular should suffice to get what you need, to fortify yourself against the constant assault of heavy metals.
  
  What would be interesting, though, is a study into the effects of adding selenium to the "safe" aluminum in vaccines. I mean, you cannot seriously tell me that we could not afford doing that and if it reduced any toxicity issues, why not?

That's about it for today, I did not post all too many new facebook news as of yet (I mean, come on, it's Saturday ;-), but if you are into medicinal horror-stories, you will certainly like the story about the flesh eating killer fungus. If you prefer microbes over fungi, you are probably better off with the latest insights into the associations of certain gutbacteria with the incidence of stroke. And if you are more into other aspects of the digestive tract you may be interested in the effects of gastric emptying time on postprandial gylcemia and insulin release.

If none of those news is to your liking, I suggest you either wait for me to post something else (could be happening within the next hours at www.facebook.com/SuppVersity), or simply enjoy the weekend and come back tomorrow when you are rested for another (hopefully) enlightening SuppVersity post.

References:

• Abubakar  MG,  Taylor  A,  Ferns  GA.  Aluminium  administration  is  associated  with enhanced  hepatic  oxidant  stress  that  may  be  offset  by  dietary  vitamin  E  in  the rat. Int J Exp Pathol 2003;84:49–54.
• Asvold BO, Bjøro T, Platou C, Vatten LJ. Thyroid function and the risk of coronary heart disease: 12-year follow-up of the HUNT Study in Norway. Clin Endocrinol (Oxf). 2012 Dec;77(6):911-7.
• Bowtell JL, Gelly K, Jackman ML, Patel A, Simeoni M, Rennie MJ. Effect of oral glutamine on whole body carbohydrate storage during recovery from exhaustive exercise. J Appl Physiol. 1999 Jun;86(6):1770-7.
• Cassetti G, Pinelli M, Bindi M, Bianchi M, Castiglioni M. [Low T3 syndrome and left ventricular diastolic function]. G Ital Cardiol (Rome). 2009 Aug;10(8):553-7. 
• Exley  C,  Birchall  JD.  The  cellular  toxicity  of  aluminium.  J  Theor  Biol 1992;159:83–98.
• Geyikoglu  F,  Turkez  H,  Ozhan  Bakir  T,  Cicek  M.  The  genotoxic,  hepa- totoxic,  nephrotoxic,  haematotoxic  and  histopathological  effects  in  rats after aluminium chronic intoxication. Toxicol Ind Health 2012;15.
• Greenfield JR, Farooqi IS, Keogh JM, Henning E, Habib AM, Blackwood A, Reimann F, Holst JJ, Gribble FM. Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am J Clin Nutr. 2009 Jan;89(1):106-13.
• Gupta  VB,  Anitha  S,  Hegde  ML,  Zecca  L,  Garruto  RM,  Ravid  R,  et  al.  Alu- minium  in  Alzheimer’s  disease:  are  we  still  at  a  crossroad?  Cell  Mol  Life  Sci 2005;62:143–58.
• Hashimoto K, Ishida E, Miura A, Ozawa A, Shibusawa N, Satoh T, Okada S, Yamada M, Mori M. Human Stearoyl-CoA Desaturase 1 (SCD-1) Gene Expression Is Negatively Regulated by Thyroid Hormone without Direct Binding of Thyroid Hormone Receptor to the Gene Promoter. Endocrinology. 2012 Dec 7.
• Hätönen KA, Virtamo J, Eriksson JG, Sinkko HK, Sundvall JE, Valsta LM. Protein and fat modify the glycaemic and insulinaemic responses to a mashed potato-based meal. Br J Nutr. 2011 Jul;106(2):248-53. 
• Iervasi G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini M, L'Abbate A, Donato L. Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation. 2003 Feb 11;107(5):708-13.
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Standard American Diet Has 'Optimal' Fatty Acid Ratio to Induce Diabesity. Plus: Study Shows Doubling Saturated Fats Would Yield More Benefits Than Halving Them

Study confirms: The SAD diet yields 'optimal' results (img. forbes.com)

Since this post is already lengthy enough, I will spare you how saturated fatty acids have long falsely been accused as the sole driving force of the western obesity epidemic and how the tides appear to be slowly yet steadily appear to be turning, as scientists delve deeper and deeper into the interactions of the total fat content in the diet, its fatty acid composition and the interaction of both with the two other macronutrients and their specific forms and get right to the study at hand. A study that appears in the current issue of the Journal of Lipid Science and deals with the first of the aforementioned interactions. The one that focuses on the total fat content and the individual fatty acid make-up of the diet (Enos. 2012).

Fat shoot out: Saturated vs. mono vs. PUFA

As Enos et al. point out, the main purpose of their study was to examine the effects of three high fat diets differing only with respect to the percentage of total calories from saturated fats.

• SFA-6% - contained 6% saturated fats,
• SFA-12% - contained 12% saturated fats, and
• SFA-24% - contained 24% of saturated fats

While the the high fat diets were set to have an identical fat (40% of the energy), carbohydrate (45% of the energy) and protein content, the two control diets were low in total fat (12%/68%/20% of the energy from fat/carbs/protein). They did however likewise differ as far as their fatty acid composition is concerned, with the modified chow mirroring the ratios (!) not the amounts of mono- and polyunsaturated fatty acids of the high fat chow (see figure 1).

Figure 1: Fatty acid composition (left) and their sources (right) that were used in the different diets the rodents were fed for 16 weeks (based on Enos. 2012)

The diets were administered for 16 weeks. Body composition and metabolism (glucose, insulin, triglycerides, LDL-C, HDL-C, total cholesterol) were examined monthly.  Adipose tissue (AT) expression of marker genes for M1 and M2 macrophages and inflammatory mediators (TLR-2, TLR-4, MCP-1, TNF-α, IL-6, IL-10, SOCS1, IFN-γ) was measured and so on and so forth... and the results were... well, not exactly as you may have expected (the latter statement assumes that you expected the SFA to be either the savior or the doom of the human race, depending on which side of the LC/LF divide you are stading).

Figure 2: Body composition (left), adipocyte size (right) and fat pad weight (inset) of the rodents at the end of the study period (Enos. 2012) Values not sharing a common letter (abc) differ significantly over time within the given diet treatment (P≤.05)

If you take closer look at the data in figure 2, there are two things that will probably catch your eye right away. The first 'eye catcher' pertains to the influence of replacing a large amount of the omega-6 fatty acids by monounsaturared fatty acids, as you will find them in olive oil, for example.

• The rodents who received the modified standard chow, with a fatty acid composition identical to the high fat diets (SFA-6%, SFA-12%, SFA-24%) had the exact same body composition as their mates who received the standard chow with its 3.7x higher n6:n3 ratio. The removal of omega-6 fatty did thus not have any beneficial effects on adiposity in the low fat groups.

The second 'eye catcher' is the non-linear increase in adiposity with increasing amounts of saturated fatty acids in the diets. This does not mean that the expected increase in obesity and adipocyte size was totally absent (read the latest "Get Lean & Stay Lean" item for more information about the association of large fat cells and metabolic syndrome), though:

• The mice in the SF-6-24% did all gain significantly more body weight and body fat than their peers on the low fat diets, but there appears to be a turning point, when the saturated fat content exceeds 12%. After all the mice in the SFA-24% group had almost the same body composition as their peers on the SFA-6% diet.

So, what do we make of these 'eye catchers'? The first one, you could argue, shows that "omega 6 overload" is not a problem, as long as you are consuming a low fat diet, in the first place. Even with the major part of those 12.2% of energy your diet provides in form of various fatty acids belonging to the potentially inflammatory omega-6 fatty acids, that's still way too low to do any harm. It does, by the way, yet explain why low fat diets work so well in a society, where most high fat foods the public consumes are laden with omega-6 fatty acids - not an insignificant result, I would say.

The 12%-SF diet, most closely mimics the standard American diet

Apropos public, the second 'eye catcher' is even more telling in term of public health,... wait, I should write sickness. Why? Well, the 12%SFA high fat diet, which supplies ...

• 47% of energy in form of carbohydrates (380g sucrose, 100g maltodextrin, 50g cornstarch per 1kg of diet; identical for all SFA groups),
• 40% of energy in form of fats (of which 12% were saturated fats), and
• 13% of energy in form of protein (from casein),

... mimics, as the researchers point out, "most closely" (Enos. 2012) the standard American diet (SAD). And the result is obvious: Diabesity!

It's a fat balancing act of macro and micro ratios  - complex and far from being understood 

What's intriguing though, is that the adipogenic effects of the diet were ameliorated, when the SFA content was further increased and the diet contained 68.6g of lard per kg chow instead of just 35.4g and 96.7g of coconut oil instead of just 30g. Since this increase in SFA was at the expense of both mono- and omega-6 fatty acids, you could of course also argue that replacing at least the latter of the two with SFAs must be healthy. Unfortunately, even a brief glance back at figure 2 reveals that this is not necessarily correct. After all, the SFA-6% group was still better off than the SFA-24% group, although they had the highest amounts of oleic and omega-6 fatty acids in the diet.

By now you should actually have realized that this is once more a difficult balancing act. Where different baseline intakes of dietary fat and carbohydrates (total) are pair of setscrews and the individiual fatty acid composition of the diet is another one. And the way these setscrews are set will not just influence the body composition:

Figure 3: Serum IL-6, MCP-1, adiponectin and leptin levels, TNF-alpha mRNA expression in the adipose tissue (left), adipose tissue sample form the rodents receiving standard chow, the SFA-12% and the SFA-24% diet (Enos. 2012). The fat cells of the SFA-6% animals looked similar to those on the SFA-6% diets.

Based on the body composition data presented in figure 2 the marked increases in serum leptin and TNF-alpha mRNA expression in the adipose tissue of the rodents in figure 3 (left) should be about as unsurprising as the fact that the adipocytes of the SFA-12% group show the greatest macrophage infiltration and subsequent necrotic tissue.

If anything is surprising, it is the non-significance of the peak in IL-6 in the SFA-24% group (this was due to a very high standard deviation) and the fact that the serum level of MCP-1 a marker of increased macrophage activity was not elevated, while the adipose tissue mRNA expression was significantly higher (5-8x) in all SFA groups compared to both of the control diets. In the end this is yet only another clear sign that far more processes than we have previously thought happen locally and do not depend on circulating and thus endocrine signaling molecules.

Figure 4: Blood glucose and insulin levels of the mice over the course of the study period (Enos. 2012)

If you take the data from figure 4 into account as well, you will certainly agree with the statement Enos. et al. make pertaining to the negative effects of the SFA-12% diet, which is - just to remind you - the mirror image of the standard American diet:

"The 12%-SF diet, most closely mimicking the standard American diet, led to the greatest adiposity (absolute fat mass), macrophage infiltration, and IR [insulin resistance]." (Enos. 2012)

Figure 5: Total  cholesterol (TC, top) and LDL-C to HDL-C (bottom) ratios (Enos. 2012)

And I guess it would actually be about time to get to the bottom line, here, if it was not for the sentence that follows this assertion:

"Although the 24%-SF diet increased adiposity and produced IR, it did not significantly increase macrophage infiltration, it led to a lesser degree of AT inflammation, and it did not raise the TC/HDL-C ratio." (Enos. 2012)

Yep, you are reading right, as the data in figure 5 shows the total to HDL ratio of the SFA-24% group, which were those rodents who consumed the largest amount of "bad" saturated fat, was virtually identical to the one of the rodents on the standard and the modified standard chow and significantly lower than in those rodents who 'lived the American way of life' (SFA-12%). A similar trend was seen in the LDL:HDL radio and the triglyceride levels.

Bottom line: So, does that mean that we would just have to fry our potato chips in lard and all will be good? Not really, no. If we keep munching tons of plain sugar, even a saturated fat only diet is not going to save us from doom (I suspect there will be another inflection point at levels which exceed 50% SFA, anyway). What the study results do yet clearly implicate is that the macronutritent and fatty acid composition of the standard American diet is downright conspicuously obesogenic, pro-diabetic, inflammatory.

While the macronutrient ratio (high carb + high fat) appears to set the body into fat storage mode, the individual ratios of the fatty acids determine the efficacy of body fat storage, the negative effects on blood glucose management, and the degree of adipose tissue inflammation - and the standard American diet excels in all these disciplines.

As far as the saturated fats go (I wonder if it also plays a role that one of the main sources was coconut oil), the study suggests that you can achieve ameliorations of adiposity on both sides of the 'obesogenic optimum' of 12% saturated fats. If you take a last look at the data in figure 4, you will yet have to concede (or triumph?) that eating more not less saturated fat and thus frying your potatoes in lard, appears to be the more promising modification you could make, if the saturated fat content of the diet was your only set screw. Feels good to know it isn't right?

References:

• Enos RT, Davis JM, Velazquez KT, McClellan JL, Day SD, Carnevale KA, Murphy EA. Influence of Dietary Saturated Fat Content on Adiposity, Macrophage Behavior, Inflammation, and Metabolism: Composition Matters. J Lipid Res. 2012 Oct 28.

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 ;-)


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