Saturday, September 1, 2012

On Short Notice: 250% More Testosterone From Oleuropein in Olive Oil? Obese Kids, TV, Twinkies & Tortilla Chips, Vitamin D Supplementation That Works, Coffee, Green or Gomchui Tea as Fat Blocking Orlistat Alternative and More!

Image 1: A tablespoon of olive oil is probably not enough to boost your testosterone levels, right? Probably not, at least not by 250%, I should say.
Another Saturday, time is flying by and we have no time to waste, because YOU will have to dig trough a whole host of pretty long and (hopefully) interesting "On Short Notice" news, today! So let's get to business and start out with the surprising testosterone boosting corticosteroid normalizing effects of a bitter phenol in extra virgin olive oil most of you will probably be consuming on a daily basis without even knowing its name - Oleuropein. When we are through with the human equivalent dosage calculations the scientists obviously forgot to do, we will make a detour to one of those problems that are particularly dear to my heart, childhood obesity and how watching TV and eating fatty and sugary foods make a dynamic duo that can increase your (grand-)son's, (grand-)daughter's, nephew's and niece's risk to become obese by up to 30%. We will then use our flux-compensator (edit: I used the term that's used in the German version, i.e. "flux compensator" before, but edited it after Gary pointed out that the DeLorian in the original US version had a "flux capacitor" and a brief "research" made it obvious that this is a mistake of whoever translated the term for the original Back to the Future movies) and jump forward in time and see that your hopefully by the non-obese daughters and nieces can reduce their risk of visceral obesity and thus increased mortality even if the just wash the dishes, take the dog for a walk and use the stairs instead of the elevator.

Before we are eventually going to have a cup of gomchui tea, to evaluate if we can stand the taste so that we could ingest the 2-3 servings it would probably take to negate the negative effects of an occasional fatty slip on our diet, I will yet invite you to take yet a look at two studies from Saudi-Arabia, in which the researchers showed quite convincingly that vitamin D can actually have all those magical anti-obesity effects that it is hailed for, if... yeah, if you put the active calcitriol instead of its precursor cholicalciferol into the fatty chow of rodents. Sounds good? Well let's go, then!
  • Figure 1: While the results of the study, as well as the implications are impressive, the statement that one would get the respective human equivalent dose from "normal dietary intakes" is questionable, to say the least (see text for details) - and still the results of the study at hand only add to the nutritional value of the "liquid gold of the Mediterranean" with its proven antioxidant, antiinflammatory, antiageing, anti-viral, anti-microbial, anti-cancer, anti-aetherogenic and skin protectant effects (cf. Omar. 2010)
    Olive oil contains natural anabolic... well, sort of; at least according to research from the Laboratory of Nutrition Chemistry at Kobe Women's University in Japan, oleuropein, a phenolic compound in extra virgin olive oil did calm down the potentially catabolic corticosteroid overactivity in male rats fed a high protein (40%; from casein) diet (Oi-Kano. 2012). Allegedly, this alone does not yet make it an "anabolic", but with it's concomitant, but highly protein-dependent effect on the testosterone production in the testes of the male Sprague Dawley rats (see figure 1 - top, right), the ameliorative effect on the high corticosteroid expression on the high protein diet (+100% serum corticosteroids in the 40% vs.10% casein group w/out supplementation) and the consequently increased nitrogen balance (=higher net retention of protein) oleuropein aglycone does have much more of a natural anabolic than 99.9% of the expensive testosterone boosters out there.
    The increased secretion of noradrenaline and adrenaline (see figure 1 - top, right), as well as the downstream effect on the expression of uncoupling protein UCP-1 in BAT and the subsequent increase on thermogenesis should contribute to the "body recompositioning" effect of oleuropein, of which Oi-Kano et al. state that they will be particularly pronounced on a "high-fat diet, i.e., 30% fat diet" (Oi-Kano. 2012).
    The fact that humans have hardly any BAT is yet not the only problem, when it comes to the real-world significance of these results. With 10.3mg per rodent per day, i.e. 41mg/kg per day (human equivalent dose 6.68mg/kg), the "effective dose" of regular extra virgin olive oil would be unrealistically high, even if we base our estimate on the same (unpublished) data Oi-Kano et al. use in the discussion of their results and assume that there are 104 mg/kg oleuropein aglycone in extra virgin olive oil. The scientists do yet obviously believe that 5L of olive oil (80kg x 6.67mg/kg body weight divided by 104mg/L olive oil) would be a "normal dietary intake of extra virgin olive oil" - a statement that sounds even more laughable, when we use data from a study by Owen et al. which found that the oleuropein content of extra virgin olive oil ranges from 2.3 to 9.0mg/L (Owen. 2000), with higher levels of oleuropein in bitterer EVOOs (Gutiérrez-Rosales. 2003), or base our estimates on another study from Oi-Kano et al. in which they measured an oleuropein aglycone content of ~19mg/kg extra virgin olive oil (actually we would even hate to make up for the lower density of olive oil and divide that by 0.91 to convert it mg/L). And let's be honest in view of the sheer amount of studies investigating the beneficial effects of extra virgin olive oil in animals and humans, I doubt that a +250% testosterone boosting effect of "normal dietary intakes of extra virgin olive oil" could actually have remained unnoticed...
    It also remains to be seen if olive leaf extracts provide a better alternative. In 2008, Jemai et al. report that the Chemlali olive leaves they used in their rodent study, yielded 4.32 g oleuropein and 3.82g oleuropein aglycone per 100g dried leaves (Jemai. 2008). In view of the fact that the yield will necessarily depend on both the cultivar an the extraction method, you should thus make sure that any extract you buy has a standardized content of oleuropein / oleuropein aglycone. Moreover, if you are mainly interested in the better-established antioxidant, antiinflammatory, antiageing, anti-viral, anti-microbial, anti-cancer, anti-atherogenic and skin protectant effects of olive oil (cf. Omar. 2010),  5L /day are not necessary, anyway ;-)
  • Figure 2: Vicious cycle of childhood obesity (top); childhood obesity trends - state rates (data according to Childhood Obesity Action Network. 2009)
    In children under the age of 10 television watching increases risk of obesity by +30% This is the alarming result of a subgroup analysis (N = 1,696 schoolchildren) from the IDEFICS study, a large scale epidemiological study that involved a total of 15,144 children aged 2-9y from Italy, Estonia, Cyprus, Belgium, Sweden, Germany, Hungary, and Spain. Contrary to comparable analyses, which tend to simply correlate obesity data with data from a questionnaires on the total daily or weekly TV consumption, the Lissner study had a more sophisticated approach towards "TV watching" which included (a) the kids habitual television exposure time, (b) television viewing during meals, and (c) whether or not the children had a televisions in their bedrooms.
    After correlating these data with additional information about taste preferences, Lissner et al. found that all three aforementioned parameters, i.e. total TV consumption, watching TV during meals and having a TV in their room, were associated with profound (21-30%) increases in obesity risk.
    The actual novelty of these results is yet that all these TV watching behavior correlated (in most cases monotonously) with the propensity to eat sugary and/or fatty foods - and that despite the fact that the same kids who were eating nothing but chips and dingdongs, when they were sitting in front of the boob tube did not show similar preferences for fatty and sweet in the contextual different testing sessions all 1,696 kids had undergone.
  • Figure 3: A few steps a day can go a long way (based on Ayabe. 2012)
    Frequent everyday activity prevents visceral fat gain This is the result of a study which investigated the relationship between the frequency of everyday physical activity and visceral adipose tissue mass in 42 Japanese women, aged between 40 to 60 years (Ayabe. 2012). A brief look at the figure on the right will suffice to see that the problem of our society (and the US society probably even more than the European or Japanese) is not necessarily too little exercise, but much more fundamentally no movement at all during our everyday lives. I mean, 2 of the women did not even have 1 bout of 1-min moderate physical activity, 9 did not move for 3 min a day - is it a wonder we are having serious problems, then?
    Tip: Take a WALK! The results of another recently conducted study, which found that 30 min of brisk walking at approximately 60% of maximum heart rate after a meal reduce post-prandial lipidemia in healthy normolipidemic men, only corroborates the importance of daily physical activity (standing for 45min did not make a difference, btw; cf. Miyashita. 2012). While we do have the stress right after launch, we don't have the "exercise" that would historically be associated with the latter - and as of late this is not just the case for white collar workers like me ;-)
  • Active vitamin D does what vitamin D3 doesn't do, ameliorate the oxidative damage due to high fat diets. While the few vitamin D3 supplementation trials in rodents and humans were real non-starters, when it came to the purported effects of "everyone's darling vitamin" against diet induced obesity, diabetes, inflammation, etc. a group of Saudi Arabian researchers has just published the second of two papers within the past two months which deal with the effects of active vitamin D, aka calcitriol, on the diet induced damage in muscle and liver tissue (Alkharfy. 2012).
    Figure 4 (Zhu. 2012): Vitamin D3 is converted to the active metabolite 1,25(OH)2D3 by sequential 25-hydroxylation and 1a-hydroxylation. If this conversion does not take place (for possible reasons see text) , though, it could be that you don't see any benefits even from exorbitantly high amounts of supplemental vitamin D3
    In the July issue of Molecules, the scientists had already presented data on the preventive effect calcitriol had on the myocyte damage (weak, pre-degenerate mitochondria, loss of connections among myofibrils) they observed in the muscle fibers of mice who had been fed a high fat diet for 12 weeks. Now, roughly a month later, the researchers from the King Saud University in Riyadh, Saudi Arabia, report similar beneficial effects on weight-related systemic inflammation and ultrastructural changes of the liver during a 16-week rodent study. Compared to the non-supplemented mice, the mice on the calcitriol enriched high fat diet had reduced concentrations of TNF-α, CRP and IL-6 (p < 0.05) and a way higher insulin sensitivity (C-peptide and insulin levels of 539.4 ng/ml versus 718.9 ng/ml and 0.77 ng/ml versus 1.7 ng/ml, respectively; p <0.05). Moreover, the potentially toxic calcitriol protected the liver of the mice from the marked accumulation of fat droplets Alkharfy et al. observed in 60-70% of the hepatocytes of the mice that were fed the non-supplemented high fat diet.
    The profound weight loss the animals in the HFD + calcitriol trials experienced in both trials (even the LFD control did gain some weight!), should yet remind you that there is a good reason that you can't buy calcitriol over-the-counter at your local GNC and better don't reach out to whatever other sources you may just have been thinking about!
    That said, it is still remarkable that in a mouse model of prostate and breast cancer, dietary vitamin D3 (cholecalciferol) and thrice weekly injections of calcitriol worked equally well (Swami. 2012), while the cholecalciferol from your average vitamin D supplement sucks, when it comes to the metabolic effects everyone is promising you, you would see if you just bumped your 25-OHD levels to whatever novel heights. At least in the case of the obese rodents, a possible reason could simply be that obesity prevents it's conversion. That this appears to be the case is something we have already discussed in the context of the defect in the enzymatic cascade in obese patients in a previous installment of "On Short Notice". And if it's not obesity that hinders vitamin D from doing its purported job, you still got my hypothetical rants about the exuberant phosphate intake from the average western diet and its negative impact on the conversion of cholecalciferol to calcitriol (see "Hypothesis: Does Vitamin D 'Deficiency' Protect Us From Phosphorus Overload?")
  • Figure 5: ECGC may be more potent in the in-vitro essay (left, background; anti-lipase effect rel. to Orlistat), its susceptibility to digestion (bottom, right) renders it yet ineffective as a "fat blocker" (left, foreground; FFA during simulated digestion). Appropr. dosed (1-3 serv./day), coffee and gomchui tea thus appear to be better suited to reduce fat digestion and absorption (Cha. 2012).
    With di-O-caffeoylquinic acid, Gomchui (Ligularia fischeri) Tea easily outperforms coffee and green tea as an inhibitor of fatty acid breakdown in the stomach - what could in fact turn against you on an already fat-deficient (yeah, there is such a thing!) diet, could be a useful tool for the transient phase from diet-induced obesity to natural leanness on a totally revamped diet + exercise regimen, as well as the occasional "binge", you may planning to have if you are already following a healthy whole foods diet.
    Published in the July issue of the Journal of Agriculture and Food Chemistry a recent the study by Cha, Song, Kim and Pan  shows quite conclusively that a tea that's brewed from Lingularia fischeri (gomchui) can decrease the activity of the fat-digesting enzymes in your gut and thus minimize the energy influx from free fatty acids.
    What's also intriguing about this research is that green tea, despite having the highest content of EGCG and thus theoretically the most potent lipase inhibitor of all the three beverages (green tea, coffee and gomchui tea) had - as soon as a certain dosage threshold of 2-3 servings was achieved, the least effect on on lipase activity in the digestion model the scientists used. If your goal is to ameliorate the potential weight gain right after a binge, gomchui or even a strong black coffee would probably be better choices than a cup of green tea.
    Figure 6: The effect green tea extracts have on the synthesis (FAS), transport (CPT II) and oxidation (ACO) of fatty acids in the liver, depend on both EGCG and caffeine (Suigiura. 2012)
    In this context, it is also worth mentioning that a related study by Sugiura et al. that has been published in the Journal of Obesity found that the inhibitory effects of EGCG on FAS (fatty acid synthase, i.e. the exact opposite of lipase) expression in the liver, reach statistical significance only in the presence of caffeine (Sugiura . 2012).
    This would render the use of decaffeinated green tea extracts for weight-loss purposes at least less effective than the consumption of real green tea. You could probably still grasp the beneficial downstream effects of the anti-inflammatory effects of EGCG, but would miss out on the "fat burning" and "anti-fat depositioning" effects (esp. in the liver), as those are obviously reliant on the simultaneous presence of caffeine. Needless to tell you that this is exactly the way nature has intended it, right? I guess it's about time to have a cup of good tea now... or maybe coffee - or Gomchui?
That's it already for today, but never mind, there will be more. In the next installmenta of "On Short Notice", my daily news-updates on the SuppVersity Facebook Wall (today with news on the muscle building effects of cortisol + IGF1 and more) and - from now on - every Thursday on Super Human Radio (click here to download the first installment of the thursdaily "Super Human Radio + SuppVersity Joint Research Update"). And aside from that there are of course your daily "regular" SuppVersity News!

  • Alkharfy KM, Al-Daghri NM, Ahmed M, Yakout SM. Effects of vitamin d treatment on skeletal muscle histology and ultrastructural changes in a rodent model. Molecules. 2012 Jul 31;17(8):9081-9. 
  • Alkharfy KM, Al-Daghri NM, Yakout SM, Ahmed M. Calcitriol Attenuates Weight-Related Systemic Inflammation and Ultrastructural Changes of the Liver in  a Rodent Model. Basic Clin Pharmacol Toxicol. 2012 Aug 21. 
  • Ayabe M, Kumahara H, Morimura K, Sakane N, Ishii K, Tanaka H. Accumulation of Short Bouts of Non-Exercise Daily Physical Activity is Associated with Lower Visceral Fat in Japanese Female Adults. Int J Sports Med. 2012 Aug 17.  
  • Cha KH, Song DG, Kim SM, Pan CH. Inhibition of Gastrointestinal Lipolysis by Green Tea, Coffee, and Gomchui ( Ligularia fischeri ) Tea Polyphenols during Simulated Digestion. J Agric Food Chem. 2012 Jul 25;60(29):7152-7. 
  • Childhood Obesity Action Network. State Obesity Profiles, 2009. National Initiative for Children's Healthcare Quality, Child Policy Research Center, and Child and Adolescent Health Measurement Initiative. Retrieved 06/02/2010 from
  • Gutiérrez-Rosales F, Ríos JJ, Gómez-Rey ML. Main polyphenols in the bitter taste of virgin olive oil. Structural confirmation by on-line high-performance liquid chromatography electrospray ionization mass spectrometry. J Agric Food Chem. 2003 Sep 24;51(20):6021-5.
  • Jemai H, Bouaziz M, Fki I, El Feki A, Sayadi S. Hypolipidimic and antioxidant activities of oleuropein and its hydrolysis derivative-rich extracts from Chemlali olive leaves. Chem Biol Interact. 2008 Nov 25;176(2-3):88-98. Epub 2008 Sep 7.
  • Lissner L, Lanfer A, Gwozdz W, Olafsdottir S, Eiben G, Moreno LA, Santaliestra-Pasías AM, Kovács E, Barba G, Loit HM, Kourides Y, Pala V, Pohlabeln H, De Henauw S, Buchecker K, Ahrens W, Reisch L. Television habits in relation to overweight, diet and taste preferences in European children: the IDEFICS study. Eur J Epidemiol. 2012 Aug 22.
  • Oi-Kano Y, Kawada T,Watanabe T, Koyama F,Watanabe K, Senbongi R, et al. Extra virgin olive oil increases uncoupling protein 1 content in brown adipose tissue and enhances noradrenaline and adrenaline secretion in rats. J Nutr Biochem. 2007;18:685–92.
  • Oi-Kano Y, Kawada T, Watanabe T, Koyama F, Watanabe K, Senbongi R, Iwai K. Oleuropein supplementation increases urinary noradrenaline and testicular testosterone levels and decreases plasma corticosterone level in rats fed high-protein diet. J Nutr Biochem. 2012 Aug 15. 
  • Omar SH. Oleuropein in olive and its pharmacological effects. Sci Pharm. 2010;78(2):133-54. Epub 2010 Apr 23.
  • Owen RW, Giacosa A, Hull WE, Haubner R, Spiegelhalder B, Bartsh H. The antioxidant/anticancer potential of phenolic compounds  isolated from olive oil, Europ. J. Cancer. 2000; 36:1235–1247. 
  • Sugiura C, Nishimatsu S, Moriyama T, Ozasa S, Kawada T, Sayama K. Catechins and Caffeine Inhibit Fat Accumulation in Mice through the Improvement of Hepatic Lipid Metabolism. J Obes. 2012;2012:520510.
  • Zhu J, DeLuca HF. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet? Arch Biochem Biophys. 2012 Jul 1;523(1):30-6