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. 2013).

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. 2013)

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. 2013) 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. 2013) 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. 2013). 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. 2013)

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. 2013)

Figure 5: Total  cholesterol (TC, top) and LDL-C to HDL-C (bottom) ratios (Enos. 2013)

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. 2013)

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. 2013 Oct 28.

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. 2013). 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. 2013).
  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. 2013)

  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. 2013). 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. 2013). 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. 2013).

  

  Figure 4 (Zhu. 2013): 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. 2013), 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. 2013).

  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. 2013)

  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 . 2013).
  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!

References:

• 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. 2013 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. 2013 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. 2013 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. 2013 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 http://wwww.nschdata.org/content/07obesityreportcards.aspx.
• 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. 2013 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. 2013 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. 2013;2013:520510.
• Zhu J, DeLuca HF. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet? Arch Biochem Biophys. 2013 Jul 1;523(1):30-6

On Short Notice: Ghrelin & GH Boosting Fats for Intermittent Fasting, 4-AD, 5-AA, Testosterone & Co in "Pod", Too Much Vitamin D for Your Prostate, Estrogens in Milk & More

Image 1 (fidged-group.co.uk): Being average may not be sexy, but one thing I did not mention in the summary of what you are going to learn today is that an average amount of body fat (not the new average American though ;-) could hold the key for a longer life - ah, I almost forgot: This is only valid if it comes with an appropriate amount of lean mass, which is still the best predictor of a long and healthy life!

Somehow these On Short Notice posts become increasingly longer... I had to "outsource" a couple of items, to reduce today's installment to a manageable length, but don't worry a couple of them will turn up in the next installment or make it into the regular news in the days to come. For now you will have to settle for valuable and at least in part surprising insights into the broad range of effects different types and loads of dietary fat can have on your appetite, metabolism and your, or rather your bacterial subtenants' methane production. You will also learn what TAC means and why you want more than 1,080 units of it in every 100g of whatever you are stuffing down your pie-hole. You will be surprised to hear that SuppVersity student FatFree instinctively chose the low estrogen variety of dairy, when he "downed 1l of raw goat's milk" from his local farmer earlier today (see respective comment) and you will attend another lesson of the "what's good for your obese neighbor, is not necessarily good for you" class. All that will be topped of with some testosterone laden, WADA prohibited "pod", too much vitamin D for your prostate to handle and a glass of bone-conserving wine for the habitual drinkers among the ladies ;-)

Fat Interactions - MUFA, PUFA, SUFA and How They Influence Your Metabolism

The idea that "not all fats" are created equal is meanwhile broadly accepted. What is still a matter of constant debate, though, is which of the three main classes, i.e. saturated, mono- and polyunsaturated fatty acids exert beneficial and which of them detrimental effects on our health. A recently published on the differential effects of butter (saturated fat), olive oil (mono-unsaturated; oleic acid + a relative high amount of omega-6), fish oil (polyunsaturated; high omega-3) and soybean oil (polyunsaturated; mainly omega-6 + some omega 3) on the expression of the purported "hunger hormone" ghrelin (note: acetylghrelin, which was measured in this study, is the "active" variety of ghrelin) may yet help to get a better grasp of what exactly we should be looking for (Saidpour. 2013), when it comes to the downstream metabolic effects of high amounts of certain fatty acids - and no, it is not for maximal ghrelin suppression.

Figure 1: Food intake (in g, left), body weight (relative to control group on regular diet, middle) and acetylghrelin levels in the fasting and fed state during the 8-week experimental period (data based on Saidpour. 2013)

As the data data in figure 1 shows, the 5-week old male Wistar rats who had been randomly assigned to either standard rodent chow or calorically identical (3.98kcal/g of food) high fat diets who were fed ad libitum every other day only to maximize the ghrelin response) for 8 weeks did not, as common sense would suggest, eat the least and gain the least on the saturated fat (butter) diet with its long lasting satiety effect (as evidenced by the lowest fasting ghrelin levels).

In fact, the exact opposite was the case: The acute satiety effect of the fish oil and olive oil diets (as evidenced by the plummeting acetylghrelin levels in the fed state) turned out to be the main determinant of the amount of food the rodents, who were effectively intermittently fasted (though with a pretty long fasting window of 24h), consumed.  And while the low ghrelin levels in the fed state reduced the food intake, the fasting induced rise of acetylghrelin to 23% higher levels than in the butter fed animals has probably given them the metabolic advantage of elevated growth hormone levels. At least this is what we must expect based on the ability of ghrelin to directly bind to the GHS receptor and induce the release of the fat annihilating 191-amino acid, single-chain polypeptide from the lateral wings of the anterior pituitary gland (Kojima. 1999).

Bottom line: While this is certainly only another small piece to the oftentimes puzzling effects of fatty acids (check the "On Very Short Notice" items in this installment for more "puzzling" effects ;-), it does not only provide another mechanism by which the original "Mediterranean diet", which is rich in both fish and olive oil and by no means as fat free as its latest mainstream interpretation would suggest, could in fact provide a metabolic edge. And though the "intermittent fasting" feeding pattern may reduce the significance of the results for the "average" inhabitant of the Western hemisphere, who can hardly go 2h without a Snickers bar or at least a sugar-laden coffee, it does suggest that all the "lean gainers" and "intermittent fasters" out there could derive great benefits from a huge piece of salmon and couple of tablespoons of high MUFA olive, macadamia or artichoke oil in their "feeding windows".

A Diet High in Dietary Antioxidant Keeps you Lean & Healthy

Image 2: Clover is among the most potent antioxidant foods.

You know that I am very critical when it comes to the supply of exogenous antioxidants (cf. "Multivitamins, a question of Faith?!"; more on multivatmins), but would never even remotely consider limiting the supply of whole foods that are rich in antioxidants. I was thus not very surprised, when I read that the consumption of high amounts of dietary antioxidants was associated with statistically significant lower body weight and abdominal fat gain in a 3-year longitudinal (this is where scientists analyze data from the same persons on different time-points) study from the University of Medical Sciences in Teheran (Bahadoran. 2013).

Foods	TAC
Cloves (see image), Cinnamon, Oregano, Tumeric, Acai (all dried or grounded)	300,000 -100,000
Cacao, Parsley, Basil, Currry, Sage, Peppercorns, Mustard, Ginger, Marjoram	100,000 -25,000
Rice bran, Chili, Pecans, Paprika, Choke berries, Elderberries, Kidney Beans (dried), Oregano, Walnuts	25,000 -10,000
Hazelnuts, Cranberries, Artichoke hearts, Blueberries, Prunes, Pistachios, Blackcurrant, Artichokes, Plums, Blueberries (cult.) Lemon balm (fresh) Blackberries, Garlic, Coriander,	10,000 -5,000
Raspberries, Basil (fresh), Almonds, Apples, Dates, Strawberries, Figs, Peanuts, Raisins, Cherries, Asparagus, Spinach	5,000 -2,500
Cornflakes, Red Cabbage, Gooseberries, Cashews Avocado, Pears, Peaches, Oranges, Oats, Macadamia, Tangerines, Broccoli, Potatoes, Grapefruit, Red grapes	2,500 -1,500
Carrots, Olive oil, Green grapes, Mango, Lettuce, Radish Eggplant, Kiwi, Banana, Red pepper, Pineapple, Artichoke, Nectarines, Pine nuts, Cauliflower, celery	1,250 -500
Leeks, Lettuce, Baby carrots, Tomatoes, White wine, cantaloupe, Honeydew, Watermelon, Cucumber	500 -100

In particular, Zarah Bahadoran and her colleagues found that the consumption of foods with an average total antioxidant capacity equal to 1,080µmol TAC essay units per 100g - something your would get from oats + blueberries or a handful of pecans and an apple - was associated with a -38 % decrease in the risk of central obesity (note: The TAC essay is an experimental measure of the total antioxidant capacity of food and is independent of whether it's phenols, vitamins, thiols or whatever that contribute to the antioxidant effects of a food; the clear disadvantage of this method is that it does not really tell you what exactly the compounds will do outside of a petri dish, but, but this is the topic for another blogpost ;-)

And while some of the confounding factors have been eliminated from the above hazard risk calculations, it is still worth to take note of the fact that...

• people with the highest antioxidant intake consumed food with the lowest energy density (so they cannot be eating nuts and chocolate only ;-)
• women consumed significantly more antioxidants than men, with +10% more women in Q3 (959-1080µmolTE/100g) and +15% more women in the critical Q4 (>1,080µmol/kg) quartiles
• the more leisure time the subjects had, or I should say allowed themselves, the higher was their antioxidant intake
• high antioxidant consumers were also dairy lovers with 81% more dairy consumption in the highest quartile, exactly those people, thus, who consumed the >1,082 µmolTE/100mg diets
• needless to say that people who are reckless enough to smoke also consumed the least antioxidants

Aside from these significant differences, the non-existence of other differences people often take for granted, such as the notion that education and job activity, or different macronutrient compositions would have an impact on the total amount of antioxidants you consume, is certainly worth mentioning.

  On Very Short Notice

• 

  Figure 2: "Pod" contains a hell lot of steroids. Unfortunately, most of them will be dumped by right into the urine specimen for the WADA agents (data based on Thevis. 2013)

  "Pod" doping could get you banned, but probably won't increase your performance - While I cannot tell you what the swimmers at the Olympics have been taking to break world record after world record (some even in consecutive races on the same day), I can tell you that it were not the reddish-brown musk grains from the dried secretion from the preputial follicles of the male musk deer , which are located in the "pod", a small sac in close proximity to the preputial orifice (see figure XYZ, upper right), because none of these athletes would have passed the WADA doping controls had he or she taken a couple of grams of those steroid-containing staples of Traditional Chinese Medicine.
  Now, despite the fact that we do see "classics" such as 4-AD, Androsterone, Epiandrosterone, DHEA and even minuscule amounts of the "Big T" (1-6µg/g with the highest level in the pod from the zoo animals from Leipzig, Germany - read more about testosterone's ability to build muscle in the "Intermittent Thoughts on Building Muscle") testosterone , the total amount of those compounds which could actually induce noticeable performance increases may be high enough to show up during doping controls as the five cases during the last FIFA Women World Cup show(cf. Thevis. 2013), it does not appear reasonable to assume that the rumored performance enhancing effects of musk (pod) extracts would stand the test in a placebo controlled supplementation trial.

• 

  Figure 3: When administered at a HED of ~750mg/day sodium salicates reduce the glucose (left axis) and insulin (right axis) levels in response to a standardized intraperitoneal glucose injection in obese mice, they do the opposite in lean mice (based on Nixon. 2013).

  Salicates block cortisol expression in fat cells and increase insulin sensitivity in obese mice, but... as we have seen for alpha lipoic acid (see "ALA? You are Better of Without the Purported Nutrient Repartitioner") and tons of other "wonder-supplements", things that are good for your obese neighbor will rarely work out for lean folks like, yourself; and thus it should not come as a surprise that the blockade of adipose tissue 11-beta-HSD, the enzyme that converts cortisone, the inactive form of cortisol into it's active twin, exerts no, if not the exact opposite effect (see figure 3; adapted from Nixon. 2013).
  So, if you are lean and want to stay lean, leave the aspirin, the 7-ketos and other overpriced 11-beta-HSD inhibitors or "cortisol blockers" to those who need them - inflamed, overweight (pre-)diabetics.
• Purportedly anti-carcinogenic high vitamin D levels increase risk of prostate cancer - Swedish scientists found a statistically significant trend towards an increased risk of developing prostate cancer with rising vitamin D levels. In the 7th and 8th decile which corresponds to plasma vitamin D levels of 91-97 nmol/L the calculated risk of developing prostate cancer was 67% higher than in the lowest decile (Brändstedt. 2013). Other than previous studies which reported associations between high calcium intake and prostate cancer risk, Brändstedt et al. observed an association between high serum calcium levels and prostate cancer levels only among men aged 55-65 who had a BMI < 25. It is thus very unlikely that the underlying reason of the pro-carcinogenic effects was an increase in calcium absorption... hmm, I don't have to remind you of (a) the antagonism between vitamin D and vitamin A and (b) last weeks news on the anti-carcinogenic effects of the latter, do I?

• 

  Image 3: Although the scientists controlled the compliance by measuring the serum concentration of fatty acids instead of using unreliable food logs, there are still  a lot of uncontrolled confounding variable, here. Hower, the same can be said of those studies on which the concept of the pro-inflammatory omega-6s is based. Anyway, I will still eat butter, not margarine and if olive oil is one of staple sources of dietary fat, you will be getting plenty of omega-6 from this purported GH booster (see previous new item)

  High omega-6 diet reduces insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides - Helena Bjermo and her colleagues from the Uppsala University in Sweden report that feeding 67 abdominally obese patients (15% were diabetic) either a butter-based high saturated fat diet or a diet that was particularly rich in linoleic acid (omega-6 mainly from sunflower oil; 15% of the total energy intake) for 10 weeks had very differnt effects on the hepatic fat content an other highly relevant markers of metabolic health. Despite the fact that both diets were isocaloric, the butter-based high saturated fat diet increased the hepatic fat content of the study participants (measured by MRS) by 10% while the subjects in the high PUFA group were able to reduce the fat content of their livers by -35%. Similarly, the basal insulin level, triglycerides, as well as total and LDL cholesterol increased in the butter eaters and decrease or remained the same in the 15% linoleic acid group.
  The results are honestly not what I had expected, but in essence only further evidence there is still a lot to learn about the shades of grey that exist between the dichotomous black and white that is still so characteristic of the way we think about fats.
• Goat's milk is the better choice for people concerned with limiting their intake of exogenous estrogens - According to analyses that were conducted at the Laboratory of Proteomics and Analytical Technologies in Frederick (Farlow. 2013), cow's milk contains significantly more estrogens (estrone and 17beta-estradiol) than goat's milk and that irrespective of whether it was organically produced or not. Bad news for the reproductive health of the North Americans and Europeans, where the consumption of cow's milk exceed that of goats milk by several magnitudes and good news for the fertility of the rest of the world, where goat's milk still is the "milk of choice".

• 

  Image 4: Looks like this was not the only potential side effect of methane producing bacteria in your gut.

  High fat diets increase the ratio of methane producing to other bacteria and thus increase obesity risk - Most of you will probably remember the finding that mice without gut microbiome are more or less resistant to dietary induced obesity. A recent study does now suggest that (as it was to be expected) not all bacteria are created evil.. ah, pardon... equal ;-) In the lab mice of Ruchi Mathur and his colleagues, the tendency to develop obesity correlated with the amount of gastrointestinal (GI) methanogens, including Methanobrevibacter smithii, and was independent of the presence of other bacteria (Mathur. 2013).
  With the pro-methanogenic (=allows those little bastards to grow) effects of high fat diets Mathur et al. may in fact have found another potential co-founder in the development of the metabolic syndrome. Interestingly enough Methanobrevibacter smithii is also the predominant methanogen in patients with constipation-dominant IBS and methane breath (Kim. 2013) - so if that is you, this could be one of the few cases where the use of a broadband antibiotic could save you from a lot of ailments, because you would thus not have to care about contradictory results from Million et al., as well as dozens of other studies, each of which identifies another type of bacteria as 'the root cause' of the obesity epidemic - in Million's case the name of the scapegoat is Lactobacillus reuteri, by the way (Million. 2013).
• Mediocrity guarantees a long life - At least when it comes to body fatness being too lean and being too fat are equally detrimental to the life expectancy of male 65+ agers (Toss. 2013). If you are women, though, the results Fredrik Toss and his colleagues published in the latest issue of Age and Ageing suggest that being on the chubbier side of things can actually be life-saving, as long as you carry the fat in the gynoid and not the abdominal area. Most importantly, however, lean mass, or as my buddy Carl Lanore calls it, "metabolic currency" is yet still the most significant predictor of survival in older subjects - in other words: Don't even think of emulating the skinny fat celebrities with their starvation diets and endless cardio sessions if you intend to live your grand- and grand-grand-children, better check out yesterday's news on the "Iranian HIIT Solution for Improved Insulin and Leptin Sensitivity".

• 

  Image 5: If you are concerned about bone health, menopause is not the best time to stop drinking... unless you start weight lifting, of course ;-)

  Don't stop drinking alcohol in menopause! At least if you don't want to increase bone-resorption, i.e. the leeching of calcium from your bones. This is the surprising result of a recently published study by Jill A. Marrone and colleagues, who had  investigated the effects of total abstinence from alcohol in 40 healthy postmenopausal women (mean ± SE age, 56.3 ± 0.5 y) who consumed the alcohol equivalent of ~1 glass of wine per day (Marrone. 2013). Interestingly, the bone formation marker osteocalcin and the resorption marker C-terminal telopeptide (CTx) returned to their normal values, once the women resumed their former drinking habits.
  In view of the fact that there was also a significant correlation between baseline bone-density, as measured dual-energy x-ray absorptiometry, and the extent of mild to moderate alcohol consumption, these results raise the question whether "bone health" would be another factor to add to the list of the "minimalist approach" to alcohol consumption.

References:

• Bjermo H, Iggman D, Kullberg J, Dahlman I, Johansson L, Persson L, Berglund J, Pulkki K, Basu S, Uusitupa M, Rudling M, Arner P, Cederholm T, Ahlström H, Risérus U. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr. 2013 May;95(5):1003-12. 
• Brändstedt J, Almquist M, Manjer J, Malm J. Vitamin D, PTH, and calcium and the risk of prostate cancer: a prospective nested case-control study. Cancer Causes Control. 2013 Aug;23(8):1377-85.
• Farlow DW, Xu X, Veenstra TD. Comparison of estrone and 17β-estradiol levels in commercial goat and cow milk. J Dairy Sci. 2013 Apr;95(4):1699-708.
• Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., Kangawa, K. Ghrelin is a growth hormone releasing acylated peptide from stomach. Nature. 1999; 402, 656-660.
• Mathur R, Kim G, Morales W, Sung J, Rooks E, Pokkunuri V, Weitsman S, Barlow GM, Chang C, Pimentel M. Intestinal Methanobrevibacter smithii but Not Total Bacteria Is Related to Diet-Induced Weight Gain in Rats. Obesity (Silver Spring). 2013 Jun 7. 
• Marrone JA, Maddalozzo GF, Branscum AJ, Hardin K, Cialdella-Kam L, Philbrick KA, Breggia AC, Rosen CJ, Turner RT, Iwaniec UT. Moderate alcohol intake lowers biochemical markers of bone turnover in postmenopausal women. Menopause. 2013 Jul 9.
• Million M, Maraninchi M, Henry M, Armougom F, Richet H, Carrieri P, Valero R, Raccah D, Vialettes B, Raoult D. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int J Obes (Lond). 2013 Jun;36(6):817-25.
• Nixon M, Wake DJ, Livingstone DE, Stimson RH, Esteves CL, Seckl JR, Chapman KE, Andrew R, Walker BR. Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization. Diabetes. 2013 Apr;61(4):790-6.
• Saidpour A, Kimiagar M, Zahediasl S, Ghasemi A, Vafa M, Abadi A, Daneshpour M, Zarkesh M. The modifying effects of fish oil on fasting ghrelin mRNA expression in weaned rats. Gene. 2013 Jul 25.
• Thevis M, Schänzer W, Geyer H, Thieme D, Grosse J, Rautenberg C, Flenker U, Beuck S, Thomas A, Holland R, Dvorak J. Traditional Chinese medicine and sports drug testing: identification of natural steroid administration in doping control urine samples resulting from musk (pod) extracts. Br J Sports Med. 2013 May 6.
• Toss F, Wiklund P, Nordström P, Nordström A. Body composition and mortality risk in later life. Age Ageing. 2013 Jul 20.

Tocotrienols: What They Are, What They Do & How They Work + Why the RDA of Palm Olein is NOT 1xCup Per Day

Image 1: If you wanted to get the tocotrienol levels a producer of respective supplements says are  "required", you would have to eat at least 200g palm fruits a day. Alternatively, you can resort to 4kg of oats, if you like those better... What? you are wondering that you are not dead by now? After so many years of tocotrienol deficiency from not getting your 4kg of oats?

The long lists of pathologies related to vitamin E deficiency include, among others, all sorts of degenerative diseases from ataxia over general muscle degeneration to degeneration of sperm and subsequent infertility. But despite the fact that there is a pretty substantial amount of evidence that would suggest that a diet rich in vitamin E could not just prevent the aforementioned pathologies, but would also protect us from many of the currently prevalent ailments of western society such as obesity and coronary vascular disease (Mishra. 2003; Rimm. 1993), respective trials with dietary supplements usually show no, or even negative effects. I have already addressed a couple of  reasons why the benefits of dietary vitamin E intake often cannot be replicated with supplements in previous posts. The most significant one, probably is the absence of the "right" mixture and ratio of alpha-, beta-, gamma- and delta-tocopherols and, as an emerging contributer, the total absence of tocotrienols in the vast majority of vitamin E supplements and almost 99.9% of the pertinent trials.

What are tocotrienols? And what do they do?

I could now rant about the structural differences between the two, with the tocotrienols being an unsaturated variety of the tocopherols with a isoprenoid side chain, but I guess it is enough to know that due to  differences in their molecular structure, they also differ in their effects on the human body, of which you may already have apprehended that their cholesterol lowering effects were the first to attract the attention from researchers (Qureshi. 1986). Within the last 26 years researchers from all around the world have identified additional health benefits, the most prominent of which are...

• Anti-cancer effects (Kato. 1985; Sundram. 1989; Weng. 2009),
• General antioxidant effects (Newaz. 1999),
• Brain specific antioxidant effects (Khanna. 2003),
• Exercise-specific antioxidant effects (Lee. 2009),
• Cardiovascular disease (Shibata 2009)
• Diabetic neuropathy (Kuhad. 2009)
• Bone health (Ahmad. 2005)
• Metabolic syndrome (Weng. 2011)
• Antithrombotic effects (Qureshi. 2011)
• Endocrine health (Yu. 2005)
• Liver health (Patel. 2013)

The purpose of today's SuppVersity article is yet not so much to compile the most extensive list of potential, purported or demonstrated benefits of tocotrienols, the major dietary sources of which are (Kobayashi. 1975; Tan. 2011)

• rice bran oil (50:50 tocopherol:tocotrienol ratio), 
• palm oil (25:75 tocopherol:tocotrienol ratio), and 
• annatto (0.1:99.9 tocopherol:tocotrienol ratio) oil
• human breast milk (!) [though this is probably no major source for you ;-]

but rather to take a look at an intriguing chart of the various molecular targets (Aggarwal. 2010) and discuss the implications:

Figure 1: Molecular targets (left) and proteins that directly interact with tocotrienols (right; adapted from Aggarwal. 2010)

As you can see  without even looking really close at the above graphic, the number of those targets is vast. Another thing you should see right away is that the effect of the tocotrienols is mostly inhibitory (red ovals in the left) and include a couple of old foes, such as:

• the inflammatory cytokines & transcription factors: IL-1, IL-6, TNF-alpha, nf-kappabeta, IL-8 (probably involved in auto-immune reactions), PF-A4 (increases platelet aggregation and thus thrombosis risk)
• factors involved in angiogenesis and cardiocascular disease: VEGF (vascular growth factor, involved in CVD) and its receptor VEGF-r, VCAM-1 (increases adhesion of immune cells to the endothelial wall)
• kinases involved in the cell cycle and apoptotic regulators: CDK's, PKC, pERK, etc. & survivin, IAP-1 & 2 etc., but also telomerase, which are all involved in the proliferation of cancer
• enzymes involved in inflammatory processes: eNOS, iNOS, COX-2, etc.

On the upregulatory side of things, we have

• enzymes from the CYP cascade, which are among other involved in the clearance of estrogen, and other hormone like substances and the metabolism of drugs,
• MAPK and JNK, which exert anti-catabolic effects on muscle tissue, or 
• GPX and SOD, two of the major enzymes involved in the antioxidant defenses

Now, if we take a look at all these, you may remember that low COX-2 levels have only recently been identified with profound overtraining (cf. "Overtraining inflammation insufficient repair"), that AKT (not mentioned above, but in figure 1) is one of the driving forces of skeletal muscle anabolism and telomerase, extends cell life in general, not just in cancer cells. Which brings us back to the issue of ...

...how much anti-oxidants do we actually need?

Figure 2: Total tocopherol and tocotrienol content of high vitamin E foods / oils (top) and tocopherol ratios (bottom) , data based on Whittle. 1967 and Slover. 1971

Or, in this particular case, how much tocotrienols are still beneficial? Neither I, nor anybody else knows the exact answer to this question. And against this fact, the recommendations I came across on the website of a major producer of respective supplements, which state that you would need

• 80g of palm oilen (cooking oil),
• 160g of rice bran oil,
• 3kg of barley,
• 1.5kg of wheatgerm, or 
• 4kg of oats

to (I quote) "achieve the required [my emphasis] level of tocotrienols" should tell any reasonable person that those "required" levels (~150mg) are probably required to generate the target revenue of the said company, yet probably not required for you or any other human being to thrive.

Do not stack one more, but take one out!

Instead of adding another overpriced (and probably overdosed) tocotrienol supplement to your regimen, it is thus probably wiser to simply drop any superflous and potentially harmful alpha-tocopherol only supplements which do would offset the alpha- to gamma- and delta- tocopherol ratio (this could potentially be ameliorated by taking a natural blend) and limit the total tocopherol intake to reasonable levels, as the latter has also been shown to hamper the absorption and retention of tocotrienols (Ikeda. 2003). In this context it is also noteworthy that Ping Tou Gee writes in a 2011 paper with the aptly chosen title "Unleashing the untold and misunderstood observations on vitamin E" that this fact alone would suggest that "there is a need to review critically on the dietary reference intakes recommendations" for alpha tocopherol (α-T). His bold statement that

[i]t is not known whether α-T is still essential to humans in long terms, α-T₃ [alpha tocotrienol] diet appeared to produce healthy rats over five generations.

is yet probably an attribution to Palm Nutraceuticals Sdn. Bhd. (which is not the aforementioned company which wants to force-feed you either their supplements or 2 cups of rice bran oil), of which he states in the acknowledgments that he thanks them "for permission to publish this paper" and further evidence for how pathetic parts of the research in the medical field is - awful this science business, isn't it?

References:

1. Aggarwal BB, Sundaram C, Prasad S, Kannappan R. Tocotrienols, the vitamin E of the 21st century: its potential against cancer and other chronic diseases. Biochem Pharmacol. 2010 Dec 1;80(11):1613-31. Epub 2010 Aug 7.
2. Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S. Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone. Clin Exp Pharmacol Physiol 2005;32:761–770 
3. Gee PT. Unleashing the untold and misunderstood observations on vitamin E. Genes Nutr. 2011 Feb;6(1):5-16. Epub 2010 Jul 20.
4. Ikeda S, Tohyama T, Yoshimura H, Hamamura K, Abe K, Yamashita K. Dietary alpha-tocopherol decreases alpha-tocotrienol but not gamma-tocotrienol concentration in rats. J Nutr. 2003 Feb;133(2):428-34.
5. Kato A, Yamaoka M, Tanaka A, Komiyama Ka, Umezawa I. Physiological effect of tocotrienol. J
   Japan Oil Chem Soc (Yukugaku) 1985;34:375–376.
6. Khanna S, Roy S, Ryu H, Bahadduri P, Swaan PW, Ratan RR, et al. Molecular basis of vitamin E
   action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced
   neurodegeneration. J Biol Chem 2003;278:43508–43515.
7. Kobayashi H, Kanno C, Yamauchi K, Tsugo T. Identification of alpha-, beta-, gamma-, and delta-
   tocopherols and their contents in human milk. Biochim Biophys Acta 1975;380:282–290.
8. Kuhad A, Chopra K. Attenuation of diabetic nephropathy by tocotrienol: involvement of NFkB
   signaling pathway. Life Sci 2009;84:296–301.
9. Lee SP, Mar GY, Ng LT. Effects of tocotrienol-rich fraction on exercise endurance capacity and
   oxidative stress in forced swimming rats. Eur J Appl Physiol 2009;107:587–595.
10. Mishra GD, Malik NS, Paul AA, Wadsworth ME, Bolton-Smith C. Childhood and adult dietary vitamin E intake and cardiovascular risk factors in mid-life in the 1946 British Birth Cohort. Eur J Clin Nutr. 2003 Nov;57(11):1418-25.
11. Newaz MA, Nawal NN. Effect of gamma-tocotrienol on blood pressure, lipid peroxidation and total antioxidant status in spontaneously hypertensive rats (SHR). Clin Exp Hypertens 1999;21:1297–1313.
12. Patel V, Rink C, Gordillo GM, Khanna S, Gnyawali U, Roy S, Shneker B, Ganesh K, Phillips G, More JL, Sarkar A, Kirkpatrick R, Elkhammas EA, Klatte E, Miller M, Firstenberg MS, Chiocca EA, Nesaretnam K, Sen CK. Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients. J Nutr. 2013 Mar;142(3):513-9. Epub 2013 Feb 1. 
13. Qureshi AA, Burger WC, Peterson DM, Elson CE. The structure of an inhibitor of cholesterol biosynthesis isolated from barley. J Biol Chem. 1986 Aug 15;261(23):10544-50.
14. Qureshi AA, Karpen CW, Qureshi N, Papasian CJ, Morrison DC, Folts JD. Tocotrienols-induced inhibition of platelet thrombus formation and platelet aggregation in stenosed canine coronary arteries. Lipids Health Dis. 2011 Apr 14;10:58.
15. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993 May 20;328(20):1450-6.
16. Slover HT. Tocopherols in foods and fats. Lipids. 1971 May;6(5):291-6.
17. Sundram K, Khor HT, Ong AS, Pathmanathan R. Effect of dietary palm oils on mammary
    carcinogenesis in female rats induced by 7,12-dimethylbenz(a)anthracene. Cancer Res 1989;49:1447–1451
18. Shibata A, Nakagawa K, Sookwong P, Tsuduki T, Oikawa S, Miyazawa T. delta-Tocotrienol
    suppresses VEGF induced angiogenesis whereas alpha-tocopherol does not. J Agric Food Chem
    2009;57:8696–8704.
19. Tan B. Tocotrienols: The New Vitamin E. Spacedoc.net. http://www.spacedoc.com/tocotrienols
20. Weng-Yew W, Selvaduray KR, Ming CH, Nesaretnam K. Suppression of tumor growth by palm
    tocotrienols via the attenuation of angiogenesis. Nutr Cancer 2009;61:367–373.
21. Weng-Yew W, Brown L. Nutrapharmacology of tocotrienols for metabolic syndrome.
    Curr Pharm Des. 2011;17(21):2206-14. 
22. Whittle KJ, Pennock JF. The examination of tocopherols by two-dimensional thin-layer chromatography and subsequent colorimetric determination. Analyst.1967 Jul;92(96):423-30.
23. Yoshikawa S, Morinobu T, Hamamura K, Hirahara F, Iwamoto T, Tamai H. The effect of gamma-tocopherol administration on alpha-tocopherol levels and metabolism in humans. Eur J Clin Nutr. 2005 Aug;59(8):900-5.
24. Yu FL, Gapor A, Bender W. Evidence for the preventive effect of the polyunsaturated phytolside chain in tocotrienols on 17beta-estradiol epoxidation. Cancer Detect Prev. 2005;29(4):383-8.

Oleic Acid Modulates Gut Bacteria and Induces Weight Loss on HFD Diet. Wondertoothpaste w/ 32 Herbals Promises Cancer Protection. 2% Cholesterol Diet Bad For the Testes.

While Adelfo did not have the time to write a whole update, he still send me some current progress pics, I am allowed to publish. I guess you would agree that the his "carboholism" has not done signficicant damage to his physique, won't you? If  you want to know more about his current workouts click here. For some info on his diet check out this post or simply go through all of his recent and not so recent guestgposts, here.

Just in case you have not already figured it out based on the longish, 3-item title title and the absence of a "Plus: Sneak Preview on the SuppVersity Science Round-Up" at the end: There is no SuppVersity Science Round-Up, today: When I emailed him yesterday to say that I would not make it in time to the show today, it turned out that Carl was just about to let me know that he would not be in the studio and we would be doing the next installment of the Science RoundUp next week - strange coincidence, right? Anyway, now you can blame whomever you want for not being able to listen to my catastrophic German accent today ;-)

That being said, I guess some of you may have thought that there would be an update from Adelfo Cerame Jr. today. Unfortunately, that's not the case either. What I have to offer today is nothing more, but also nothing less than two impressive progress pics of our common friend and a triplet of news that I had lying around here for you to educate yourself in Carl's and my radio and Adelfo's blog absence. Judged by the huge interest the "Saturated Fatty Acids Cause Post-Prandial Endotoxemia" post generated the other day, I suppose many of you will like the first one best. Don't fret about the rest, though, but take it as a generous giveaway ;-)

Oleic acid supplementation prevents obesity by modulating gut flora

With 60-80% olive oil is one of the best sources of oleic acid. And the additional polyphenols make it an even better choice as a staple of your diet (read more about the polyphenol content of regular and extra virgine olive oil, here at the SuppVersity); also don't forget macadamia oil, which has >60% oleic acid

(Mujico. 2013) Once again, we are back to Saturday's post on the influence of different fatty acids on the gut microbiome and and your health. Today, we are yet not talking about pigs and saturated fats, but about rats and oleic acid, a monounsaturated omega-9 fatty acid, which has - at least according to this recent study by scientists from Spain and Brazil the ability to prevent the formation of an obese phenotype in response to high fat feeding via its obviously beneficial effect on the composition of the gut bacteria.

"Consumption of a HFD induced changes in the faecal microbiota (an increase in all the tested groups of Firmicutes, as well as the order Enterobacteriales, and a decrease in Bifidobacterium spp. and the phylum Bacteroidetes), which were associated with the appearance of an obese phenotype.

Correlation analysis revealed that body weight correlated positively with the phylum Firmicutes and clostridial cluster XIVa, and negatively with the phylum Bacteroidetes. Supplementation of the HFD with S1 counteracted HFD-induced gut dysbiosis, together with an improvement in body weight." (Mujico. 2013).

In that supplement group 1 (S1) denotes the administration of an oleic acid-derived compound at 1500 mg/kg per day, which did - much contrary to supplement group 2 (S2), a fish oil based n-3 fatty acids (EPA and DHA, 3000 mg/kg per day) do an awesome job as far as the decrease in weight gain is concerned (see figure 2).

Figure 1: Bacterial composition of the feces at the end of the supplementation period (Mujico.2013).

Interestingly, the most notable change in the gut microbiome in response to oleic acid supplementation was an increase in bifidobacteria and bacteroidetes (as mentioned in the quotation above the latter was significantly correlated with the reduced obesity), the otherwise often hailed amount of lactobacilli, on the other hand, did increase only in the fish oil group and it did, as the data in figure 1 goes to show you not have any ameliorative effect on the weight. Moreover, the rodents who received the high fat diet in conjunction with the oleic acid had by far the highest count of total faecal bacteria.

Figure 2: Weight development of the pre-fattened rodents in week 0-7 of the supplementation phase (Mujico. 2013)

Bottom line: Now despite the fact that all that sounds great and more than promising, you should keep two things in mind: (a) you are (hopefully) not over-consuming a diet that's both high in fat and carbohydrates (which is the standard HFD in rodent experiments) and (b) it still remains to be seen if and to which degree results from a rodent model can be transferred into the human reality. Still, maybe the benefits of the Mediterranean which is per se high in oleic acid (way higher than it is in omega-3, by the way) are actually related to it's effects on the gut microbiome and not to it's direct effect on the fatty acid composition of either the blood lipids or the cell membranes as we have long been speculating.

Wondertoothpaste contains herbal overkill, is supposed to protect from oral cancer

(Chowdhury. 2013) If you are into "kitchen sink" approaches, you will probably love the toothpaste a group of scientist from the West Bengal University of Technology in India have just formulated. It does contain not one, not two and not three herbals, but alongside baking soda (teeth whitener), egg shell powder (calcium source), clove oil (sensitivity), glycerin (preservative), and other basic ingredients, but rather 32 ranging from popular and well-known stuff such as

Choti elaichi (green cardamon) is - as exotic as it may sound actually still the most straight forward ingredient of the "kitchen sink" toothpaste. After all, it has a well established anti-microbial activity.

• curcumin - as an anticarcinogen,
• green tea - as free radical scavenger, and
• echinacea - as an immune stimulant

to more exotic herbals such as

• nayantara -as an anti-mitotic and anti-microtubule agent,
• choti elaichi (green cardamon) - as a desinfectant for the oral cavity and
• ajwain - usually used to prevent kidney stones, it's also supposed to have anti-cancer effects

I am not sure, whether I would be inclined to buy this toothpaste, but having the sentence "the toothpaste is theoretically as well as experimentally serve the basic properties of general toothpaste with an advantage of having the medicinal properties of 32herbs which makes it unique in its category" from the conclusion of the paper as a marketing argument would probably call peoples' attention. I mean, the kitchen sink, even caught mine ;-)

Excess dietary cholesterol is bad for your testes

Just to make sure you don't get scared hat all the healthy eggs you're eating would all of a sudden damage your testes. An egg has 0.4% cholesterol, so that it is 100% impossible to get the equivalent amount of cholesterol from eggs, even if you ate them all day. Plus, eggs have all your body needs to make best use of the cholesterol (learn more)

(Moustafa. 2013) --- While I would hope that most of you do know that all your hormones are eventually manufactured from  cholesterol and you would end up without any sex hormones, if you ate a cholesterol free diet and your body did not have the raw material it needs to manufacture its own cholesterol, a recent study from the Al-Azhar University in Cario, Egypt, clearly shows that having too much of it in your diet - in this case 2% - will lead to alterations in spermatogenesis and morphoogical changes in the epdididymal sturcture.

Interestingly, the provision of the essential amino acid methionine (0.5% of the diet) ameliorated some of the negative side effects (remember: methionine is the precursor to cysteine; learn more about the sulfur amino acids, here). Contrary to what common sense would dictate, this beneficial effect of methinonine was not dose dependent and decreased, when the dose was escalated to 2%.

References:

• Chowdhury, BR, Garai A, Deb M, Batthacharya S. Herbal toothpaste-A possible remedy for oral cancer. Journal of Natural Products. 2013; 6:44-55.
• Mujico JR, Baccan GC, Gheorghe A, Díaz LE, Marcos A. Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice. Br J Nutr. 2013 Jan 10:1-10.
• Moustafa NA, Elnga A. Effect of Cholesterol and /or Methionine on the Testis of Rats. The Egyptian Journal of Hospital Medicine. 2013; 49: 857-878.