Science Round-Up Seconds: Follow-Up on Gum Arabic for Fat Loss. DMAA or Schizandra, Which Caused a Stroke in a Young Soldier? Low Doses of Resveratrol Better Than High Ones? Vitamin E Keeps Diabetic Brains Intact.

When it's served like this, Gum Arabic looks more like a healthy snack than a weight loss adjuvant.

I guess everyone who has already listened to the podcast of yesterday's show or was even able to listen live, will have noticed that the audio quality - yet not my German accent - have improved significantly, now that Carl and I did eventually switch to Skype instead of the landline. I know, you have been telling me that all along... be that as it may, unless my Internet connection hangs up for whatever reasons we will continue to do the SuppVersity Science Round-Ups via Skype from now on. Apropos, there will definitely be another show next Thursday (assuming that the world did not collapse by then ;-)

Follow up on Gum Arabic: Dosing & mechanism

In addition to that, I was actually presently surprised how much ground we were able to cover. Allegedly, we have gone way over the scheduled 60min, and I guess I could have said a couple of additional words on the Gum Arabic study and the astonishing fat loss results what I did mention was that it works astonishingly well, what I did not tell you about - or I have forgotten I did (too little caffeine I guess ;-) - is the dosage and the mechanism of action. At least as far as the former is concerned there is no debating that the fat loss magic (-2.1% from ~20% body fat to ~18% in 6 weeks; cf. Babiker. 2013) happened with just 30g of the substance that's derived  from exudates of Acacia senegal or Acacia seyal trees per day. Oher than the diarrhea and bloating, I did already mention on the show, the on average 19-year old perfectly healthy young women in the active arm of the study complained about nausea (82% in the first week) and an  "unfavourable oral viscous sensation" (100% in the first week). The latter is particularly interesting, because it does actually give us a hint on the underyling mechanism which is "not yet fully elucidated, because of a small number of conducted studies" (on its weight loss effects, but could be related to the increase in plasma leptin (without resistance obviously) as well as the increased fatty acid oxidation in muscle tissue in response to viscous fiber ingestion Islam et al. have reported only recently in Obesity (Silver Spring) earlier this year (Islam. 2013). I guess that we are going to see follow up studies on this one pretty soon and you all know that the Science Round Up and of course the SuppVersity news is where you are going to read about them first ;-)

Now that we lost the working weight loss adjuvants behind us, let's get to one which doesn't have any record of helping with weight and was still in each and every fat burner on earth before it was banned: DMAA (1,3 dimethylamylamine) aka geranium oil or geranium extract.

DMAA induced stroke in young soldier!? Or is it maybe the Schizandra that's to blame?

We all know that the job of a soldier is dangerous. A recently published case-report in Military Medicine does yet show that these dangers may not always be due to standing in the line of fire, but can also arise as a consequence of having too much DMAA supplements in your stash (Young. 2013) :

Is schizandra to blame? While the data is in fact scarce and the overall understanding of it's effects would suggest that the TCM herb would rather protect than harm the brain, it is at least worth noting that (a) schizandra has been found enhance the stimulation of the dompaminergic system (Chang. 1991) and (b) that we know that the abuse of cocaine has very similar effects on neurotransmitters (Prakash. 1993) and is associated with an increased risk of hemorrhagic stroke (Kousik. 2013)

"A 26-year-old male was presented to a military treatment facility in Afghanistan shortly after taking a weight-lifting supplement called Jack3d with a severe headache and was subsequently found to have suffered a Dejerine-Roussy variant right thalamic hemorrhagic stroke. Jack3d active ingredients include geranamine, schizandrol A, caffeine, β-alanine, creatine monohydrate, and L-arginine α-ketoglutarate. A literature search revealed case reports suggesting some of the constituent ingredients may predispose to stroke and hemorrhage and also revealed a substantial paucity of data existed regarding schizandrol A, a herb used in traditional eastern medicine." (Young. 2013)

Now, you always have to take case reports like this with an appropriate amount of skepticism - specifically, when the subject has a personal interest of not disclosing all the "supplements" he may have been taking in order not to lose is job. That being said, you know my take on DMAA from the round-table discussion with Patrick Arnold, Kurtis Frank, and one of the guys from Ergo Log. Bottom line: There really isn't any reason to be pissed of by the ban. Even if it's not to prevent stroke, it will prevent the onset of chronic fatigue syndrome in many aspiring physical culturists.

A re-appreciation of vitamin E and resveratrol

"Regular" vitamin E, i.e. alpha tocopherol, has gotten somewhat of a bad rep as of late and whenever resvertatrol is found to produce any the myriad astonishing health effects scientists have identified, it's either these effects occur either in the petri dish or in a rodent model with (often injected) mega-doses you imply couldn't afford taking on a regular basis. In this regard, a recently published paper which reports profound reductions in the fatty acid synthase, and fatty acid oxidation in the livers and adipose tissue of mice in response to a 0.005% resveratrol enriched high fat chow (this would be ~36mg/day for a human) is yet more than only an exception to the rule (Cho. 2013).

Figure 1: Metabolic effects of high fat diet (HFD) or HFD with two different doses of resveratrol; data expressed relative to mice on a standard diet (Cho. 2013)

I mean, take a look at the effects this low dose had compared to the 4x higher dosing in a second group of mice who received the human equivalent of ~142mg/day (see figure 1). Is this really another instance where more does not only yield no additional benefits, but actually reduces the effect (incidentally, de la Lastra et al. have discussed the pro-antioxidant effects of high doses of resveratrol in 2007 already; cf. de la Lastra. 2007)? Or is this just because "mice are no little human beings" and the results are therefore meaningless for us?

If you believe the latter is the case, I suggest you simply scroll down to the overview of some recent facebook news instead of reading how the adminstration of vitamin E to alloxan-induced diabetic rodents (standard model for type II diabetes) did ameliorate the shrinkage of Purkinje cells and apoptosis of cells in the granular layer, the mitochondrial defects, the splitting  of the myelin sheaths and widening axonal spaces, as well as the decrease in the number of GFAP-positive astrocytes (those that still produce a protein, namely GFAP that's responsible to keep their structure intact) in the cerebellar cortex (Mohammed. 2013)

 + + + + + + + + + + + + + +

That's it for today: You know the holiday season is coming so having too many Seconds isn't a particular good idea these days. If you still need something I suggest you pick one of the easily digestible Facebook news, for example...

• GI, GL and cancer risk - While there are statistically significant associations, only the ones for the glycemic load, which adds another quality factor namely GI + carbs per 100g to the equation, appear to have real world significance, though (read more)
• Folic acid in pregnancy - It's not all gold that glitters in ads and carries the letters "RDA". Among the profound epigenetic effects that have been observed in rodent studies, some sound as if they were from a list of the most rampant current pathologies (read more)
• Adiposity will shrink your brain - Leptin resistance is associated with reduced brain volume, associations persist even when they are corrected for BMI (read more)

You know there is more and there is even more to come. So in case the world does not explode within the next hours you know where to go if you are bored waiting for the "Zombie Repopulation" to happen.
 
References:

• Babiker R, Merghani TH, Elmusharaf K, Badi RM, Lang F, Saeed AM. Effects of gum Arabic ingestion on body mass index and body fat percentage in healthy adult females: two-arm randomized, placebo controlled, double-blind trial. Nutr J. 2013 Dec 15;11(1):111. 
• Cho SJ, Jung UJ, Choi MS. Differential effects of low-dose resveratrol on adiposity and hepatic steatosis in diet-induced obese mice. Br J Nutr. 2013 Dec;108(12):2166-75.
• de la Lastra CA, Villegas I. Resveratrol as an anti-oxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem Soc Trans. 2007;35:1156–1160.
• Islam A, Civitarese AE, Hesslink RL, Gallaher DD:  Viscous dietary fiber reduces adiposity and plasma leptin and increases muscle expression  of fat oxidation genes in rats. Obesity (Silver Spring)2013, 20(2):349–355.
• Kousik SM, Napier TC, Carvey PM. The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation. Front Pharmacol. 2013;3:121.
• Prakash A, Das G. Cocaine and the nervous system. Int J Clin Pharmacol Ther Toxicol. 1993; 31:575–581.
• Young C, Oladipo O, Frasier S, Putko R, Chronister S, Marovich M. Hemorrhagic Stroke in Young Healthy Male Following Use of Sports Supplement Jack3d. Military Medicine. December 2013; 177(12): 1450-1454(5).
• Zhang L, Niu X. [Effects of schizandrol A on monoamine neurotransmitters in the central nervous system]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1991 Feb;13(1):13-6.

Pistachio Phenols 90% Bioavailable. Phe, Leu, Glu & Trp - Four Satiating Aminos. Artificial Sweeteners Act as Anti- Convulsants. Dendrobium for Glucose, Lipids & Kidneys

Since I am a little pressed in time, I won't beat around the bush, but rather get to the meat of the matter of this Nutrition Quickie, right away... well, actually today's nutrition quickie has no item on meats, but is has one Dendrobium, which is actually rather a supplement - be that as it may, here you go:

• 

  Since you (hopefully ;-) haven't swallowed a bomb colorimeter, it's actually no wonder that your body can only access 75% and 95% of the energy this little oven can squeeze out of almonds and pistachios. If you went with the Atwood factor (which says fat = 9kcal/g) and simply added fats, proteins and carbs the discrepancy for almonds would even increase to ~35% (Nowotny. 2013)

  Almonds deliver 25% less calories that the nutritional label will tell you (Gebauer. 2013) -- At the FASEB meeting in April 2013, already, scientists from nowhere else than the mighty USDA, respectively the Beltsville Human Nutrition Research Center of the USDA presented the results of a human study that clearly shows that our tummies cannot squeeze out more than 75% of the nutrients a bomb calorimeter does. Nutrition Quickie: 25% Less Kcal in Almonds Than Label Says.
  
  The caloric value on both food labels and respective nutrient tables is thus off 25% too high. And the corrected energy content per 100g of almonds is 456kcal/100g not 575kcal/100g (nutritiondata.com), or even higher values you will find when you google  "almonds kcal" - I am curious if at least the nutrition labes will ever be updated.
  
  A similar but less pronounced mismatch has been found for pistachios by the same researchers earlier this year, already. According to a paper published in the January edition of the British Journal of Nutrition (Bear. 2013), the actual energy content of these heart healthy nuts 565kcal/100g, which is ~5% less than the currently established value. 

• Bioavailability of pistachio polyphenols, xanthophylls, and tocopherols is very high - until you put them into a muffin (Mandalari. 2013) -- Bioavailability, i.e. the ratio of the total amount of a certain molecule that's in the food we eat in intact or at least active form in our bloodstream, can be a real issue for many of the good things the spectral analyzer of brainy scientists detects in our foodstuff.
  
  

  

  Table 1: Phenol, lutein and tocopherol content of the raw, roasted and salted pistacchios and regular and pistaccio (17g/100g) muffins (Madalari. 2013)

  In the upcoming January issue of Nutrition a group of researchers from the UK and Italy report the results of an investigation into the bioavailability of polyphenols, xanthophylls (lutein), and tocopherols (among them the rare gamma-variety) from raw pistachios, roasted salted pistachios, and muffins made with raw pistachios. You can see the original polyphenol, xanthophyll and tocopherol (mind the 90% gamma-tocopherol content, which has better chemoprotective effects than alpha-tocopherol; see "Vitamin(S!) E" post from 2011) content in table 1.
  
  Interestingly enough the availability of the tocopherols was almost identical for all three tested forms (raw, roasted, in muffins) and even the muffin reduced only the bioaccessability of protocatechuic acid (78%) and luteolin (36%), the rest of the phenols achieved the same ~90% Madalari et al. observed for the raw and roasted + salted pistachios in their million dollar model of the human digestive tract (click here for an article about this "artificial gut")

• When the gut "tastes" phenylalanine (PHE), leucine (LEU), glutamate (GLUT) and tryptophane (TRP), satiety ensues (Daly. 2013) -- In their most recent paper Christin Daly et al. report on the cholecystokinin (CCK) release in the gut. According to the scientists from the University of Liverpool (UK) and the Kyushu University (Japan), the effect is mediated by interactions with the gastrointestinal bitter taste receptors. Since CCK inhibits food intake and reduces appetite, this provides another mechanistic explanation for the satiety promoting effects of high protein intakes. The effects was observed only for the L- and not the D-amino acids.
  
  Interestingly, the beneficial effects of  PHE, LEU and GLUT on CCK (but not the TRP-stimulated CCK secretion) were blunted in the presence of gurmarin. "Gurmarin?" Yeah, that's the rodent specific  sweet taste inhibitor in Gymnema sylvestre (note gurmarin does not work in humans; cf. Sigoillot. 2013), which is sold as an anti-diabetes supplement. Inosine, on the other hand increased the CCK release n response to all of the amino acids.
  
  How significant that is specifically for those who have a problem keeping their ravenous appetite in check is however questionable. After all the satiety response to CCK has been shown to be disturbed (at least in rodents; cf. Balaskó. 2013)

• 

  Table 2: Number of mice protected by the administered drug in the MES test (Talevi. 2013)

  Acesulfame potassium, cyclamate and saccharin are potential anti-convulsants (Talevi. 2013) -- It may sound counter-intuitive in view of all the bad stuff you have probably heard about artificial sweeteners, but it is their particular molecular structure and similarities between the T1R3 sweet taste receptor they are supposed to bind to ant several metabotropic glutamate receptors from different species that is probably behind the anticonvulsant effects a group of researchers from the Department of Biological Sciences at the Faculty of Exact Sciences of the National University of La Plata (UNLP) in Buenos Aires, Argentina.
  
  The overall effect size the scientists observed in their rodent model (see table 2) is yet far from earth shattering and generally more pronounced if the sweeteners had been ingested 4h instead of just 20 min before a Maximal Electroshock Seizure (MES) test. Whether this makes them worth "supplementing" is however more than questionable.
  
  Suggested additional reads:
• Stevia - More Than Super Sweet: More Scientific Evidence, More Potential Implications for Weight Loss & -Maintenance, Anti-Diabetic & -Autoimmune and Even Pro-Anabolic Effects
• Fructose Epimer D-Psicose First Sweetener to Actively Promote Weight Loss? Reduced Weight Gain and Direct Inhibitory Effect on Adipocyte Maturation in Rodent + Reduced Postprandial Glucose & Insulin in Human Trial
• The Unsatiating Truth About Aspartame, Acesulfam K, Sucralose & Co: They Don't Induce Glucose or Insulin Spikes, But Do They Make You Hungry?
• other posts with the tag "artificial sweetener"

• Putting things into perspective: While the DPPH radical scavenging activity is not a really good measure of the in-vivo anti-oxidant potency of a given molecule it may yet still be worth mentioning that the one of Dendrobium (IC₅₀ = 29.6 μg/mL) is more than 80% lower than that Areca catechuvar. Cinnamon cassia, Paeonia suffruticosa and Alpinia officinarum extracts which share IC₅₀ values <6µg/mL (Lee. 2003). In other words, you need 80% more Dendrobium than cinnamon, for example, to neutralize the same amount H2O2 radicals.
  Dendrobium extract ameliorates renal fat accumulation, hyperglycemia and hyperlipidemia in rodents on "high fat" diet (Lee. 20012) -- While I cannot say if this is the same Dendrobium extract that's used in a pre-workout supplement that's "all the craze", these days, I can tell you that a group of researchers just published a paper on the renoprotective, hypoglycemic and hypolipidemic effects of an extract from Dendrobium moniliforme (a cursory search revealed that even within this genus of orchids there are at least 90 sub-types ranging from Aochidori to Yuten).
  
  Lee et al. administered the methanolic extract at dosages of 200mg/kg (HED ~16mg/kg) for nine weeks and reduced the elevated serum glucose, total cholesterol concentration and renal lipid accumulation in the HFD-fed mice. It also ameliorated renal dysfunction biomarkers including serum creatinine and renal collagen IV deposition. So that the scientists conclude that methanolic extracts from Dendrobium moniliforme exhibit pleiotropic effects on obesity induced parameters and exert renoprotective effect in HFD-fed mice.

---

That's it for today, unless you are are interested in one of the following facebook news:

• Crape ginger (Costus speciosus Koen) has significant anti-arthritic properties - at least in a rodent model (read more)
• Ayurvedic polyherbal Unani formulation shows promising results in Acne vulgaris patients - 45 days, 45 subjects, significant improvements on Cook's acne scale (read more)
• Endocannabinoids increase, leptin decreases a "sweet tooth" - And you can take this almost literally, since they do actually modulate sweet taste receptor sensitivity (read more)

There are actually a couple more and they will "proliferate" *rofl* even before the next official SuppVersity  post will be published. Reason enough to check by from time to time, or simply "like" the SuppVersity on Facebook in order to keep up with the news.


References:

• Baer DJ, Gebauer SK, Novotny JA. Measured energy value of pistachios in the human diet. Br J Nutr. 2013 Jan;107(1):120-5.
• Balaskó M, Soós S, Párniczky A, Koncsecskó-Gáspár M, Székely M, Pétervári E. Anorexic effect of peripheral cholecystokinin (CCK) varies with age and body composition (short communication). Acta Physiol Hung. 2013 Jun;99(2):166-72.
• Gebauer SK, Novotny JA, Baer DJ. Macronutrient absorption from almonds: the measured energy value of almonds in the human diet. FASEB Journal. 2013;26:820.25.
• Lee SE, Hwang HJ, Ha JS, Jeong HS, Kim JH. Screening of medicinal plant extracts for antioxidant activity. Life Sci. 2003 May 30;73(2):167-79.
• Lee W, Eom DW, Jung Y, Yamabe N, Lee S, Jeon Y, Hwang YR, Lee JH, Kim YK, Kang KS, Kim SN. Dendrobium moniliforme Attenuates High-Fat Diet-Induced Renal Damage in Mice through the Regulation of Lipid-Induced Oxidative Stress. Am J Chin Med. 2013;40(6):1217-28.
• Mandalari G, Bisignano C, Filocamo A, Chessa S, Sarò M, Torre G, Faulks RM, Dugo P. Bioaccessibility of pistachio polyphenols, xanthophylls, and tocopherols during simulated human digestion. Nutrition. 2013 Jan;29(1):338-44.
• Novotny JA, Gebauer SK, Baer DJ. Discrepancy between the Atwater factor predicted and empirically measured energy values of almonds in human diets. Am J Clin Nutr. 2013 Aug;96(2):296-301. 
• Sigoillot M, Brockhoff A, Meyerhof W, Briand L. Sweet-taste-suppressing compounds: current knowledge and perspectives of application. Appl Microbiol Biotechnol. 2013 Nov;96(3):619-30.
• Talevi A, Enrique AV, Bruno-Blanch LE. Anticonvulsant activity of artificial sweeteners: a structural link between sweet-taste receptor T1R3 and brain glutamate receptors. Bioorg Med Chem Lett. 2013 Jun 15;22(12):4072-4.

Low Fat Toddler, High Fat Adult?! Intra-Workout Carbs More 'Anabolic' Than Protein!? Iron Prevents Gastric Cancer & Insulin Resistance?! Plus: A Sixpack of Kettlebell Studies

If you want to know exactly how your neighbors or rather your county did, check out the CDC's brand new County Data Interactive Atlas (may take some time to load), select your state and click on your county. Unfortunately, it's not exactly likely that you will be pleasantly surprised after all, places with rates below 6.5% (white on the map) have become rare, while those with 11.2% or more are becoming the norm.

"100%" - In words: One hundred percent, that's the SuppVersity figure of the week and at the same time the rate at which the prevalence of diagnosed diabetes in 14 of the US states grew faster in the years between 1995 and 2000 than previous estimates had predicted. The CDC has published this figure along with more information and the link to their brand new County Data Interactive Atlas in their weekly report on November 15, 2013. The Top 5 offenders on the list that's attached to the report are (1) Oklahoma (226 percent), (2) Kentucky (158 percent), (3) Georgia (145 percent), (4) Alabama (140 percent), and (5) Washington (135 percent).

No reason to worry, though, my American friends! According to their own assessment, the CDC and its partners are working on "a variety of initiatives to prevent type 2 diabetes and to reduce complications in those already diagnosed."... you see,all is going to be good! Your well-meaning government is taking care of the problem ;-)

I guess that's enough sarcasm and useless statistics for the day. Let's get down to some serious On Short Notice business, now. And what would be more obvious than to start with something that's probably still not on the radar of the CDC or any its smart partners over at the NIH who are still promoting a high carb + low fat diet to people who can hardly tolerate the amount of carbohydrates in a TicTac. What I am talking about? The predispositioning effects of a fat-deficient toddler diet...

• Fat loving toddlers grow up to be leaner adults (Rolland-Cachera. 2013) -- To determine whether nutritional intakes in early life are associated with body composition and hormonal status at 20 years, a group of researchers from the University of Paris analyzed data from 73 subjects, who had been part of a two-decade-long prospective study (ELANCE, Etude Longitudinale Alimentation Nutrition Croissance des Enfants).
  
  
  Associations of specific factors that increase the risk of being obese in the kindergarten as based on another study that's also been published ahead of print in the online version of Obesity (Flores. 2013):
  

  • born to an obese mother + 240% risk
  • gestational diabetes and gestational diabetes + 190%
  • drinking tea or coffee between meals before bedtime at 2 years old +230% and drinking sugary beverages at kindergarten age at least weekly + 130%
  • Latino or multiracial + 130% race ethnicity
  • ever-attending center-based daycare -70%
  • eating fruit at least weekly at kindergarten age -70
  • maternal history of a prior newborn birth weight greater than or equal to 4000g -90%

  If you do have or plan to have kids, you should maybe make a mental note on some of these.
  The kids, now all young adults had been examined twice, at the age of 10 months and with 2 years. During the recent followup, the  body weight, height, subscapular and triceps skinfold thicknesses, fat mass (FM), fat-free mass (FFM) and serum leptin concentration of the young adults (now twenty years of age) were recorded in order to identify associations between early nutrition and adult body weight.
  
  The adjusted linear regression models Rolland-Cachera and colleagues used to analyze the data actually showed a couple of significant associations, the first one of which, i.e. the fact thatan increase by 100 kcal in energy intake at 2 years was associated with higher subscapular skinfold thickness (β=6.4%, P=0.002) and higher FFM (0.50 kg, 0.06–0.95, P=0.03) at 20 years, seems to stand in line with the hilarious calories-in-vs-calories-out hypothesis. However, these associations could also be related to the fact that early nutrition will program our satiety response, so that those programmed to be "good eaters" by a less nurturing diet in their earliest childhood will remain "good eaters", even when they switch to the energy-laden standard American diet.
  
  Against that background, the second significant association the researchers observed, i.e. the fact that an increase by 1% energy from fat at 2 years was associated with lower subscapular skinfold thickness (−2.3% SF, −4.41 to −0.18, P=0.03), lower FM (−0.31 kg, −0.60 to −0.01, P=0.04) and lower serum leptin concentration (−0.21 μg l−1, −0.39 to −0.03, P=0.02) at 20 years appears to be even more important. After all, it looks like the Rolland-Cachera et al. had found the first relatively convincing evidence (not proof, yet) for the negative metabolic effect of early low fat diets in human beings:
  

  "Low-fat intake in early life was negatively associated with body fat (particularly at the trunk site) and serum leptin concentration at 20 years, suggesting that early low-fat intake could increase the susceptibility to develop overweight and leptin resistance at later ages. These findings substantiate current recommendations against restricting fat intake in early life and open new directions for investigating the origin of obesity." (Rolland-Cachera. 2013)

  Now let's just hope that scientists are actually tackling these "new directions" and - more importantly - that the respective results are recognized by the public and incorporated into the "dietary guidelines".
• Study suggests: If you could chose only one, your intraworkout nutrition should be a carbohydrate not a protein supplement (Kazemzadeh. 2013) -- This is at least the authors' own interpretation of the results of a recent study that was conducted by three researchers from the Azad University and the Teheran University in Iran.
  
  

  

  Figure 1: Changes in hormone levels from pre to post exercise (Kazemzadeh. 2013). If you focus solely on statistical significance you can be likewise mislead as, when you don't even check whether you findings are significant at all.

  According to the statistically significant part of the hormonal response of the 18-25-year-old subjects (university students who selected physical training course, but had no prior training experience), the consumption of an intra-workout supplement containing either 10 ml/kg of a 6% glucose solution was in fact "less catabolic" than during the same strength training routine with a 0.2 g/kg protein shake (PRO group) as an intra-workout supplement. On paper that's certainly true: The increased insulin response "enhances removal of amino acids and synthesis of proteins after the resistance exercise, on the one hand, and decreases the activity of proteolytic enzymes" (Kazemzadeh. 2013) and the non-existant increase in cortisol is in fact what scientists have long heralded as the goto indicators of anabolism.
  
  
  Note: Just as most of these studies the participants did not consume breakfast before the resistance exercise session, which comprised six selected exercises: The bench press, biceps curl with barbell, side stretch, leg press, knee stretch, knee bending. If the study had been conducted after a regular breakfast ~2-3h before the workout, the study could have yielded totally different effects with respect to both, the blunted insulin, as well as the increased cortisol response. On the other hand, the GH spike in the protein group would most certainly have been lower as well. After all, the latter is - as you may have read in the SuppVersity Facebook News earlier today - basically only a means by which your body taps into its fat reservoirs to satisfy his acute energy demands and not strictly a way to protect lean mass (Gahete. 2013).
  I do still have serious doubts about the real-world significance of the temporary blunt in cortisol. After all, the immediate post-workout response is, in contrary to sustained elevations of cortisol levels for hours or days after a workout, associated with an increase, not a decrease in skeletal muscle hypertrophy (West. 2013) and in essence nothing else, but a physiological adaptation that's necessary to maintain stable blood glucose levels during strenuous workouts and sooth the early burst of inflammation after a workout. Moreover, despite being only borderline significant, only the protein shake did increase growth hormone (p=0.057), testosterone (p=0.52) and IGF-1 (p=0.51) levels during the workout.
  
  This does not necessarily refute the benefits of carbohydrate supplementation during a workout, but if you insist on maximizing gains (not necessarily all lean I would guess) at all costs, it may be wise to consume a slow digesting protein + some fiber-laden carbs like oats 1-2h before a workout, to sip a light carbohydrate + BCCA drink intra- and wash everything down with another shake w/ whey protein and one or two bananas afterwards instead of just drinking some sugar water while you are lifting.
• Iron is a negative predictor of gastric cancer in humans and lowered hemoglobin and hematocrit levels induce insulin in rodents (Cook. 2013; Davis. 2013) -- While the alpha-tocopherol, beta-carotene cancer prevention study was a failure (at least with respect to the expected benefits of the anti-oxidants), there are still a couple of interesting side-findings.
  
  

  

   Meat-Ology: The Link Between Red Meat, Cooking Techniques & Prostate Cancer

  One of these side-findings pertains to the touted effects of increased iron intake on the etiology of gastric cancer, which is simply not existent. According to Cook et al. there were statistically significant negative associations for ferritin in the 2nd, 3rd quartile (-33% risk and -48% risk, respectively) and a borderline significant risk reduction of -31% for overall gastric cancer in the highest quartile (>241 ng/ml) and statistically nonsignificant decreases in gastric cancer risk for total iron, transferrin saturation and total dietary iron intake per 1,000kcal/day in the 2nd-4th quartiles of the respective serum parameters.
  
  That said, subsequent adjustments for H. pylori and then gastric atrophy did not materially affect a majority of the estimates ...
  

      "[...] the only exception was that the relationship  between ferritin and GNCC [Gastric noncardia cancer] was attenuated  There was little evidence for direct associations between iron metrics and H. pylori seropositivity or gastric atrophy (low pepsinogen I)—only serum ferritin appeared to share a relationship with these variables, and this relationship was stronger between ferritin and gastric atrophy." (Cook. 2013)

  So if "red meat is bad for you" it is probably not the iron content of the meat that is responsible for the observed associations of gastric cancer and high red meat intake in some previous studies (cf. WCR Fund. 2011).
  
  And with respect to its effect on glucose metabolism, a recent rodent study has just shown that a reduction in hemoglobin and hematocrit due to a lack of dietary iron does actually impair, not improve glucose management in otherwise healthy rodents fed an iron-deficient diet:
  

  

  Figure 2: Blood glucose, insulin and triglyceride on iron sufficient / deficient high sugar (AIN-76) or high starch (AIN-93) died (Davis. 2013)

  "Hemoglobin and hematocrit were significantly reduced in both ID groups compared to the C  and PF groups. Similarly, animals in the both ID groups exhibited elevated steady-state levels of blood glucose and insulin [...]
  
  [Moreover, hepetic]epatic gene expression analyses revealed a ~4-  and 3-fold increase in the expression of glucokinase and pyruvate dehydrogenase kinase-4 mRNA, respectively, in the ID group on either diet compared to their respective PF [pairfed on iron sufficient diets] counterparts" (Davis. 2013)

  The accompanying negative effects on triglycerides and fatty acid synthesis and storage Davis et al. observed were yet exclusive to the animals who received a high succrose iron-deficient diet.
• Vitamin C, D & E in health not disease - Only alpha-tocopherol shows negative correlation with markers of inflammation (Garcia-Bailo. 2013)-- A very recent study that has been conducted by researchers from the University of Toronto and the University of Guelph did not find any relation between the novel and the old savior of the human race, i.e. vitamin D and C, respectively and expression of inflammatory cytokines.
  
  

  

  Suggested read: "Are Vitamin Supplements Bad For Me (1/2)? The wrong Vitamin E Supplements Increase Cancer Risk."

  Plain Vitamin E in its alpha-tocopherol form, which has almost been written off after the selenium + E (and E only) cancer trials, on the other hand, showed statistically significant correlations with interferon-gamma and RANTES, a pro-inflammatory cytokine that is also known as CCL5 and the acronym for "egulated and normal T cell expressed and secreted" plays an important role in various immune processes, such as recruitment of leukocytes to sites of inflammation and mediating T cell and monocyte traffic. In view of the fact that this cytokine has also been shown to increase angiogenesis and is generally elevated in several inflammatory conditions, including atherosclerosis, these results would suggest that keeping an eye on your E-levels is about as, if not more important for young healthy individuals than vitamin C and D.
  
  If you also consider the fact that IL-1RA (by the way not necessarily inflammatory), interferon gamma, IP-10, PDGF-bb and RANTES were the only out of 27 cytokines the researchers initially measured with high enough concentrations to be detect accurately in the 1007 subjects with a BMI of ~23 and a weekly activity level of ~7Met, these results do also provide substantial evidence that it would probably be worth spending more money on studies that investigate  what it is that makes normal people healthy, instead of spending bazillions of dollars into the 1001st study on how people with XYZ (pt your favorite disease here) have low vitamin D levels *yawn*.

• 

  Check out the Website of the Reigning Canadian Kettlebell Biathlon Champion, Ameer Rosic for some workout videos

  A sixpack of kettlebell studies to remind trainers and trainees, alike, that there are more things you can lift than just dumbbells and barbells (various authors) -- I have never gotten hooked to kettlebells myself and would never agree to exchange my barbells and dumbbells for the finest set of kettlebells for more than one week, but if you take a look at some of the studies that have been published in the past 12 months or so, there is sufficient evidence to suggest that the incorporation of kettlebell workouts into your routine, as a means to provide new muscular and metabolic stimuli, could yield highly beneficial results:
  

  Kettlebell swings restore and enhance back health and function (McGill. 2013) On the basis of electromyography, ground reaction forces (GRFs), and 3D kinematic data the researchers determined that kettlebell swings create a "hip-hinge squat pattern characterized by rapid muscle activation-relaxation cycles of substantial magnitudes (∼50% of a maximal voluntary contraction [MVC] for the low back extensors and 80% MVC for the gluteal muscles with a 16-kg kettlebell) resulting in about 3,200 N of low back compression." The way the swings activate the abs and the unique loading patterns of the posterior shear of the L4 vertebra on L5, which is opposite in polarity to a traditional lift could make it a valuable tool in re- and prehab.	Kettlebell swing training improves maximal and explosive strength (Lake 2013) 21 healthy men  were randomly assigned to either a kettlebell (KB) or jump squat (JS) training twice a week. The KB group performed 12-minute bouts of KB exercise (12 rounds of 30-second exercise, 30-second rest with 12 kg if lower than 70 kg or 16 kg if higher 70 kg). The JS group performed at least 4 sets of 3 JS with the load that maximized peak power—Training volume was altered to accommodate different training loads and ranged from 4 sets of 3 with the heaviest load (60% 1RM) to 8 sets of 6 with the lightest load (0% 1RM). The increase in maximum strength of 9.8%, as well as explosive strength (+19.8%) were identical in both groups
  Kettlebell training has "has potential for improving some components of MetS in middle-aged women." (Moreno. 2011): While the changes the author of the thesis observed in response to 10 weeks twice weekly kettlebell training did not reach statistically significance (probably due to the low subject size of N=6 physically inactive women, mean age (mean age 48.8y, BMI 31.8) the trends in " fasting glucose and body fat were encouraging and suggest that kettlebell training has potential for improving some components of MetS in middle-aged women."	Kettle bell workouts can decrease blood pressure (Douglass. 2013): Eight resistance trained pre-hypertensive and HTN males saw statistically and more importantly clinically significant declines in blood pressure (to normal levels!) in the course of a randomized cross-over designed study which included 12 minutes of continuous two-handed swings (THS), three sets of a 6 exercise circuit (CIR), and a resting control (CON).
  Kettlebell training can improve strength, power and and endurance (Mannocia. 2013):  23 subjects (age 18-72 years) were required to perform a10-week kettlebell training program that took place in a group setting two times per week. Post hoc pairwise comparisons of assessments barbell clean and jerk, barbell bench press, maximal vertical jump, and 450 back extensions performance revealed significant time x group interaction and a main effect (p < 0.05) for the bench press, a trend toward a time x group interaction and a significant main effect for clean and jerk. These observations suggest "that kettlebells may be an effective alternative tool to improve performance in weight- and powerlifting".	10 min of treadmill running may burn more more energy, than a short 10-min kettlebell drill, but pro-anabolic & strength edurance effects speak in favor of 'the bells' (McGill. 2013): Only those who still believe in santa... ah, I mean the calories in vs. out theory of weight loss, will probably care, whether they are burning 12.5 or 17.1kcal/min and therefore this "advantage" would hardly be important even if the participants had not been sprinting part of their 10min on the treadmill just to make sure to achieve the prescriped (identical) rates of perceived exertion. And as usual, there is no reason, why you could not switch back and forth from one "drill" to another.

That's it once more for this week's installment of pretty longish short news. I hope you liked one or another and will see you tomorrow for some more information on the latest and greatest from the world of exercise and nutrition sciences. And just in case you have not seen those already, I guess there are a handful of news on facebook you may be interested in:

• 

  If you just skip the hookers and the transdermal cocaine and take a regular bath, this may speed up your regeneration and propel your gains - if timepoint and temperature are spot on!

  Transdermal 'cocaine' in "bath salt" - 3,4-methylenedioxypyrovalerone (MDPV) in OTC "bath salt" is 10x more potent than cocaine and unquestionably hazardous
• The anti-cancer effect of 'active vitamin B6' - High levels of pyridoxal 5'-phosphate, the active form of vitamin B6 appear to have protective effects against breast cancer... or is it exactly the other way around?
• Bisphenol A is a local fat synthesizer - Study shows how Bisphenol A increases obesity: it ramps up the local cortisol production in adipose tissue and thus 'helps' you stash away more body fat

As usual there is more on facebook and further news to come, but I guess you got other things to do on a Saturday than reading SuppVersity posts all day ;-)

References:

• Cook MB, Kamangar F, Weinstein SJ, Albanes D, Virtamo J, Taylor PR, Abnet CC, Wood RJ, Petty G, Cross AJ, Dawsey SM. Iron in relation to gastric cancer in the alpha-tocopherol, Beta-carotene cancer prevention study. Cancer Epidemiol Biomarkers Prev. 2013 Nov;21(11):2033-42. 
• Davis MR, Hester KK, Shawron KM, Lucas EA, Smith BJ, Clarke SL. Comparisons of the iron deficient metabolic response in rats fed either an AIN-76 or AIN-93 based diet. Nutr Metab (Lond). 2013 Oct 30;9(1):95.
• Douglass, MJ. The blood pressure response of two popular kettlebell routines. M.S. thesis in  Kinesiology (Exercise Science). California State University, Sacramento, 2013.
• Flores G, Lin H. Factors predicting severe childhood obesity in kindergarteners. Int J Obes (Lond). 2013 Nov 13.
• Gahete MD, Córdoba-Chacón J, Luque RM, Kineman RD. The Rise in Growth Hormone during Starvation Does Not Serve to Maintain Glucose Levels or Lean Mass but Is Required for Appropriate Adipose Tissue Response in Female Mice. Endocrinology. 2013 Nov 13.
• García-Bailo B, Roke K, Mutch DM, El-Sohemy A, Badawi A.Association between circulating ascorbic acid, alpha-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study. Nutrition & Metabolism 2013, 9:102. 
• Hulsey CR, Soto DT, Koch AJ, Mayhew JL. Comparison of kettlebell swings and treadmill running at equivalent rating of perceived exertion values. J Strength Cond Res. 2013 May;26(5):1203-7.
• Kazemzadeh Y, Gaeini A, Abasrashid N. Comparison of the Effect of Consuming Carbohydrate or Protein during Exercise on Hormonal Response. Zahedan Journal of Research in Medical Sciences. 2013; 15(2): 90-93. 
• Lake JP, Lauder MA. Kettlebell swing training improves maximal and explosive strength. J Strength Cond Res. 2013 Aug;26(8):2228-33.
• Moreno KIK. Effects of kettlebell training on metabolic syndrome in women. M.A. Thesis, San Jose State University, 2011, 138 pages.
• McGill SM, Marshall LW. Kettlebell swing, snatch, and bottoms-up carry: back
  and hip muscle activation, motion, and low back loads. J Strength Cond Res. 2013
  Jan;26(1):16-27. 
• Manocchia P, Spierer DK, Lufkin AK, Minichiello J, Castro J. Transference of kettlebell training to strength, power and endurance. J Strength Cond Res. 2013 May 3.
• Rolland-Cachera MF, Maillot M, Deheeger M, Souberbielle JC, Péneau S, Hercberg S. Association of nutrition in early life with body fat and serum leptin at adult age. Int J Obes (Lond). 2013 Nov 13.
• WorldCancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity and the prevention of cancer: a global perspective. Washington, DC: AICR; 2007.
• West DW, Phillips SM. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. Eur J Appl Physiol. 2013 Jul;112(7):2693-702. 

Science Round-Up Seconds: Vitamin E Succinate, How It's Extracted from Barley Leaves, Kills Cancer, Ramps up Growth Hormone & Spikes Prolactin. Plus: Testostosterone & Thyroid Hormone Decline Due To Plyometrics & HIIT

Regardless of all the hypocritical hoopla around his persona, Lance Armstrong has always been able to push himself like no one else. No wonder that intense plyometrics were part of his regimen.

If the SuppVersity Science Round Up was a meal, I guess you could say that Carl Lanore and I were sort of gluttonous, yesterday (click here to download the podcast, if you have not already done so). We almost raced from one topic to another and therefore all the good stuff from the list is gone already and I am a bit pressed on time to get some "private life" in, so that I am not psyched about the idea of writing about auxiliary stuff.

Against that background and in view of the fact that I felt that the pace of yesterday's show did not really leave enough room for some important details, I will stick to rehashing and expanding on the stories about Vitamin E succcinate and the detrimental effects of beating the crap out of yourself doing plyometrics or crazy HIIT workouts (too regularly), in today's installment of the SuppVersity Science Round-Up Seconds.

Let's see. Why don't we start at the end of yesterday's show?

• Vitamin E succinate the most potent anti-cancer tocopherol known to man. As you have heard on the show, vitamin E succinate attaches directly to a protein that's preferentially expressed in carcinogenic or pre-carcinogenic cells. It goes by the name α-Tocopherol-associated protein (TAP) and was found to be one of the major α-tocopherol binding proteins in serum, liver, brain and prostate. What has as of yet not been so clear, though, is that the expression of this protein increases with the malignancy of (breast) cancer (Tam. 2013). 
  
  

  

  Figure 1: Effects of alpha tocoperyl succinate alone (TOS), doxorubicin alone (DOX) or both (DOX + TOS) on cell viability in human MB231 breast cancer cells (my edits, original from Tam. 2013) - note: The effect was less pronounced in other cancer cells, so that it is reasonable to assume that the efficacy of the therapy will depend on the exact genotype of the cancer (for those tested in the study it was MB231 > SKBR3 > MCF 10A)

  When alpha tocopherol succinate binds to the protein on the cancer cells, this will either alone, or in combination with chemotherapy trigger apoptosis and cell death. It is as of yet not fully elucidated why vitamin E succinate is highly cancer-specific and leaves the healthy cells intact, but this could be related to the high metabolic rate and exuberant ROS production of cancer cells. There is however some research that would suggest that the cancer cells literally suffocate in their own radical oxygen specimen (ROS), which can no longer be cleared from the cell, due to the alpha-tocopheryl succinate induced displacement of ubiquinone from CII and the subsequent blockade of succinate dehydrogenase (SDH) activity (Dong. 2013).  If this hypothesis holds true it would therefore appear that long-term chronic supplementation with vitamin E succinate cannot be recommended until future studies on its general safety have been undertaken. As an adjuvant to chemotherapy, on the other hand, it could drastically reduce the dosage requirements during chemotherapy in specific types of cancer (see figure 1) and thus minimize side effects.
  
  You see, there is more to it than you can say in two minutes on the radio and this is why I will make sure we don't rush through the items that fast, in the next show. Ah,... of course the dietary source. I had almost forgotten about that one. As mentioned on the show, alpha tocopheryl succinate was originally extracted from Barley leaves. An while this may not be the first paper dealing with this "natural vitamin E analog", the one by Badamchian et al. is probably the one you will be most interested in.
  
  Published in the Journal of Nutritional Biochemistry the paper does not only describe the isolation of vitamin E succinate from green barley leaf extract (BLE)...
  

  "BLE [barley leaf extract] powder (50 mg/mL) was suspended in water and stirred for 1 hr at room temperature. The mixture was then centrifuged at 3000g for 30 minutes using a bench-top centrifuge. The pellet was discarded and the supernatant was pre-filtered through a Millipore DEPTH filter. The filtrate was then filtered through 0.45 I.tM mem- brane and stored at -20 ° C for HPLC or biological assays." (Badamchian. 1999)

  ... it does also shine another spotlight on its potential biological effects, as far as it's ability to increase growth hormone, but (unfortunately?) also prolactin in isolated anterior pituitary cells from female rodents:
  

  

  Figure 2: Prolactin and growth hormone release in anterior pituitary cells of female rodents after incubation with different amounts of green barley extract in which vitamin E succinate had been deterimed as the main ingredient before (based on Badamchian. 1999)

  It's really hard to estimate whether or not one of these effects would translate from a rodent cell in the petri dish to you or me popping a cap with vitamin E succinate everyday. That's particularly true in view of the fact that the underlying mechanism of the increase in GH and the imho more concerning increase in prolactin is neither mediated by increases in intracellular C-AMP, as it would be the case for GRF (old acronym for growth hormone releasing hormone), nor is it induced by the hydrolysis of polyhoshpoinositide, which is the underlying mechanism of the stimulative effect of TRH (thyrotropin releasing hormone). So basically we neither know how it works, nor do we know, whether the oral ingestion of vitamin E-succinate would be sufficient to produce serum concentrations in the pituitary that would be high enough concentrations to make any difference at all (note: the scientists excluded the influence of other components of the extract by testing alpha tocopherol succinate on its own in a separate trial)
  
  Bottom line: Based on roughly one dozen of in-vitro studies there is simply still to little evidence to decide who, outside of people with a history of cancer or someone who is just undergoing chemotherapy would benefit. Therefore, I suggest you wait before you add vitamin E succinate to your list of 'must have' supplements. Is it promising? Sure! Is it exciting, yeah! Is it save for a healthy being to be taken chronically??? I can't tell.
• The detrimental hormonal effects of pushing yourself beyond the tolerable threshold - Hardcore plyometrics and heavy HIIT and their impact on testosterone, cortisol, thyroid hormone and co: I guess you did already get the main message when you listened to the show, but just to give you an idea about the actual quantities, I thought it would be nice to provide you with two graphs as a reference.
  

  

  Figure 3: Comparison of the hormonal responses measured in the plyometrics (left) and the HIIT vs. LISS (right) study (based on Ozen. 2013 and Hackney. 2013)

  If you focus mainly on the differential cortisol responses in the two studies, it would appear likely that we are dealing with two very different forms of 'overtraining' here. While the HIIT protocol (90s at 100-110%, 90s active recovery at 40% matched for workload with steady state jogging at 60-65% of the VO2 max) probably wouldn't be a problem, if the athletes would get adequate rest and nutrition in the days after the session, the 6-weeks of plyometrics (15 session, increasing density, 90-195 reps per session) were enough to send the participants right into the vicious circle of the Athlete's Triad (if you have not done so already, I suggest you read up on that in the eponymous SuppVersity series).
  
  And you know what? Despite, or I should probably rather say due to their compromised hormone levels the guys in the plyometrics study did not lose a single gram of body weight. Good for their muscle, bad for the fat which was likewise preserved by the hormonal shut down, which affected both cortisol and testosterone in a similar way. So is that good or bad news? Well, let me say it this way:. Usually I see people training for a purpose and while the outcome often is stagnation and chronic fatigue, I would suspect that only few of you will have that on their mind, when they are hitting the gym, right?

Apropos viscous circle, and overtraining in order to avoid "overblogging" I will call it a day for today. Come back tomorrow for a couple of wholly new studies from the realms of exercise and nutrition sciences and in case you are planning to drink this evening, I highly suggest you check out the SuppVersity Facebook newspost on the effects of green tea extract on the uptake of alcohol. It may well be that those old fatburner caps of yours can be put to a way better use ;-)

References:

• Badamchian M, Spangelo BL, Bao Y et al. Isolation of a vitamin E analog from green barley leaf extract that stimulates the release of prolactin and growth hormone from rat anterior pituitary cells in vitro. Journal of Nutritional Biochemestry. 1994; 5: 145-150.
• Dong LF, Low P, Dyason JC, Wang XF, Prochazka L, Witting PK, Freeman R, Swettenham E, Valis K, Liu J, Zobalova R, Turanek J, Spitz DR, Domann FE, Scheffler IE, Ralph SJ, Neuzil J. Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II. Oncogene. 2008 Jul 17;27(31):4324-35. Epub 2008 Mar 31.
• Hackney AC, Kallman A, Hosick KP, Rubin DA, Battaglini CL. Thyroid hormonal responses to intensive interval versus steady-state endurance exercise sessions. Hormones (Athens). 2013 Jan-Mar;11(1):54-60.
• Ozen, SV. Reproductive hormones and cortisol responses to plyometric training in males. Biol Sport.2013; 29 (3).
• Tam KW, Ho CT, Lee WJ, Tu SH, Huang CS, Chen CS, Lee CH, Wu CH, Ho YS. Alteration of α-tocopherol-associated protein (TAP) expression in human breast epithelial cells during breast cancer development. Food Chemistry. 2013 [ahead of print]

Frying Does not Just Oxidize Oils, It will Also Decimate the Tocopherol & Tocotrienol Content of the Oils and Can Thus More Than Double the Oxidative Burden on Your Body

Fried butter on a stick - I bet there are more peroxides in the crust than in the butter beneath it.

Yesterday we have taken a look at the saturated fat content of the diet and its effects on body composition, insulin resistance and inflammatory markers (see "Study Shows Doubling Saturated Fats Would Yield More Benefits Than Halving Them"). Today, we are going to look at the effects of a way not just Americans, but more or less half of the globe likes to process their foods on the oils and subsequent health of someone who would consume these oils on a regular basis. By now, you will probably already know into which direction this post is heading. Right, we are talking about frying, about lipid oxidation and about the health effects of oxidized soy bean and palm oil the #1 "choices" in processed foods.

Oxidized frying oils and their effects on our health

The paper by Jaarin and Kamisah, two researchers from the Department of Pharmacology at the Universiti Kebangsaan Malaysi in Malaysia is certainly not the only, maybe not even the latest study dealing with this issue, what I like about it though, is the fact that they don't use some sort of standardized oxidized oil, but actually went through the following unquestionably not unrealistic procedure to obtain their frying oils:

"A kilogram of sweet potato slices were fried in a stainless steel wok containing two and half litres of palm oil or soy oil for 10 minutes at 180°C. Upon completion of the frying process, once heated oil was obtained. The process was repeated four times to obtain five times heated oil with a cooling interval of at least five hours. The food quantity was proportionately adjusted with the amount of vegetable oil left. No fresh oil was added between the frying processes to make up for the loss due to uptake by the frying materials." (Jaarin. 2013)

After the oils had been heated, a small quantity was extracted and the peroxide value, fatty acid composition and vitamin E content measurements (another strength of the study, most other studies discard the fatty acid composition and vitamin E content).

Figure 1: Peroxide levels (data expressed relative to fresh palm oil) of palm and soy oil after frying at 180°C for 10minutes once or five times (based on Jaarin. 2013)

If you take a look at the peroxide values in figure 1 you see that the peroxide values in both the palm and the soy oil increased significantly after only one heating process (10min at 180°) already and -- at least in the case of soy oil -- exceeded the established maximally allowed value (red line). The palm oil, on the other hand is slightly below the margin. Now that obviously does not mean that the palm oil was still 100% healthy, while the soy oil was toxic waste - it's rather an artifice due to the arbitrarily set 10meq/kg limit for lipid peroxides in oils that are meant for human consumption (the Japanese must by the way be 'peroxide proof' because their laws allow concentrations up to 30meq/kg!).

Figure 2: Relative fatty acid composition of the fresh, once or five times heated oils (based on Jaarin. 2013)

A mechanistic explanation for the fact that the soy oil presents a higher total peroxide level than the palm oil can easily be derived from the data in figure 2. As you can see,...

"[...t]he fresh soy oil contained about five times more polyunsaturated fatty acid compared to the palm oil. It seemed that five times heating had reduced about 10% of the polyunsaturated fatty acid content in the soy oil. The content of monounsaturated fatty acid in the fresh palm oil was higher than that of the fresh soy oil. Palm oil had a quite balanced ratio of saturated and unsaturated fatty acids, whereas more than 70% of soy oil fatty acid was unsaturated (polyunsaturated and monounsaturated). This unique fatty acid composition of palm oil renders its stability against oxidative insult." (Jaarin. 2013)

Now, both the oxidation process during heating as well as the in vivo oxidative effects of the consumption of those oils does not depend on their fatty acid makeup and oxidation status, only, but is also affected by the amount of antioxidants, in particular vitamin E, the respective oil brings to the table.

Figure 3: Relative amount of tocopherols and tocotrienols that remained in the oils after frying (left) and effects of the consumption of a diet containing 15% of the oils + 85% standard rodent chow for 4 months on male and ovariectomized rats that received additional +2% cholesterol in their diets on thiobarbituric acid reactive substances (TBARS), astandard marker of lipid oxidation (right;(based on Jaarin. 2013)

In that, the vitamin E content is not only important to protect you from the effects of the peroxides that are already in the oil, they are at least as important to protect the polyunsaturated fatty acids you consume from being oxidized in your body.

Against that background, is should be obvious that the profound reductions in both tocopherols and tocotrienols will augment the negative effects, so that it is actually not that surprising that the amount of thiobarbituric acid reactive substances (TBARS = standard marker of lipid oxidation) in the blood of the rodents which consumed the diets with 15% of the five times heated palm and soy oil more than doubled.

Figure 4: While olive oil is more stable than corn and soy, it's not 'oxidation proof either' what's also intriguing is the amount of oxidation that is induced just by exposing the oil to air or air and light for 30 days! (Naz. 2013)

Putting things into perspective: While I would hope that no one of you will use the same oil for frying twice or thrice, let alone five times, I am not so sure about the foods you would be served at the university canteen, let alone the fast food store around the corner. Against that background, it is however still at least unsettling to see that even when you are frying potatoes or meats in a pan at home, the T-BAR levels rise significantly.

I assume that no one of you will use soy oil and only few will be cooking with palm oil, but I know that many people still use olive oil in a hot pan for several minutes. And while I do not have data from the same study, the data in figure 5 would suggest that olive oil is probably as susceptible to heat as palm oil (if you go by the relations of palm:soy in the study at hand and olive:soy in the study by Naz et al.). If we go by this rule of thumb estimate, baking your potatoes in olive oil may not kill you, but clearly isn't the best way either.

Coconut oil!? No, unfortunately even the wonder oil does not come to a rescue. At least if we go by the data Matthäus obtained in 2007, it produces about as much peroxides as palm oil during the frying process (Matthäus. 2007). That's better than soy, and way below the critical margin, but still not without consequences on the overall oxidative burden you are exposing yourself to, when you consume significant amounts of fried foods on an everyday basis - and since I know that you do only have your occasional piece of fried grass fed butter on a stick, you won't have to be afraid anyway ;-)

Suggested reads:

• Pimp my virgin olive oil - Discusses among other things how the polyphenols stabilize the vitamin E and render EVOO more heat stable than regular olive oil.
• Vitamin(s)! E - A brief reminder that there is more than alpha-tocopherol + some evidence that delta tocopherol is king, when it comes to protect dietary oils

References:

• Matthäus, B, Use of palm oil for frying in comparison with other high-stability oils. Eur. J. Lipid Sci. Technol. 2007;109: 400–409. 
• Jaarin K, Kamisah Y. Repeatedly Heated Vegetable Oils and Lipid Peroxidation. Intech. 2013.
• Naz S, Siddiqi R, Sheikh H, Sayeed SA. Deterioration of olive, corn and soybean oils due to air, light, heat and deep-frying  Food Research International, Volume 38, Issue 2, March 2005, Pages 127–134.

Reishi Protects Against Cancer & Contains Anti-Androgen; Adrenalin Rejuvenates Brown Fat; Mild Stress Normalizes Cortisol / DHEA Ratio in Elderly; DHEA, Aromatase Inhibitors & BPA vs. Joint & Brain Health; Vitamin E Battles Lymphoma

I am not happy with how the short news on Facebook simply disappear into oblivion.

The SuppVersity figure of the week is "920"! "920" as in "920 published posts" here at the SuppVersity. The reason that's the figure of the week is that I have been thinking about ways to reorganize the archive, but am a bit lost on how to structure things in a better way using blogger. This beast simply isn't made for anything that goes beyond a weekly classic blogpost a la "last week I did this and that, read about..." *yawn*

What's yet even more enervating is that despite having the huge advantage of being easily posted and directly accessible for all of you, the tons of short news items I post on a daily basis on the SuppVersity Facebook Wall simply disappear into the 'Facebook nirvana'. I currently cannot spend any time on those technical / organizational matters, but in the course of 2013 things are going to change.

In the mean time, follow the SuppVersity on Facebook and read the news, right when I post them + use google to find articles you are looking for. You will be laughing, but that's the way I dig through those 920 posts, as well ;-) Simply type whatever you look for and add a "+site:suppversity.blogspot.com" to it.

Chinese fungi are laden with cancer-protective molecules and 5a-reductase (DHT) inhibitors

In view of a recent paper from the Universitat de Valencia (Rios. 2013) it appears that it would actually be hard not to decrease your risk of developing cancer if you include extracts from Ganoderma lucidum and other related fungi, such as Poria cocos, Laetiporus sulphureus, Inonotus obliquus, Antrodia camphorata, Daedalea dickinsii, and Elfvingia applanata in your supplement regimen. With a total of 81 compounds from Ganoderma lucidum and other species from this genus, as well as 96 compounds isolated from other fungi, principally Poria cocos. It appears that these creatures (fungi are no plants, neither are they animals, but still sort of living beings) could hold the key to hundreds o natural anti-cancer agents.

Ganoderma lucidum better known as Rheishi mushroom may have cancer protective effects, but does not taste so bitter that no sane human being would eat it for a reason (photo by Eric Steinert)

I guess, I don't have to tell you that Chinese Medicine, of course, knew about the powerful anti-inflammatory and anti-proliferative effects of the lanostanes in these fungi, all along. Intuitively and probably by trial and error, the Chinese have found the tetracyclic triterpenoids that are derived from lanosterols in these fungi to be effective in the treatment of various diseases including different types of cancer. As of late the mostly anecdotal effects are backed by more and more research. A preliminary study by Sliva et al. (Sliva. 2002), for example, found that a hot water extract of both spores and the dried fruiting body of G. lucidum inhibited the progression of cancerous growth by reducing the expression of constitutively active growth and inflammation promoting transcription factors AP-1 and NF-κB: 

"The extracts also inhibited the secretion of uPA, thereby suppressing the migration of breast cancer MDA-MB-231 and prostate PC-3 cells. [...] High levels of both uPA and uPAR are associated with advanced tumors and decreased survival time in different malignant human cancers." (Rios. 2013)

These benefits do however come with a downside. At least in vitro, some of the fungi, particularly G. lucidum, obviously exert their effects via anti-androgenic pathways (Liu. 2007). A compound in Reishi that goes by the name ganoderol B, for example, does not just have inhibitory activity against 5α-reductase, but can also bind to the androgen receptor directly (if you will you could say it acts like an anti-anabolic SARM). Now, this was good news in a study that has been conducted by Liu et al., because it inhibited androgen-induced cell growth in an LNCaP cell line while suppressing testosterone-induced regrowth of the ventral prostate in rats. If those effects are however non-selective, you are about to run into problems once the molecules bind to receptors outside the prostate -- epression for example, if they block the androgen effects in the brain, etc.

That reminds me: What did Carl say on Thursday's installment of the SuppVersity Science Round Up? "The good thing about supplements is that they work, the bad thing about them is that they work!" I guess you can basically say the same about Reishi. Good that you as a SuppVersity reader always know about both, the good and the bad sides of supplements!

More short news

With me posting stuff on the fly on facebook, I am actally 'wasting' many of the very short news items, but nevertheless, here are a couple of relatively short news to round things up.

• 

  If you missed Monday's new on the quasi non-existent thermogenic effects of ephedrine, this would be a good time to read that post.

  Stress-induced browning of the fat? Chronic overexpression of noradrenaline (re-)generates wasted brown fat! In a way this is a follow up on the ephedrine post "Fat Burners Don't Work" as well as an addendum to a news on the role of GABA and brown fat in obesity, I just posted on facebook. According to an allegedly old study in the International Jornal of Obesity (Lee. 1986),  the chronic overexpression of noradrenaline as it is observed in humans with a certain form of adrenal tumor known as phaeochromocytoma can actually reactivate the intra-abdominal fat of human adults, including the omental fat, which is brown adipose tissue in infancy.
  
  Lee et al. see this as one of the main contributing factors to the weight loss which is typically seen with phaeochromocytoma. Sounds, logical, since the same stimulus that rejuvenates the Brown fat will also have it burn energy continuously - the overexpression of noradrenaline.
  
  
  Symptoms of overtly high noradrenaline levels include abdominal pain, chest pain, irritability, nervousness, pallor, palpitations, rapid heart rate, severe headache, sweating, hand tremor, high blood pressure, sleeping difficulties, and also weight loss.
  Even patients with Cushing's syndrome (hypercortisolemia) there is an increase in brown fat compared to healthy individuals. That the latter is not as profound is probably due to the ameliorative effect of cortisol on nor-adrenaline. After all, cortisol comes into play, when the stress becomes chronic and the acute nor-adrenaline response to stress, when it was prlonged any further would actually pose a direct threat to your health (just as phaeochromocytoma does, by the way; see red box on the right)
• Repeated moderate stress exposure increases DHEA production and normalizes corticosteriod levels in old apes (Goncharova. 2013). Yep, you are reading right we are not just talking about no rodent studies (although macacs are not exactly very human either ;-), but also about the role of repeated moderate stress in the normalization of aged induced abnormalities in the expression of adrenal hormones.
  

  

  Figure 2: Cortisol/DHEA ratio before and after 2h/day of immobilization stress.

  "In old monkeys the basal DHEAS levels were lower, while the [cortisol]/DHEAS ratio was higher than in young animals. Repeated immobilizations inhibited [cortisol] elevation on day 3, caused no changes in DHEAS reaction, led to increase of basal DHEAS levels and to a reduction of [cortisol]/DHEAS ratio on days 2, 3, 4, 10, 11." (Goncharova. 2013)

  In figure 2 you can see how profound the differences between acute, subchronic (3-day) and chronic responses actually are and that after 10 days of daily stress exposure in the form of daily 2-h immobilization stress actually are. Since I assume you don't want to be bound or enchained (well, maybe you want?), I suppose a viable alternative could be a shorter not too intense workout, although the acute responses to the latter vary with age as well (cf. Lennartsson. 2007).
• Monitor your DHEA levels closely, if you are concerned about joint degeneration According to a study that's about to be published in the next issue of the Journal of Steroid Biochemistry and Molecular Biology, DHEA, or the estradiol your body generates from it via local aromatization, exerts major protective effects against osteoarthritis (Li. 2013).
  
  
  An additional note of caution with respect to the abuse of aromatase inhibitors, natural or not. Since they have the potential to reduce the expression of estrogen at the neuronal level in the brain they can precipitate  Alzheimer's dementia. While estrogen appears to decrease the MMP-3 & 13 expression in the cartilage reasearch by Merlo et al. suggests that it will increase others, namely namely MMP-2 and MMP-9  in the brain and thus facilitate the clearance of the ameloid beta plague that's rendering the brains of AD patients more and more dysfunctional (Merlo. 2013). You see, it's no chance that pre-menopausal women are protected from Alzheimer's yet more susceptible to multiple sclerosis (MS). After all, high MMPs 7 & 9 have only been observed in kids with MS, as well (Unsal. 2013).
  In their experiments on a rabbit model of osteoarthritis the scientists from the Zheejiang University in China tried to nail down the beneficial effects of DHEA on chrondocites and cartilage to estrogen by co-administering DHEA with the aromatase inhibitor letrozole, and/or the estrogen receptor inhibitor fulvestrant and observed that the
  

  "[e]xpression of MMP-3 and MMP-13 increased in both DHEA-treated chondrocytes and cartilage in the presence of letrozole and/or fulvestrant, while the expression of TIMP-1 and collagen type II (Col-II) decreased." (Li. 2013)

  With the former metalloproteinases (MMPs) being proteolytic enzymes, which break down cartilage and the latter, i.e. the tissue inhibitors of metalloproteinases (TIMPs), acting as their antagonists, it appears clear why both patients on testosterone replacement therapy who use too high of a dose of aromatase inhibitors and athletes who abuse respective products on cycle or during PCT often suffer from severe cartilage degeneration - I mean, combine the endogenous cartilage destruction due to high MMPs and low TIMP levels with the wear and tear of weight lifting... what good could come out of that?
  
  Note: A very similar effect has been reported for bisphenol A by Wang et al. in 2010, already (Wang. 2010). No wonder, after all BPA decreases the local expression of aromatization in joints and cartilage so that less estrogen will be floating around to keep the MMP levels in check and TIMP up (Watanabe. 2013).
• Alpha tocopherol to prevent lymphoma Regular vitamin E, i.e. the alpha-version of the tocopherols is no longer the star at the supplement sky it has once been hailed to be. A recent study by Renu Sharma Manjula Vinaya that's been published ahead of print in the journal Molecular Biology Reports shows however that this does not mean that it's outdated and useless (ask Ray Peat about it ;-).
  
  

  

  Figure 3: Lifespan (top) and ascite volume (=water accumulation in the abdominal area) of lymphoma carrying mice treated with what would be in human terms ~325, 650 and 975 IU/day of an alpha tocopherol only supplement  (Sharma. 2013)

  In order to test the hypothesis that the ROS scavenging abilities of vitamin E should help with cancer prevention (as a student of the SuppVersity you know that respective data from epidemiological studies are equivocal, some suggesting the exact opposite; read more), the researchers initially induced the growth of lymphomas in 10-15 week old male mice and subsequently treated them with either 1.5 mg (50 mg/kg bw), 3 mg (100 mg/kg bw) or 4.5 mg (150 mg/kg bw) of alpha-tocopherol for 14 days.
  
  As the data in figure 1 goes to show you, the treatment increased the lifespan of the rodents by 25% and reduced the ascite fluid volme (see image in figure 1) by ~46%. This was accompanied by reductions in protein carbonylation and increases in the "master anti-oxidant" GSH, as well as several other markers showing that vitamin E exerted profound anti-inflammatory effects in this rodent model of lymphoma.
  
  At least in my humble opinion that does not change the fact that your best sources of vitamin E are natural and that's smart to stay away from alpha-tocopherol only supplements and prefer a whole spectrum tocopherol + tocotrienol supplement. Remember: More is not better, when the one thing that counts are the ratios (read more about vitamin E)!
  

That's it for this week's installment of On Short Notice. As mentioned in the introduction, there are more and even shorter news on the SuppVersity Facebook Wall, which usually gets updated 3+ times per day with I would guess 9-12 items total - depending on whether it's a slow news day or not and the time I have to skim studies and popular science mags and repost summaries and links of and to the latter. Let's see what did we have today, already? Ah, yeah: "Review concludes: Just being patented makes Kinesio® no better than conventional taping" (more), "Interesting stupid science finds that GABA directly mediates energy expenditure." (more), or maybe you are interested in "If rapamycin blocks seizures in model of epilepsy. Is mTOR to blame for both?" (more)?

References:

• Goncharova ND, Vengerin AA, Chigarova OA. Repeated Moderate Stress Stimulates the Production of Dehydroepiandrosterone Sulfate (DHEAS) and Reduces Corticosteroid Imbalance in Old Macaca Mulatta.  Bulletin of Experimental Biology and Medicine Volume 153, Number 5 (2013), 750-753. 
• Lean ME, James WP, Jennings G, Trayhurn P. Brown adipose tissue in patients with phaeochromocytoma. Int J Obes. 1986;10(3):219-27. 
• Lennartsson AK, Kushnir MM, Bergquist J, Jonsdottir IH. DHEA and DHEA-S response to acute psychosocial stress in healthy men and women. Biol Psychol. 2013 May;90(2):143-9.  
• Li WJ, Tang LP, Xiong Y, Zhou XD, Wu LD. The chondroprotective effects of dehydroepiandrosterone probably exerted by its conversion to estradiol. J Steroid Biochem Mol Biol. 2013 Oct 18. 
• Liu J, Shimizu K, Konishi F, Kumamoto S, Kondo R. The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum. Bioorg Med Chem. 2007 Jul 15;15(14):4966-72. 
• Merlo S, Sortino MA. Estrogen activates matrix metalloproteinases-2 and -9 to increase beta amyloid degradation. Mol Cell Neurosci. 2013 Apr;49(4):423-9.
• Ríos JL, Andújar I, Recio MC, Giner RM. Lanostanoids from Fungi: A Group of Potential Anticancer Compounds. J Nat Prod. 2013 Oct 23.
• Sharma R, Vinayak M. α-Tocopherol prevents lymphoma by improving antioxidant defence system of mice. Mol Biol Rep. 2013 Oct 14.
• Sliva, D.; Labarrere, C.; Slivova, V.; Sedlak, M.; Lloyd, F. P., Jr.; Ho, N. W. Biochem. Biophys. Res. Commun. 2002, 298, 603– 612.
• Unsal Y, Kıvılcım G, Ayşegül A, Arzu A, Esra G, Ercan D, Ayşe S. Matrix metalloproteinase-7 and matrix metalloproteinase-9 in pediatric multiple sclerosis. Pediatr Neurol. 2013 Sep;47(3):171-6.
• Wang KC, Lin YF, Qin CH, Chen TL, Chen CH. Bisphenol-A interferes with estradiol-mediated protection in osteoarthritic chondrocytes. Toxicol Lett. 2010 Oct 5;198(2):127-33. 
• Watanabe M, Ohno S, Nakajin S. Effects of bisphenol A on the expression of cytochrome P450 aromatase (CYP19) in human fetal osteoblastic and granulosa cell-like cell lines. Toxicol Lett. 2013 Apr 5;210(1):95-9.