Get Lean & Stay Lean with Emedin, Galangin & Antibiotics. Plus: Breakfast & Morning Glucose Metabolism. Diet Once, Never Eat to Satiety Again? Adipocyte Size & NAFLD

Instead of making excuses for posting yet another "short news" collection instead of the next installment of the Athlete's Triad series, I will honestly tell you that I simply wasn't in the mood. Moreover, I have the feeling that I have already outlined what is going to work, i.e. train less, eat more and don't get all psyched up about being lean and looking good. Live your life! Against that background my gut tells me that any further details would just get you off track and back into the viscous cycle of overtraining, overdieting and overthinking why things don't work out for you by evoking the impression that as long as you take supplement X you could get away with doing a little bit 'less less' and eat a little bit 'less more'.

This would be about as counter-productive as the eternal quest for the ultimate body fat blocker or fat burner of which today's Get lean and Stay Lean Quickie does actually feature three. While the temporary use of all of them as a crutch or 'afterburner' to a reasonably planned diet and workout regimen certainly makes sense, it's not like anyone of us got fat, because he or she was "fat burner deficient". A fat burner is not an essential nutrient and only an adjunct to diet and exercise! Keep that in mind not just when you read the following short news items, but also whenever you enter a supplement store (real or on the Internet) and find a new "revolutionary fat burner" on sale -- regardless of whether it has Dr. Oz or Mr. O on the packaging it won't actively, i.e. on its own and in the absence of a dialed in nutritional regimen, make you lose body fat.

• Cassia tora (Leguminosae) seed, yet another "next big thing" to get rid of the blubber?  (Tzeng. 2012 --) The results the scientists from the Department of Internal Medicine, at the Pao Chien Hospital in  Ping Tung City will be publishing in the January 2013 issue of Food Chemistry do at at least look intriguing.  Although - and this goes to show you that SuppVersity readers always (well "almost always" ;-) are the first know first - at least one of the active ingredients in Cassia tora, which is also known as Senna tora and is, besides its use in Ayurveda medicine, also used in Sri Lankan cousin, is an old friend: Emodin! The stuff that gives rhubarb the fat burning prowess you read about in not  too long ago, here at the Suppversity.
  
  

  

  CSEE  had dose dependent ameliorative effects on body weight gain and visceral body fat levels that were - ad the highest dose - identical to those of the thiazolidinedione (TZD) drug pioglitazone (Tzeng. 2012)

  After fattening them for 2 weeks with the notorious high fat diet, the Koreans assigned their now obese lab rats to groups who received either
  
  • Cassia seed ethanol extract (CSEE) by oral gavage, once per day for 8 week with CSEE doses of 100, 200, and 300 mg/kg in a volume of 2 ml/kg distilled water,
  • the diabetes drug pioglitazone dosed at 20mg/kg/day, or
  • a placebo, containing just the distilled water.
  Without any effects on the amount of food the animals consumed, the Cassia seed ethanol extract totally blunted the HFD induced weight gain (weight gain was identical to control group on normal chow, see figure to the right).
  
  In that. the highest dosage had the greatest effect on both body weight gain, as well as plasma lipid levels and epididymal WAT sizes in HFD-fed rats. These effects were probably mediated by CSEE's beneficial effect on the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase. In addition, the researchers found that the cassia seed extract directly increased genes that are responsible for fatty acid oxidation and down-regulated their fat synthesizing counterparts in the visceral white adipose tissue of the animals.
  
  Whether CSEE is going to be a go-to supplement of the future cannot be said, now. What is certain, however, is that it constitutes yet another example of a potentially highly effective natural alternative to the established pharmacological 'treatment' (or rather management) of the diabesity epidemic.
  
• Obese, once and forever, unless you diet for the rest of your life? (Kirchner. 2012) -- A paper that's been published in the latest issue of the Journal of the American Diabetes Association, clearly suggests that the ravenous appetite of "reduced-obese" individuals, i.e. people who have been dieting for weeks and months to shed they weight they have accumulated over years is not (solely) psychologically induced gluttony.
  
  

  

  Suggested read: "Longterm 5% Calorie Restriction & Longterm Dieting Make You Fat and Insulin Resistant." (read full article)

  When Kirchner et al. put their diet-induced obese mice were on a  food restricted for 5 weeks, they did in fact reach the same body fat levels as age-matched rodents who had never received anything but the standard chow. Their  blood glucose levels normalized and their insulin sensitivity increased, but the "reduced-obese" mice also showed markedly increased fasting-induced hyperphagia. In fact, when they given ad libitum access to their beloved high fat diet, they ate like there was no tomorrow and ended up gaining weight at a much faster pace than their never-obese peers, who were likewise allowed free access to the HFD.
  
  And it gets even worse, as the conclusion the scientists draw based on their results says that despite the fact that "caloric restriction on a HFD provides metabolic benefits", it may actually require a previously obese dieter to continue on the path of caloric restriction (i.e. never eat to 'satiety') for the rest of his/her life!
  
• Morning to evening decline in insulin response to carbs suggests breakfast is the time where your body reacts most sensitive to carbs (Saad. 2012) -- Likewise published in the latest issue of Diabetes is a study by Ahmed Saad and colleagues from the Mayo College of Medicine in Rochester and the the University of Padova in Italy, which does at first not really sound like it was revolutionary new. Two definitive advantages of the study at hand were yet that the scientists used healthy individuals as subject and gave them regular mixed meals instead of a glucose solution in order to confirm the existence and identify the characteristic features of the diurnal pattern of glucose tolerance most people take for granted.
  
  

  

  The implications of this study for intermittent fasting are not as clear as you may think and certainly don't imply that you must break your fast in the morning (read more about breaking the fast, here)

  Overall 20 healthy volunteers with normal fasting glucose (4.8 ± 0.1 mmol/L) and HbA_1c (5.2 ± 0.0%) participated in the study. They were provided with identical mixed meals during breakfast, lunch, or dinner at 0700, 1300, and 1900 h in a random order on 3 consecutive days. Physical activity was held constant so that e.g. muscle glycogen depletion and subsequent increases in AMPK induced GLUT-4 expression  would not skew the results.
  
  What Saad et al. fonud was that the postprandial glucose excursion was significantly lower (P < 0.01) at breakfast than lunch and dinner. At the same time the β-Cell responsivity to glucose was higher. This means there was more insulin released per unit of glucose, than during lunch or dinner.
  
  The time the hepatic insulin extraction was also lower at breakfast; although the difference reached statistical significance only in comparison to the dinner condition. Since the overall meal glucose appearance did not differ between meals and that the suppression of endogenous glucose production "tended to be lower (P < 0.01) and insulin sensitivity tended to be higher (P < 0.01) at breakfast than at lunch or dinner" (Saad. 2012), it is no wonder that the spike in blood glucose was largely augmented, when the subjects consumed the standardized meal for breakfast.
  
• Adipocyte size is a determinant of non-alcoholic fatty liver disease (NAFLD) risk (Petäjä. 2012) -- One thing scientists still have not really understood is how some obese people seem to be way better off than others, although their BMIs, fat and lean mass appears to be identical. In view of the latest paper by a group of researchers from Finland and Sweden on the association between the average fat cell size and the occurrence of NAFLD, it could well be that ratio of the total adipose volume to the total fat cell number, which obviously is the adipocyte size, may be providing at least another piece to the puzzle that holds the answer to this question.
  
  

  

  In a previos post on the yoyo effect, I already discussed some aspects of adipocyte morphology - read more

  The scientists have studied 119 non-diabetic subjects in a cross-sectional study. The participants had a median age of 39 (26-53) years, and a mean BMI of 30.0±5.7kg/m². Subcutaneous abdominal fat cell size, as well as the total amount of liver fat were measured by proton magnetic resonance spectroscopy, intra-abdominal (IA) and abdominal subcutaneous adipose tissue (SC) volumes by magnetic resonance imaging (MRI) and an additional gene analysis yielded information about the genotype (susceptible or not susceptble to metabolic syndrome) of the individuals.
  
  Simply based on a multiple linear regression analysis, age, gender, BMI, the intra-abdominal to subcutaneous fat ratio and the subject's PNPLA3 genotype, the results were only able to explain 42% of the variation of the liver fat. The inclusion of the adipocyte sizes increased the predictive value by 11%, so that "21% of the known variation in liver fat could be explained by adipocyte size alone" (Petäjä. 2012) This does yet also mean that once we are up to a 90% explanation  (which is unrealistic, by the way) the adipocyte size will only be able to explain "of the known variations".
  
• Antibiotic that's commonly used in animal fattening kills body fat (Szkudlarek-Mikho, 2012) -- Reserachers from the College of Medicine at the University of Toledo in Ohio have found that polyether ionophoric antibiotics including monensin, salinomycin, and narasin, which are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming have toxic effects on adipose cells.
  
  

  

  Whether eating the chicken that ate antibiotics is going to make  you lean does still have to be established. Based on the results of the study at hand, it does however appear likely that eating antibiotics could - I do however doubt that they will achieve that without potentially serious side effects.

  Although previous studies suggest that salinomycin has anti-carcinogenic effects (Huczyński. 2012), the sharp increase in poultry consumption over the last decade(s) and the increased use of these "growth promoting" antibiotics by veterinaries and poultry farmers has often been suspected to be involved in the increase in metabolic and autoimmune diseases.
  
  At least in view of the former, i.e. metabolic diseases in general and obesity, in particular, it may therefore be surprising that the scientists from the University of Toledo discovered that the tested ionophoric antibiotics did not just inhibit the differentiation of cancer, but also that of preadipocytes into adipocytes:
  

  "The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ." (Szkudlarek-Mikho. 2012)

  Now, I would fully subscribe to the scientists suggestion that these "ionophoric antibiotics can be exploited as novel anti-obesity therapeutics", but until that has been done and we know which other cells' differentiation they may inhibit, as well, I'd strongly discourage anyone from 'supplementing' with the antibiotics from his or her poultry farmer next door. After all, you may well end up not just with less body fat, but with less brain tissue, as well... what? You don't care? Oh I see. The doctor must have inserted the cannula into your ears instead of your belly on your last liposuction, right?
  
• Alpinia officinarum, a plant in the ginger family, stops fat gains in its tracks (Jung. 2012) -- Jung, Jang, Ahn and the rest of the researchers from the Korea Food Research Institute in Seongnam, report in their latest paper that an ethanol extract from Alpinia officinarum, a plant in the ginger family that's cultivated in Southeast Asia and is also known as lesser galangal, is yet another mainstay of traditional medicine with significant anti-obesity effects.
  
  

  

  It looks almost like ginger and works almost like ginger, but A. officinarum contains galangin, not gingerol and works via the PPAR-gamma pathway, as well. That's something gingerol doesn't do (Huang. 2012)

  Originally used throughout Asia in curries and perfumes, A. officinarum contains a dietary flavenol called galangin, which has already been shown to exert profound anti-cancer effects (Kapoor. 2012), whether it is solely responsible for the in vitro and in vivo inhibitory effects on lipid accumulation during the differentation of 3T3-L1 adipocytes is not certain, but appears to be likely.
  
  Via its effects on the fat synthesis and breakdown and PPAR-gamma activity the A. officinarum extract (AOE) lead to dose-dependent decreases in body weight gains of mice who were fed a high fat diet. It also reduced the visceral and liver fat deposition and partially restored the abnormally elevated insulin and leptin levels of the rodents.
  

  "Collectively, these results suggest that AOE prevents obesity by suppressing adipogenic and lipogenic genes. AOE has potential for use as an antiobesity therapeutic agent that can function by regulating lipid metabolism." (Jung. 2012)

  Certainly another nice find, but let's be honest, what's the real value of all this herbs? I mean yeah they work almost as effectively (in some cases even better) than pharmacological drugs, but both share a detrimental downside, that's not mentioned under "side effects" on the package insert or supplement bottle: They will only manage a problem the root course of which is the net result of a totally messed up diet.

That's it and since you've gotten the bottom line in advance and another time, just to make sure nobody can over-read it, in the last paragraph of the last news item, I just want to remind everyone that there are a couple of other interesting science news and links, for example about ...

• the pro-carcinogenic effects of shift work and to a lesser degree constantly working at night (read),
• the connection between high GI carbs and prostate cancer (read), or
• the idiocy of battling the high GI carb induced decline in cognitive performance with even more sugar (read)

waiting for you on Facebook. Have a nice day and get lean and stay lean ;-)

References

• Huang TH, Teoh AW, Lin BL, Lin DS, Roufogalis B. The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome. Pharmacol Res. 2009 Sep;60(3):195-206. Epub 2009 Apr 7.
• Huczyński A, Janczak J, Antoszczak M, Wietrzyk J, Maj E, Brzezinski B. Antiproliferative activity of salinomycin and its derivatives. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7146-50.
• Jung CH, Jang SJ, Ahn J, Gwon SY, Jeon TI, Kim TW, Ha TY. Alpinia officinarum Inhibits Adipocyte Differentiation and High-Fat Diet-Induced Obesity in Mice Through Regulation of Adipogenesis and Lipogenesis. J Med Food. 2012 Nov;15(11):959-67.
• Kapoor S. Galangin and its emerging anti-neoplastic effects. Cytotechnology. 2012 Oct 25.
• Kirchner H, Hofmann SM, Fischer-Rosinsky A, Hembree J, Abplanalp W, Ottaway N, Donelan E, Krishna R, Woods SC, Müller TD, Spranger J, Perez-Tilve D, Pfluger PT, Tschöp MH, Habegger KM. Caloric restriction chronically impairs metabolic programming in mice. Diabetes. 2012 Nov;61(11):2734-42. doi: 10.2337/db11-1621.
• Petäjä EM, Sevastianova K, Hakkarainen A, Orho-Melander M, Lundbom N, Yki-Järvinen H. Adipocyte size is associated with NAFLD independent of obesity, fat distribution and PNPLA3 genotype. Obesity. 2012. Ahead of Print.
• Saad A, Dalla Man C, Nandy DK, Levine JA, Bharucha AE, Rizza RA, Basu R, Carter RE, Cobelli C, Kudva YC, Basu A. Diurnal pattern to insulin secretion and insulin action in healthy individuals. Diabetes. 2012 Nov;61(11):2691-700.
• Szkudlarek-Mikho M, Saunders RA, Yap SF, Ngeow YF, Chin KV. Salinomycin, A Polyether Ionophoric Antibiotic, Inhibits Adipogenesis. Biochem Biophys Res Commun. 2012 Oct 31.
• Tzeng TF, Lu HJ, Liou SS, Chang CJ, Liu IM. Reduction of lipid accumulation in white adipose tissues by Cassia tora (Leguminosae) seed extract is associated with AMPK activation. Food Chem. 2013 Jan 15;136(2):1086-94. doi: 10.1016/j.foodchem.2012.09.017.

Forget the Blood Type Diet, Embrace the Gut Type Diet: Eating According to the Likes or Dislikes of Your Bacterial Subtenants Could Keep You Healthy, Lean & Sane.

Image 1: You better feed them right, or your gut bacteria could will disbehave just like the Alien in Ellen Ripley (Sigourney Weaver) in Alien 3 (20th Century Fox).

Eating right for your type, probably is not what it takes to have dietary success. Scientists from the US and Brazil have now found that eating according to the likes an dislikes of your bacterial subtenants seems to could eventually have a much greater potential (Wu. 2011) in keeping you healthy and, as the results of the joint research efforts of Canadian and Irish scientists shows, psychologically sane (Bravo. 2011).

Scientists estimate that the genome of the sum of our gut microbia is about 100x more complex than our own gene-sequence and the type and ratio of the 300-1000 different species within your intestinal tract have a major impact not only on how you digest your food, but also on how you look, feel and perform. It is therefore particularly interesting that Gary D. Wu and his colleagues established (for the first time) the existence of a stable microbiome composition that appears to be specialize to strive on a specific diet.

Note: Currently, the data is still too scarce and the variety of gut microbia, as well as their interactions too complex, for any reliable conclusions on whether it is "optimal" to eat according to your current gut biome or whether and in which way it would benefit your health, performance or body composition to modify / tweak the composition of the latter by dietary strategies and/or supplements or even medications. Even the idea of "optimizing" the microbial composition of our guts for "optimal" macro-nutrient usage is illusive, as it could well be that the specialization of our gut bacteria, i.e. their efficiency in using only little of the dietary energy for themselves and redirecting the rest to us, could theoretically be among the reasons for the obesity epidemic, as well.

In a preliminary analysis Wu et al. had established that in 98 healthy volunteers, whose stool they had analyzed for its individual microbiome composition there was a high correlation between habitual diets (measured by dietary questionnaires; data cf. figure 1, below) and the predominant type of bacteria.

Bacteroide enterotype was highly associated with animal protein, a variety of amino acids, and saturated fats, suggesting that meat consumption as in a Western diet characterized this enterotype. [...] The Prevotella enterotype, [...] was associated with [...] high values for carbohydrates and simple sugars, indicating association with a carbohydrate-based diet more typical of agrarian societies.

As one would expect, "self-reported vegetarians (n = 11) showed enrichment in the Prevotella
enterotype (27% Prevotella enterotype vs. 10% Bacteriodes enterotype; p = 0.13)" and the one self-reported vegan was in the Prevotella enterotype group, as well.

Image 2: Prevotella histicola is a major driving force of tooth decay (King's College). Its relatives in the gut, on the other hand, have been found to be implicated in insulin resistance and infertility due to endotoxin-related inflammation.

Now, if you are a dentist or did some research in the area of "caries" for whatever reason, the name "Prevotella" will probably sound remotely familiar. After all, the Prevotella species has been found to be associated with severe early childhood caries (e.g. Tanner. 2011). These are also the guys, whose poisonous lipolysaccharide dung increases the synthesis of the inflammatory cytokine TNF-alpha (Kim. 2007), which, in turn, has long been known to induce insulin resistance (Hotamisligil. 1999) - quite smart from the bacteria, isn't it? After all, if your body does not suck up the glucose the Prevotella will have more sugar to feed on. What may be less smart, though ,is that the endotoxin (lipolysaccharides are considered endotoxins) induced inflammation will also compromise testicular function on multiple levels, which in turn would deprive future generations of bacteria of their hosts.

Figure 1: Associations (Spearman correlation; -1: max neg. / +1 max pos.) between habitual dietary intake of sugars, vitamins & minerals, fats, amino acids, proteins and micronutrients and bacterial composition, where enterotype 1 is bacteriode dominant, and enterotype 2 is prevotella dominant (data adapted from Wu. 2011)

The polysaccharide A (PSA) produced by Bacteroides, an even larger class of bacteria which obviously strives on a high fat, high protein diet (or rather what mainstream dietitians call "high protein"), on the other hand, has recently been implicated in beneficial modulations of the immune system (Troy. 2010) and apparently even protects the nerves from he central nervous system from demyelation (Ochoa-Repáraz. 2010), i.e. the destruction of the insulating myelin layer. There is however a broad variety among the Bacteroides and as Wexler in his aptly titled paper "Bacteroides: the good, the bad, and the nitty-gritty." points out (Wexler. 2010):

The bacteria maintain a complex and generally beneficial relationship with the host when retained in the gut, but when they escape this environment they can cause significant pathology, including bacteremia and abscess formation in multiple body sites.

Based on the results of Wu's study, which also showed that a short-term dietary intevention (10 days) could not change the Bacteriode dominance of the 10 subjects who had been randomly assigned to high fat/low or a low fat/high fiber diets, we can thus only say that we probably are "optimized" for a certain macronutrient composition. Whether this is a beneficial or detrimental adaptation has still to be determined. What has however been established (in a rat model) is that chronic treatment with the probiotic bacteria Lactobacillus rhamnosus

[...] induced region-dependent alterations in GABAB1b mRNA in the brain [, ...] reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus [and] reduced stress-induced corticosterone and anxiety- and depression-related behavior.

Bravo et al. ascribe these beneficial psycho-physiological effects to the "modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain". And highlight the "bidirectional communication of the gut–brain axis" as a possible target to treat stress-related disorders.

Image 3: The antibiotic vancomycin could potentially induce obesity month after treatment.

Did you know that Thuny et al. clearly showed that (Thuny. 2010) combined treatment with vancomycin-plus-gentamycin in patients with infective endocarditis was associated with a significant gain in BMI of +2.3kg/m² in the first year after discharge from hospital. For a man of 180cm this would be ~7.5kg. Vancomycin, by the way happens to be the cousin of Avoparcin an antimicribial growth promoter that has been used in the EU for fattening animals for about a year before it was prohibited in 1997.

In defense of "antibiotics" and as a word of caution against exuberant enthusiasm for all bacteria it should yet be mentioned that alternative antibiotics did not exhibit the same profound effects in the Thuny study. Moreover, observations in germ-free mice suggest that (Bäckhed. 2006)

[germ-free] animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1α; and (ii) increased AMPK activity.

In view of the ever increasing resistance towards antibiotics, it is however unrealistic to assume that we will see similar effects in humans after the administration of individual or even combined high-dose antibiotics.

Moreover, more and more scientists argue that, based on the growth-promoting effects of antibiotics in food animals (Linn. 2011), it is more than likely that the long thought of relation between gut microbiota and the human obesity epidemic is real and that research into the detailed working principles of antimicrobial growth promoters (AGP) in animals may reveal hitherto overlooked underpinnings of obesity an respective treatment strategies.

We will see what future research will bring. Yet, while you are waiting for me to keep you on par with the results, I suggest you better stay away from growth or non-growth promoting antibiotics if you want to stay healthy, sane and slim.