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

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

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

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

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

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

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

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

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

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

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

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

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

How does it work and how effective is it?

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

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

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

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

Lemon Juice, Resistant Starch, Coffee, Blueberries, Chili, Ginseng, Ginger, Mate, Gymnema Sylvestre, Bitter Melon. Supplements to Improve & Restore Insulin Sensitivity #4

Lemon Juice, Resistant Starch, Coffee, Blueberries, Chili, Ginseng, Ginger, Mate, Gymnema Sylvestre, Bitter Melon - they are all in this fourth serving of the insulin sensitizing supplements series and they are all in this collage. Can you identify all of them?

First of all, let me thank you for flooding me with good suggestions for supplements that should be discussed in this last installment of the series. It's Friday now that I start writing this post and it is probably going to be Sunday, before I find the time to finish the last of your suggestions; and that despite the fact that I am going to try to cut the infos short when I can foresee that it is not worth going into more details, anyway.

Not worth going into details? Yep, one of the supps, where this is clearly the case was suggested by Colby who wants me to address sodium-R-lipoic acid, which is nothing else but R-ALA and in my mind a scientifically unsupported spin-off of ALA that may in fact be inferior to the regular racemic form of lipoic acid which contains both the R- as well as the purportedly pro-inflammatory S-form of ALA (more about the benefits of inflammation in the context of hormesis).

Before we start, just a brief reminder: Do not consider spending your money on any of these supplements before you've not made / begun to make the lifestyle changes described in episode one of this series. Otherwise all of these supplements are nothing but a crutch supporting you on your journey along the Royal Road to Diabesity.

Ok, enough of the finger wagging for today; let's get to "your" supplement wishes. Let's see, what have we got?

• Lemon juice (citric acid) - This is another of Colby's suggestions (also asked for by "anonymous" who just missed his chance of becoming semi-famous). Colby says, he read about lemon juice in Tim Ferriss' Four Hour Body (a fascinating book, by the way; the only problem is that people forget that it's an N=1 experiment and few things that worked for Tim will work for you or anyone else, as effectively).
  
  

  

  Not citric acid specific enough, but worth mentioning: In a study where citric acid (the purported active ingr. in lemon juice) was admin. w/ thiamine, arginine and caffeine it lead to FAT GAIN in normal weight individuals (Muroyama. 2003) - this should remind you of the smart rules of supplementation, right?

  Ferris claims that in his experiments only lemon juice, but not vinegar, which happens to work by the same mechanism, i.e. slowing down the absorption of carbs, did actually lower his postprandial blood glucose levels. Unfortunately there is no research to support this claim and thus lemon juice is at best of as limited use as vinegar (see previous post).
  
  Using lemon juice for cooking purposes, on the other hand, has been shown to reduce the formation of pro-diabetic glycation end products during cooking.
  
  Using a marinade with lemon juice for example will reduce the production of AGEs in beef by 10%  (Uribarri. 2010)
  
  Overall, lemon juice is thus another "C" as in "you C-an try it if you are looking for yet another C-rutch", but certainly nothing that is going to solve any of your problems.
• Resistant Starches - Starches that cannot be broken down in the small intestine and will thus not release any glucose are a no-brainer, as far as improvements in insulin sensitivity are concerned. Think of them as fat, because that is what the "really resistant" starches, i.e. those that make it almost unharmed to the long intesine (RS-3 for the natural ones and RS-4 for the artificial ones). Once they have arrived there they are metabolized to short chain fatty by the bacteria in your gut.
  
  

  

  WMHDP pancakes are not good for you, but maybe better than regular ones.

  Now, the one thing that renders this starches still interesting is the fact that the fatty acids the gut bacteria produce are "short chain fatty acids" (SCFA) . These are, as the name implies "short" and thus easier digested than their nasty long-chain brethren that make up the lion's share of regular keto diets. Moroever, the SCFA have direct (receptor mediated) effects on the production of the "satiety hormone" GLP-1 that has positive effects on both glucose and lipid metabolism (Yadav. 2013).
  
  It is thus the conversion to SCFA and not the resistant starches which come in the varieties RS1 (=physically inaccessible or digestible resistant starch, such as that found in seeds or legumes and unprocessed whole grains),  RS2 (=resistant starch that occurs in its natural granular form, such as uncooked potato, green banana flour and high amylose corn), RS3 (=resistant starch that is formed when starch-containing foods are cooked and cooled such as in legumes, bread, cornflakes and cooked-and-chilled potatoes, pasta salad or sushi rice) and  RS4 (= starches that have been chemically modified to resist digestion, e.g. WMHDP), due to which RS1-4 get a "B" as in "B-etter than regular starches or sugars, B-ut no quick fix for sure". They are useful only in conjunction with the previously mentioned life-style changes from episode I (no, I will never tire of repeating this ;-).

• 

  From an anti-diabetes perspecitve more coffee appears to help more; in view of its effects on the central nervous system you still better limit your intake to max. 3-4 cups per day (Matusheski. 2012)

  Coffee (caffeine & other stuff) - Is certainly too extensive to be treated in detail, so I will refer you to the numerous previous posts on coffee at the SuppVersity, as well as "Warding Off Holiday Weight Gain 2.0: The Anti-Diabesity Effect of Coffee Goes Beyond its Caffeine Content" | read more.
  
  In addition, I would like to invite you to take a look at the image to the right that shows quite clearly that the anti-diabesity effect, of which you have learned that it could mediated by the benefits of caffeine on the liver (cf. "Diabetes & the Liver - Chicken vs. Egg" | read more) are reversed when you are already obese, diabetic & hyperlipidemic.
  
  While I refuse to officially rank coffee, I can tell you that most of the negative side effects are dose-dependently brought about by its caffeine content, and that I personally have a "never consume more than 500mg caffeine or 2-3 cups per day" rule in place and regret it deeply whenever I defy my rule for more than 2-3 days in a row - not on the diabetic side of things (I am rather a low blood glucose guy), but as far as overall well-being and energy levels are concerned. 

• 

  SuppVersity suggested read: "Want to Relieve Insulin Resistance? Eat your Blueberries!" | read more

  Blueberries (real food) - Let me first tell you that I do not intend to give you an overview of the myriad of proven and purported health benefits of blueberries. If that's what you are looking for, I suggest you take a peak at the latest review by Noerberto et al. 2013 (see references).
  
  What I want to give you instead is a real world example: A 2010 study by Stull et al. who found that the provision of isocaloric smoothies with and without 22.5 g blueberry bioactives to 32 obese, nondiabetic, and insulin-resistant subjects for 6 weeks led to a significant improvement of insulin sensitivity in the absence of changes in adiposity.
  
  According to the scientists the same effects could be achieved with 2 cups of fresh blueberries (or 45g of the powder they used to prepare the study) that makes blueberries an "A" as in "A must, but A bit expensive to have them every day". That does not change that consuming blueberries on a regular basis is going to help you improve or maintain you insulin sensitivity.
  
  Thanks for reminding me of including such a reasonable whole food in the series, Erik - ah and Ian, if you want pterostilbene, just eat your blueberries.

• 

  MCT + Chili a fat loss duo that will reduce your insulin sensitivity. That does not matter while you are dieting or low-to-no-carbing, but is a no go when you are doing neither of that.

  Chili (capsaicin) - Capsaicin is another suggestion from Erik, of which I am not quite sure, where he picked it up. Being mislabeled as "fat burner" capsaicin is just like caffeine a substance that increases the efflux of fat from the fat cells and will thus increase the serum level of free fatty acids. This will promote, not inhibit, insulin resistance. Against that background it is not surprising that Islam et al. report that capsaicin had no hypoglycemic, but insulinotropic (more insulin, but same amount of glucose in the blood = decreases insulin sensitivity) effects in a rodent model of type II diabetes (Islam. 2008).
  Note: If you are wondering why I am so bold to state that MCTs reduce your insulin sensitivity (see caption of the image), here is the study (Marcal. 2013) and this is the explanation: Fast fats = increase in FFA in the blood = insulin resistance. At least in an "average" = non-low carb + non-calorically restricted scenario it's as easy as that. When you replace the "Atkins fats" (= long chain fatty acids) with MCTs, on the other hand, you will obviously see benefits from medium chain triglycerides (cf. De Vogel-van den Bosch. 2011).
  In other words, if it's not used to cut body fat (in conjunction with diet and exercise) it's unlikely that capsaicin will help with insulin sensitivity, which is why it gets a "D" as in "D-on't use". And that would be the case even if capsaicin did not have some dubious effects on the Langerhans cells in the pancreas Gram. 2007). It's weight loss effects are totally overblown (see today's Facebook news) and it has been shown to blunt the beneficial effects of the "satiety hormone" cholecystokinin two decades ago (Ritter. 1985). If you want a "hot" alternative, you should thus go for plain onions (Babu. 1997).
• Ginseng (purported active ingredient ginsenoside Rh2): While there are plenty of rodent studies available, Cho et al. were the first to investigate the effect of Korean red ginseng in human beings and the results of their study which has been published in March this year are not exactly impressive.
  
  

  

  It's easy to see: Ginseng doesn't help healthy people. While the reduction in insulin sensitivity in response to 6g ginseng was not significant, it's obvious that healthy individuals won't benefit (Cho. 2013)

  The Korean researchers administered 6 g of  Korean red ginseng rootlets (n=34) or a placebo to a group of 68 participants (average BMI 26kg/m², average body fat 30.7%) for 12 week period and observed that
  

  "Korean red ginseng had no significant effect on improving the insulin sensitivity over time." (Cho. 2013)

  This is significant, because you can safely assume that its effects on individuals with lower body fat percentages (like you?) are probably bordering zero.
  
  Other studies report a physiologically irrelevant improvement in postprandial glycemia, when ginseng (in this case American) was administered exactly 40min before an oral glucose challenge (Vuskan. 2001). And the (non-significant) reduction in insulin sensitivity in the healthy but chubby subjects of the Cho study (see figure on the top right of this paragraph) is a perfect example of the previously cited imperative of applying the selectivity and specificity principles, when you select and buy your dietary supplements (learn more).
  
  In view of the fact that there is some allegedly inconclusive and "not convincing" (Kim. 2011) scientific support for the usefulness of ginseng in sick people, it still qualify for a "C-" as in "C-ould be useful for those who are already suffering from what we call the "metabolic syndrome". Of these, especially those who suffer from high blood lipids (e.g. Mucalo. 2012) could benefit and in these individuals you will probably also observe downstream improvements in glucose metabolism. These are however secondary to the reduction in blood lipis and will not occur in people like yourself, people who work out regular and lead the lives of someone who has found his / her way to physical culture.

• 

  Suggested read: "Beyond Warding Off Holiday Weight Gain: 250-1000mg of Freeze-Dried Ginger Reduce Visceral Fat In Rodents on High Fat Diet" | read more
  

  Ginger - SuppVersity readers will remember ginger from the list of "20+ Anti-Obesity Agents That Have the Potential to Inhibit Fat Gain Right at the Cellular Level" (read full article). If you do remember this article, you may also remember that the anti-obesity effect is brought about by ginger's ability to inhibit the pro-adipogenic peroxisome proliferator-activated gamma receptors (PPAR-gamma).
  
  Ginger has also been shown to exhibit appetite suppressant effects (Mansou. 2012), to improve the thermic effect of food (ibid.), to hold potential as an anti-NAFLD (non-fatty liver disease) "drug" (Sahebkar. 2011), to ameliorate the negative side effects of diabetes (Li. 2012), and to improve glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients (Mahluji. 2013)
  
  For whole ginger (i.e. not ginger extracts) the dosages are usually in the 2-4g range. And while this is probably not going to hurt anyone, there is simply too little evidence that the beneficial effects of ginger are not "solely" mediated by its potent anti-inflammatory action to award an "A"-level recommendation with respect to its insulin sensitizing effects.
  
  So, assuming that its usefulness is more or less limited to individuals with underlying inflammatory problems ginger gets a "B" as in "there are few B-etter general health foods out there, B-ut its benefits in lean individuals are probably not glucose specific". If you are looking for general anti-obesity effects, on the other hand, I'd suggest you go and grab a couple of ginger roots right now ;-)
• Mate tea (Ilex paraguariensis): The evidence from human studies for or against the usefulness of the last supplement on Erik's wishlist is not exactly what I would call extensive. A study by Klein et al. from 2011 is probably as good as it gets and, as it was to be expected, the results suggest that we are once more dealing with an anti-inflammatory agent that will have the greatest impact on people who already suffer from diabetes / the metabolic syndrome.
  
  

  

  SuppVersity suggested Read: "The Leptin-Ilex!? Does Yerba Mate (Ilex Paraguariensis) Restore Leptin Sensitivity or Does it Just Help You Lose Body Fat by Curbing Your Appetite?" | read more, but don't forget that fat loss and glucose sensitivity are not one and the same. While The former usually entails the latter, it does not always work the other way around.

  Contrary to the diabetic patients in the Klein study, the pre-diabetic mate-tea consumers (3x330ml of tea made from roasted mate tea) in his study, did not register any benefits in glucose metabolism and the improvements in lipid parameters may well be a mere consequence of the concomitant dietary changes Klein et al. observed (Klein. 2011).
  
  Just like many other purported "insulin sensitizers", Mate is thus another food / supplement that has only secondary effects on blood glucose. It's another "C" supplement with "C as in C-an be used by the obese diabetic". Drinking liters of mate, even if you don't like it, just to increase your glucose sensitivity does however seem to be pretty useless for anyone who ain't suffering from abnormal lipid levels and increased whole body inflammation.
• Gymnema Sylvestre - While there are a couple of human studies on gymnema their significance suffers from heavy sponsoring and / or the co-administration of other supplements. If you plod through the research that's out there you will however find some evidence for its usefulness in full-blown type II diabetics (500mg/day; Kumar. 2010) and some interesting effects on the sweet taste receptors (Sigoillot. 2012). The latter are blocked by gymnemic acid and could, at least when we are talking about the glucose receptors in the gut, modify both the absorption kinetics and hormonal response of / to glucose.
  
  In the end, the said effects on the sweet taste receptors may also be involved in the effects Shanmugasundaram et al. describe in a 1990 paper. In their study, the administration of 400mg of an GS extract lead to significant improvements in glucose management in 27 patients with insulin-dependent (=severe) diabetes. Since we do not really know that, and in view of the occasional reports of adverse reactions to gymnema supplements (e.g. a case-report by Shiyovich et al. (2010) that links the consumption of gymnema supplements to toxic hepatitis), I will still rank it as "D" as in "D-o wait until there is more and better research available".
  
  I personally consider the risk of consuming corresponding supplements very low, but the same goes for any potential benefits ... and one thing is certain, it's not "a potential panacea for the management of diabetes" which is what MJ Leach writes to attract attention to his 2007 review of the literature in the Journal of Alternative Complementary Medicine (Leach. 2007)

• 

  Suggested Read: "Purported Health Supplement Bitter Melon Induces Oxidative Damage in Rat Testes and Reduces Testosterone Levels by >50%" | read more

  Bitter melon (Momordica charantia): While the hype has already abated, the marketing guys did a pretty damn good job in pimping bitter melon as the goto panaceum for whatever health problem may have befallen you. With respect to it's insulin sensitizing effects Basch et al. wrote about a decade ago:
  

  "Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring." (Basch. 2003)

  Did that change over the course of the past 10 years? Of course not.
  
  So unless Google and sensationalist advertisements that are supposed to look like real journal articles are your main sources of "information" about dietary supplements you will probably have to concede that
  

  "[...] clinical trial data with human subjects are limited and flawed by poor study design and low statistical power [and] the clinical data regarding the anti-diabetic potentials of M. charantia and calls for better-designed clinical trials to further elucidate its possible therapeutic effects" (Leung. 2009)

  and conclude that
  

  "[t]here is insufficient evidence on the effects of momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice." (Ooi. 2013)

  That does not necessarily mean that it does not work, at all, but as a direct comparison with metformin shows, it's not a real alternative for type II diabetics (Fuangchan. 2011), whose HbA1c levels declined by meager 0.24% after being treated with a bitter melon supplement three times a day for three months (undisclosed amount of active ingredients in the caps; cf. Dans. 2007). I hope I do not have to point out that it is unrealistic to expect that you would see better effects in non-diabetics.
  
  I guess, it's probably not necessary to say that, but bitter melon is a bitter pill that gets a "D" as in "D-on't fall for the hype".
  

No block buster supps in this serving: Ok, I have to admit this last installment of the series had a couple of supplemental non-starters in it. Honestly, Ginger is the only one of the items listed above that stands a chance to make it into the insulin sensitizing protocol that's about to conclude this series next Sunday.

Until then, I hope all of you enjoy the rest of this weekend and come back for your daily dose of SuppVersity news tomorrow (all muscle heads listen up, you will like tomorrows news ;-)!

References:

• Babu PS, Srinivasan K. Influence of dietary capsaicin and onion on the metabolic abnormalities associated with streptozotocin induced diabetes mellitus. Mol Cell Biochem. 1997 Oct;175(1-2):49-57. 
• Fuangchan A, Sonthisombat P, Seubnukarn T, Chanouan R, Chotchaisuwat P, Sirigulsatien V, Ingkaninan K, Plianbangchang P, Haines ST. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J Ethnopharmacol. 2011 Mar 24;134(2):422-8.
• Islam MS, Choi H. Dietary red chilli (Capsicum frutescens L.) is insulinotropic rather than hypoglycemic in type 2 diabetes model of rats. Phytother Res. 2008 Aug;22(8):1025-9.
• Kim S, Shin BC, Lee MS, Lee H, Ernst E. Red ginseng for type 2 diabetes mellitus: a systematic review of randomized controlled trials. Chin J Integr Med. 2011 Dec;17(12):937-44. 
• Kumar SN, Mani UV, Mani I. An open label study on the supplementation of Gymnema sylvestre in type 2 diabetics. J Diet Suppl. 2010 Sep;7(3):273-82.
• Leach MJ. Gymnema sylvestre for diabetes mellitus: a systematic review. J Altern Complement Med. 2007 Nov;13(9):977-83. Review.
• Leung L, Birtwhistle R, Kotecha J, Hannah S, Cuthbertson S. Anti-diabetic and hypoglycaemic effects of Momordica charantia (bitter melon): a mini review. Br J Nutr. 2009 Dec;102(12):1703-8. doi: 10.1017/S0007114509992054. Epub . Review.
• Li Y, Tran VH, Duke CC, Roufogalis BD. Preventive and Protective Properties of Zingiber officinale (Ginger) in Diabetes Mellitus, Diabetic Complications, and Associated Lipid and Other Metabolic Disorders: A Brief Review. Evid Based Complement Alternat Med. 2012;2012:516870.
• Mansour MS, Ni YM, Roberts AL, Kelleman M, Roychoudhury A, St-Onge MP. Ginger consumption enhances the thermic effect of food and promotes feelings of satiety without affecting metabolic and hormonal parameters in overweight men: a pilot study. Metabolism. 2012 Oct;61(10):1347-52.
• Marçal AC, Camporez JP, Lima-Salgado TM, Cintra DE, Akamine EH, Ribeiro LM, Almeida FN, Zanuto RP, Curi R, Boldrini SC, Liberti EA, Fiamoncini J, Hirabara SM, Deschamps FC, Carpinelli AR, Carvalho CR. Changes in food intake, metabolic parameters and insulin resistance are induced by an isoenergetic, medium-chain fatty acid diet and are associated with modifications in insulin signalling in isolated rat pancreatic islets. Br J Nutr. 2013 Jun 28;109(12):2154-65. doi: 10.1017/S0007114512004576.
• Matusheski et al. Coffee and Type 2 Diabetes Risk. In "Coffee: Emerging Health Effects and Disease Prevention" edited by Yi-Fang Chu.John Wiley & Sons, Mar 27, 2012.
• Mucalo I, Rahelić D, Jovanovski E, Bozikov V, Romić Z, Vuksan V. Effect of American ginseng (Panax quinquefolius L.) on glycemic control in type 2 diabetes. Coll Antropol. 2012 Dec;36(4):1435-40. Review.
• Muroyama K, Murosaki S, Yamamoto Y, Ishijima A, Toh Y. Effects of intake of a mixture of thiamin, arginine, caffeine, and citric acid on adiposity in healthy subjects with high percent body fat. Biosci Biotechnol Biochem. 2003 Nov;67(11):2325-3.
• Norberto S, Silva S, Meireles M, Faria A, Pintado M, Calhau C. Blueberry anthocyanins in health promotion: A metabolic overview. Journal of Functional. Foods, Available online 21 September 2013.
• Ritter RC, Ladenheim EE. Capsaicin pretreatment attenuates suppression of food intake by cholecystokinin. Am J Physiol. 1985 Apr;248(4 Pt 2):R501-4. 
• Sahebkar A. Potential efficacy of ginger as a natural supplement for nonalcoholic fatty liver disease. World J Gastroenterol. 2011 Jan 14;17(2):271-2. doi: 10.3748/wjg.v17.i2.271. 
• Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol. 1990 Oct;30(3):281-94.
• Shiyovich A, Sztarkier I, Nesher L. Toxic hepatitis induced by Gymnema sylvestre, a natural remedy for type 2 diabetes mellitus. Am J Med Sci. 2010 Dec;340(6):514-7.
• Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J Nutr. 2010 Oct;140(10):1764-8. doi: 10.3945/jn.110.125336.
• Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010 Jun;110(6):911-16.e12.
• Yadav H, Lee JH, Lloyd J, Walter P, Rane SG. Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion. J Biol Chem. 2013 Aug 30;288(35):25088-97.

Weightloss Threesome: TV or Sleep, Black Pepper, Ginger, Horseradish or Mustard, PolyGlycopleX (PGX) or Psyllium?

Image 1: True or false - Is three really better than two?

Since the On Short Notice columns turns out to be a major success, I decided that I could put out studies in packages of shorter items, on a more regular basis - at least if I stumble across pairs such as those in today's Fat Loss Threesome and have time to compile them in to a comprehensive blogpost. But enough of the prelude, let's get right to our threesome: Television or Sleep, Black Pepper, Ginger, Horseradish or Mustard, PolyGlycopleX (PGX) or Psyllium - What do you think, which of these is will spice up, which will water down your weight loss efforts; and for the bros out there: Can you stack all of them or do they have to be cycled?

TV Watching and Insufficient Sleep - A Dynamic Duo for (Childhood-)Diabesity

Image 2: Watching TV eating junk is only part of the equation; what's missing here is the lack of sleep kids don't get, when they watch TV canned with coke and energy drinks all night.

Facebook friends and followers of the SuppVersity Facebook Channel may be familiar with at least some of the recent articles on the negative impact of TV watching alone and in conjunction with sleep deprivation on the body composition and metabolic health of our children. My personal favorite in this regard is a letter to the editor of the British Journal of Nutrition, in which Travis John Saunders and Jean-Philippe Chaput argue that obesity prevention could be as simple as turning off the television and having a nap (Saunders. 2012). The authors reference a whole host of studies to support their hypothesis that TV consumption and the associated lack of sleep esp. during the early hours of the night contribute to the rise of the obesity epidemic:

• TV viewing burns energy at a slower rate than most other waking activities and yet still most available evidence suggests that it may be energy intake, rather than expenditure, which leads the scientifically established association between screen time and weight gain, Saunders and Chaput ascribe to several confounding factors such as
• TV viewing provides opportunities for snacking & food eaten in front of the TV is generally high in calories and low in nutrients (Thorp. 2011)
• TV commercials reinforce the unhealthy dietary habits
• Sleeping also burns less energy than regular waking activities, but reducing sleep time usually increases, not decreases weight gain, due to
• increased consumption of high energy, specifically high sugar foods to compensate for the lack of energy (cf. "Fat Content Per Energy Drink 0g, Body Fat Gain Per Energy Drink 18g!")
• decreased energy expenditure through fatigue-related reductions in physical activity and lower basal metabolic rates

"Pah, that's guesswork!" If that's what you think, when you hear about Saunders' & Chaput's hypothesis, you may want to take a look at another recently published study by Calamaro et al. who report that (1) children who consume caffeinated beverages (not even directly before bed) get 15min less sleep and (2) children with 3 technology items in their room got 45min less sleep (Calamaro. 2012). Significant correlations with BMI were yet present for the intake of caffeinated softdrinks, only!

In other words, although both are characterized by physical inactivity TV watching and sleep "exert opposing influences on energy balance and body weight" - an observation which leads the authors to humorously conclude that

Reducing TV viewing and/or getting adequate sleep require little in the way of resources or expertise, and may therefore be more sustainable than more traditional interventions focused on diet and exercise. If having a good night's sleep truly is better for your weight than watching TV, this would be a lifestyle modification which may be substantially easier to implement than adopting a new diet or exercise routine. This change of focus is certainly worth consideration, right after a short nap. (Saunders. 2012)

Assuming that you did not already take your nap or have exceeded your daily combined TV + Internet screen time, you will probably also be interested to hear that another recently published paper by Caroline Fitzgerald et al. reports that "a child who watches 18 hours of television (per week) at 4.5 years of age will by the age of 10 have an extra 7.6 milllimetres of waist because of his or her habits" (Fitzgerald. 2012). Does not sound much, but you know how things go, proper with 5, chubby with 10, obese with 20 and dead before 40... you don't really think your kid could have invested those 3.5 years(!) of he would have been sitting in front of his television screen into more productive, more healthy and more sustainable hobbies, do you?

Implications: The best way to avoid TV & sleep related weight gain and / or propel your weight loss is to start planning your screen time instead of simply planting your (fat?) ass on the sofa, whenever you have a minute to spare.

1. Go to one of the free online TV magazines and create a schedule pick only those shows you really feel you have to see and try to reduce your screen time by 20min every week. 
2. Never eat in front of the television spontaneously, if you have a planned, healthy meal, make sure you don't have more on your plate than you plan to eat(!), and don't have anyone tell you cannot enjoy the SuperBowl or the latest Hollywood blockbuster without chips, popcorn and a soft-drink. 
3. Get yourself a time-limit switch program it so that it the TV has no power, after 9PM, which is when you will be grabbing your new blindfolds and earplugs and head to bed, weeknights.

If you stick to those simple rules and use your iPhone or iPad only for your obligatory daily class at the SuppVersity you will not just improve your physique, you will also live a couple of extra years! After all, scientists from the University of Queensland calculated in 2011 that "every single hour of TV [i.e. one hour per day] viewed after the age of 25 reduces the viewer's life expectancy by 21.8 min" (Veermann. 2011)!

Mustard, Horseradish, Black pepper & Ginger - Useless Thermogenics

Image 3: Although it's more effective than horseradish, black pepper or ginger It would probably take more hot mustard than your tummy can handle to get ripped to the shreds.

If you are already not watching TV and getting enough sleep (see above) and still don't look as lean and jacked as you would like to, a group of Danish researchers has some suggestions on which supplements you should not waste any money on (Gregersen. 2012): Mustard, horseradish, black pepper and ginger! While the latter two did not exert any measurable effects on either diet induced thermogenesis or energy intake (obviously the intention was to reduce the latter), when they were administered at oral dosages of 1.3 g and 20g, respectively, the addition of 8.3g of horseradish or 21g of mustard to standardized brunch meal did at least have some effects on the 22 young (age 25y), normal-weight (BMI 21.8kg/m²) men in the randomized cross-over study by Gregersen et al.:

• 8.5g of horseradish decreased the postprandial heart rate and increased the blood pressure to a statistically significantdegree, while
• 20g of mustard increased the thermogenic response to the testmeal by 14%

Now, while the former sounds dangerous and the latter as if "Mustard-o-burn (TM)" was just around the corner, none of these statistically significant effects were physiologically relevant. After all, it would take roughly 1 years to shed an additional lbs of body weight from the +14% increased diet induced thermogenesis from mustard (even if that lasted 24/7), because +14% added to 13kcal/h are only 1.82kcal/h. Even if we assume that you eat 5 meals a day this would hardly amount to more than 10kcal/day or 1.5min of light jogging... but hey, we all know how futile calculations like these are - no? Well, then you should check out my "Busting the 3,500kcal Equals 1 Lbs of Fat Loss" post!

Implications: If anything the use of tons of spices will render your food so unpalatable that you will simply eat less. Aside from those anorexic effects the use of copious amounts of spices, as they would obviously be necessary to illicit significant thermogenic effects, will probably produce more negative than positive (side) effects and could thus even contradict the established beneficial effects of having a "normal" (=tasty) amount of spices in your diet (Kochhar. 2008).

And in case you still insist on "spicing" up your fat loss regimen beyond the reasonable level your taste buds (and gastrointestinal mucosa; cf. Jensen-Jarolim. 1998) can handle, the topical route as in "Topical Fat Loss: Capsaicin Cream Blunts Weight Gain in Rodent Model and Increases Leptin, Adiponectin, Lipolysis and Fatty Acid Oxidation in Visceral Fat Depots" could in fact be worth a try.

Viscous Weight Loss Alternatives: Psyllium Seed Gum and PGX^(R)

Now it would be unfair if I left you with "nothing" else but the advice to switch of the TV, get more sleep and refrain from spicy food (unless you eat it simply 'cause you like it). Luckily, there are yet two additional hitherto unpublished FirstView Articles in the queue of the British Journal of Nutrition which do suggest that dietary fibre, viscous dietary fiber, to be precise could make a valuable addition to your no-TV + lots of sleep regimen.

Figure 1: GI (measured according to ISO 26 642-2010) with and without addition of PGX viscous fiber supplement in 2x250ml water to the 50g carbohydrate meal (Brand-Miller. 2012)

When you ingest it prior to bread, rice, boiled potatoes, french fries cornflakes or instant outs (GI range 65-84) it, a novel dietary fiber supplement that goes by the ingenious brandname PolyGlycopleX
(PGX) leads to dose dependent reduction in the GI of a subsequent carbohydrate meals of 16.5% and 31% for the 2.5g and 5g dose of PGX, respectively - or, physiologically speaking, a 15-33% reduction in blood glucose elevations in the 120min after the consumption of the test meals.

Now that certainly does not sound earth-shattering, but a previous human study has already established that the reduced postprandial glycemia goes hand in hand with increases in PYY expression (Reimer. 2010) and reduced food intake on subsequent meals (Vuskan. 2009). Moreover, earlier rodent studies have established that PGX can improve glycaemic control and protein glycation (Grover. 2011), most probably due to the far-reaching metabolic effects of increased glucagon-like peptide 1 (GLP-1; read more about this incretin hormone in  "Eat More, Burn More and Lose Fat Like on Crack with GLP-1!?") levels.

Will eating 25g of psyllium /day reprogram your genes to burn not store fat?

What's even better though is that the last FirstView Article in today's fat SuppVersity news clearly suggests that you don't have to buy InoviBiologic's patented purified polysaccharide supplement that is extracted from konjac, sodium alginate and xanthan gum by the means of a proprietary process the company calls EnviroSimplex^®, to benefit from those health and weight loss effects. If the results Togawa et al. observed in their C57BL/6J who were kept on high-fat (40%) diets with or without the addition of 5% psyllium (as psyllium seed gum, PG-200) for 10 weeks translate to humans, the only reason I could see to spend the extra money would be the whopping dose of ~25g/day (0.32g/kg body weight; learn how to calculate Human Equivalent Doses).

Figure 2: Visceral fat mass and parameters of glucose and lipid metabolism after 10 weeks on the low fat control vs. the supplemented or unsupplemented high fat diet (data expressed relative to control; Togawa. 2012)

If the results do translate to human beings, you can stomach this amount of fiber without negative side effects and are still able to consume adequate amounts of "real" food, though, the data in figure 2 will probably have you hack "psyllium fibre buys" into google in no time. After all, the profound upregulation of genes involved in fatty acid oxidation and lipid transport Naoyuki Togawa and his colleagues from the Yokohama Corporate Research Laboratories and the Laboratory of Food and Nutrition, Graduate School of Horticulture at the Chiba University in Chiba, Japan, detected in fat and skeletal muscle tissue of their lab animals were not just statistically, but also physiologically significant. So significant, in fact, that the mice who consumed ~148g of the psyllium enhanced high-fat diet before they were euthanized at the end of the 10-week study period did not just gain 10% less body weight than their unsupplemented peers, they also had lower cholesterol, lower triglyceride and above all lower visceral body fat masses than the "control" animals on the supposedly healthy low-fat diet.

Image 4: Fiber or no fiber - those abs want to be worked out.

Implications: While ginger, pepper, horseradish and cool are still "hot", dietary fiber is (pun intended) somewhat poopooed upon by many of the "everything mainstream must be wrong" nutrition gurus and fitness enthusiasts. From a scientific perspective, however, it does make more sense to spice your meals up with fiber than with spices that burn away your intestinal mucosa and turn your gut into an open barndoor (cf. Jensen-Jarolim. 1998) for all sorts of things you should better leave where a huge amount of the fiber will go - in the toilet bowl.

That being said, we need further studies to elucidate if and at which dosages similar epigenetic changes as they were observed by Togawa et al. occur in human beings before making any definite recommendations. For the time being, I will simply repeat my advice to

1. fill yourself up with fiber-laden veggies and consume a balanced (!) amount of saturated, mono- and polyunsaturated fats from whole foods,
2. aim for a mild energy deficit (~20%) and a reasonable carbohydrate intake of roughly 700-900g per week; either by low-carbing + refeeding (e.g. 6x 50-75g + 1x 250-400) or a constantly low intake of preferably low(er) GI carbs (don't count carbs from green veggies and co!)
3. eat at least 20-25g of a complete protein (count only meats, fish, eggs and dairy) with every meal and supplement with protein powders / bars, whenever you have no whole food source with 10+g of EAAs in it at hand
4. follow a sound workout regimen (e.g the "Fat Loss Support Routine" from the Step By Step Guide), don't do hours of "cardio" in the non-existent fat burning zone and cherish the fat-burning effects of glycogen depleting strength and HIIT workouts without overtaxing your central nervous system

If you follow 1-4 on 330 of 365 days of the next year you even the ugliest blubber that may still be covering your abs should disappear - and guess what!? All that without patented or non-patented viscous fiber supplements ;-)

References:

• Brand-Miller JC, Atkinson FS, Gahler RJ, Kacinik V, Lyon MR, Wood S. Effects of added PGX®, a novel functional fibre, on the glycaemic index of starchy foods. British Journal of Nutrition, 2012; 108, pp 245-248
• Fitzpatrick C, Pagani LS, Barnett TA. Early childhood television viewing predicts explosive leg strength and waist circumference by middle childhood. Int J Behav Nutr Phys Act. 2012 Jul 16;9(1):87.
• Gregersen NT, Belza A, Jensen MG, Ritz C, Bitz C, Hels O, Frandsen E, Mela DJ, Astrup A. Acute effects of mustard, horseradish, black pepper and ginger on energy expenditure, appetite, ad libitum energy intake and energy balance in human subjects. British Journal of Nutrition, Available on CJO
• Grover GJ, Koetzner L, Wicks J, Gahler RJ, Lyon MR, Reimer RA, Wood S. Effects of the soluble fiber complex PolyGlycopleX® (PGX®) on glycemic control, insulin secretion, and GLP-1 levels in Zucker diabetic rats. Life Sci. 2011 Feb 28;88(9-10):392-9.
• Jensen-Jarolim E, Gajdzik L, Haberl I, Kraft D, Scheiner O, Graf J. Hot spices influence permeability of human intestinal epithelial monolayers. J Nutr. 1998 Mar;128(3):577-81.
• Kochhar KP. Dietary spices in health and diseases (II). Indian J Physiol Pharmacol. 2008 Oct-Dec;52(4):327-54.
• Marshall SJ, Biddle SJ, Gorely T, Cameron N, Murdey I. Relationships between media use, body fatness and physical activity in children and youth: a meta-analysis. Int J Obes Relat Metab Disord. 2004
• Reimer RA, Pelletier X, Carabin IG, Lyon M, Gahler R, Parnell JA, Wood S. Increased plasma PYY levels following supplementation with the functional fiber PolyGlycopleX in healthy adults. Eur J Clin Nutr. 2010 Oct;64(10):1186-91.
• Saunders TJ, Chaput JP. Is obesity prevention as simple as turning off the television and having a nap? Br J Nutr. 2012 Jun 14:1-2.
• Thorp AA, Owen N, Neuhaus M, Dunstan DW. Sedentary behaviors and subsequent health outcomes in adults a systematic review of longitudinal studies, 1996-2011. Am J Prev Med. 2011 Aug;41(2):207-15.
• Veerman JL, Healy GN, Cobiac LJ, Vos T, Winkler EA, Owen N, Dunstan DW. Television viewing time and reduced life expectancy: a life table analysis. Br J Sports Med. 2011 Aug 15.
• Vuksan V, Panahi S, Lyon M, Rogovik AL, Jenkins AL, Leiter LA. Viscosity of fiber preloads affects food intake in adolescents. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):498-503.

Diet + Exercise + Kitchen Sink Fat Burner Promote Weight Loss in Two-Months Study on Overweight Adults. Additional 2kg Fat Loss - Are Ozzy's Raspberries to "Blame"?

No this is not Liza Oz after taking Mehmet's beloved RK supplements ;-)

The Journal of the International Society of Sports Nutrition is one of the few "major" scientific journals, where scientists can actually publish those studies, "healthy freaks" (no, not "health freaks", but people who are still healthy and thus freaks ;-) like us are interested in. Studies such as the one Hector L Lopez and his colleagues conducted; studies that investigate the effects and effectiveness of dietary supplements such as Prograde Metabolism (TM), a proprietary blend "fat burner" containing your usual blend of B-vitamins, chromium, caffeine, citrus aurantium, ginger, garlic, capsaicin, l-theanine and piper nigrum... ah, and of course as the #1 ingredient on the label Raspberry-K(TM).

Too much blubber? "Grab the rasp and berry it off!" Ah, well...

Hold on, another of those "proprietary blend studies"? Can we even trust the data? Allegedly, the authors Lopez and Ziegenfuss have worked for raw material suppliers, nutraceutical and dietary supplement companies in the past and openly declare that in the paper at hand, but guess how many of the authors of studies on medications have worked for the pharma industry and were / are still involved in the development of the respective drugs? If we really started to question the results of each and every study on the basis of the mere assumption that it was a product pimp job, we would probably have to discard 95% of the currently available research. Just remember: In 99.9% of the cases it's the conclusions and interpretations that can be problematic, and not the data, itself.

If we take a closer look at the ingredient profile of "METABO", we notice that Dr. Oz's beloved raspberry ketones are right on the top of the ingredient list of the 1,000mg proprietary blend single 2-cap serving of the product contains. With caffeine and a 10% synephrine extract from citrus aurantium, which are usually dosed at around 200mg and 100-150mg (to deliver 10-15mg of synephrine as part of the Advantra-Z formula; cf. Seifert. 2006), respectivley, being the #2 and #3 on that list, we can safely assume that the maximal amount of Razberi K in a single serving of the supplement is 600mg.... that's actually quite nice, because that's so little that we do not even have to use a calculator to know that this is hilariously underdosed compared to what the rodents in the heavily cited anti-obesity (I repeat: anti-obesity, not weight loss) trials by Morimoto et al. reaceived as part of their regular chow (1-2% of the whole chow was nothing but pure raspberry ketones; cf. Morimoto. 2005)

Figure 1: Body weight, fat mass, lean mass and waist circumference after 4 and 8 weeks of dieting + exercise + supplement / placebo (Lopez. 2013)

In the end, that's yet good news. Firstly, we can safely assume that this is way too little to induce any of the anti-androgenic effects Ogawa et al. observed in their 2010 in-vitro study (Ogawa. 2010).

And secondly, the low dose of raspberry ketones left some room for the other ingredients, of which you can see in the data I plotted in figure 1 that they were very well capable of promoting the weight loss success of the 70 "obese but otherwise healthy subjects" in the Lopez study.

Effects? Yes! Effects due to raspberries? Questionable.

There is no debating that the combination of multiple "thermogenic", appetite suppressing and anti-oxidant / insulin sensitizing weight loss adjuvants in METABO did promote the loss of fat mass over what the diet + exercise progra alone could achieve. The former, i.e. the diet, had by the way been designed by a "state-licensed, registered dietitian" to provide three meals and two snacks per day (the latter are obviously useless; cf. Whybrow. 2007) and a total energy intake that would deliver approximately 500 kilocalories per day less from a 40% carbohydrate, 30% protein and 30% fat diet than the subjects actually "required" (dietary requirements that were calculated with the Mifflin-St. Jeor equation and an activity factor of 1.2; learn more).

This dietary regimen was accompanied by an 8-week workout regimen of which I would usually write that it was "surprisingly sound". In view of the fact that the study, appeared in the Journal of the International Society of Sports Nutrition and not Obesity or JAMA it is yet only "sound" and not surprising that the subjects had to work out three times per week for 60 minutes of which not a single minute was wasted on steady state cardio in the non-existing fat-burning zone. Instead, they performed a...

It sure sounds ufair, but women have a harder time shedding fat. Against that background it's all the more important for the average "I don't eat meat" lady to get her share of fat burning protein - after all a reasonable amount of protein speed fat loss in both sexes (learn more).

• 10 minute warm-up (i.e. walking, light jogging, or biking),

• 30 minutes of circuit training (upper and lower body each session, which consisted of a combination of 
• mountain climbers, squat thrusts, 
• jumping jacks, squat kickouts, walking lunges, 
• push-ups, dips, 
• resistance band elbow flexion, extension and 
• shoulder presses, 

• additional 10 minutes abdominals/core work, and 

• a subsequent 10 minutes cool down/stretching

Against that background it is however "surprising" that the fat loss in the placebo group was pretty pathetic (~115g per week), after all the participants had more than enough (32.6kg) of fat to lose.

Dieting alone "fails", the supplement "works" - what's more surprising

Now, the first thing that comes to mind, whenever a diet fails, is a bogey called "non-adherence". With the supervised and controlled exercise protocol and the official data on the energy and nutrient intake not showing significant inter-group differences, it is however difficult to pin the success / failure of the groups exclusively on non-compliance. The consistently higher food cravings in the placebo group do yet put another questionmark behing behind the accuracy of the already notoriously unreliable self-reported food intakes.

Figure 2: Cravings for energy, sweets, fatty fast food, fat in general, carbs and healthy foods in the subjects in the placebo and MTEABO group (Lopez. 2013)

According to the latter, the subjects in the placebo group consumed almost the same amount of energy, which does not appear totally unlikely in view of the fact that the cravings in the placebo group were so real that they even started to crave "healthy foods" (figure 2, orange) - a tell-tale sign that diters are seriously hungry and don't just want to satisfy their food-cravings.

Significant fat loss without significant health benefits? Surprisingly, the measured markers of glucose and lipid metabolism, namely total cholesterol, HDL, LDL, cholesterol/HDL ratio and TAG did not show significant improvements in any of the groups. There was however "a strong trend (p < 0.07) for TAG concentrations to decrease more in the  METABO group (-15.9%) compared to the placebo group (-2.6%)" (Lopez. 2013) and a significant decrease in leptin that was likewise observed exclusively in the supplement group.

Since hunger is associated with increased ghrelin levels and those have only recently been confirmed as a significant correlate and potential cause for weight loss interventions to fail (Liu. 2013), it may in the end not even matter, whether the subjects gave in to their cravings and "cheated" or whether they starved and their bodies simply stopped shedding body fat - the net result would have been identical in both conditions and if a single agent or the synergy of all of the ingredients in METABO was responsible for the satiety effect the weight loss advantage would in fact have been brought by the dietary supplement.

---

If you clicked on the links that redirect you to the overviews of SuppVersity articles on capsaicin, piperine, citrus aurantium etc. you will have realized that many of them were also on my list of PPAR-gamma antagonists (learn more).

Bottom line: The most likely explanation for the beneficial effects Lopez et al. observed as a result of 2,000mg of the proprietary blend are thus the...

1. fat loss benefits (I initially wanted to write "effects", but that's probably an exaggeration) of ingredients such as caffeine (Greenway. 2001), capsaicin (Snitkner. 2009), citrus aurantium (Bent. 2004; Stohs. 2012), ginger (Mahmoud. 2013), piperine, and / or 
2. satiety effects of caffeine (Westerterp-Plantenga. 2005a), capsaicin (Westerterp-Plantenga. 2005b), ginger (Mansour. 2012), ...

... I guess you see the picture that's emerging here. It is, as the scientists point out, "the combination of ingredients with potentially complementary and interactive mechanisms of action" (Lopez. 2013) which does the trick.

Against that background it is pretty useless to single out any of the ingredients, but if we wanted to do just that, it would certainly be the raspberry ketones which are the least-proven weight-loss adjuvant in Prograde Metabolism - an ingredient celebrated as the goto fat burner by the uneducated mainstream and an ingredient without any scientific backup from human studies. So, if I had to answer the gonzo rhetoric question in the title of this article in a binary = yes/no fashion, the most likely answer would be "no!" ;-)

References:

• Bent S, Padula A, Neuhaus J. Safety and efficacy of citrus aurantium for weight loss. Am J Cardiol. 2004 Nov 15;94(10):1359-61.
• Greenway FL. The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Obes Rev. 2001 Aug;2(3):199-211.
• Ogawa Y, Akamatsu M, Hotta Y, Hosoda A, Tamura H. Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2111-4.
• Lopez HL, Ziegenfuss TN, Hofheins JE, Habowski SM, Arent SM, Weir JP, Ferrando AA. Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women. Journal of the International Society of Sports Nutrition. 2013; 10(22).
• Mahmoud RH, Elnour WA. Comparative evaluation of the efficacy of ginger and orlistat on obesity management, pancreatic lipase and liver peroxisomal catalase enzyme in male albino rats. Eur Rev Med Pharmacol Sci. 2013 Jan;17(1):75-83. 
• Mansour MS, Ni YM, Roberts AL, Kelleman M, Roychoudhury A, St-Onge MP. Ginger consumption enhances the thermic effect of food and promotes feelings of satiety without affecting metabolic and hormonal parameters in overweight men: a pilot study. Metabolism. 2012 Oct;61(10):1347-52.
• Morimoto C, Satoh Y, Hara M, Inoue S, Tsujita T, Okuda H. Anti-obese action of raspberry ketone. Life Sci. 2005 May 27;77(2):194-204.
• Snitker S, Fujishima Y, Shen H, Ott S, Pi-Sunyer X, Furuhata Y, Sato H, Takahashi M. Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications. Am J Clin Nutr. 2009 Jan;89(1):45-50. 
• Stohs SJ, Preuss HG, Shara M. A review of the human clinical studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine. Int J Med Sci. 2012;9(7):527-38. Epub 2012 Aug 29.
• Westerterp-Plantenga MS, Lejeune MP, Kovacs EM. Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obes Res. 2005a Jul;13(7):1195-204.
• Westerterp-Plantenga MS, Smeets A, Lejeune MP. Sensory and gastrointestinal satiety effects of capsaicin on food intake. Int J Obes (Lond). 2005b Jun;29(6):682-8.
• Whybrow S, Mayer C, Kirk TR, Mazlan N, Stubbs RJ. Effects of two weeks' mandatory snack consumption on energy intake and energy balance. Obesity (Silver Spring). 2007 Mar;15(3):673-85.

Fighting to Stay Lean? These 20+ Anti-Obesity Agents Have the Potential to Inhibit Fat Gain Right at the Cellular Level

No, none of the 20 agents in the list below is going to do the work for you, but they could help you "conserve" the results, keep you lean on a bulk and/or avoid the hazardous Yoyo effect when you go off a die.

It's actually normal that the introduction is the last part of an article I write. What's special about today's SuppVersity article is thus not that I write the introduction at the end, but that I did not really know what I would be writing here, when I set out to compile the unsorted (but not chaotic) list of potential anti-obesity agents below. All of them act by pathway(s) you as a SuppVersity reader will have read about before, most prominently AMPK, and the peroxisome proliferator receptors (PPARs), of which the blockade of the obesogenic PPAR-gamma pathway, which is the main working principle of CLA turned out to be the go-to explanation for the ability of these agents to block both the differentiation of adipocytes and the storage of triglycerides in existing fat cells.

20 more or less proven anti-obesity agents for the weekend

As you are about to see, the list, which was never intended to be complete, got pretty and I guess I could add a couple of additional items, if I spent more time digging. In order not to steal your and waste more of my precious time on this sunny (finally!) Sunday, I did yet decide to call it a day, when I hit the 20-items mark. Now it's up to you to invest some of your sunny Sunday time, to read up on the details. 

• On a side note: The "holy" vitamin D does the exact opposite, if you incubate preadipocytes with 25(OH)D(3) this will lead to a significant increase in the active 1,25(OH)(2)D(3) and enhanced adipogenesis in primary mouse. Reason enough for a group of Thai researchers to conclcude that "vitamin D status may [actually] regulate human adipose tissue growth and remodeling." (Nimitphong . 2012)
  Vitamin A - Retinoic acid upregulates the expression of the adipogenesis inhibitors Pref-1, Sox9, and Kruppel-like factor 2 (KLF2) to "suppress adipogenesis in vivo and that the activity significantly contributes to the ability of the hormone to counteract diet-induced obesity." (Berry. 2012) Previous studies have also shown that all-trans-retionic acid directly increases the activity of PPARbeta/delta and so that Berry & Noy conclude "RA may be a uniquely efficacious agent in the therapy and prevention of the metabolic syndrome." (Berry. 2009) Similar results have been reported and conclusions have been drawn by Brun et al. and Sagara et al. (Brun. 2012; Sagara. 2013). Finally, Hisada et al report that - just like testosterone (learn more) - retinoic acid ensures that mesenchymal stem cells (MSCs) become osteoblasts (bone precursor cells), not fat cells (Hisada. 2013).

• Bromocriptine - If you do know it at all, then probably for it's ability to decrease the "milk hormone" prolaction. If you take a look at the broad spectrum of physiological effects of prolactin, the effect it has on the mammalian mammary gland is really negligible. A recent study from the Department of Biotechnology at the Daegu University in The Republic of Korea does now suggest that the inhibition of adipogenesis (formation of new fat cells) and lipogenesis (storage of lipids in existing fat cells) via decreased expressions of the adipogenic activators Pparα, Pparγ, and Cebpα, as well as major lipogenic target genes, including Me1, Acc1, 6Pgd, Fasn, and Prkaa1 is one of these "auxiliary functions" (Mukherjee. 2013)

• 

  EC also boosts erectile performance and testosterone (learn more)

  Ecklonia cava (EC) - or rather the dioxinodehydroeckol (DHE) molecules that are contained in this type of brown seaweed "exert[s] its anti-adipogenic effect on adipocyte differentiation through the activation and modulation of the AMPK signaling pathway" (Kim. 2010a). As a SuppVersity reader, you will be aware that this effect has been confirmed in in-vivo studies, later on (learn more).
  
  What's probably Interestingly DHE is not the only anti-adipogenic agent in brown sea algae, Fucoidan, a sulfated polysaccharide from brown seaweeds has likewise been reported to affect the development of adipocytes. In 2010, Kim et al. were able to show that it targets the MAPK kinase pathway by inhibiting the the expression of both early CCAAT-enhancer-binding proteins alpha (C/EBPalpha) and peroxisome proliferator-activated receptors gamma (PPARgamma), as well as the late activating protein 2 (aP2) adipogenic transcription factors (Kim. 2010b).

• Curcumin - While you my get the impression there was nothing curcumin cannot do (learn more), I am not whether the anti-PPAR gamma effects of curcumin are a result of it's anti-inflammatory effects or not... be that as it may, Lee et al. have demonstrated in 2009 already that the stimulatory effect curcumin exerts on the AMPK expression of adipocytes results in a down-regulation of PPAR-gamma in 3T3-L1 adipocytes (Lee. 2009).

• Resveratrol - Similar popularity, similar "cures it all" status and similar effects on AMPK and downstream PPAR-gamma expression in 3T3-L1 adipocytes... actually I would not need another bulletin point for resveratrol which acts by the exact same pathway(s) s curcumin to inhibit fat cell differentiation (Chen. 2011)

• 

  Creatine RT by Athletic Edge Nutrition; contains a cousin of ASL and is supposed to be another "super creatine" -  True or False? The 2011 SuppVersity article has the answer (read it!).

  Artemisia sacrorum Ledeb. (ASL) - Extracts from the small shrub have been used in Oriental Medicine for centuries, in 2011 Yuan et al. were able to show that ASL "down-regulate[s] the adipogenesis-related gene expression of the sterol regulatory element-binding protein 1c (SREBP1c) and its target genes, such as fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) and glycerol-3-phosphate acyltransferase (GPAT) in a concentration-dependent manner" (Yuan. 2011) The effects are meediated by a reduced expression of the peroxisome proliferator-activated receptor γ (PPARγ) and of the CCAAT/enhancer binding protein-α (C/EBPα), both of which are key transcription factors in adipogenesis.
  
  With the concomitant reduction in adipocyte fatty acid binding protein (aP2) gene expression, ASL is another potential anti-obesity agent of which Yuan et al. propose that it works its  anti-adipogenic magic via AMPK activation. In view of the fact that the same is true for the fat accumulation in human liver cells, it could serve a viable tool "in the prevention of serious diseases such as fatty liver and type-2 diabetic mellitus" (Yuan. 2010). Related increases in fatty acid oxidation have been observed in a rodent study by Hong later in 2009 with another variety of Aertemisia, namely Artemesia Capillaris (Hong. 2010). The human equivalent dosage in this trial wast 8mg/kg of the ethyl acetate fraction of the shrub.

• Phosphorylated glucosamine - While you will probably remember that large doses of regular glucosamine have been associated with insulin resistance (see previous installment of "True Or False"), it's phosphorylated variety glucosamine-6-phosphat (PGlc), Kong et al. synthesized using methanesulfonic acid, phosphorus pentoxide (P(2)O(5)), NH(2)NH(2) and DMF "significantly reduced lipid accumulation during adipocyte differentiation and induced down-regulation of peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein 1 and CCAAT/enhancer binding protein-alpha in a dose-dependent manner." (Kong. 2010)
  

  

  Phosphorylated glucosamine works (like most of the anti-obesity agents, including the well-known conjugated linoleic acid by reducing the expression of PPAR-gamma (left). It's dose-dependent effects are yet not restricted to the peroxisome proliferator receptor, but affect the pro-adipogenic genes C/EBP-alpha and SREBP1, as well (right; Kong. 2010)

  What's also worth mentioning is that the in-vitro study from the Marine Bioprocess Research Center at the Pukyong National University in South Korea also revealed that PGcl also hampered the maturation of pre-adipocytes by down-regulating adipocyte-specific gene promoters such as adipocyte fatty acid binding protein, fatty acid synthase, lipoprotein lipase and leptin. In conjunction "[t]hese results suggest that the inhibitory effect of PGlc on adipocyte differentiation might be mediated through the down-regulation of adipogenic transcription factors, such as peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein 1 and CCAAT/enhancer binding protein-alpha, which are related to the downstream adipocyte-specific gene promoters" (Kong. 2010) 

• 

  Add. reads: "Temporary +100kcal/Day Cold Thermogenesis Response W/ Exotic Ginger Extract" (more) "250-1000mg of Freeze-Dried Ginger Reduce Visceral Fat Even When Rodents Are Fed an Obesogenic High Fat Diet" (more).

  6-gingerol (6G) - The active ingredient in ginger has just been shown to block the obesity effects of the anti-diabetes med rosiglitazone (Tzeng. 2013). It does so by blocking the PPAR-gamma mediated effects of the "store the superfluous energy as body fat"-drug and was thus able to suppress the oil droplet accumulation and reduce the sizes of the droplets in the course rosiglitazone(RSG)-induced adipocyte differentiation in 3T3-L1 cells. Since it also blunted the increased levels of mRNA and protein in adipocyte-specific fatty acid binding protein 4 and fatty acid synthase induced by RGZ, it can be expected that 6G will not only inhibit the accrual of new, but also the (re-)filling of existing fat cells. 

• Piperine and capsaicin - In view of the fact that piperine is a "quasi-cousins" of 6-gingerol, it is actually not really surprising that it shares similar effects on the expression of PPAR-gamma (Park. 2012). It is therefore not surprising that the third member of this spicy triumvirate, i.e. capsaicin, shares the exact same PPAR-gamma reducing effects (Joo. 2010).

• Berberin - Contrary to many other items on the list, berberin's anti-PPAR-gamma effects are actually pretty well-known. There is ample evidence from in-vitro (Huang. 2006; Liu. 2009) and in-vivo (Lee. 2006) evidence that it blunts fat gain by increasing the catabolism of high energy intermediates, upregulating AMPK, modulating the expression of the GATA-2 and 3 gene and reducing the expression of (you guessed it) PPAR-gamma (Hu. 2009).

  

  Table 1: Berberine content of various commercially available supplements (Brown 2008)

  Berberine has also been shown to improve endothelial function in man (Wang. 2009) and promote the "longevity and mitochondrial health gene" SIRT1 in obesity ridden, insulin resistant skeletal muscle (Gomes. 2012).

• Ginsenosides (spec. ginsenoside Rg3) - Just like ginereol (see above) ginsenoside Rg3 has been shown to block the adipogenic effects of the anditiabetic drug rosiglitazone via an AMPK/PPAR-gamma dependent pathway (Hwang. 2009). It may be worth mentioning that at least the effect triglyceride storage was not dose-dependent. Once  a threshold amount of 40µM was reached, the adipocytes that were incubated with Rg3 did not "lose" any additional triglycerides, when the dosage was increased to 80µM.

• On a side note: Although promoted in the same health and longevity circles as CAPE, the hailed "telomerase lengthener" Astraglaus is a PPAR-gamma promoter and will thus "enhance the accumulation of lipid drops, and increase the terminal differentiation of preadipocytes" (Liu. 2007)
  Caffeic acid phenethyl ester (CAPE) - You've heard about the anti-inflammatory, muscle protective ability of this compound from bee propolis only recently (go back). In addition to being a potent anti-inflammatory, the natural phenolic compound that's also found in a variety of plants, has also been found to block the conversion of mouse fibroblasts into fat cells (Juman. 2010). As for most of the other agents the effects of CAPE appear to be mediated by a reduction inperoxisome proliferator-activated receptor (PPAR) gamma and CCAAT/enhancer-binding protein (C/EBPalpha) and concomittant reduction isn fatty acid synthetase and the expression of adipocyte-specific fatty acid binding protein (aP2). 

• Lysimachia foenum-graecum (LFE) - LFE is a Chinese herb and well-known anti-inflammatory from Oriental Medicine. The anti-obesity effect of L. foenum-graecum extract was first discovered by Seo et al., when they simply screened a whole host of potential natural agents for their anti-adipogenic effects. In 2011 the researchers found that "LFE blocked the differentiation of 3T3-L1 preadipocyte in a dose-dependent manner with an IC50 of 2.5 μg/ml". The underlying mechanism which has also been observed in an in-vivo rodent study with 100 mg/kg/day, are - how else could it be - mediated by the inhibition of PPARγ and C/EBPα expression.

  

  Effects of the administration of an lysimachia foenum-graecum ethanol extract on lipid and glucose metabolism and adipokine signalling in mice on an obesogenic diet (Seo. 2011)

  Moreover, LFE stimulated fatty acid oxidation in an AMPK-dependent manner, greatly improved serum levels of obesity-related biomarkers such as glucose, triglycerides, and adipocytokines leptin, adiponectin, and resistin and lead to an effective decrease in total body weight gain in mice who received 30, 100, and 300 mg/kg/day of an Lysimachia foenum-graecum ethanol extract (50:6; LFE) in addition to their obesogenic high fat diet (see figure above). The mice in the HFD + LFE group did simply have lower body weights, they also had a reduced amount of adipose tissues especially within the metabolically active and highly unhealthy abdominal subcutaneous, epididymal, and perirenal adipose tissue.

• 

  Photos of the lean (A and D), HFD-fed (B and E) and HFD-fed + SRLE supplemented (C and F) mice in the Thounaojam study (2011).

  Sida rhomboidea. Roxb leaf extract (SRLE) - SRLE does only sound like the stuff many supplement companies used after the ban of mua huang (natural source of ephedrine). It is however a different variety of Sida (Batyάlaka, Sida cordifolia)... well, at least it is from the same family which lacks the CNS stimulating activity of mua huang. With its ability to prevent high fat diet (HFD) induced visceral adiposity by down-regulation of PPARγ2 and leptin gene expression it could in fact work synergistically with ephedrine, though. After all the HED of the 24% w/w water extract Thounaojam et al. used to prevent the obesogenic effects of a hypercaloric high fat diet in their rodent study amounts to no more than ~40mg/kg and since SRLE has been shown to be non-toxic up to 3g/kg (in mice; HED ~240mg/kg) it would be interesting to see studies that probe whether it works in humans (Thounaojam. 2011).

• SH21B is an anti-obesity composition composed of seven herbs: Scutellaria baicalensis Georgi, Prunus armeniaca Maxim, Ephedra sinica Stapf, Acorus gramineus Soland, Typha orientalis Presl, Polygala tenuifolia Willd and Nelumbo nucifera Gaertner (active ingredients; see figure below) that has been used for the treatment of obesity in traditional medical clinics in Korea and has recently been shown to decrease the expression of major transcription factors of the adipogenesis pathway and result in the down-regulation of lipid metabolizing enzymes involved in the transport, uptake and synthesis of lipids - unfortunatedly, only in vitro (Lee. 2009)

  

  Effects of SH21B on fat droplet formation in 3T3-L1 cells (top) and size of adipocytes in adipose tissue. (bottom), as well as active ingredients in SH21B (based on Lee. 2009)

  As you can see in the stains from the adipose tissue of the above, the effects are clearly mediated by both an inhibition of the maturation of preadipocytes (top) and the inhibition of fat storage... now you tell me the world needs "new" anti-obesity agents!? I mean, it's quite obvious that the Koreans knew all along what keeps you lean ;-)

• Lactobacillus plantarum KY1032 cell extract - Before you begin to jubilee about the triumph march of probiotics, let me tell you this: I am not sure how on earth the remnants of a gut bacterium are supposed to reach your adipocyte tissue in a healthy individual without a leaky gut. Against that background I am not sure, whether it is even necessary to mention that Park et al. observed in 2011 that a cell exctract of the KY1032 strain of lactobacilli is another compound that can down-regulate the expression of peroxisome proliferator-activated receptor-γ2, CCAAT/enhancer binding protein-α, fatty acid synthase, and adipocyte-fatty acid binding protein and thus blunt fat gains in vitro... ah, now I wrote it down, so I'll just leave it here ;-) 

• Irvingia gabonensis seed extract - Likewise not a newcomer to the supplement the African / Southeast Asian tree, respectively an extract from its seeds has been shown to dose-dependently decrease the expression of PPAR-gamma in murine adipose cells in the petri dish in a 2008 study by scientists from  Faculty of Science, University of Yaoundé in Cameroon and the Wake Forest University School of Medicine in Winston-Salem, USA (Oben. 2008).

The in-vitro study shows, CAF may inhibit fat storage, but it does not "squeeze" the fat out of the cells (data based on Kim. 2012)

• Citrus aurantium falvenoids (CAF)- Despite the fact that most of you will probably have realized in N=1 experiments that citrus aurantium is a supplemental non-starter as a fatburner. It has (in-vitro) the ability to reduce the epxression of C/EBPβ and subsequently inhibit the activation of PPARγ and C/EBPα. So unless you have taken tons of pure CAF supplements during your last bulk, it is no wonder that you did not realize any effect from the fat burner you bought last summer. After all you are not storing any fat when you are dieting anyway... and I guess you have been dieting, when you took that product, right?
  
  Apropos dieting, the data in the figure on the right also shows that citrus aurantium, alone, won't help with that. After all it lacks the ability to increase LPL and thus the release of free fatty acids from the triglyceride stores in your fat stores.

• Silibinin (from milk thistle) - You will probably have heard that milk thistle can help replenish the antioxidative defenses of your liver and thus prevent all sorts of systemic toxicities (learn more). At least in-vitro silibinin (aka silybin), the major active ingredient in silymarin, can also prevent the accumulation of triglycerides in existing, as well as the formation / maturation of future adipocytes. From a mechanistic point of view, the effect is mediated by the usual suspects respectively their downregulation (CAAT/enhancer binding protein-alpha, fatty acid synthase, sterol response element binding protein 1c, adipocyte-specific lipid binding protein, peroxisome proliferator-activated receptor gamma and lipoprotein lipase; cf. Ka. 2009).

• Stem bromelain (SBM) - Just as so many of the previously mentioned agents, SBM, a specific member of the bromelain family you may know as "pineapple enzyme", is by no means a "new kid on the anti-fatloss block". Rather than that it has been used for centuries in traditional medicine as - guess what? - an anti-obesity agent. Now, I would never suggest that all TCM medicines work, but for stem bromelain it does at least seem as if the in-vitro studies, Dave et al. conducted about a year ago would support the notion that the ingestion of respective supplements can in fact exert beneficial effects on the accumulation of body fat (Dave. 2012).

  

  Illustration of the mechanism and selected downstream effects of stem bromelain (SBM) on fat cells in the petri dish (compiled based on data from Dave. 2012)

  At the molecular level, SBM targets the same adipogenesic genes as (almost all) of the previous agents. What's interesting though, is the fact that the scsientists also found that "SBM's ability to repress PPARγ expression seems to stem from its ability to inhibit Akt and augment the TNFα pathway." (Dave. 2012) In other words, it's the increase in "bad" TNF-alpha and the decrease in the purportedly muscle, but in fact simply "mass building" Akt-TSC2-mTORC1 pathway that entails the apoptosis (controlled cell death) of mature adipocytes and lipolysis.

With the stem bromelain this comprehensive, but by no means all-encompassing list of "proven" (mostly only in vitro) anti-adipogenic agents, has come full circle. After all, Dave et al. point out that their data would indicate that stem bromelain, together with all-trans retinoic-acid (atRA), which is a metabolite of vitamin A, the first item on our list "may be a potent modulator of obesity by repressing the PPARγ-regulated adipogenesis pathway at all stages and by augmenting TNFα-induced lipolysis and apoptosis in mature adipocytes." (Dave. 2010).

It's not just beyond the scope of this article, but - in the majority of the cases simply not known - whether or not the TNFα increase is an integral part of the anti-obesity effects of all of the aforementioned compounds. As far as the inhibition of PPAR-gamma is concerned things are different, though. With PPAR-gamma being the central "fat storage" switch, its deactivation and the entailing blockade of adipocyte differentiation, pre-adipocyte maturation and triglyceride storage is currently probably the most effective anti-obesity  mechanism we know. A mechanism that is way more fundamental than the diet-induced and stimulant / alpha/beta-agaonist (caffeine, ephedra, clenbuterol, yohimine) supported emptying of existing adipocyte triglyceride stores.

---

I know it's not popular, but in the case of vitamin D we already have evidence of it's obesity promoting effects (read more). It's straight forward experimental evidence, much contrary to the epidemiological guesswork on the basis of which people are popping vitamin D pills, these days.

Keep in mind: Most of the data is derived from in-vitro studies. Few compounds do have actual evidence from rodent studies and the number of substances that showed beneficial effects in human studies is even smaller.

Nevertheless, the above list harbors a number of compounds which could be of great interest for the lean physical culturist, for whom (at least physique-wise) stuff like vitamin D (note: the effects could be dose-dependent with benefits at low, and detrimental effects at high levels), astragalus and the rest of the healthy, but pro-adipogenic agents that can help obese individuals to stash away the tons of sugar and fat floating through their arteries are of little use.

Against that background I want to close this post with a warning, or I should say a reminder of the the fact that the effects of PPAR-gamma are physiologically important (e.g. prevention of lipotoxicity, Medina-Gomez. 2007) and go beyond "just making you fat" in how it would be worth striving to suppress it altogether is thus questionable (suggested read: CLA Destroys Body Fat). Since for all of the previously discussed agents that have in-vivo data to support their efficacy have postivite, not negative "side effects" (think of curcumin, gingerol, ginseng, etc.), it is yet unlikely that the use of reasonable amounts of one or a stack of many of them is going to harm you.

Just keep in mind: The goal should be to keep the PPAR-gamma activity in check, not to annihilate it. Consequently you should not and cannot expect to be able to "eat whatever you want and still stay lean" by supplementing with any of the agents above. On the other hand, they can hardly be even less useful than the vast majority of currently available arsenal of OTC "fat burners" ;-)

References:

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