Capsaicin or Plant Oxysterol 28-Homobrassinolide (28-HB) - Two Candidates for a Natty Test Booster that Works?

In am not sure if people got afraid that I rip their papers apart by pointing with a figure at the non-existent real-world significance of their revolutionary findings about the testosterone boosting effects of herb X from the deepest jungle in Y. What I do know however, is that for whatever reason studies like these have become rare as of late. I have still been able to pick up two of them, to do what Carl usually calls the SuppVersity Sniff Test on Capsaicin *achoo!* ... sorry! And the oxysterol 28-Homobrassinolide, which is present in miniscule amounts in Chinese cabbage, for example.

Capsaicin: The hotter, the better?

The first of the two studies we are going to tackle, today, comes right from the Department of Histology & Embryology at the Faculty of Veterinary Medicine of the University of Uludag in Turkey... and yes, the fact that it comes from the "Department of Histology & Embryology at the Faculty  of Veterinary Medicine" is in fact a first indicator that some of the initially mentioned "sniffing" and an appropriate amount of healthy skepticism are probably indicated. But let's not make any hasty judgments; after all, this study is not about herb X from the deepest jungle in Y, but a simple investigation into the effects of capsaicin on the morphology of rodent testes.

While capsaicin seems to be better used topical as a fat burner, here is a serious warning: Don't rub any capsaicin based fat burner onto your scrotum  in the false hope to turn it into a test booster ;-)

As a SuppVersity student you will be aware that capsaicin, the "hot stuff" in hot peppers, is quite a remarkable substance (e.g. "Capsaicin Cream for Topical Fat loss?").

Aside from topical (and at least in rodents) systemic effects on fat loss and the metabolic syndrome, there have also been several reports linking capsaicin to improvements in testicular morphology in diabetic and otherwise sick animals. Others report direct stimulative effects of capsaicin on testicular development and modulatory effects on the local and systemic expression of ghrelin, which has been shown to exert inhibitory effects of testosterone secretion in the testes (Tena-Sempere. 2005).

The latter, i.e. the connection between capsaicin, ghrelin and testicular morphology, development and function was obviously what Ilhan and Erdost must have had in mind, when they devised an experiment in the course of which they treated adolescent and adult mice with capsaicin (CAP) hoping to observe a change in the local expression ghrelin and subsequent changes in gonadal testosterone production.

"The animals were divided into two age groups: puberty and adult. Control groups for both age groups were fed with standard diet and experimental groups were fed with a diet containing 0.02% CAP. Testes were collected quickly after sacrifice. After dehydration, the specimens were embedded in paraffin and 5 μm sections were cut, and Crossman's triple staining and immunohistochemical staining for ghrelin were applied." (Ilhan. 2012)

The immunohistochemical stains of the testicular tissue the scientists conducted revealed that ghrelin was present in the testosterone producing Leydig and Sertoli cells of all animals. It was yet not expressed in any of the spermatogenic cells of either the adolescent or adult rodents.

The capsaicin treatment, on the other hand, reduced the immunoreaction in both groups - a clear sign of a local reduction in ghrelin.

Against that background and the previously cited findings by Tena-Sempera (as well as similar studies), it is not surprising that these local reductions in ghrelin went hand in hand with statistically significant increases in serum testosterone levels in both experimental groups, yet especially in adults (see figure 1).

Figure 1: Ghrelin and testosterone levels in response to control or capsaicin supplemented diet (base on Ilhan. 2012)

Since the increase in circulating testosterone took place in presence of an increase in systemic ghrelin levels, it is obvious that capsaicin does not block the release of ghrelin, but rather it's local effects - the exact mechanism, however has still to be elucidated.

The same goes for the beneficial effects of which is probably a "side effect" of the increase in testosterone, since any amelioration of the local inhibition of spermatogenesis in the the spermatogenic cells would require the presence of the "hunger hormone" in this cells. And, as mentioned above, the immunostaining did not reveal any significant amounts of ghrelin in the testes of both the treated and untreated animals.

Right, right, I don't bother about mechanisms as long as it works - So how much do I need?

Figure 2:  Capsaicin content (mg/100g) of different varieties of pepper fruits (Supalkova. 2007)

In view of all of these "may bes" and "could bes" the researchers conclusion that capsaicin "appears to enhance testicular cell proliferation and can affect the release of ghrelin and testosterone directly or indirectly" (Ilhan. 2012) is not very satisfying. If we do yet simply discard that we don't know why capsaicin boosts testosterone and further assume that the results will translate to human beings, capsaicin certainly sounds like an easy and cost-effective way to boost both testosterone and fertility, after all, the human equivalent of those 0.02% capsaicin amounts to no more than 200-300mg per day!

What may yet sound like a very reasonable for a good reason not achievable by eating peppers alone and could in fact burn right through your stomach lining. 

It stands out of question 200mg , that does not sound much, but if you take a closer look at the data in figure 2 you will be able to estimate that it will "taste" or rather "burn" like too much, already. After all, you would have to consume at least 100g of the ovaries  of the hottest variety of peppers the group of Czech researchers could find, when they did the analysis on which the data in figure 2 is based

Ovaries in a pepper? Are you serious? The "ovaries" are the parts inside a pepper on which the seeds are sitting... yeah, the stuffy you usually throw away, because you can't stand how "hot" it is (the illustration on the left a slightly modified version of figure 2 in Supalkova. 2007).

That said, milder varieties are obviously even less suitable, after all, you would need 1kg or even 10kg of the ovaries of those... Not exactly something anybody would expect to yield great health benefits, anyways, right?
So what about those  28-homobrassinolides, then? Those must be great, right?

I guess most normal people will immediately think of their touted cholesterol lowering effects, when they hear about "plant sterols". Not the average muscle-head, though for him (and mostly it's just "him" who falls for this idea) their structural resemblance to steroid hormones is what counts and their ability to totally mess up your own endocrine system is what is ignored as soon as the "Big T" is mentioned (click here to read all about the role of testosterone in building muscle). No wonder the "T-word" is also at the heart of the bro-scientific sales pitches the companies who are bottling respective products will have their reps propagate on the bulletin boards of the bodybuilding and fitness world. The scientific perspective is slightly different, though and the truth is probably, as so often, anywhere in the middle. And in this regards the recent study on possible pro-androgenic effects of 28-homobrassinolides (28-HB) that was founded on the rationale that 28-HB has been shown to ameliorate high blood glucose levels, while the latter have been shown to compromise testicular function and testosterone production is no exception.

Figure 3: Effect of 28-HB on lipid peroxidation, superoxide dismutase activity and catalase activity in rat testis (based on Premalata. 2012)

"Studies investigating the effects of 28-homobrassinolide (28-HB) on diabetic male rats indicated antihyperglycemic potency in this phytohormone. Since hyperglycemia was known to suppress testicular and ovarian steroidogenesis in the rat, it provided a basis for evaluating the biopotency of this oxysterol in rat testicular steroidogenesis. The present study was designed to elucidate the effects of 28-HB on testicular steroidogenesis in normal and streptozotocin (STZ)-induced diabetic rats." (Premalath. 2012)

Fortunately, though the researchers had a normal control group which received the same dose of 50µg of 28-HB in 50mL of 50% ethanol per day in their study. This gives the otherwise very artificial data at least some significance for the average, hopefully non-diabetic trainee as well.

A plant sterol that's obviously not for diabetics only

As the data in figure 3 shows all the expected beneficial effects on the streptozotocin-induced downregulation of superoxide dismutase (SOD) and catalase activity (CAT, as well as a reduction in reduced glutathione; not shown in figure 3) and partial reversal of the increase in lipid peroxidation were present in the diabetic rodents. And even in the healthy control, the ratio of anti- to pro-oxidant factors improved significicantly.

Figure 4: Changes in the levels of ABP and StAR protein, as well as testosterone in the testis of 28-homobrassinolide-treated rats (Premalatha. 2012)

The corresponding, or I should say "corollary" changes in steroidogenic acute regulatory protein (StAR), and androgen-binding protein (ABP) expression, but even more so increase in intratesticular (not(!) serum!) testosterone levels you see in figure 4 do however raise the question, whether what we are seeing here - specifically in the diabetic rodents - is actually (still) healthy or not (see figure 4).

To potent to be healthy?

In this regard it may also be worthwile to take into account what the scientists say about the enzymatic conversion of cholesterol to testosterone and how it may and does figure in this context:

"It is known that the synthesis of T in animal tissues is under the influence of 3b- and 17b-hydroxy steroid dehydrogenases. Increase in the activities of 3b- and 17b-HSD observed in the present study was suggestive of the active involvement of these enzymes in rat testicular steriodogenesis. Elevated 17b-HSD activity due to 28-HB was noted in relation to the elevated StAR content in normal rat testicular tissue. However, elevated 17b-HSD activity did not correlate with the StAR content of diabetic rat testis, suggestive of a disproportionate link between HSD activity and StAR content in the diabetic rat testis probably influenced by 28-HB. [...] It is reported that androgens reduced T biosynthesis in adult Leydig cells and in Leydig cell lines in an autoregulatory man-ner through receptor-mediated inhibition of StAR expression under normal physiological conditions. On the contrary, the increase in StAR protein level along with the relatively high level of T (figure 4) detected in the testis of male rats used in this study is due to the specific effect of the phytooxysterol 28-HB. Even though StAR and ABP were positively regulated by administered 28-HB, the observed increase in testicular
T content in diabetic rat is to be considered excessive." (Premalatha. 2012)

My gut feeling is that the attribute "excessive" Premalatha et al. use in their paper is absolutely spot on. And this goes despite the fact that similar yet way less pronounced effects effects have been observed in the absence of 28-HB administration simply as a result of streptozotocin administration in previous studies in both male and female rodents (Ho. 1991; Leaming 1982). These short term effects are probably a result of a skewed negative feedback at the level of the hypothalamus, where the increased circulating testosterone levels should actually lead to a corresponding decrease in gonadotropin-releasing hormone (GnRH). This regulatory mechanism, however does not work correctly in the early phase of STZ-induced diabetes, so that it take up to 120-140 days until a new "normal" and in this case supra-physological (= low testosterone) steady state is achieved.

Both, the questionable mechanism, as well as the "overshoot" in testicular testosterone levels and the absence of respective information on the levels of circulating testosterone -- what if it simply accumulated in the testis (remember the difference in systemic and local ghrelin in the capsaicin study!)? -- make the usefulness and even the safety of 28-HB as a test booster more than questionable.

Looking for more promising alternatives? Check out my previous post on "+180% Testosterone w/ Taurine"

Bottom line: If we go back to the original question whether one of the two supps could be the long-awaited breakthrough "natural" testosterone booster everyone expect me appears to be waiting for (what is "natural" about eating 100g+ of red pepper ovaries or using plant sterol extracts, by the way?), it appears as if none of the two would qualify.

Whether dihydrocapsiate, which has been pimped by Ajinomoto as a more potent, and safer fat burner than capsaicin and could be a more tolerable alternative to capsaicin, would even have the same effects on the testis is about as questionable as its value as a fat burner, of which Galgani and Ravussin found in 2010, already, that the <50kcal/day increase in energy expenditure in response to 1 month of supplementation with 9mg/day of the said capsiate "is in the range of day-to-day RMR variability" (Galgani. 2012) and therefore negligible.

Anyhow, in the unlikley case that some mad or sane scientists find non-negligible effects of supplementation with either dihydrocapsiate (or another more tolerable variety of capsaicin, such as a nano-encapsulated  for example) or 28-homobrassinolide in a future human trial, you know that the SuppVersity is the place to go to read about those results first, right?

References:

• Galgani JE, Ravussin E. Effect of dihydrocapsiate on resting metabolic rate in humans. Am J Clin Nutr. 2010 Nov;92(5):1089-93.
• Ho SM. Prostatic androgen receptor and plasma testosterone levels in streptozotocin-induced diabetic rats. J Steroid Biochem Mol Biol. 1991;38(1):67-72.
• Ilhan T, Erdost H. Effects of capsaicin on testis ghrelin expression in mice. Biotech Histochem. 2012 Sep 27.
• Kwon DY, Kim YS, Ryu SY, Cha MR, Yon GH, Yang HJ, Kim MJ, Kang S, Park S. Capsiate improves glucose metabolism by improving insulin sensitivity better than capsaicin in diabetic rats. J Nutr Biochem. 2012 Sep 28. pii: S0955-2863(12)00213-6.
• Leaming AB, Mathur RS, Levine JH. Increased plasma testoster-one in streptozotocin-diabetic female rats.Endocrinology.1982; 111(4):1329-1333.
• Premalatha R, Jubendradass R, Rani SJ, Srikumar K, Mathur PP. A Phytooxysterol, 28-Homobrassinolide Modulates Rat Testicular Steroidogenesis in Normal and Diabetic Rats. Reprod Sci. 2012 Sep 25.
• Supalkova V, Stavelikova H, Krizkova S, Adam V, Horna A, Havel L, Ryant P, Babula P, Kizek R. Study of Capsaicin Content in Various Parts of Pepper Fruit by Liquid Chromatography with Electrochemical Detection. Acta Chim. Slov. 2007, 54, 55–59.
• Tena-Sempere M. Ghrelin: novel regulator of gonadal function. J Endocrinol Invest. 2005;28(5 Suppl):26-9.

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.

Capsaicin - 2.56mg to Keep Your Metabolism Running on a Diet. Cold Thermogenesis - 5°C for 6kcal/h. Mobile Phones - 0.853 W/kg Pulsed EMR to Mess Up Neurotransmitters

You don't have to worry, the "guidelines" do not require you to perform either your 150 minutes of moderate cardio, or your 75 minutes of vigorous-intensity aerobic activity, and not even your two weekly full-body workouts in these shorts.

24% that's the SuppVersity Figure of the Week and it is actually not so low as I would have expected it to be, after all those 24% describe the ratio of US adults who meet the Physical Activity Guidelines for muscle-strengthening physical activity. Which guideline? Ah, you are the US guys and gals, so you should know that you are advised to

"perform muscle-strengthening activities that are moderate or high intensity and involve all major muscle groups on 2 or more days a week, because these activities provide additional health benefit" (2008 Physical Activity Guidelines for Americans)

Additional benefit? Well, it goes without saying that the 150 minutes of moderate aerobic training and the reduction of salt, as well as the use of healthy vegetable oils are the primary object for every 'true American'.

Not That Hot: Cold Thermogenesis

Figure 1: An avg. effect size of 6kcal/h, non-responders + "negative-responders"; it doesn't work for those past the 30y mark - how on earth is cold thermogenesis going to help us solve the obesity pandemic?

(Chen. 2013) In a single-blind, randomized crossover intervention 24 volunteers (14 men, 10 women) were exposed to a 5°C temperature reduction (from 24°C to 19°C). During that treatment they wre sitting in a whole-room indirect calorimeter to measure their energy expenditure and lay in a positron emission tomography (PET) scanner afterwards (results, see image to the right).

Now, based on previous SuppVersity articles on the matter, you'll know that it is not exactly easy to find people who actually harbor a "significant" (and in this case this means "any at all") amount of metabolically active brown adipose tissue to get the thermogenesis going.

And with 23cm³ and 35cm³ for the men and women participating in the study at hand, the amount of the "good fat" they were carrying around is still pretty stingy. No wonder ...

• there was no thermogenic response in the male participants, but a
• 10% increase in energy expenditure in the female participants

I already see your eyes glow in the cold, ladies, but you crow too soon - those 10% were 6kcal/h, I repeat in full words "six additional calories per hour". Or roughly as much energy as a single set of body weight squats would be burning .

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If you are looking to shed 18% fat in 21 days, increase your health and your physical appearance, turn up the heat during your workouts, clean up your diet and don't move into the fridge (learn more)!

Bottom line: Against the background that there were neither significant changes in the hormonal profile (thyroid, adrenal, etc.) and considering the fact that the effect declined with age and was hardly measurable for 5 and negative (=lower energy expenditure in the cold) for 4 subjects, I stick to previous assessment: cold thermogenesis as a means of "expending more energy to get rid", is about as stupid as the whole concept of expending more energy to lose fat and it certainly does not, as the scientists state "represent a novel environmental strategy in obesity treatment".

If you want a "environmental strategy in obesity treatment", ban all the junkfood, switch off the elevators, hand out bikes and increase the health insurance cost for everyone who refuses to get his or her ass off the couch on a regular bases. Zealous? Unrealistic? Yeah, it is - but not more unrealistic than the hilarious notion that cooling the overweight majority of the inhabitants of the Western Obesity Belt down by 5°C would solve the obesity problem.

Mobile phones mess with neurotransmitter levels

Andreassen et al. have already developed a "Facebook Addiction Scale" and found that Facebook junkies tend to be

neurotic and extraverted, but lack a reasonable amount of conscientiousness (Andreassen. 2012)

(Aboul Ezz. 2013) I am well aware that many of you don't want to hear this and will discard the results researchers from the Cairo University present in their latest paper in the European Review forMedical and Pharmacological Sciences as "just another worthless rodent study" and I freely admit, you may be right.

It is well possible that rodents are more susceptible to the pulsed electromagnetic radiation from mobile phones than humans are, but I gather you will have to agree that the chance that there are still residual effects in human beings is by no means zero... and based on my personal observations, I would even argue that you see certain abnormalities in mobile phone junkies, already. Ok, those could have psychological and behavioral roots, but ...

Before I digress even further into the abyss of the "I cannot live without my mobile" virus that has already befallen many of my real world students, let's rather take a look at the outcome of Aboul Ezz et al.'s latest experiment.

Table 1: While the first six are actually the TOP (=low SAR) phones that are currently on the market, the others are random picks of mine from the data on SARdatabase.com

In the course of the latter, the scientists exposed a group of adult rats to the pulsed electromagnetic radiation of a mobile phone having a power density of 0.02W/cm² and an average specific absorption rate (the notorious SAR-value) of 0.843W/kg for 1h/day (that happens to be a little less of what your neat iPhone5 is pumping into your brain day in and day out) and measured the monoamine levels after one, two and four months, as well as on a follow-up one month after the last exposure and found:

The exposure to EMR resulted in significant changes in DA [dopamine], NE [norepenephrine] and 5-HT [serotinine levels] in the four selected areas of adult rat brain" (Aboul Ezz. 2013)

And the Egyptian researchers add, these chance could well explain the adverse effects that have been reported in conjunction with chronic "low level" exposure to pulsed electromagnetic radiation, which are usually related to memory problems and chronic stress.

What they don't mention in the abstract though is that the changes were not really consistent. It appeared as if there was some cyclicity involved with an initial increase in 5HT, a concomittant decrease in dopamine a newly established "balance" between the two leading to an increase in norepinephrine (=chronic stress) in months four.

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Bottom line: That being said, I can only repeat that even in the absence of direct physiological effects of the EMR exposure, the constant state of "being available" to whoever wants to reach you, as well as the addictive potential of being in contact with all your (often fake) facebook friends alone should be reason enough to re-evaluate your own mobile phone use.

Capsaicin keeps fatty acid oxidation & total energy expenditure up, when you're dieting

No this is not Liza Oz after taking Mehmet's beloved RK supplements - and it is not one of the subjects from the "Kitchen Sink Approach to Fat Loss study"... although, who knows? (learn more about that study)

(Janssens. 2013) Right from the Department of Human Biology, School for Nutrition, Toxicology and Metabolism (NUTRIM) at the Maastricht University in The Netherlands comes a new study that confirms that capsaicin a long-touted "fat burner" and anti-obesity agent  that's also turning up your heat, when you consume hot peppers, will maintain your energy balance and fatty oxidation rates in the normal zone, when you are dieting.

The 15 healthy Caucasian subjects underwent four 36 h sessions in a respiration chamber, which allowed the scientists to accurately measure their energy expenditure, the ratio of glucose / fat oxidation and blood pressure after receiving a dose of 2.56mg (1.03g of red chili pepper worth 39,050 Scoville heat units (SHU)) with every meal.

Now, this wouldn’t be something we have not seen in previous studies, already. With the study at hand, however, the capsaicin intake, was not the only controlled variable. In addition to simply checking what happens, when you consume one serving of capsaicin with each meal, the scientists also assessed the influence of the baseline energy intake of the subjects, with them being randomly assigned to receive adequate amounts of energy (= 100% of the daily energy requirements), or a calorically reduced diet (=75% of the daily energy requirements) during the tests.
 
The first noteworthy observation the scientists made is the adaptiation induced amelioration of the energy deficit. Contrary to what the simply calories in vs. calories out equation would suggest, the participants who received 25% less energy than they would need ended up having an effective energy deficit of only 20.5% - in other words, the missing 4.5% were simply conserved by the dreaded metabolic downregulation that’s one of the most important reasons for weight loss plateaus.

Figure 2: Changes in energy expenditure at rest, during sleep in response to food intake and activity, as well as substrate oxidation in 15 healthy Caucasian subjects (seven women, eight men) during the supplemented (CAP) and non-supplemented (PLA) energy sufficient (100) and restricted (75) conditions (Janssens. 2013).

Now this is where the capsaicin comes into play, as the results of the study at hand clearly demonstrate, the additional provision of 2.56 mg of the hot spice with every meal can negate the reduction in diet-induced thermogenesis and restore the lowered sleeping metabolic rate the 25% caloric reduction has brought about.

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Suggested read for those looking to stacking different ingredients to propel their weight loss efforts: "Forgotten Dieting Aids: Choline, Carnitine, Caffeine and the Anti-Weight-Loss Plateau Effects of Sugar and Phosphates" (read more)

Bottom line: In view of the fact that the capsaicin supplement also increased the fat oxidation during both the calorically reduced and the normal dieting conditions, it may in fact be that we've hot a pretty "hot" fat burner here... unfortunately, just with any other "fat burner", you still got to give your body the chance to actually burn the fat. Without sweat and a slightly reduced energy intake (25% does by the way make a good rule of thumb) this is yet not going to work.

Moreover, it is also questionable, whether the effects will be that noticeable after 1-2 weeks of chronic usage. I'd bet money they will either disappear completely or be drastically reduced, but that would be the topic for another study ;-)

All that's left are... *drumrolls* the Facebook news and an awesome weekend!

You know what's coming now, right? Correct, first I will enumerate a couple of Facebook News you may or may not have seen on the SuppVersity Timline (ha! I did not write "wall", am I now going to be rewarded, Mark Zuckerberg?)

• SuppVersity Highly Suggested Read - Part II of Sean Casey's summary of the ISSN conference | read more...
• Science for Science Sake - In the current scientific environment many scientists turn to biased reporting, intrinsically flawed study design & the like to produce "break through" results that are at best irrelevant, in the worst case threaten the live of participants in follow up studies | learn more... 
• Moderate Drinking Probably Lacks Life-Extending Effects - Sociologists argue: The lifestyle and not the booze of moderate drinkers is what prolongs their lives | learn more...
• Barefoot Running is Good for Your Knees: Take your shoes off to reduce patellofemoral joint stress during running | read more ...
• Can Supplements Precipitate Headaches? At least in a recent study from China the researchers observed correlations between isoflavone-supps in men and B-complex, vitamin C and green algae supplements in women | read more...

And afterwards I am telling you to have a nice weekend and reminding you of the fact that Sunday is no "off day" here at the SuppVersity ... although, for many of you it appears to be, which is why I am actually thinking about dropping the Sunday posts completely. Whatever... enjoy your weekend!

References:

• Aboul Ezz HS, Khadrawy YA, Ahmed NA, Radwan NM, El Bakry MM. The effect of pulsed electromagnetic radiation from mobile phone on the levels of monoamine neurotransmitters in four different areas of rat brain. Eur Rev Med Pharmacol Sci. 2013 Jul;17(13):1782-8.
• Andreassen CS, Torsheim T, Brunborg GS, Pallesen S. Development of a Facebook
  Addiction Scale. Psychol Rep. 2012 Apr;110(2):501-17.
• Chen KY, Brychta RJ, Linderman JD, Smith S, Courville A, Dieckmann W, Herscovitch P, Millo CM, Remaley A, Lee P, Celi FS. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab. 2013 Jul;98(7):E1218-23. 
• Janssens PL, Hursel R, Martens EA, Westerterp-Plantenga MS. Acute effects of capsaicin on energy expenditure and fat oxidation in negative energy balance. PLoS One. 2013 Jul 2;8(7):e67786.
   

Topical Fat Loss: Capsaicin Cream Blunts Weight Gain in Rodent Model and Increases Leptin, Adiponectin, Lipolysis and Fatty Acid Oxidation in Visceral Fat Depots

Image 1: If you infused your ice-water with an extract of those, that could supercharge your "cold thermogensis" (see "Ephedra vs. Cold Thermogensis" ;-)

Those last 1-2lbs of stubborn fat have been and still are the focal point of countless of discussions among trainees, trainers and  magazines even average Joes and Janes who would not even remotely consider to go to the gym to get rid of those love handles - interestingly, all these groups are similarly susceptible to one message: "Revolutionary breakthrough in topical fat loss: "Whatever-Our-Marketing-Department-Came-Up-With-Burn will obliterate the stubborn body fat that's still covering your abs, obliges, butt, and whatever else you hate about yourself in record time!" Sounds and, as the countless disappointed testimonies on the Internet confirm, is usually too good to be true.

How many scoville (SHU) does it take to burn 1lbs of body fat?

A soon to be published study by researchers from the University of Ulsan in Korea does however show that many of the companies which advertise with the afore "cited" slogans could in fact be on the right track - at least with respect to one of the key ingredients many of those topical fat-burners contain: Capsaicin, a major pungent molecule that is found in hot chilies and other peppers and has already been shown to exert direct effects on isolated adipocytes in vitro (Kang. 2007; Hsu. 2007) and anti-obesity activity in animal models (Yoshioka. 1999; Zhang. 2007). Interestingly enough, epidemiological (Wahlqvist. 2001) and controlled human trials (Bloomer. 2010) suggest that these effect do - despite the often-touted differences in the thermogenic capacity of humans and rodents - in fact manifest in all the usual steps of scientific experimentation in the medical field, i.e. the petri dish, the animal model and the controlled, randomized, placebo-blinded human trial.

From the mouth onto the skin

As far as its topical usage is concerned the main focus of scientific research has yet been on the ameliorative effects of capsaicinoids on painful neuropathies and neuralgia (Harding. 2001; Roberts. 2011) and Lee et al. claim that their study is the first one to investigate the effects of in vivo application of 100mg of a 0.075% hydrophillic capsaicin cream applied to the shaved abdominal skin of pre-fattened mice who were pair-fed (=equal caloric intake for rodents in both groups to exclude reduced appetite as a cause for the observed effect) for 7-weeks.

Figure 1: Body composition (left) and adipocyte size (right) after 7-weeks on HFD with our without topical application of 100mg 0.075% capsaicin cream to the abdomen of obese mice (based on Lee. 2012)

As the data in figure 1 clearly shows, the topical application of capsaicin elicited similar beneficial effects on the blood lipids (not shown) as its oral ingestion in a previous HFD rodent trial (Kang. 2010). What is however particularly striking is that it did at the same time totally blunt further increases in body weight and reduced body fat storage in both the mesenteric, as well as the epididymal, visceral fat depots. The latter went hand in hand with profound changes in the adipocyte morphology of both fat depots which shifted from fewer large, to many small adipocytes - a feature which is usually associated with lower adipocyte inflammation and thus reduced risk of cardiovascular disease & co.

Topical application, systemic effects?

Both results, the improved lipid profile, as well as the reduction in visceral (intra- not super-abdominal) obesity appear to suggest that the effects of the capsaicin cream was by no means as localized as the producers of respective "supplements", would have it.

Figure 2: Adiponectin, leptin, TNF-alpha, lipoprotein lipase, UCP-2 and PPAR expression in mesenteric fat pads of the animals at the end of the 7-week study period (based on Lee. 2012)

The localized decreases in TNF-alpha, a central regulator or inflammation and the profound increases in adipokine expression (adiponectin + leptin), lipoprotein lipase, as well as UCP-2 and all three varieties of the peroxisome proliferator receptors (PPARs), Lee et al. observed in the mesenteric fat pads of the animals do yet confound this theory - capsaicin is, at least partially, a topical fat burner in the literal sense.

Caution! Stimulant-laden fire hazard!

Aside from the fact that its certainly non-negligible effects on visceral fat should not be of great interested for any avid trainee who is following a wholesome whole-foods diet, as those last slabs of body fat that are covering your abs belong to your subcutaneous and not visceral fat depots, there are two more things you should be aware of before you (most likely) waste your money on one of those products.

1. The capsaicin itself will make the body part you rub the product on look like a tomato on fire and burn worse than stinging nettle and that usually for hours!
2. The systemic effects of the stimulants most of these products contain can become an issue especially for leaner folks, as the dosages are usually adjusted for customers with a thick "insulation" that has to be penetrated, first. 

If you still feel that you have to give one or another of those preparations a shot, start with a moderate dose first and wait for a couple of hours to see what it does (don't expect it to do anything to your body fat in that time - if your waistline goes down within the first days of application that's simply water loss!).

My personal recommendation would still be to keep away from any of these products. Regardless of your personal tolerance to stimulants or the specific composition of the different formulas that are currently on the market - 99% of the feedback I have heard and read about states that these products are much better money- than fat-burners  ;-)

References:

1. Bloomer RJ, Canale RE, Shastri S, Suvarnapathki S. Effect of oral intake of capsaicinoid beadlets on catecholamine secretion and blood markers of lipolysis in healthy adults: a randomized, placebo controlled, double-blind, cross-over study. Lipids Health Dis. 2010 Jul 15;9:72.
2. Kang JH, Kim CS, Han IS, Kawada T, Yu R Capsaicin, a spicy component of hot peppers, modulates adipokine gene expression and protein release from obese-mouse adipose tissues and isolated adipocytes, and suppresses the inflammatory responses of adipose tissue macrophages.FEBS Lett. 2007;581:4389-96. 
3. Kang JH, Goto T, Han IS, Kawada T, Kim YM, Yu R. Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesity (Silver Spring). 2010 Apr;18(4):780-7.
4. Lee GR, Shin MK, Yoon DJ, Kim AR, Park NW, Yu R, Han IS. Topical application of capsaicin reduces visceral adipose fat by affecting adipokine levels in high-fat diet (HFD)-induced obese mice. Obesity (Silver Spring). 2012 Jun 18. doi: 10.1038/oby.2012.166. [Epub ahead of print]
5. Hsu CL, Yen GC Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells.J Agric Food Chem. 2007;55:1730-6. 
6. Wahlqvist ML, Wattanapenpaiboon N Hot foods--unexpected help with energy balance? Lancet. 2001;358:348-9.
7. Yoshioka M, St-Pierre S, Drapeau V, Dionne I, Doucet E, Suzuki M, Tremblay A Effects of red pepper on appetite and energy intake.Br J Nutr. 1999;82:115-23. 
8. Zhang LL, Yan Liu D, Ma LQ, Luo ZD, Cao TB, Zhong J, Yan ZC, Wang LJ, Zhao ZG, Zhu SJ, Schrader M, Thilo F, Zhu ZM, Tepel M Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity.Circ Res. 2007;100:1063-70.

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.

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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.