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:

• Berry DC, Noy N. All-trans-retinoic acid represses obesity and insulin resistance by activating both peroxisome proliferation-activated receptor beta/delta and retinoic acid receptor. Mol Cell Biol. 2009 Jun;29(12):3286-96.
• Berry DC, DeSantis D, Soltanian H, Croniger CM, Noy N. Retinoic acid upregulates preadipocyte genes to block adipogenesis and suppress diet-induced obesity. Diabetes. 2012 May;61(5):1112-21. 
• Brown PN, Roman MC. Determination of hydrastine and berberine in goldenseal raw materials, extracts, and dietary supplements by high-performance liquid chromatography with UV: collaborative study. J AOAC Int. 2008 Jul-Aug;91(4):694-701.
• Brun PJ, Yang KJ, Lee SA, Yuen JJ, Blaner WS. Retinoids: Potent regulators of metabolism. Biofactors. 2012 Dec 22. doi: 10.1002/biof.1056. 
• Chen S, Li Z, Li W, Shan Z, Zhu W. Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Can J Physiol Pharmacol. 2011 Nov;89(11):793-9.
• Gomes AP, Duarte FV, Nunes P, Hubbard BP, Teodoro JS, Varela AT, Jones JG, Sinclair DA, Palmeira CM, Rolo AP. Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis. Biochim Biophys Acta. 2012 Feb;1822(2):185-95.
• Hisada K, Hata K, Ichida F, Matsubara T, Orimo H, Nakano T, Yatani H, Nishimura R, Yoneda T. Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes. J Bone Miner Metab. 2013 Jan;31(1):53-63.
• Hong JH, Hwang EY, Kim HJ, Jeong YJ, Lee IS. Artemisia capillaris inhibits lipid accumulation in 3T3-L1 adipocytes and obesity in C57BL/6J mice fed a high fat diet. J Med Food. 2009 Aug;12(4):736-45.
• Hu Y, Davies GE. Berberine increases expression of GATA-2 and GATA-3 during inhibition of adipocyte differentiation. Phytomedicine. 2009 Sep;16(9):864-73. doi: 10.1016/j.phymed.2009.03.002. Epub 2009 Apr 28.
• Huang C, Zhang Y, Gong Z, Sheng X, Li Z, Zhang W, Qin Y. Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochem Biophys Res Commun. 2006;348:571–578.
• Hwang JT, Lee MS, Kim HJ, Sung MJ, Kim HY, Kim MS, Kwon DY. Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-gamma signal pathways. Phytother Res. 2009 Feb;23(2):262-6.
• Joo JI, Kim DH, Choi JW, Yun JW. Proteomic analysis for antiobesity potential of capsaicin on white adipose tissue in rats fed with a high fat diet. J Proteome Res. 2010 Jun 4;9(6):2977-87.
• Juman S, Yasui N, Okuda H, Ueda A, Negishi H, Miki T, Ikeda K. Caffeic acid phenethyl ester inhibits differentiation to adipocytes in 3T3-L1 mouse fibroblasts. Biol Pharm Bull. 2010;33(9):1484-8.
• Ka SO, Kim KA, Kwon KB, Park JW, Park BH. Silibinin attenuates adipogenesis in 3T3-L1 preadipocytes through a potential upregulation of the insig pathway. Int J Mol Med. 2009 May;23(5):633-7.
• Kim SK, Kong CS. Anti-adipogenic effect of dioxinodehydroeckol via AMPK activation in 3T3-L1 adipocytes. Chem Biol Interact. 2010a Jun 7;186(1):24-9.
• Kim KJ, Lee OH, Lee BY. Fucoidan, a sulfated polysaccharide, inhibits adipogenesis through the mitogen-activated protein kinase pathway in 3T3-L1 preadipocytes. Life Sci. 2010b May 22;86(21-22):791-7.
• Kim GS, Park HJ, Woo JH, Kim MK, Koh PO, Min W, Ko YG, Kim CH, Won CK, Cho JH. Citrus aurantium flavonoids inhibit adipogenesis through the Akt signaling pathway in 3T3-L1 cells. BMC Complement Altern Med. 2012 Apr 3;12:31.
• Kong CS, Kim JA, Eom TK, Kim SK. Phosphorylated glucosamine inhibits adipogenesis in 3T3-L1 adipocytes. J Nutr Biochem. 2010 May;21(5):438-43. 
• Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006;55:2256–2264. 
• Lee YK, Lee WS, Hwang JT, Kwon DY, Surh YJ, Park OJ. Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 in cancer cells. J Agric Food Chem. 2009 Jan 14;57(1):305-10.
• Lee H, Kang R, Yoon Y. SH21B, an anti-obesity herbal composition, inhibits fat accumulation in 3T3-L1 adipocytes and high fat diet-induced obese mice through the modulation of the adipogenesis pathway. J Ethnopharmacol. 2010 Feb 17;127(3):709-17.
• Liu Y, Wang WJ, Chen WH, Yin J. [Effects of Astragalus polysaccharides on proliferation and differentiation of 3T3-L1 preadipocytes]. Zhong Xi Yi Jie He Xue Bao. 2007 Jul;5(4):421-6.
• Liu Y, Lou SY, He YM. [Effects of berberine on cell proliferation, peroxisome proliferation activated receptor gamma, CAAT/enhancer binding protein mRNA and protein expression in 3T3-L1 pre-adipocytes]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2008 Nov;28(11):1005-9.
• Medina-Gomez G, Gray SL, Yetukuri L, Shimomura K, Virtue S, Campbell M, Curtis RK, Jimenez-Linan M, Blount M, Yeo GS, Lopez M, Seppänen-Laakso T, Ashcroft FM, Oresic M, Vidal-Puig A. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet. 2007 Apr 27;3(4):e64.
• Mukherjee R, Yun JW. Bromocriptine inhibits adipogenesis and lipogenesis by agonistic action on α2-adrenergic receptor in 3T3-L1 adipocyte cells. Mol Biol Rep. 2013 May;40(5):3783-92.
• Nimitphong H, Holick MF, Fried SK, Lee MJ. 25-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ promote the differentiation of human subcutaneous preadipocytes. PLoS One. 2012;7(12):e52171.
• Oben JE, Ngondi JL, Blum K. Inhibition of Irvingia gabonensis seed extract (OB131) on adipogenesis as mediated via down regulation of the PPARgamma and leptin genes and up-regulation of the adiponectin gene. Lipids Health Dis. 2008 Nov 13;7:44.
• Park DY, Ahn YT, Huh CS, Jeon SM, Choi MS. The inhibitory effect of Lactobacillus plantarum KY1032 cell extract on the adipogenesis of 3T3-L1 Cells. J Med Food. 2011 Jun;14(6):670-5.
• Park UH, Jeong HS, Jo EY, Park T, Yoon SK, Kim EJ, Jeong JC, Um SJ. Piperine, a component of black pepper, inhibits adipogenesis by antagonizing PPARγ activity in 3T3-L1 cells. J Agric Food Chem. 2012 Apr 18;60(15):3853-60.
• Sagara C, Takahashi K, Kagechika H, Takahashi N. Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells. Biochem Biophys Res Commun. 2013 Mar 29;433(1):102-7. 
• Seo JB, Choe SS, Jeong HW, Park SW, Shin HJ, Choi SM, Park JY, Choi EW, Kim JB, Seen DS, Jeong JY, Lee TG. Anti-obesity effects of Lysimachia foenum-graecum characterized by decreased adipogenesis and regulated lipid metabolism. Exp Mol Med. 2011 Apr 30;43(4):205-15.
• Thounaojam MC, Jadeja RN, Ramani UV, Devkar RV, Ramachandran AV. Sida rhomboidea. Roxb Leaf Extract Down-Regulates Expression of PPARγ2 and Leptin Genes in High Fat Diet Fed C57BL/6J Mice and Retards in Vitro 3T3L1 Pre-Adipocyte Differentiation. Int J Mol Sci. 2011;12(7):4661-77.
• Tzeng TF, Chang CJ, Liu IM. 6-Gingerol Inhibits Rosiglitazone-Induced Adipogenesis in 3T3-L1 Adipocytes. Phytother Res. 2013 Mar 21.
• Wang JM, Yang Z, Xu MG, Chen L, Wang Y, Su C, Tao J. Berberine-induced decline in circulating CD31+/CD42- microparticles is associated with improvement of endothelial function in humans. Eur J Pharmacol. 2009;614:77–83.
• Yuan HD, Yuan HY, Chung SH, Jin GZ, Piao GC. An active part of Artemisia sacrorum Ledeb. attenuates hepatic lipid accumulation through activating AMP-activated protein kinase in human HepG2 cells. Biosci Biotechnol Biochem. 2010;74(2):322-8.
• Yuan HD, Piao GC. An active part of Artemisia sacrorum Ledeb. inhibits adipogenesis via the AMPK signaling pathway in 3T3-L1 adipocytes. Int J Mol Med. 2011 Apr;27(4):531-6.

Epigallocatechin Gallate (EGCG), Capsaicins, Piperine & Carnitine: Rather a Health Than a Fat Loss Stack?

That's not what the ultimate weight loss diet looks like. The pill remains a supplement, i.e. something to supplement (and support) your dietary and exercise efforts, nothing more, but - as long as you pick the right one for your type and goal - also nothing less (photo ehow.com)

Let me first remind you of the fact that something that works in your obese neighbor does not necessarily work as effectively in someone like yourself, a devoted physical culturist who is only a couple of steps away from the six pack he has always been dreaming of. Let me also emphasize the fact that taking the supplement alone, i.e without the -600kcal reduction in energy intake all of the 86 overweight subjects (healthy males and females aged 25–45 years, with a body mass index greater than 25 kg/m² less than 35 kg/m²) had to stick to, there probably wouldn't have been any weight loss at all. And lastly, let me also formulate the hypothesis that the various health benefits, such as the increases in insulin sensitivity, the improvements in the leptin/adiponectin ratio or the decreasing LDL levels would probably have been less pronounced without the game-changing reduction in energy intake.

Simple Truth: The right diet, not the right supplements is the key factor in losing body fat

Apropos reduction in energy intake, one of the most underrated but practically highly relevant beneficial effects the administration of the epigallocatechin gallate (EGCG from green tea), capsaicins, piperine, L-carnitine and a few minor ingredients (see figure 1, left) probably brought about certainly were the psychological benefits, such as the 3.3 pts decrease on the Beck depression inventory (BDI-II), since the ability and will to adhere to a diet - whether this may be for 8 weeks as in the study at hand or (preferably) for life - obviously hinges on the question: "Can you stick to it?"

Figure 1: Energy content (primary axis in kcal) and macronutrient composition (secondary axis in g) and ingredients of the of the weight loss supplement (Rondanelli. 2012)

That said, the diet composition in figure 1 (left) certainly raises another question: "Would it even be wise to adhere to this diet for longer than 8 weeks?" I mean it stands out of question that living on a caloric deficit for the rest of your life is not an option. If you look a the macronutrient composition of the diet, on the other hand, my personal  prognosis is that this program will not yield long-term success. Not because it's high in carbs, but because it is too low in protein and lacks an exercise component - typical mainstream dieting = typical mainstream failure - with or without "bioactive food ingredients" (Rondanelli. 2012).

Fat loss or anti-diabesity stack? That is the question!

The combination of a lack of exercise stimuli and a relatively low dietary protein intake (certainly below the threshold limit of 10g+ of EAA per meal) is probably also the main reason for the slight loss in lean muscle tissue, a phenomenon  - and that's interesting, although the difference did not reach statistical significance - occured only in the supplemented  group.

Figure 2: Changes in body composition (left) and selected markers of glucose management and fatty acid metabolism, adipokine expression and inflammation (Rondelli. 2012)

Now, there are obviously dozens of potential reasons for the minimal muscle loss in the supplement group. In my humble opinion the most likely explanation does yet relate to the very same increase in resting energy expenditure (+120.6kcal/day) that's (alongside the metabolic improvements, cf. figure 2, left) behind the additional 600g of body fat, the subjects in the supplement group shed in the course of the 8-week dietary intervention.

"600g in 8 weeks? Are you kiddin' me?"

Yep, you read me right, 600grams is all the supplement yielded as far as additional fat loss is concerned. That, plus the fact that neither this, nor any of the differences in between the changes in anthropometric data reached significance does tell you something about the actual weight loss effects even obese and insulin resistant subjects can expect from taking an epigallocatechin gallate (EGCG from green tea), capsaicins, piperine and L-carnitine based dietary supplement.

What? That's pathetic? Well, it would be if these changes were not accompanied by way more important and statistically significant different effects on the insulin sensitivity of the 41 overweight subjects in the supplement group who completed the study.

As far as the inhibition of diet induced weight gain and insulin resistance are concerned, there is no synergism of green tea and the L. plantarum, a probiotic. Green tea does the job, the bacteria stand by and watch in awe (read more)

Bottom line: As I've pointed out numerous times before. There are a different types of weight loss adjuvants, with one of the most general, if you will "fundamental" distinctions between (a) those weight loss supplements that have a more or less pronounced direct effect on the energy balance (=carb/fat blocker, beta-agonists, thyroid mimetics, appetite suppressants etc.) and (b) their healthier cousins that promote your weight loss efforts by ironing out acquired metabolic obstacles, such as leptin and insulin resistance. And though you could certainly make a point that green tea exhibits some features of both categories, the overall stack used in this study belongs to the second category and it's efficacy is therefore going to drop the healthier (=less inflamed, insulin & leptin sensitive) you are, when you start dieting.

You may want to keep that, as well as the (un-)fortunate truth that there simply is no "fat burner pill" on the market that will do the allegedly hard dieting and exercising for you, in mind, whenever you pass by the storeboard with the virtual or real shelves of a supplement store and are tempted to invest 50$ or so into yet another "next generation fat burner"... without having a diet and workout plan and the will to stick to it, you can just as well save the 50$.

References:

• Rondanelli M, Opizzi A, Perna S, Faliva M, Solerte SB, Fioravanti M, Klersy C, Edda C, Maddalena P, Luciano S, Paola C, Emanuela C, Claudia S, Donini LM. Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months' consumption of a combination of bioactive food ingredients in overweight subjects. Endocrine. 2012 Dec 28. [Epub ahead of print]

-16% Abdominal Fat on a Cornstarch Diet? No Problem If You Add 4 Teaspoons of Black Pepper to Your Meals!

Image 1: According to Wood et al. (1988) black pepper contains between 3-8% piperine. A teaspoon of black pepper would thus deliver have 60-160mg piperine, which would mean that you would have to swallow roughly 4 of those to get the fat loss effect (if it does translate to humans)

I don't know if you have realized it, but if you are taking any "high quality" dietary supplements, chances are that one of the minor ingredients on its label is "piperine", the alkaloid that is responsible for the pungent taste of black pepper. The reason, why manufacturers keep adding this spicy ingredient to their formulas is not its anti-oxidant potency, not its stimulating effect on the digestive enzymes of pancreas or even its ability to significantly reduce the gastrointestinal food transit time, no it is because piperine messes with the way your liver metabolizes drugs (piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4; Bardhwaj. 2002). Yet, while everybody seems to be freaking out about possible medical interactions of St. John's Wort, nobody appears to care about piperine... the credo seems to be "As long as it enhances the delivery of my curcumin it must be a good thing!" That it could as well enhance the bioavailability of a lot of other things, you'd rather have your liver clear from your system as fast as possible, is largely ignored, though.

Note: It always amazes me how scientists design their experimental diets. Usually we have those "high fat diets" that then turn out to be high fat + high carb (like 40% carb, 50% fat, 10% protein). So I was curious what a "high carbohydrate, high fat" diet (HCHF) would look like. Well, let me put it like that. I am not sure, whether the control diet that consisted of a meat-free rat and mouse feed (Specialty Feeds, Australia) that was mixed with cornstarch (yes, the devil! ;-) and water was so much "healthier" than the fattening HCHF diet where part of the cornstarch and the water was replaced with condensed milk, fructose and beef tallow... I mean, condensed milk and beef tallow do sound pretty good, and let's be honest even "normal" corn starch is probably not much better than pure fructose... what do you say? "Scientific Idiocy?" Well, I didn't say that ;-)

So far for the bad news. Now for the good one: A recent study from the University of Southern Queensland found that the addition of ~30mg piperine per kg body weight to the chow of 8-9 week old male Wistar rats, who were fed a high carbohydrate + high fat diet for 16 weeks (cf. red box above), ...

[...] reduced blood pressure, improved cardiac and liver structure and function, reduced oxidative stress, and attenuated inflammatory and metabolic changes induced by HCHF diet as compared to CS diet.

Moreover, the addition of 30mg/kg piperine (=4.86mg/kg for humans) kept the rats on the "typical Western diet" (high carbs + high fat) healthy, it also kept them reasonably lean and, more importantly, it also reduced the weight of the abdominal fat pads by -16% in the "control" (=high carb) group (cf. figure 1).

Figure 1: Changes in dietary intake and body composition of male Wistar rats receiving 30mg/kg piperine in their cornstarch (control) or high carbohydrate + high fat (HCHF); values relative to unsupplemented control (data calculated based on Diwan. 2011)

If you have a closer look at the dietary and body compositional data, I've compiled for you in figure 1, you will also realize that all that happened, although the rats who received the piperine in their chow consumed +7% (cornstarch) and +16% (HCHF) more calories than their peers. This is not only further evidence for the ludicrousness of the calories in vs. calories out hypothesis it also goes to show that the rats did not simply stop eating, because they felt that their chow was too spicy ;-)

Figure 2: Changes in inflammatory markers and anti-oxidant status of male Wistar rats receiving 30mg/kg piperine in their cornstarch (control) or high carbohydrate + high fat (HCHF); values relative to unsupplemented control (data calculated based on Diwan. 2011)

For those of you who are also interested in their health (for the general public, I often get the impression that looking good is more important for many than feeling good), it may also be worth to have a look at the changes in inflammatory markers and anti-oxidant status in figure 2. After all, the data indicates that the piperine supplemented animals exhibited statistically significant (* p<0.05) reductions in the high carb + high fat induced elevations in C-reactive protein (one of the few markers of which scientists still believe that it is a realiable predictor of heart disease), uric acid and reactive oxygen specimen. Moreover, the total antioxidant status of the HCHF + piperine fed rats improved and was not statistically different from the rats in the cornstarch group at the end of the 16 weeks treatment period.

A potential fat-burner with a bitter after taste

Although Kim et al. observed similar effects in another recent study on mice, who were fed the classic high-fat diet for 3 weeks (the study compared piperine to pipernonaline, and dehydropipernonaline, Kim. 2011), these positive results do yet still have a peppery, ahh... I mean bitter after-taste. Yes, piperine exerted beneficial effects on body composition in both groups and had ameliorated the negative effects of the high carbohydrate + high fat diet on inflammatory markers (most importantly C-reactive protein) and anti-oxidant status and thusly prevented fibrosis, inflammation, and the accumulation of mast cells in the heart and liver of the animal, BUT in view of the colorful poly-pharmacological OTC self-doctoring approaches of many of the self-proclaimed "health conscious" consumers, I am kind of worried that the addition of 400mg of piperine per day (that would be the HED for an 80kg human being) could have unpredictable consequences. That being said, I am not even convinced that we would see similarly profound effects in human studies. After all, it would not be the first "proven" fat burner that turns out to be a non-starter in human trials... if you insist on trying it, do me a favor and not mix it with a lot of other supplements or even medical drugs!

Bioperine: Why is it Part of Your Fat Burner?

Chemical structure of piperine
from Piper nigrum (Wikipedia.com)

More and more fat burners and other dietary supplement contain the patented pepper extract Bioperine. Supplement producers as well as patent holders claim that the extract that is highly standardized (95%) for piperine, a polysaccharide from black pepper (Piper nigrum), would (Sabinsa. 2009)

• increases blood supply to the GI tract
  
• increases emulsifying content of the gut
  
• increases active nutrient transport
  

and thus facilitate nutrient absorption. Unfortunately, respective advertisements, as well as the information provided on the website of the patent holder, do not give references to scientific investigations. Reason enough for the SuppVersity to try and differentiate fact from fiction, BRO- from PRO-science.