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.

Temporary +100kcal/day Cold Thermogenesis Response W/ Exotic Ginger Extract. Plus: Green Tea Reduces Shivering

 Grains of paradise pods - do they hold the secret to "true" fat thermogenic fat burning for those who are lucky enough to have a significant amount of brown adipose tissue (BAT) on their frame? (Photo by Inna Moody / Flickr: innamoo)

Just got an email from my friend Carl Lanore, who dug up a soon-to-be-published study on the thermogenic effects of ginger... well, not exactly ginger as in Zingiber officinale but rather "ginger" as in Grains of paradise (GP). Huh? Yeah, sounds more as if you had bought it in a "coffee shop" or another outlet for legal highs, but it's actually a species of the ginger family, Aframomum melegueta to be precise that contains a similar composition of the characteristic pungent, aromatic ketones such as 6-paradol, 6-gingerol and 6-shogaol. In previous rodent studies an alcohol extract of GP seeds and 6-paradol has been shown to activate BAT thermogenesis in small rodents and in the study at hand it did the exact same for 12 out of 19 healthy male volunteers aged 20–32 years who underwent 2h of cold-exposure.

4 weeks Aframomum melegueta extract can promote, but not induce cold thermogenesis (CT)

In the four weeks prior to the study, the subjects had ingested four capsules of an ethanol extract from the seeds of Grains of paradise for breakfast, three capsules after lunch and three capsules after dinner without noticing any adverse events.

Photo montage - BAT(-) subject no black = metabolically active spots in the supraclavicular and paraspinal regions (left), right BAT(+).

The seeds the scientists used in the study at hand, had been bought from a spice supplier at the Côte d’Ivoire, had been soaked for extraction in five times volume of 95% ethanol for 24 h at reflux condition, the resulting ethanolic extract was filtrated and the solvent was removed under vacuum. According to Sugiat et al. this procedure yielded an extract with 4.2% of the original weight of the GP seeds containing 15.2% 6-gingerol, 12.5% 6-paradol, 1.7% 6-shogaol and 4.0% 6-gingeredione. 10mg of the extract were capped with 190mg of a mixture of rapeseed oil (158mg) and beeswax (32mg) in a capsule, so that all participants ended up consuming the same dosage of ~33mg of active ingredients on a daily basis.

Ah, and since I know you would ask: I do believe regular ginger will do the job "as well". Not necessarily as in "as potently", but it will certainly do something. After all you will find the same main active ingredients (in put them in italics above) in the "grains of paradise" in HPLC analysis of regular Zingiber officinale, as well.

Cold thermogenesis (CT) works in some, yet not all subjects

I've written about cold thermogenesis the influence of body fatness and the lack of BAT in many humans before (read more)

As previous human studies have show, the first and most important determinant of the effects to cold exposure was yet not the extract, but rather the presence of BAT in the subjects supraclavicular and paraspinal regions.

Now what's interesting is that those subjects with without any significant BAT were not significantly lighter / heaver, leaner or muscular than their peers who showed a thermogenic response of max. +100kcal (vs. placebo) in response to the Grains of paradise seed (GP) preload.

The latter it interesting as previous studies have suggested that body-fatness is a negative modulator cold thermogensis (cf. "Cold Thermogenesis - A Safe Ephedra Alternative? 70kcal Increase in 24h Energy Expenditure is Negligible, 50% Lower Than Ephedrine, Not Likely to Occur Obese or Older People" read full-post). On the other hand the inter-group differences between resonders and non-responders were so small that the results of the study at hand are actually pretty meaningless with respect to the issue of identifying probable responders and non-responders by body type (which was virtually identical in all the participants).

You better know in advance whether you are BAT(+) or BAT(-) ...

... because otherwise you would not just be wasting your time while sitting for 1h in an air-conditioned room at 19.8°C with light clothing after an overnight fast (that was the exact procedure in the study). but also your money on any (certainly soon to be commercially available) Aframomum melegueta extract.

Figure 1: Changes in energy expenditure during cold exposure (value scaled to daily equivalents values, left). Area under the curve of the energy expenditure for BAT(+) and BAT(-) subjects (right), please mind that these are the "real" non-scaled energy expenditures in kcal/h (Sugita. 2013)

After all the data in figure 1 shows quite conclusive that in the BAT(-) subjects the addition of the GP extract actually blunted the already minimal (and non-significant) thermogenic response to cold exposure.

And what about green tea? While the title of a recent study suggests that green tea could be another CT adjuvant (Gosselin. 2012), the effect size Gossselin et al. observed in their trial that involved eight healthy non-cold acclimatised men, was laughable. Or do you think that it makes a difference whether you spend 5.4kcal/h or 5.9kcal/h extra? No, well me neither. So unless you are not into the ~15% reduction in shivering or the minimal shift from glucose to fat oxidation that occurred in the subjects who ingested 600mg of EGCG and 600mg of caffeine before their 2h in a liquid-conditioned suit perfused with 15°C.

So what? I know a few lazy asses won't like to hear that, but you can as well jog 15 minutes, do a single 10min HIIT session, hit the weight or simply stand at your office desk instead of sitting in front of your computer all day if you want to expose the gigantic amount of 100kcal per day. So what on earth do you even care about all that?

Contrary to taking supps for weeks before sitting in the cold, working out, moving and even standing (though to a lesser degree) will also increase your fitness level and shift your energy consumption from glucose to fat, something freezing and pill-popping won't do. And what's more all these methods will be more not less effective (cf. previously cited post, red box) if you are still obese.

That does not say that ginger, grains of paradise and EGCG (see box on the right) could not help you lose weight, but if they do, it's probably mostly due to their profound health effects, which are probably a way better reason to drink your ginger and green tea or take respective supplements if you don't like those, anyway.

Read more about ginger and green tea at the SuppVersity and or learn more about "the magic of Ginger and its pleiotropic effects on health, well being, performance and cancer prevention" on SHR Episode 753 (without my contribution, though ;-).

References:

• Gosselin C, Haman F. Effects of green tea extracts on non-shivering thermogenesis during mild cold exposure in young men. Br J Nutr. 2012 Dec 14:1-7.
• Sugita J, Yoneshiro T, Hatano T, Aita S, Ikemoto T, Uchiwa H, Iwanaga T, Kameya T, Kawai Y, Saito M. Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men. Br J Nutr. 2013 Jan 11:1-6.