Science Round Up Seconds: 30-60% More Testosterone w/ 2.5g D-Aspartic Acid in Fertility Trial and Nicotine Amplifies Cardiotoxic Effects of ECA. Plus: Data on DHEA & Estrogen & Breast Cancer, Fermented Teas, AMPK, AKT & Co

DAA is probably not going to hurt your heart, but it's more likely to father a child than to build those abs. Ephedrine & Caffeine on the other hand, could help you get there, but esp. if you are also smoking you are increasing the risk that the kids you fathered using DAA will soon be without their begetter.

I guess most of all will have listened to the podcast of yesterday's installment of the SuppVersity Science Round Up already. If you didn't you have been missing Carl and me discuss new on the pro-carcinogenic effects of aspartame, the never-ending story of the fattening artificial sweeteners, the benefits of oat beta-glucans for weightloss, -maintenance and gut health, the way sorghum proanthocyanidins can lower the GI of carbohydrates and make them less susceptible to enzymatic breakdown in the small intestine, and more.

Actually this more, i.e. the news on DHEA, its metabolits and their proliferative effect on breast cancer cells, as well as the information about the beneficial effects of fermented teas on blood glucose management, reminded me of the fact that as how like the SuppVersity Science Round Up is a very good place discuss and explain things, but not exactly the place to present detailed data. Therefore, I decided to prelude the Seconds by adding a couple of graphs which illustrate what has been said on the last show. Thus, you can look at the figures while listening to the podcast.

Supportive material for the DHEA and fermented tea news

For this first installment of the Seconds I did, you guessed it, pick the aformentioned news on DHEA and the different fermented teas (see figure 1) that are  based on studies by Miller (2012) and Yamashita  (2012), respectively.

Effect of 7 days of oolong tea, black tea, pu-erh tea, instead of water on Δglucose AUC (left), AMPK, AKT and PI3K expression in skeletal muscle  of male mice (Yamashita. 2012)

Effect of estradiol (E2), DHEA and its metabolits 7-OXO,  androstenediol, and androstenedione on breast cancer cell proliferation (based on Miller 2012)

So much for the additions to visuals for the podcast, let's get to the new stuff... or actually the seconds. Of course, the seconds ;-)

• How to brew your own sodium d-aspartic acid The best thing about this study actually is that the scientists disclose how you can easily make your own PH stable sodium-d-aspartate from the cheap stuff you buy at your favorite bulk supplier: Take 2.66 g of D-aspartic acid neutralize it with 0.46 g of NaOH in 10 ml distilled water and you get a final pH of 6.5 - 7-0 - that's it, you are good to go.
  New study on d-aspartic acid confirms - 30-60% increase in testosterone and LH in infertile men (D’Aniello. 2012) Despite the fact that this is a non-sponsored study by researchers from the Hospital “S. Luca” in Vallo della Lucania, Italy, I am about as 'unpsyched' about the data the scientists present, as I am about the real world results of d-aspartic acid (DAA) supplementation in young weight training men.
  
  It's already telling that D'Aniello et al. mention the increase in testosterone and luteinizing hormone (LH) only as an aside and consider it as a "save", or I guess you better say "tolerable" side effect of a treatment  that did effectively double the amount of D-aspartic acid in the seminal plasma and did thus (at least the scientists belive in a mechanism here) increase the fertility in both, patients with reduced sperm motility and sperm count, and those who suffered only from reduced motility.
  
  The actual 'success rate' in terms of pregnancy rates after 2-3 months of treatment with 2.66g/day of DAA per day was however not exactly really earth-shattering, either. Of the patients with both low sperm count and sperm motility (oligo-asthenozoospermia) 4% fathered a child; of those who suffered 'only' from a low sperm motility (asthenozoospermia) 33% eventually managed to become daddy.
  
  Without baseline testosterone levels, of which I would not be surprised if they had been rock bottom (both oligo-asthenozoospermia and asthenozoospermia usually go hand in hand with increased oxidation and that in turn is associated with low testosterone and suppressed LH levels), this study is however about as worthless in terms of the purported ergogenic effects of DAA, as all previous human trials. That said, you could obviously mix yourself the above concussion in case you and your significant other are planning to start a new or to expand your existing family in the near future. I guess, it's unlikely that it's going to hurt.
  
  Suggested read: All About the Role of Androgens & Co in Building Muscle
   
• Putting an "N" as in "nicotine" into "EC" amplifies the negative effects of ephedrine and caffeine on your heart and may well be the reason for many of the (few) deadly side effects that occurred in the day before the ban (Brown. 2012) When a group of researchers from the Arkansas State University tried to get to the bottom of the (in some cases) fatal cardiovascular side-effects, which were the main reason for the FDA to pull ephedra-containing supplements from the market, Christopher E. Brown and his colleagues observed ...

  "[...] a synergistic effect on the rat cardiac morphology [...] as a result of intera tions between nicotine, caffeine, and Ephedra. The cardiotoxicity caused by combination dosing of Ephedra and caffeine has already been shown; however, the present study revealed an enhancement of cardiotoxicity when nicotine was administered in combination with Ephedra and caffeine." (Brown. 2012)

  The scientists had exposed male Sprague-Dawley rats to (1) synthetic combinations of nicotine (0.2 mg/kg/day), ephedrine (0–30 mg/kg/day), and/or caffeine (0–24 mg/kg/day) as well as (2) an extract from a caffeine-containing Ephedra supplement (Metabolife 356). The relatively high dose treatments were administered for only 3 days either in the full or half dose and with and without nicotine pre-treatment to model the effects of different dosing regimen on smokers and non-smokers.
  
  

  

  Figure 1: Light micrograph of representative nuclear pro-files (background, red = atypical, green = normal nuclei; my emphasis) and volume (%) of atypical cardiac cells in anterior left ventricle of the rodents (Brown. 2012)

  As far as the results go, a a brief glance on the exemplary data in figure 1 should actually suffice to see, that a baseline "N" + "EC"  stack (as in any smoker who would take ephedrine + caffeine to lose weight or psyche himself up) could eventually pave the way to the emergency room.
  
  While the data from the anterior left ventricle and anterior interventricular septum (not shown) would suggest that the identically dosed synthetic versions of caffeine and ephedrine were slightly more detrimental, than the herbal supplement  in which the Ephedra came from a standardized Ma Huang extract and part of the caffeine from Guarana, this effect was not present in either the posterior left or the anterior right or posterior right ventricle (data not shown).
  
  Apropos interventricular septum (IVS), with increases in atypical cardiac cell volume of up to 1.5% in the anterior IVS even without nicotine pre-treatment, the stout wall that separates the lower chambers was most susceptible to the effects of caffeine and ephedrine:
  

  "In the anterior section of this region, both caffeine + ephedrine combination as well as the multicomponent supplement Metabolife 356 resulted in larger numbers of atypical cells compared to water controls, in both saline- and nicotine-pretreated rats. However, only rats pretreated with nicotine responded negatively to supplements in the posterior region of the IVS. " (Brown. 2012)

  If you consider the high-pressure forces it must sustain for proper ejection volume to the arterial vasculature it should be obvious that "these changes to the ventricular tissue could be particularly detrimental to overall cardiovascular health" (Brown. 2012). Bad news? Why? At least you do now have another good reason to stop smoking... what, oh yeah, I forgot: This is irrelevant because Ephedra has been banned anyway ;-)

While I do have a couple of other Seconds I am a bit pressed on time, today. Don't worry sooner or later they will appear ither on the SuppVersity Facebook Wall, where I am posting at least half a dozen of exclusive links and mini-items, comments and more you won't find on www.suppversity.com. So, I'd suggest you do now first listen to the podcast (if you have not already done so), then check out the latest SuppVersity Facebook News and when you are done with that wait till tomorrow for this weeks installment of On Short Notice.  

References

• Brown CE, Trauth SE, Grippo RS, Gurley BJ, Grippo AA. Combined Effects of Ephedrine-Containing Dietary Supplements, Caffeine, and Nicotine on Morphology and Ultrastructure of Rat Hearts. Journal of Caffeine Research. 2012; 2(3).
• D’Aniello G, Ronsini S, Notari T, et al. D-Aspartate, a Key Element for the Improvement of Sperm Quality. Advances in Sexual Medicine, 2012, 2, 47-53.
• Miller KKM, Al-Rayyan N, Ivanova MM, Mattingly KA, Ripp SL, Klinge CM, Prough RA. DHEA metabolites activate estrogen receptors alpha and beta. Sterespectivelyroids. November 01, 2012. Ahead of print.
• Yamashita Y, Wang L, Tinshun Z, Nakamura T, Ashida H. Fermented Tea Improves Glucose Intolerance in Mice by Enhancing Translocation of Glucose Transporter 4 in Skeletal Muscle. J Agric Food Chem. 2012 Nov 5.

Fat Burners Don't Work in the Obese!? BAT Activity Almost Zero, Even after the Ingestion of ~290mg Ephedrine!

Do thermogenic fat burners only work if you already look like this? I mean, what would be the sure, then and why did the ECA stack work for overweight people, as well?

I don't know if you have ever thought about the problems mostly involuntarily obese individuals are facing in their everyday lives!? Even if you discard the constant bullying and the subliminal messages they receive from their peers, not fitting into a regular seat in an airplane certainly is more than just an embarrassment. Now what would you say, if I told you that they are discriminated against even, when they shop at their local GNC, or whichever other supplement vendor they may be using? And I am not talking about the lean guys and girls on the labels of the supplements, here! No, I am referring to a discrimination that takes place on a more fundamental level and it happens right in front of the shelf with every overweight person's favorite supplements: The so-called fat burners!

Ok, now that I got everyone's attention, I guess its about time to break the news: Fat burners don't burn fat!

If this does not happen to be your first visit, here, at the SuppVersity you may now be asking yourself how an (unfortunately still not so) common wisdom like this could make it into the news... right? Well, the answer is simple: In addition to the fact that the active fat burning effects of almost all thermogenics are negligible, so that they can - if anything - support your nutritional weight loss efforts by making it easier for you to stick to your diet and training regimen, a recent study by Carey et al. suggests that the minimal effects they do actually have diminish with each pound of superfluous body fat you are carrying around (Carey. 2012).

"Hold on! 2.5mg/kg ephedrine? That's 170mg and 287.5mg ephedrine. That's madness!" Usually I would say "yeah, you are right", but based on previous studies (Nedergaard . 2011), Carey et al. knew that 1.0mg/kg did not elicit any BAT activity, despite significant physiological adrenergic responses (blood pressure and heart rate; cf. Astrup. 1985a,b). I still don't have to tell you not to "try that at home" - and this is more than just a "parenteral advisory" ;-)

In a randomized, double-blinded, crossover trial, the Australian researchers administered 2.5 mg/kg of ephedrine to nine lean (BMI 22±1 kg/m²) and nine obese (BMI 36±1 kg/m²) young men and measured the thermogenic response of their "fat burning" brown adipose tissue (note: BAT burns glucose as well and the activity of the latter is usually measured by [18F]fluorodeoxyglucose, which can be detected via PET-CT imaging).

Figure 1: PET-CT scan of lean (left) and obese (right) individual (Carey. 2012)

As the images in figure 1 clearly shows the actual BAT activity (located in the neck, where humans carry almost all their BAT; cf. Zingaretti. 2009), which has long been hailed as the underlying reason of the real-world effects the administration of ephedrine HCL, ephedra or mua huang, was far from earth-shaking and by no means comparable to what you would expect based on the almost legendary status of ephedrine as "the most potent thermogenic" that ever hit the market.

Keep in mind: There are also inter-individual differences in the amount of BAT people have. Still the differences between lean and obese were so pronounced that you can hardly argue that the results of the study were mere coincidence.

What is even more striking than the overall magnitude of BAT activity the scientists observed is however that the latterw was more or less completely absent in the obese individuals -- and that despite the fact that I am honestly wondering none of them collapsed after ingesting his 287mg of ephedrine (remember the dosages were scaled according to body weight!). When you think about it, the scientists subsequent conclusion that they have...

"[...] demonstrated for the first time that BAT can be activated in the majority of lean, but not in obese humans with a single dose of ephedrine" (Carey. 2012)

could in fact have far reaching consequences that are not simply restricted to the use of respective dietary supplements, but extend into the realms of the development of future anti-obesity drugs and the use and usefulness of "alternative" obesity "treatments", such as cold exposure, as well.The latter for example may be a more potent activator of BAT activity than ephedrine, but it's falling short, when it comes to the centrally mediated effects, of which it is now becoming increasingly clear that they and not the insignificant BAT activity must be responsible for the indisputable real-world weight loss effects, both, lean and overweight individuals, have seen in the past, when they consumed much lower doses of ephedrine, than the subjects in the study at hand.

Figure 2: BAT activity, nor-adrenaline response, changes in systolic (SBP) and diastolic (DBP) blood pressure in response to 2.5mg/kg body weight ephedrine in lean and obese subjects (data based on Carey. 2012)

If we also take into account that ephedrine is probably still one the most potent inducers of BAT activity among the (formerly) OTC thermogenics and most currently available (and recently banned) ingredients are nothing but central nervous system stimulants, the scientists' remark that their "data highlight[s] the poor responsiveness of BAT to systemic adrenergic stimulation compared with that of the cardiovascular system", should actually make it pretty obvious why so many of the purported (and in some cases even factual) thermogenics don't deliver the "fat burning" results their consumers are expecting: At the moment they start to work, the cardiovascular side-effects are already in the "danger zone", so that anything but a negligible increase in thermogeneisis is rare in the lean and - as the study at hand would suggest - probably totally absent in the average obese diet pill junkie.

Thermogenics won't work for you, but you can work with them... not infinitely, though! 

You can't light the candle from both sides and still expect it to last forever. Stims and meditation are like Jing and Jang, and you got to master them both (read more about how meditation can increase telomere length by 50%).

That many of these products do still work and that they do so even in the obese, as long as they are willing to accept that these products are adjuvants to and not replacements for a sound nutrition and exercise regimen, is thus probably more of a result of their ability to keep you training and dieting longer and harder, than due to any real "thermogenenic" effect. That said, I guess, I don't have to tell you that you cannot light the candle from both sides and expect to last it forever, do I?

Oh, I see, ... I would first have to to tell you what that's supposed to mean, right?! Well, basically it means that unless you want to make the acquaintance of "adrenal fatigue", "central fatigue syndrome" and the "athlete's triad", you better restrict the use of respective products to short time periods of max. 4-6 weeks and make sure not to (ab-)use them to simply ignore the physical necessity of rest and recovery! Believe it, or not, both of them are equally, if not more important, when you are trying to get ripped, as they are, when you are trying to get buffed.

References:

• Astrup A, Lundsgaard C, Madsen J, Christensen NJ. En-hanced thermogenic responsiveness during chronic ephedrine treatment in man. Am J Clin Nutr. 1985a; 42:83–94
• Astrup A, Bulow J, Madsen J, Christensen NJ. Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man. Am J Physiol. 1985b; 248:E507–E515
• Carey AL, Formosa MF, Van Every B, Bertovic D, Eikelis N, Lambert GW, Kalff V, Duffy SJ, Cherk MH, Kingwell BA. Ephedrine activates brown adipose tissue in lean but not obese humans. Diabetologia. 2012 Oct 13.
• Nedergaard J, Bengtsson T, Cannon B. New powers of brown fat: fighting the metabolic syndrome. Cell Metab. 2011 Mar 2;13(3):238-40.
• Vosselman MJ, van der Lans AA, Brans B, Wierts R, van Baak MA, Schrauwen P, Lichtenbelt WD. Systemic β-Adrenergic Stimulation of Thermogenesis Is Not Accompanied by Brown Adipose Tissue Activity in Humans. Diabetes. 2012 Aug 7.
• Zingaretti MC, Crosta F, Vitali A et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J, 2009; 23:3113–3120.

Ephedra is Back! 'Mahabala', Featuring PEA, Ephedrine, Choline, Betaine & More, Is Nature's Hypolipidemic, Anti-Diabetic and Cardioprotective Fat Burning Stack

Image 1: Sida rhomboidea
leafs contain ephedrine and
other fat loss related alkaloids
(Tan Hoard Exports)

If you are a supplement producer, I suppose you will soon drop me an email to get the phone number of Ranjitsinh V. Devkar from the Division of Phytothrapeutics and Metabolic Endocrinology at the Department of Zoology of the M. S. University of Baroda in Gujarat, India. And, I must admit, if I had not always believed that "Nature knows best!", I would probably have been similarly surprised as some of you will have been, when they read the title of this blogpost - the 'ingredient profile' of Sida rhomboidea (also Sida rhombifolia), or  "Mahabala", a weed that is found in marshy places all across India and that has been used in Ayurvedic medicine for centuries to treat fever, heart disease, ever, heart diseases, burning sensations, urinary disorders, piles and all kinds of inflammation, looks like it had been printed on a non-FDA-approved (and thus potentially effective ;-) fat burner.

Figure 1: Alkaloid content of Sida rhomboidea extract (data adapted from Prakash. 1981)

If you have been following the exponential growth of the supplement market and the allegedly creative ideas the supp-designers had as far as fat burners were/are concerned, you will notice that, vasicinol and vasicinone aside, all the alkaloids, as well as choline and betaine Prakash et al. found in an extract from 5kg of Sida rhomboidea sound vaguely familiar.

Figure 2: Chemical structure
of the alkaloid vasicinone
(extracted from seeds of
Peganum Nigellastrum
by Zhang. 2009)

Vasicinol, vasicinone? What is that? Despite the fact that there is not much reliable data on the pharmacology of vasicinol and vasicinone, the two less well-known alkaloids in Sida rhomboidea, the available scientific data and information on their traditional use in Ayurveda suggests that these compounds, which are also present in other Ayurevedic herbs, exhibit hyopglycemic, as well as weak anti-acetylcholinesterase (Zhang. 2009) and bronchodilatory (Amin. 1959) effects. All three of these, which entail lower blood sugar levels, increased levels of acetylcholine and beta-adrenergic activity (which is the most likely explanation for bronchodilatory effect of the alkaloids), could synergistically help facilitate weightloss.

In view of this potent 'ingredient profile', it is no wonder that the addition of 1% of this natural fat loss wonder to the hypercaloric high fat diet (+58% more energy than low fat chow) of male C57BL/6J mice (6–8 weeks of age) staved off >25% of the 20-week weight gain (cf. figure 3) the unsupplemented HFD group experienced with respect to a low fat fed control group in the most recent of a whole series of rodent studies, Devkar et al. have conducted over the course the last years (Thounaojam. 2011).

Figure 3: Weight [in g] of mice during 20 weeks on control, high fat (HFD) and high fat diet with 1% Sida rhomboeidea extract (data adapted from Thounaojam. 2011)

From a health perspective, it may yet be even more important that the Mahabala supplement also prevented the "HFD induced increment in [...] plasma lipids and leptin, visceral adiposity and adipocyte hypertrophy" the scientists had observed in the unsupplemented group. The authors attribute these effects to the down-regulation of PPARγ2 and leptin gene expression that went hand in hand with an attenuation of food intake in the C57BL/6J mice.

Image 2: Mice on low fat (A), high fat (B)
and high fat diet + 1% Sida rhomboeidea
extract after 20 weeks (Thounaojam. 2011)

The decline in food intake, the scientists had already observed in previous studies , makes it quite difficult to give a definite number on the absolute amount of Sida rhomboeidea extract the mice consumed on a daily basis. It ranges from 25mg at the beginning of the study to ~13mg at the end and would translate into a human equivalent dose of 2mg/kg and 1mg/kg of Sida rhomboeidea extract per day. If the simple mathematical calculation that is solely based on the ratio of body surface to weight would suffice to reliably translate data from a rodent model to humans, an 80kg human being would thus have to consume somewhere between 80mg and 160mg of Mahabala per day to see similar effects.

Now, you may argue that, after all, this "wonder extract" turns out to be just another appetite suppressant. Yet, while Mahabala did affect the appetite of the laboratory animals, its profound in-vitro effects on pre-adipocytes differentiation and leptin release, as well as the previously mentioned changes in PPARγ2 and leptin gene expression, the scientists observed in the rodent model, suggest that the primary mechanisms for Mahabala's preventive effects against weight and fat gain (-56% less abdominal fat, -46% less epidididymal fat) is unrelated to the reduction in food intake.

Figure 4: Effect of Sida rhomboeidea extract (SR) and Rosiglitazone (ROS) on insulin tolerance in C57BL/6J mice after 16 weeks on low fat (LFD) or high fat diet (HFD) containing 1% (SR1) or 3% (SR2) SR or  0.05% ROS (data adated from Thounaojam. 2010)

Add to that its profound (as potent as the anti-diabetes drug Rosiglitazone) effects on insulin sensitivity (cf. figure 4) the researchers had observed in a previous study (Thounaojam. 2010) and remind yourself of the fact that not ephedrine, but its foolish and unnecessary abuse / overconsumption were responsible for the unfortunate deaths of a handful of people, the majority of whom had preexisting health problems (yes, being severely overweight is a health problem), and you will probably agree with Ranjitsinh V. Devkar and his colleagues who conclude that their findings "validate the potential application of SRLE as a therapeutic agent against obesity". And, if you asked me, I bet that it won't take long until you see the first Mahabala supplements hit the highly competitive fat loss market - despite the fact that an ephedrine-containing Ayurvedic herb probably ain't FDA compliant ;-)

Bofu-Tsusho-San: Ephedrine Based Kampo Kitchen Sink Fat Burner Cuts 10kg Body Weight, Boosts Metabolism by +15% & Reduces Insulin of Diet-Resistant Woman by 50%

Is there a Japanese  weight loss wonder supplement not even Dr. Oz knows about? And could it be more effective than Oz's raspberry ketones?

Sometimes the most inconspicuous articles turn out to be the most interesting ones. I mean, who would have guessed that a case report titled "Japanese herbal medicine for weight loss in a morbidly obese patient: A case report" would make it into the SuppVersity news? Being as heavy as tall, in this case 154.8 kg distributed not very proportional on a 157 cm frame with an 155cm waist, is - as unfortunate as that may seem - not exactly uncommon these days - even for a 22-year old woman. The words "japanese herbal medicine" and the line "her resting metabolic rate (RMR) increased from 2260 to 2440 kcal/day" (Haruta. 2013) the abstract mentions right after discussing her 10kg weight loss peaked my interest.

How bad off was the subject?

The subject had obviously been yoyo-dieting for years, when she was as hospitalized in the researchers' department for the purpose of weight loss.

"Her heart rate was approximately 100 beats per minute and her blood pressure was 156/108 mm Hg. Upon initial admission, we performed blood work, abdominal ultrasonography (US), and a head computed tomography (CT) to exclude secondary adiposis."

A biochemical examination of her blood yielded

To eat or to diet, what's worse? Some people argue that "dieting just makes you fat" and we all know about the yoyo effect, but is that (a) true and (b) what effects does it have on your over and metabolic health? (learn more)

• marginally elevated ALT levels;
• marginally elevated uric acid, but 
• normal creatinine and BUN levels;
• low HDL levels (bottom of the range), and 
• high-normal LDL levels;
• elevated HbA1c and fasting blood glucose levels,
• highly elevated insulin levels (2.7x), and
• highly elevated (5.5x) CRP levels
• normal cortisol, normal growth hormone, but 
• slightly elevated ACTH levels
• slightly elevated testosterone levels, but 
• otherwise normal endocrine function

Although the  elevation of ALT was marginal and the other parameters of liver health appeared in range, a fatty liver and a left ovarian tumor were detected by abdominal ultrasound.Unfortunately both not exactly uncommon in subjects with full blown metabolic syndrome, which is - according to International Diabetes Federation criteria - defined as having...

• hypertension, blood pressure>130/85 mm Hg, 
• abdominal circumference > 80 cm

• HDL-C < 50 mg/dL, and 
• plasma glucose>100 mg/dL

The doctors at the Department of Psychosomatic Internal Medicine of the Kagoshima University Graduate School of Medical and Dental Sciences in Kagoshima, Japan, prescribed a reasonable exercise program and a calorically restricted diet containing 2,000kcal and thus ca. 12% less than the subjects resting metabolic rate (measured by respiratory exchange ratio; 2260 kcal/day). That did help her to lose ~5kg during her stay at the hospital, but at 150kg the weight loss stalled until....

Things changed, when the scientist prescribed bofu-tsusho-san

Bofu-tsusho-san  has been used in Kampo, the Japanese study and adaptation of Traditional Chinese medicine (TCM), for decades and though I have to admit I had not heard about it before, there is actually existing evidence for its efficiacy as a weight loss adjuvant:

Figure 1: Bofu-tsusho-san (BTO) does what you expect from a potent weight loss helper. It keeps your metabolic rate up - and even better BTO even increases it on a per lbs of body mass basis (Hioki. 2004)

• higher body fat loss, greater weight loss, no reduction in BMR + improved insulin response and lower homa-IR in 40 Japanese women (body mass index (BMI) 36.5 +/- 4.8 kg/m2) with IGT and insulin resistance (IR), who had been treated with a low-calorie diet (5016 kj/day: 1200 kcal) and an exercise regimen (1254 kj/day: 300 kcal) compared to 40 women in the placebo group (Hioki. 2004).

• blunts the weight gain patients on anti-psychotics (Zyprexa = olanzapine) often experience (Yamamoto. 2009).
   
• works by three distinct pathways, i.e. via the inhibition of triglyceride synthesis in the liver, and the enhancement of lipolysis in adipocytes and of thermogenesis in brown adipose tissue. At least that's what early studies in rodents suggest (Morimoto. 2001). 

The preparation has an overall favorable safety profile, with a tolerable intake of 2g/kg in rodents and thus ~325mg/kg in humans. Nevertheless, Bofu-tsusho-san is not totally devoid of side effect, there are two case reports of pneumonitis that occured after ~1 months of treatment with the drug and went away when the herbal was discontinued (Masushima. 2002; Suzuki. 2004).

For the subject in the study at hand, it may yet eventually turn out to be a life saver. After all the fat that had been coming back for more after each and every diet kept melting away, even after her stay at the hospital and when she reported back for the last examination before the paper was written, she had lost 10kg. That left her still morbidly obese, but with the initially mentioned +8% in resting metabolic rate (+15% if you express that relative to her body weight), improved fasting glucose levels (-31%) an HbA1c of 5.5.% (-17%) and immuno reactive insulin levels of 27.9 mU/mL (-45%!) she may not have been on her way to the cover of Shape, but (and this may be even a contrast) to a non-life-threatening body weight.

Let's look at the formula: Some old acquaintances in here

Did you know... that ephedrine HCL is not just a beta agonist, but also a potent anti-inflammatory? According to the results a group of scientists presents in the latest issue of Cellular & Molecular Biology, ephedrine HCL is "a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection"!? This conclusion is based on the observation that EHCL increases the levels of the anti-inflammatory interleukin-10 (IL-10) and decreases the release of proinflammatory cytokines (IL-6, TNF-alpha, IL-12 and IL-1beta) in immune cells that are stimulated with a component of the cell walls of gram-positive bacteria (Zheng. 2013)

Bofu-tsusho-san has also been shown (in vitro; Katoh. 2009) to inhibit beta-estradiol 3-glucuronidation, which is yet probably only a problem if you ingest it in very high amounts, an undertaking that could pose other problems even before you realize that its blocking your estrogen metabolism due to the sympathetic overactivation caused by ingredient #1 on the list below:

• Ephedrae herba (EH; contains ephedrine),
• Glycyrrhizae radix (GR; contains licoricidin), 
• Forsythiae fructus (FF; contains D-pinoresinol), and
• Schizonepetae spica (SS; inhibits phosphodiesterase enzymatic activities).

Looks pretty much as if it came right from the labs of an innovative supplement company, who've been following the SuppVersity news and articles pretty closely, right? Ok, everybody knowas about the beta-agonist qualities of ephedrine that may not have been important, but the fat-loss prowess of licorice (cf. "All about cortisol"), as well as the potential application of phosphodiesterase inhibitors to alleviate insulin resistance and promote fat loss (cf. Jansson. 2010; Murdolo. 2012) Carl and I mentioned on one of the past episodes of the Science Round Up would be something they may have picked up, here...

"Enough of the bragging, Adel!"

Ok, ok. I have to admit that it would have required some research on their part to come up with the additional Forsythiae fructus extract and the

• antihyperglycemic (Wikul. 2012), 
• antihypertensive (Greeneway. 2011),
• antifungal (Hwang. 2010) and 
• antioxidant effects - particularly in the gut (Jung. 2010; During. 2012) 

of its D-pinoresinol glycosoids, to come up with this ingenious invention, if it had not already been invented by an unknown Japanese Kampo practitioner decades ago, I should say ;-)

---

The Kitchen Sink Approach to fat loss is surprisingly effective(learn more)

Bottom line: While I believe nobody will be arguing that the ephedra part of the formula is probably the most effective ingredient, it's interesting to see that traditional medicine has already come up with "drugs", or rather herbals, that make use of synergies such as the weight loss benefits of PDE inhibtors, the Western allopathic medicine starts to understand, only now.

That these synergies can do the trick in commercially available supplements, as well, is something we have seen about a week ago, with the "Kitchen Sink Fat Burner" (learn more).

And still, not knowing which of the ingredients are actually responsible for the observed benefits is an unquestionable downside. A downside due to which I can't tell you if the classic E+C stack would be as, less or even more effective than the "kambo version of ECA". What I can tell you, though, is that the addition of Schizonepetae spica to the legendary "fat loss classic" makes sense. The same would go for Glycyrrhizae radix and Forsythiae fructus, which appear to make particularly good match as the latter will counter potentially blood pressure elevations due to the former.

References:

• During A, Debouche C, Raas T, Larondelle Y. Among plant lignans, pinoresinol has the strongest antiinflammatory properties in human intestinal Caco-2 cells. J Nutr. 2012 Oct;142(10):1798-805.
• Greenway F, Liu Z, Yu Y, Gupta A. A clinical trial testing the safety and efficacy of a standardized Eucommia ulmoides Oliver bark extract to treat hypertension. Altern Med Rev. 2011 Dec;16(4):338-47. 
• Hioki C, Yoshimoto K, Yoshida T. Efficacy of bofu-tsusho-san, an oriental herbal medicine, in obese Japanese women with impaired glucose tolerance. Clin Exp Pharmacol Physiol. 2004 Sep;31(9):614-9.  
• Hwang B, Lee J, Liu QH, Woo ER, Lee DG. Antifungal effect of (+)-pinoresinol isolated from Sambucus williamsii. Molecules. 2010 May 14;15(5):3507-16.
• Jansson PA, Murdolo G, Sjögren L, Nyström B, Sjöstrand M, Strindberg L, Lönnroth P. Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes. Diabetologia. 2010 Oct;53(10):2205-8. doi: 10.1007/s00125-010-1819-4. Epub 2010 Jun 10. 
• Jung HW, Mahesh R, Lee JG, Lee SH, Kim YS, Park YK. Pinoresinol from the fruits of Forsythia koreana inhibits inflammatory responses in LPS-activated microglia. Neurosci Lett. 2010 Aug 23;480(3):215-20.
• Katoh M, Yoshioka Y, Nakagawa N, Yokoi T. Effects of Japanese herbal medicine,
  Kampo, on human UGT1A1 activity. Drug Metab Pharmacokinet. 2009;24(3):226-34.
• Lee MY, Shin IS, Seo CS, Kim JH, Han SR, Shin HK. Subchronic oral toxicity
  studies of the traditional herbal formula Bangpungtongseong-san in Crl: CD (SD)
  rats. J Ethnopharmacol. 2012 Dec 18;144(3):720-5.
• Matsushima H, Takayanagi N, Ubukata M, Tokunaga D, Mori S, Sato N, Kurashima K, Yanagisawa T, Sugita Y, Kawabata Y, Kanazawa M. [A case of pneumonitis induced by Bofu-tsusho-san]. Nihon Kokyuki Gakkai Zasshi. 2002 Dec;40(12):955-9.
• Morimoto Y, Sakata M, Ohno A, Maegawa T, Tajima S. [Effects of bofu-tsusho-san, a traditional Chinese medicine, on body fat accumulation in fructose-loaded rats]. Nihon Yakurigaku Zasshi. 2001 Jan;117(1):77-86.
• Murdolo G, Sjöstrand M, Strindberg L, Lönnroth P, Jansson PA. The selective phosphodiesterase-5 inhibitor tadalafil induces microvascular and metabolic effects in type 2 diabetic postmenopausal females. J Clin Endocrinol Metab. 2013 Jan;98(1):245-54. 
• Suzuki S, Tanaka A, Arai T, Adachi M. [Case of interstitial pneumonitis induced by a Chinese herbal medicine, bofu-tsusho-san]. Nihon Kokyuki Gakkai Zasshi. 2004 Aug;42(8):777-81. Japanese.
• Yamamoto N, Inada T. Bofu-tsusho-san effectively attenuates the weight gain
  observed after receiving olanzapine. Psychiatry Clin Neurosci. 2008
  Dec;62(6):747.
• Wikul A, Damsud T, Kataoka K, Phuwapraisirisan P. (+)-Pinoresinol is a putative hypoglycemic agent in defatted sesame (Sesamum indicum) seeds though inhibiting α-glucosidase. Bioorg Med Chem Lett. 2012 Aug 15;22(16):5215-7.
• Zheng Y, Yang Y, Li Y, Xu L, Wang Y, Guo Z, Song H, Yang M, Luo B, Zheng A, Li P, Zhang Y, Ji G, Yu Y. Ephedrine hydrochloride inhibits PGN-induced inflammatory responses by promoting IL-10 production and decreasing proinflammatory cytokine secretion via the PI3K/Akt/GSK3β pathway. Cell Mol Immunol. 2013 Apr 22.

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

Image 1 (odditycentral): Jin Songhao, one of China’s most seasoned icemen and not exactly as lean as you may expect based on what you currently read around the blogosphere, managed to beat the previous world record for the longest ice bath - 120min! Congrats, Jin!

Ephedrine for years the go-to OTC fat burner for physique athletes and average Joe's and Jane's alike is no longer (officially) available: No matter how bold the label claims about X mg of "ephedra extract" may be - NONE(!) of the currently available "ephedra based" over-the-counter (OTC) fat-burners contains significant amounts of the active alkaloids, which made the old Mua huang based herbal ephedra products so effective. Against that background, dieters are constantly on the look-out for novel "gimmicks" to help them finally get rid of those annoying love-handles. One of those gimmicks, which has caught quite some attention as of late, is called "cold thermogenesis" and revolves around the idea that our bodies should consume more energy to keep a normal body temperature in a cold, compared to a normal temperature environment.

How is that different from a "thermogenic fat burner"

The most obvious difference between cold thermogenesis and "thermogenic fat burners" is actually so straight forward that I hardly dare stating that the former is induced by exposing yourself to low(er than normal) temperatures, while the promise of the latter is that the various ingredients of currently or formerly available OTC "fat burners" will induce a thermogenic response, irrespective of the current ambient temperature.

Figure 1: Antropomorphic data of the study participants (Cypess. 2012)

The results of a recently published study from the the Boston Harvard Medical School does yet provide somewhat more sophisticated insights into the differences between cold exposure and a sympathomimetic (i.e. an activator of the sympathetic nervous system), such as ephedrine. On three separate, independent study visits that took place in random order the ten healthy volunteers (age 27.1 years) who participated in the study (see figure 1 for DEXA based anthropometric data) and had been fasting since 12am the day before were exposed to one of the following "stimuli":

• ephedrine - a single intramuscular dose of 1mg/kg ephedrine
• saline control - an equal volume of saline
• cold exposure - in a surgeon’s cooling vest (Polar Products) w/ water temperature 14 °C

60min after the injection of ephedrine, saline, or the initiation of cold exposure, the change in metabolic rate was measured and blood was drawn to determine several metabolic and endocrine markers. Another 60min later, PET-CT scanner images (cf. figure 2, right) to quantify BAT mass and activity were taken. Since the participants obviously had to get rid of their cooling vests for this procedure, the total cold exposure time was limited to 120min, so that it is questionable how valid the 24h energy expenditure calculation (cf. figure 3) actually is. After all, it is not very likely that the norepinephrine levels would constantly stay at 200% over baseline (cf. figure 2).

Figure 2: Metabolic and endocrine effects (expressed relative to saline) of ephedrine injection and cold exposure (main image); CT scans with green arrows in the combined scans indicating  the principal cervical, supraclavicular,
and thoracic depots of BAT (Cypess. 2012)

As far as the acute phase is concerned, it is yet quite obvious that both cold exposure and ephedrine elicited statistically significant effects on various metabolic and endocrine parameters. The exact nature and the purported mechanism that is responsible for these metabolic and endocrine effects are however very different for both treatments:

• while ephedrine lead to an increase in blood glucose (probably subsequent to increased glyconeogenesis), cold exposure did not 
• while ephedrine lead to significant increases in lactic acid levels (corresponding to increases in glucose + glucose oxidation), cold exposure did not
• while ephedrine lead to profound increases in β-hydroxybutyrate (increased ketone productions from fat), cold exposure did not
• while ephedrine increased serum non-esterified fatty acid (NEFA) concentrations (due to increased lipolysis), cold exposure did not
• while ephedrine elevated insulin production (probably due to stress induced insulin resistance), cold exposure did not (p = 0.29)
• while ephedrine lead to highly significant (p < 0.001) increases in C-reactive peptide, cold exposure elicited "only" significant elevations (p = 0.005)
• while ephedrine produced already highly significant increases in noripenephrine levels, those were even more pronounced upon cold exposure
• while ephedrine lead to statistical significant increases in thyroid hormone Total T3 (+14%, p = 0.026) and Free T4 (+19%, p = 0.014), cold exposure did not
• while ephedrine lead to a profound (-22%) and statistical significant (p = 0.007) drop in ghrelin ("hunger hormone" and metabolic regulator), cold exposure did not

In conjunction with the combined CT scans from figure 2 these differences clearly indicate that contrary to ephedrine, which is a mere sympathomimetic (put simply a potent "stim" ;-) without depot-specific (here brown adipose tissue) thermogenic effects, mild cold exposure (remember: those were no ice-baths!) has the ability to stimulate brown adipose tissue (BAT) energy expenditure without significant systemic effects on heart rate or thyroid hormone metabolism.

What does that mean? Is GNC soon going to carry cooling vests instead of fat burner pills?

If you read the scientists' rave conclusion that "[i]n contrast to ephedrine [...] mild cold exposure stimulates a specific response by the SNS [sympathetic nervous system] to activate BAT and increase energy expenditure with few other metabolic effects" and their subsequent reference to the "obesity and diabetes pandemics" and the demand for "safe and novel treatments" of the latter, it is quite understandable that people who are referred by their gurus to "scientific evidence" like this are willing to believe that "cold thermogenesis" would help them to finally get rid of their beer-, burger- and burrito-bellies.

Figure 3: Increase in 24h energy expenditure (kcal/day, left) and detectable BAT volume (right; Cypess. 2012)

If you do yet take a look at the actual metabolic effects (cf. figure 3) the 2x more pronounced effect of ephedrine on 24h energy expenditure (+140kcal/day vs. 70kcal) confirms what my previous overview of the metabolic and endocrine effects of ephedrine and cold exposure already suggested: Ephedrine does not simply have more "side effects" it is also more effective.

Figure 4: Activity of BAT activity in relation to body fat levels (van Marken Lichtenbelt. 2009)

Important:  One thing the scientists wink at in both the abstract as well as the conclusion are the profound inter-individual differences in terms of detectable BAT volume and activity. While the median volume of detectable brown adipose tissue in men and women was 22mL and 20mL, respectively, there was one female subject with a BAT mass of 190mL (85x over median!), one with 7ml and one woman without any detectable brown adipose tissue. Similarly, the BAT mass in the men ranged from 46mL to 12mL. Both the existence of individuals without any significant amounts of metabolically active body fat, as well as the observation of high inter-personal variability in the study at hand stand in line with previous results of Saito et al. who found a ratio of 15/32 (45%) non-responders in young (23-35y) and 22/24 (92%!) in older (38-65y) subjects (Saito. 2009). And as if that alone would not render the practical value of cold exposure as a means to battle the "obesity and diabetes pandemic" questionably enough, van Marken Lichtenbelt et al. report that exactly those people for whom ephedrine and other sympathomimetics such as sibutramine would actually pose a non-negligible health risk, i.e. obese and metabolically deranged people, don't just have 40% less brown adipose tissue, but also a -76% reduced BAT activity (van Marken Lichtenbelt. 2009; cf. figure 4). The implications of these findings should be obvious: It is a) by no means certain that sitting in a non-heated room, let alone an ice-bath, is not just going to give you a cold, but even if it works it is b) probably not going to make a difference for those people who need it most - I mean, let's do the math: "70kcal/day minus 76% of the former equals 16.8kcal per day"!

That being said, even the profoundly greater total increase in energy expenditure in the ephedrine group is of a "magnitude" (I would write "minitude" if such a word existed) that would be completely negligible if it were not for the bad and "dangerous" sympathostimulating side effects (Andraws. 2005), which will allow you to train longer, to diet harder (Astrup et al. ascribe 75% of the weight loss effect due to the ingestion of the infamous ECA stack to anorexia, i.e. loss of appetite; cf. Astrup. 1992) than any ice-filled bathtub in the world will ever do.

Skip on ice-baths, stop winning about the ephedra ban. Get your diet & workouts in check!

Image 2: I don't think Francine Sablan, IFBB Figure Pro and like Adelfo one of Myotropics' sponsored athletes, uses the air-conditioning, let alone a funky cooling vest or ice-baths to propel her fat loss. And why would she? She loves working out and she has her diet in check ;-)

I know this is not going to be a popular conclusion, but believe me, the additional +70kcal/day you could expend in the cold, if you are one of the lucky non-obese "responders" (see red box above), won't make you lose a single pound. Even the "good old" ECA stack (remember: the Cypess study used intravenously administered ephedrine; hence, the effect sizes are directly comparable with pertinent studies from the late 1980s and 1990s using orally administered herbals) worked its fat burning magic only, when it was combined with a comprehensive diet and exercise protocol - and in those scenarios it was mostly the influence of its sympathostimulating activity on your ability to adhere to your diet and to endure the hardships of strenuous workouts and not its often-touted and largely overestimated "thermogenic" effects (cf. Astrup. 1985; Astrup. 1992) that were mostly responsible for the larger-than-life results, people are still raving about.

References:

1. Andraws R, Chawla P, Brown DL. Cardiovascular effects of ephedra alkaloids: a comprehensive review. Prog Cardiovasc Dis. 2005 Jan-Feb;47(4):217-25. 
2. Astrup A, Bülow J, Madsen J, Christensen NJ. Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man. Am J Physiol. 1985 May;248(5 Pt 1):E507-15.
3. Astrup A, Toubro S, Christensen NJ, Quaade F. Pharmacology of thermogenic drugs. Am J Clin Nutr. 1992 Jan;55(1 Suppl):246S-248S.
4. Cypess AM, Chen YC, Sze C, Wang K, English J, Chan O, Holman AR, Tal I, Palmer MR, Kolodny GM, Kahn CR. Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc Natl Acad Sci U S A. 2012 Jun 4. 
5. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009 Apr 9;360(15):1500-8. Erratum in: N Engl J Med. 2009 Apr 30;360(18):1917.
6. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009 Jul;58(7):1526-31. Epub 2009 Apr 28.

Ephedrine, Exercise or Diet? Ephedra Modulates Substrate Utilization, but Exercise Melts Body Fat & Builds Muscle

Image 1: Twinlabs' made a fortune on their line of ephedra containing fat burners.

For many people ephedrine, the "E" in the infamous ECA stacks and the alkaloid from the mua huang on which Twinlab and co. made a fortune in the late 1990s, was the first and only truly working fat-burner on the supplement market. "Legendary", "unique", "unparalleled", these are the attributes by which they like to refer to their old-school fat burner. What's missing from most of these stories, though, are the hardships, the hours of intense training and weeks of radical dieting that may have become more bearable, yet by no means obsolete with the use of respective products.

A 2012 look at diet, exercise and ephedrine

In a soon to be published paper, Nikki Sclotum and her colleagues from GlaxoSmithKline, the North Caroline State University and the Purdue University report on the results of an experimental comparison of ephedrine, diet and exercise based weightloss regimen in a mouse model of diet induced obesity (Slocum. 2012). The pre-fattened mice in the study were either ...

• given 18mg/kg of ephedrine, orally (human equivalent: 1.5mg/kg, or 117mg for an 80kg adult),
• forced to do steady-state-cardio at 10m/min on a treadill for 1h per day, or
• kept on a caloric deficit that was -26% below their maintenance food intake

And the results of the 7-day experiment confirm that many of those "magical weight loss effects of ephedrine" were actually rooted in the dietary and exercise regimen of the former ephedrine consumers and, if anything, simply augmented by the drug. The non-existence of statistically significant differences in body weight and body fat loss clearly supports this notion; and while the relative body-fat changes in the ephedrine group reached borderline significance, it should be mentioned that rodents who carry significant amounts of metabolically active brown fat on their small bodies, are way more susceptible to the beta receptor mediated thermogenic effects of ephedrine and co., than human beings - a good reason to meet all the study outcomes in the ephedrine group with some skepticism (this includes the increased UCP expression discussed later).

Figure 1: Changes in total body weight (g) and body composition (%) after 7 days (data adapted from Slocum. 2012)

The reduction in body weight and, more importantly, body fat levels in the exercise group, on the other hand, are not only (more or less) independent of the thermogenic potential of brown adipose tissue, they are also quite impressive and speak to the validity of my repeatedly propounded hypothesis that exercise is the #1 body recompositioning agent. Contrary to dietary restriction (and ephedrine), it does namely not just burn off body fat, but builds muscle as well - true "recompositioning", if you will, and an investment in "metabolic currency" (TM of my friend Carl Lanore ;-), of which you can draw for the rest of your life.

"So what? Is ephedrine totally useless, then?"

Figure 2: Respiratory exchange ratio of the animals in the control, diet, exercise and ephedrine groups on day 7 of the experiment (adapted directly from Slocum. 2012)

These observations alone would clearly raise the question if ephedrine, the "one true fat burner" as which it is still touted, was in fact similarly useless as its many successors. And I guess, if it were not for another very interesting finding of the study the answer would be "YES!". With its profound effects on the so-called respiratory exchange ratio, i.e. the amount of CO2 the animals exhaled per volume unit of O2 they consumed, it does yet exhibit a "substrate repartitioning" effects. With higher VCO2 : VO2 ratios indicating greater carbohydrate and lower fatty acid oxidation and lower VCO2 : VO2 ratios  indicating lower carbohydrate and higher fatty acid oxidation rates, a brief glance at the graph in figure 2 should suffice to see that the ephedrine group derived a significantly higher amount of energy from fatty acids than their comrades in crime, whose RERs of almost 1 would suggest that their small bodies ran primarily on glucose for fuel in the dark period, which is the time of the day, when rodents exhibit the highest activity level.

Ephedrine can increase the fat and thus decrease the carbohydrate oxidation. It cannot actively "burn" fat.

In other words, on a "calorie per calorie" base, the rodents on ephedrine used more fat than any of their peers. Due to the comparably small increase in UCP1 activity (~2x for ephedrine;  ~4x for exercise),a marker of increased increased fatty acid oxidation, as well as the lower overall energy expenditure (compared to the exercise) and greater caloric intake (compared to the diet group), their metabolic advantage of being "fat adapted" did yet not translate into statistically significant decreases in body fat let alone weight - most of the fat that was liberated by the ephedrine induced norepinephrine rush was, if you will, simply restored (or replaced) to (or in) the adipose tissue from which it had been liberated.

Ephedrine can help, when it is combined with exercise and/or diet!

In view of the fact that neither exercise, nor diet had comparably significant influence on the respiratory exchange ratio, it does still stand to reason that the almost legendary "fat burning" effect of ephedra- or mua-huang-based fat-burners was achieved by combining the shift towards fat and away from carbohydrate oxidation with the exercise induced increase in energy expenditure in the presence of and otherwise constant or moderately decreased energy intake, which often was a direct result of the anorexic effects of the plant alkaloid.

Warning: The supplement industry is well aware of the legendary reputation of the "good old ECA stacks" and tries to fool customers by loading their mostly caffeine based "fat burners" with "ephedra extracts", "ephedra leaf extracts" or similar ingredients, which may come from plants that belong to the same family, but do not contain any of the active alkaloids!

If we discard those appetite reducing effects, which are probably a side effect of greater fatty acids availability and reduced dependence on glucose as a main fuel source, this confirms the afore-made statement that ephedrine is more of an "energy substrate modulator" than a "fat burner" in the literal sense.

Ditch the ECA, embrace the DECaS stack

And while the addition of caffeine another "substrate modulator" amplified this effect, the effects of A, for aspirin, which was supposed to prolong the activity of E and C, ward off high blood pressure and other CVD related side effects and even prevent the habituation effect which come with the longterm use of every stimulant as a mere physiological result of the downregulation of (in this case) the beta-adrenergic receptors  have never been scientifically validated (it is also interesting to note that, in the study at hand, the brown adipose tissue beta receptor expression was reduced, but the reduction did not reach statistical significance over this short time span).

Bottom line: With the ban of (real, see red box above) ephedra based "fat burners" you may thus have a small disadvantage compared to the "veterans from the good old days", the ban did yet not effect the fundamental rules of body recompositioning: Train hard, don't cut your calories too extreme and, by all means, get enough and restful sleep... and if that is somewhat of a relief, with the DECa (=Diet, Exercise, Sleep and Caffeine) stack, restful sleep becomes significantly easier ;-)