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

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 ;-)

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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.