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marylin monroe
Showing posts with label Glycyrrhiza radix. Show all posts
Showing posts with label Glycyrrhiza radix. Show all posts

Cinnamon, Curcumin (Turmeric), Licorice (Glycyrrhizin), Melatonin, Milk Thistle (Silymarin). Supplements to Improve and Restore Insulin Sensitivity - Serving #3

Sleep hygiene was part of the lifestyle tips in the first episode of this series, with this episode you get a tool that can help you get back into the groove: melatonin.
This is Sunday number three with supplements that may help you improve / maintain your glucose sensitivity and I can already tell you it's going to be the last one. In other words, if there are any compounds that have not yet been covered in this series - just a reminder
  • Alpha Lipoic Acid, GABA, Taurine, Green Tea, Gooseberry & Fenugreek were addressed in detail as part of supplement list #1
  • Berberine, Banaba (Corosolic Acid), Rauwolfia Serpentina, (Apple Cider) Vinegar, Chromium were addressed in detail on supplement list #2 
- this is your last chance to make a wish! So, if you have something special in mind, use the comment section at the end of this article and tell me which agents you want to see in issue #4 on next Sunday.

Ah, ... it should be obvious that none of the following agents qualifies: Cinnamon, Curcumin (Turmeric), Licorice (Glycyrrhizin), Melatonin, Silymarin - why? Well those are the ones you can read about in the paragraphs below :-)
  • Dosages for cinnamon supplements range from 1-6g+ of pure real cinnamon (cinnamomum vera) to 150-500mg of extracts (depending on their quality). You should be aware though that "fake" cinnamon (cinnamomum cassia, which is sold in the US simply as "cinnamon") contains (highly variable amounts) of coumarin a liver toxic and carcinogenic substance w/ an upper intake limit of 0.07mg/kg body weight that may easily be exceeded by eating common foodstuffs like oatmeal with cinnamon in small children (Fotland. 2012).
    According to Fotland et al. this can lead to toxicity reactions within weeks. So don't be cheap and better make sure not to buy "fake cinnamon" (=cassia) for you or your kids and loved ones.
    Cinnamon (Cimmomium verum!) [B]: Cinnamon is unquestionably one of the best known supplements for diabetics. "High blood sugar? Have some cinnamon in your sugar-laden Starbucks coffee!"... and this is exactly where the problem is. Everyone knows that cinnamon works - acutely(!), because he or she can measure his blood glucose after the ingestion of the said Starbucks coffee with and without cinnammon, but...
    1. according to the latest meta-analysis the long-term benefits of using cinnamon to manage blood glucose levels in type II diabetics are zero - the most important measure of their overall glycemic status, i.e. HbA1c, does not change significantly; or I should say: it reacts formidable in studies lik Lu et al. (2012; 120 or 360mg/day treated alongside standard diabetes drug) and deteriorates in others (Mang. 2006; Wainstein. 2011; etc.)
    2. studies in healthy individuals suggest that the blood glucose lowering effects are a mere results of an inhibition of the digestion and absorption of high GI carbs (6g regular cinammon w/ rice or pudding; Hlebowicz. 2007)
    There is however recent evidence that some of the secondary plant material, i.e. the proanthocyanidins you will find in cinnamon water extracts exert a direct protective effect on stressed pancreatic beta cells.
    Just a note for those who feel I am a "supplement hater": I am not the only one displaying a healthy degree of skepticism towards the hoopla that surrounds the use of cinnamon as an anti-diabetic. The "gold standard" review from the Cochraine Foundation says: "There is insufficient evidence to support the use of cinnamon for type 1 or type 2 diabetes mellitus. Further trials, which address the issues of allocation concealment and blinding, are now required. The inclusion of other important endpoints, such as health-related quality of life, diabetes complications and costs, is also needed" (Leach. 2013)
    Overall, cinnamon is thus a "B" as in "one of the B-est agents to protect yourself from developing insulin resistance and diabetes": It can also be interesting for type II diabetic looking to improve his blood lipids, but this is a different topic (cf. Khan. 2003). So, if you can't keep away from the sweet stuff of which you know ever since episode 1 of this series that you are not supposed to eat it, some cinnamon won't hurt - if you hate the taste, though, don't force it down. It's not really worth gagging.
  • In healthy human beings the administration of 6g of curcuma longa before a 75g glucose tolerance test does just one thing: It spikes insulin without improving the glucose uptake. Technically this is a decrease - not an increase in insulin sensitivity, which would have to be observed if curcumin was an insulin-sensitizer.
    Curcumin (Turmeric; curcuma longa) [C] - Curcumin is probably among the hottest supplements out there. Everybody appears to know exactly what it does and obviously everything is ueber-potent and super-healthy. It does therefore appear almost unquestionable that curcumin is going to help with insulin resistance, as well... right? Well, unquestionable as it may apper, the mere assumption that it would do so is not just unwarranted, but downright misleading.

    While there is evidence that its anti-inflammatory effects can help restore normal insulin sensitivity in diabetic individuals and animals, such as the streptocitozin-induced diabetic rodents in a 2011 study by Na et al., the important evidence from human studies is not there. In fact, in a 2010 study from the Skåne University Hospital in Sweden, Wickenberg, Ingemasson and Hlebowicz were able to show that curcumin worsens the insulin sensitivity of fourteen healthy subjects.

    Being first and foremost and anti-inflammatory agent, it is at imho not surprising that curcumin is not the ideal insulin sensitizer. In view of the fact that the obese and inflamed may need a little help to get their baseline inflammation back in check, before any "anti-diabesity" agent may even start working curcumin does however still qualify as a "C" as in "take in C-ombination" with other agents, but only if you're actually dealing with inflammatory problems (e.g. high CRP-1 value in serum; type 1 diabetes and problems with heme oxygenation, cf. Aziz. 2013). After all, the emerging role of reactive oxygen specimen in muscule- and thus tissue- and anti-obesity-specific glucose uptake clearly suggest that the suffocation of all inflammatory signals is not going to help, but hinder glucose uptake (Merry. 2012).
  • Licorice (glycyrrhizin) [D] - While it has a bad rep as a "cortisol increasing" agent that puts you at risk of developing high blood pressure glycyrrhizin does actually have the ability to reverse diet-induced insulin resistance and get the GLUT-4 glucose transporters back out on the cell surfaces. Sil et al., for example report that they observed corresponding improvements of insulin sensitivity in a rodent model of high frutcose feeding (which is actually not much different from the average victim of the American diet; dosage was 50mg/kg or 600-750mg/day for a human being; Sil. 2013)
    Table 1: Analysis and comparison of active ingredients in Radix Glycyrrhizae (licorice) from Europe and China by capillary-zone electrophoresis (Rauchensteiner. 2005)
    As you can see in the table above the glycyrrhizin content of different forms of licorice is somewhere between 2-3mg/100mg (Rauchensteiner. 2005). In other words, to hit the 600-750mg you will necessarily need an extract - unless you want to consume kilograms of licorice.

    What about testosterone? A larger scale 4-week trial with 100g/day of licorice containing 0.15% glycyrrhizic acid could not find any significant changes in sex steroid hormones (Sigurjonsdottir. 2005)
    Whether that's a smart thing to do is however questionable, as licorice does not just have the potential to increase blood pressure, but is also a relatively unpredictable agent. Most of the glycyrrhizin will never even make it through the gut and into your blood, but rather be converted to other metabolites by your gut microbiome. Injections on the other hand appear to be possible, but the example of a 72-year old subject of a case report from the year 2000 goes to show you that in some cases the anti-diabetic effects may be a tad bit to potent. The subject did after all end up being profoundly hypoglycemic after the injection of 80mg of glycyrrhizin (Motoo. 2000).

    Despite potential anti-diabetic effects (read more) and the potent anti-obesity effects (3g of licorice per day = 2% body fat reduction in normal weight volunteers w/out dietin → learn more) you have read about here at the SuppVersity licorice does therefore get a "D" as in "D-on't take", because it seems as if the margin between 'enough to elicit beneficial effects' and 'so much that you are risking side effects' is pretty narrow.
  • Melatonin has also been shown to have beneficial effects on glucose uptake and glycogen synthesis after exercise and scientists speculate that it could play a major (facilitative) role in skeletal muscle adaptation to exercise (learn more)
    Melatonin [C]- I know, I know, it's a "dangerous hormone" ... well, nobody will propose that, when we talk about prescribing verifiably more dangerous oral contraception to women. I wonder how that is!? After all, this "dangerous hormone" could, mitigate the negative side effects many of the oral contraceptive appear to exert on the glucose metabolism of young, previously healthy women (for an in-depth discussion see Lopez. 2012). Ah, I am digressing, once again. So let's get back to melatonin.

    Assuming you follow all the recommendations from installment 1 of this series you should not be in dire need of melatonin supplementation. Sometimes, however, life comes in the way - for me that happened in the course of the last weeks. Oftentimes it's not even necessarily the "bad things" in life that keep you from getting enough sleep and producing a truckload of endogenous melatonin. It is in these situation, where some supplemental help in pill- or capsule-form may in fact come extraordinarily handy as an acute treatment that will work by its beneficial effects on skeletal muscle glucose uptake (Ha. 2006), leptin expression in response to insulin (Alonso-Vale. 2005) and 24h glucose homeostasis (la Fleur. 2001)

    In view of its many-fold effects on the mammalian metabolism and the age-related decline in melatonin production, it is actually not surprising that the provision of melatonin to aging rodents (0.4μg/ml in drinking water) was able to restore plasma insulin and leptin levels to youthful levels and continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels without any effects on plasma corticosterone and total thyroxine (T4),  testosterone, insulin-like growth factor I (IGF-I) and total triiodothyrone (T3) compared to placeo (Rasmussen. 2002)

    That being said, for young(er) individuals, it may be sufficient to restore a normal circadian rhythm by strategically supplementing at the right times. In conjunction with a consequent "lights out strategy" (learn more), this should get you back on track and your insulin resistance up. Melatonin is thus a classic "C" as in "C-an be used by everyone"; a "C" that does however need some basic information about when you want to take the 1-10mg of melatonin to derive the greatest benefits (learn more about phase shifting your circadian rhythm) .
  • Silymarin (Milk thistle) - Not exactly one of the agents you would expect on a list like this, but contrary to many better known anti-diabetic agents milk thistle can - just like cinnnamon, by the way - inhibit the accumulation of human islet amyloid polypeptide in the pancreas and the subsequent development of the end stages of diabetes (=the inability to produce insulin). In a 2006 study from Iran the provision of milk thistle to type II diabetics (200mg silimarin, 3x daily) lead to significant reduction in acute (blood glucose) and long-term measures of (HbA1c) of glucose management, as well as improvements in insulin levels (see figure below).
    Changes in fasting blood sugar (FBS), long-term marker of FBS (HbA1c) and insulin levels in randomized controlled trial w/ 51 type II diabetics; data expressed relative to median values across all groups (Huseini. 2006)
    In view of the results from the randomized controlled human study depicted in the figure above and based on the fact that silybin / silymarin / milk thistle helps controlling NAFLD, of which you learned earlier this week that it may as well be the cause not the consequence of insulin resistance (learn more). Milk thistle deserves a "B" as in "B-etter than many more specific agents". Dosages range from 500-1,500mg per day and you should make sure you get a standardized product and not an extract with non-disclosed amounts of active ingredients in it.
I know there are more agents, but I do also know that I cannot address each and every herb that may have the potential to reduce your blood glucose levels by 1pt. So unless you want me to make the last five picks, take your chance and let me know which agents you are still missing in the comments.
    References:
    • Allen RW, Schwartzman E, Baker WL, Coleman CI, Phung OJ. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann Fam Med. 2013 Sep-Oct;11(5):452-9.
    • Alonso-Vale MI, Andreotti S, Peres SB, Anhê GF, das Neves Borges-Silva C, Neto JC, Lima FB. Melatonin enhances leptin expression by rat adipocytes in the presence of insulin. Am J Physiol Endocrinol Metab. 2005 Apr;288(4):E805-12.
    • Aziz MT, El Ibrashy IN, Mikhailidis DP, Rezq AM, Wassef MA, Fouad HH, Ahmed HH, Sabry DA, Shawky HM, Hussein RE. Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy. Diabetol Metab Syndr. 2013 Mar 12;5(1):13.
    • Fotland TØ, Paulsen JE, Sanner T, Alexander J, Husøy T. Risk assessment of coumarin using the bench mark dose (BMD) approach: children in Norway which regularly eat oatmeal porridge with cinnamon may exceed the TDI for coumarin with several folds. Food Chem Toxicol. 2012 Mar;50(3-4):903-12. 
    • Ha E, Yim SV, Chung JH, Yoon KS, Kang I, Cho YH, Baik HH. Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells. J Pineal Res. 2006 Aug;41(1):67-72.
    • Hlebowicz J, Darwiche G, Björgell O, Almér LO. Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects. Am J Clin Nutr. 2007 Jun;85(6):1552-6. 
    • Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res. 2006 Dec;20(12):1036-9.
    • Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003 Dec;26(12):3215-8.  
    • la Fleur SE, Kalsbeek A, Wortel J, van der Vliet J, Buijs RM. Role for the pineal and melatonin in glucose homeostasis: pinealectomy increases night-time glucose concentrations. J Neuroendocrinol. 2001 Dec;13(12):1025-32.
    • Lopez LM, Grimes DA, Schulz KF. Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus. Cochrane Database Syst Rev. 2012 Apr 18;4:CD006133.
    • Lu T, Sheng H, Wu J, Cheng Y, Zhu J, Chen Y. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Nutr Res. 2012;32(6):408-412.
    • Mang B, Wolters M, Schmitt B, Kelb K, Lichtinghagen R, Stichtenoth DO, Hahn A. Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J Clin Invest. 2006 May;36(5):340-4. 
    • Merry TL, McConell GK. Do reactive oxygen species regulate skeletal muscle glucose uptake during contraction? Exerc Sport Sci Rev. 2012 Apr;40(2):102-5. 
    • Motoo K et al. Non-insulin-dependent Diabetes Mellitus in an Elderly Patient with Hypoglycemic Attacks Induced By Glycyrrhizin Administration. Journal of the Japan Diabetic Society. 2000; 42(8).
    • Na LX, Zhang YL, Li Y, Liu LY, Li R, Kong T, Sun CH. Curcumin improves insulin resistance in skeletal muscle of rats. Nutr Metab Cardiovasc Dis. 2011 Jul;21(7):526-33. doi: 10.1016/j.numecd.2009.11.009. 
    • Rasmussen DD, Boldt BM, Wilkinson CW, Yellon SM, Matsumoto AM. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology. 1999 Feb;140(2):1009-12. Erratum in: Endocrinology 2002 Apr;143(4):1269.
    • Rauchensteiner F, Matsumura Y, Yamamoto Y, Yamaji S, Tani T. Analysis and comparison of Radix Glycyrrhizae (licorice) from Europe and China by capillary-zone electrophoresis (CZE). J Pharm Biomed Anal. 2005 Jul 15;38(4):594-600.
    • Sigurjonsdottir HA, Axelson M, Johannsson G, Manhem K, Nystrom E, Wallerstedt S. Liquorice in moderate doses does not affect sex steroid hormones of biological importance although the effect differs between the genders. Horm Res. 2006;65(2):106-10.
    • Sil R, Ray D, Chakraborti AS. Glycyrrhizin ameliorates insulin resistance, hyperglycemia, dyslipidemia and oxidative stress in fructose-induced metabolic syndrome-X in rat model. Indian J Exp Biol. 2013 Feb;51(2):129-38.
    • Wainstein J, Stern N, Heller S, Boaz M. Dietary cinnamon supplementation and changes in systolic blood pressure in subjects with type 2 diabetes. J Med Food. 2011;14(12):1505-1510.
    • Wickenberg J, Ingemansson SL, Hlebowicz J. Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects. Nutr J. 2010 Oct 12;9:43.

    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.