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marylin monroe
Showing posts with label cacao. Show all posts
Showing posts with label cacao. Show all posts

The Latest Gut Microbiome Modulators: Beneficial Effects of Cacao, Negative Effects of Acidic Water and Preliminary Evidence of the Negative Impact of Gluten & Whole Grains

Pancakes al cacao & your gut: Bad grains and good cacao?
There is an increasing amount of interesting scientific publications on the role of the gut microbiome in health and disease. Unfortunately, the evidence on what exactly influences the number and types of bacteria in our gut in a beneficial way and even what exactly a "beneficial way" actually is, is yet largely unknown.

In today's installment of the SuppVersity Short News, I am going to take a closer look at a selection of recent studies that may shed at least some light at the previously mentioned questions.
You can learn more about the gut & your health at the SuppVersity

Bugs Dictate What You Crave

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

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The Macrobiotic MaPi2.0 Diet
  • Cacao as a gut microbiome modulator - The first study we're going to look at deals with cacao. Cacao and its effect on the gut microbiome. In said study, 3-week-old Wistar and Brown Norway rats were fed, for 4 weeks, either a standard diet or the following three isoenergetic diets containing increasing proportions of cocoa flavonoids from different sources: one with 0·2 % polyphenols (from conventional defatted cocoa), and two others with 0·4 and 0·8 % polyphenols (from non-fermented cocoa, very rich in polyphenols).

    Only the regular theobromine containing cacao did also reduce the weight gain in the three-week study (Massot-Cladera. 2014).
    What the scientist found, when they analyzed the serum Ig concentrations, faecal IgA levels, microbiota composition and IgA-coating bacterial proportion at the end of the study and compared them to those at the beginning was a significant beneficial effect on the mucosal IgA levels and microbiota composition from all supplements. The 0.2 % cacao diet which contained a higher proportion of theobromine and fibre, however, had a more profound impact on the aforementioned parameters - in spite of the fact that there was less cacao in the diet. Obviously, the caffeine-like bitter alkaloid from cacao is contributes to the beneficial effects of cacao in a similar way as the polyphenols.

    As the body weight data in Figure 1 shows, the theobromine containing conventional cacao was also the only one that was able to reduce the diet induced weight gain in the rats. This could, but does not necessarily have to be related to the higher levels of Bacteroides, Bifidobacterium and Lactobacillus bacteria in the gut of the rodents that received the "cheap" conventional cacao.
  • Acidic water triggers type I diabetes - probably by modulating the gut microbiome - No, I am not trying to advertise bicarbonate, here. I am just reporting the results of a recent study from the Medical University of South Carolina which found that a stain of mice that's particularly susceptible to type I diabetes developed insulitis and hyperglycemia rapidly, only when the mice were maintained on acidic pH water (AW).

    Suggested Article: "High Dietary Acid Load Doubles Risk of Type II Diabetes in Lean Individuals! Causative or Corollary? Plus: Are Grains, not Meats the Main Offenders in Our Diet?" | read more.
    The scientists also observed that this effect could be countered by fecal transplants and was obviously triggered by changes in the diversity of the gut flora that occurred, when the pH of drinking water was in the acidic range and were probably related to the proinflammatory cytokine response in the intestinal mucosa.

    As you as a SuppVersity reader know previous studies in humans have already shown that a "High Dietary Acid Load Doubles Risk of Type II Diabetes in Lean Individuals!" (read more) - Who knows, this could also be related to the effect on the gut microbiome!?
  • Gluten and whole grains as modulators of the gut microbome - In two recent randomized cross-over trials, researchers from the University of Copenhagen determined the impact of dietary gluten or whole grains on the gut microbiome and host metabolic health.

    What the researchers found was what the recent backlash against gluten and "healthy" whole grains on the internet would suggest the already overweight "[p]articipants had slightly elevated fasting glucose levels and increased waist circumference" (Ibrügger. 2014).
    Table 1: Overview of the products used in the randomized controlled cross-over trials (Ibrügger. 2014)
    Whether that's related to the effects on the gut microbome is unfortunately something I can't tell you, yet. Why? Well, the currently available paper refers to a future publication that would outline the detailed results. All I can tell you now is that the study used the products listed in Table 1 and, more importantly, that it is its high statistical power, which, due to the large sample size and the crossover design, "allows detecting even small diffrences in the outcome variables" (Ibrügger. 2014).
Suppversity Suggested: "Stevia Kills Good Gut Bacteria - One Study Enough to Stop Using the Natural Sweetener? Probably Not in View of its Anti-Diabetes, Anti-LDL, Anti-Viral & Anti-Cancer Effects" | more
Bottom line: It's a pity that we still can't tell for sure what the "optimal" gut microbiome looks like. Moreover, the currently available scientific evidence suggests that what is considered "optimal" may well depend on your type of diet and / or your metabolic health.

Against that background the previously presented results offer nothing but a brief glimpse at what may become one of the hottest topics in obesity and diabetes prevention in the future. At the moment, though, all the results and any recommendations that are based on these results have to be considered preliminary. And this is also true for the gluten + whole grain study of which you will certainly read again, here at the SuppVersity | Comment on Facebook!
References:
  • Ibrügger, S., et al. "Two Randomized Cross-Over Trials Assessing the Impact of Dietary Gluten or Wholegrain on the Gut Microbiome and Host Metabolic Health." J Clin Trials 4.178 (2014): 2167-0870.
  • Massot-Cladera, Malen, et al. "Impact of cocoa polyphenol extracts on the immune system and microbiota in two strains of young rats." British Journal of Nutrition 112.12 (2014): 1944-1954.
  • Sofi, M. Hanief, et al. "pH of drinking water influences the composition of gut microbiome and type 1 diabetes incidence." Diabetes 63.2 (2014): 632-644.

    The Myostatin Inhibiting & Myogenic Effects of Epicatechin: Cacao & Tea Contain Well-Known But Overlooked Anabolic

    Does a flavanol in "real chocolate" help you shed the fat and build the muscle?
    If you are like me, you are probably already using cacao to build muscle. Whether the effects of the occasional dark chocolate bar are so profound that you'd notice if you'd skip them, is however questionable. Irrespective of the latest results from Gabriela Gutierrez-Salmean and her colleagues from the University of California, VA San Diego Health Care Systems and the Escuela Superior de Medicina del Instituto Politécnico Nacional at the Seccion de Posgrado in Mexico City present in a soon-to-be-published paper in the The Journal of Nutritional Biochemistry (Gutierrez-Salmean. 2013), by the way.

    "Epi" as in "Epistane" (*) was yesterday...

    ... "epi" as in chocolate epicatechin is the future (*Epistane was the brand name of a "pro-steroid"). This could be the take home message of future follow up studies in human beings, if the results Gutierrez-Salmean et al. observed in isolated rodent and human muscle cells translate to the real world.
    Chocolate milk is an outstanding muscle builder, but as you will remember from previous SuppVersity Articles and Facebook News, chocolate milk owes its muscle building prowess to the combination of milk protein and sugar which make it an excellent recovery fuel (Saunders. 2011; Spaccarotella. 2011; Pritchett. 2012) that can easily compete with commercial recovery drinks (Lunn. 2012)
    Other than the benficial effects of chocolate milk, which are brought about not by chocolate but by the amino acids and (milk-)sugars in the sweet brew, the myostatin inhibiting effects of chocolate appear to depend exclusively on the flavanol (-)-epicatechin which has been shown in previous studies to
    • produce a +50% increase in exercise capacity in mice (Nogueira. 2011), and
    • improve skeletal muscle structure / mitochondrial capacity in older patients with heart failure and type 2 diabetes (Taub. 2012)
    Unfortunately, the total amount of this flavenol in chocolate is not only relatively low, it does also vary according to the type and origin of your cacao (assuming that whatever chocolate product you may be using, does even have real cacao in it).
    Figure 1: Relative change in myostatin, Myf5, MyoD and Myogenin levels after incubation of cells from skeletal muscle of young vs. old rodents with (-)-epicatechin (Gutierrez-Salmean)
    It is thus by no means guaranteed that you will experience any, not even a non-significant reduction in myostatin, when you increase your chocolate consumption; and let's be honest (!) - the weight you gained on your last "chocolate cycle" was not all muscle, was it?

    Additional Read: "The Myostatin <> Clenbuterol Connetion" | read more
    As far as the myostatin suppression goes you may even argue that it's a good thing that the myostatin-inhibiting effects of a 90% cacao chocolate bar are negligible. Whe? Well, we all know what happens when you suppress myostatin too much, right? Right! Your muscles will balloon up until they eventually seize working and you will - just like the poor myostatin negative mice, no longer be able to support your own weight.

    Ok, so it could in fact be a good thing that the "next anabolic revolution", let's call it Chocobolicwon't make you look like the Belgian Blue bull in the image on the right...

    Rigth, that's really a good thing. What's not so good, though is that it would also lack the exciting effects on MyoD, Myogenin (sorry for the typo in Figure 1) and Myf5 and with them the ability for the recruitement of satellite cells and the genesis of new myonuclei (learn more) - exactly those processes that will avoid the loss of skeletal muscle function.

    Contrary to the futile "baloon"-like gains in response to an increase in protein synthesis, these "gains" are meant to stay. In fact, the presence of additionally myonuclei could be the explanation about the miraculous rapid muscle (re-)gain in "roid using mice" you've read about just yesterday in the SuppVersity Facebook News... but I am getting off topic, here - if you want to learn more about the said study and never miss news like this again go to and like the SuppVersity Facebook page.

    Remember the anti-androgenic effects of green tea catechins I wrote about in September 2011? Well guess what EPI, or here EC, is one of the exceptions to the rule that has been shown to increase testeosterone by up to +24% (EC) | learn more
    So what's the verdict then? If it were not for dosing and delivery issues, the study at hand would be pretty exciting. It does after all provide evidence that most of us have been consuming tiny amounts of an effective and above all potentially side effect-free myostatin inhibitor for years.

    There is still a long way to go from rodent and human myocytes in the petri dish to the average supplement costumer and I am not sure whether or not epicatechin will ever make it across the finish line - irrespective of the promising results Noguiera et al. and Taub et al. already observed in rodent skeletal and human heart muscle in response to the provision of 2x 1.0 mg/kg of pure (-)-epicatechin (2x HED 6.5mg; Nogueira. 2011) or dark chocolate and a beverage containing 100 mg of Epi per day for 3 months (Taub. 2012).
    References:
    • Gutierrez-Salmean G, Ciaraldi TP, Nogueira L, Barboza J, Taub PR, Hogan M, Henry RR, Meaney E, Villarreal F, Ceballos G, Ramirez-Sanchez I. Effects of (-)-epicatechin on molecular modulators of skeletal muscle growth and differentiation. Journal of Nutritional Biochemistry. Oct. 2013 [accepted manuscript].
    • Lunn WR, Pasiakos SM, Colletto MR, Karfonta KE, Carbone JW, Anderson JM, Rodriguez NR. Chocolate milk and endurance exercise recovery: protein balance, glycogen, and performance. Med Sci Sports Exerc. 2012 Apr;44(4):682-91. 
    • Nogueira L, Ramirez-Sanchez I, Perkins GA, Murphy A, Taub PR, Ceballos G, Villarreal FJ, Hogan MC, Malek MH. (-)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle. J Physiol. 2011 Sep 15;589(Pt 18):4615-31.
    • Pritchett K, Pritchett R. Chocolate milk: a post-exercise recovery beverage for endurance sports. Med Sport Sci. 2012;59:127-34.
    • Saunders MJ. Glycogen replenishment with chocolate milk consumption. Curr Sports Med Rep. 2011 Nov-Dec;10(6):390.
    • Spaccarotella KJ, Andzel WD. The effects of low fat chocolate milk on postexercise recovery in collegiate athletes. J Strength Cond Res. 2011 Dec;25(12):3456-60. 
    • Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Perkins G, Murphy AN, Naviaux R, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa. Clin Transl Sci. 2012 Feb;5(1):43-7.

    6 + 1 Convincing Reasons You Should Not Subscribe to the "Chocolate is Good For You" Hype Indiscriminately. Plus: Which Chocolate is the Healthiest? Organic, Baking, Dark?

    Your hedonic response usually isn't a good food guide
    I have never been a great chocolate eater, and the soothing and misleading news about research that would show that chocolate consumption was good for your heart, your brain and your belly have not yet changed this.

    For a good reason, as I should say. Being written for the average inhabitant of the Western Obesity Belt, the authors of these articles willingly accept that their readers will (mis-)understand them as a soothing incentive not just to maintain their overtly hedonistic lifestyle, but to top it off with an extra portion of super-sized chocolate cookies... I mean, it's "chocolate", right? So it's good for you, even the latest science says so, right? And not just that, even the NY Times writes chocolate is a "health food" (NY Times. 2009)

    Right, science says: Chocolate is good for you! But when we look closer, the chocolate that is good for you has little to no resemblance to the candy bars the lady in the photo is savoring. What scientific research really says is that small amounts of real chocolate and somewhat larger amounts of artificially pimped high polyphenol chocolate are good for you; and it goes without saying that this constraint excludes 99% of the chocolate and allegedly "chocolate" containing foods that are sold at supermarkets and even health food stores.

    Most of the "chocolate" on the market makes you fat, diabetic, hypertensive, and forgetful

    Yes, you hear me right. Regular (milk) chocolate with a phenol content of <5 gallic acid equivalents (that's the unit you use to measure the total amount of polyphenols in a given product), and the average dark chocolate with a phenol content of <15 gallic acid equivalents have the same pro-obesogenic effect as the low-polyphenol chocolate in a recent study by Farahat et al. (2014).
    Figure 1: The unfortunate truth is, for most people "bad things" happen, when they eat more chocolate.
    As you can see in Figure 1, consuming only 20g/day (=one bar) of the low-polyphenol chocolate for 4 weeks had the already overweight and obese subjects of Farhat's study gain ~500g of what certainly wasn't "muscle weight". Over the course of one year this would be 6kg of extra weight - 6kg of which a 1997 study by Ford et al., the results of which are based on data from the National Health and Nutrition Examination Survey (NHANES), shows that they would increase your type II diabetes risk by a whopping 19%!
    You can learn more about chocolate at the SuppVersity

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    Too much ado about protein?
    Those 6kg of extra weight will also more than double your risk of hypertension (Stevens. 2002) and thus increase your risk of stroke, heart & kidney disease and dementia (Chobanian. 2003).

    Real chocolate, on the other hand, will nor make you fat, improve your blood lipids, ...

    I guess before I will give away the actual three reasons, why eating real chocolate (in moderation), may be a good idea, it's worth defining the word "real" which, in this case, refers to the chocolate and polyphenol content of the brownish bars and powders you can buy in the supermarket, grocery and specialty stores.

    And as the tabular overview of the polypenol content and total antioxidant activity in Table 1 goes to show you, the latter, i.e. the specialty store, may not even always be the best choice. With a total phenol content of 26-29 gallic acid equivalents, the cheap baking chocolate is after all a viable alternative to the expensive organic cacao powder, of which I don't have to tell you that it will be hard to "eat", anyway (click here to see the brands | the scientists say it's not the same order as in Table 1):
    Table 1: Analysis of Selected U.S. Cocoa-Containing and Chocolate Products; CP, cocoa powder; BC, baking chocolate; DC, dark chocolate; SSC, semisweet chocolate chips; MC, milk chocolate; CS, chocolate syrup. b - VCEAC units expressed as vitamin C equivalents(mg/g), c - total polyphenols expressed as gallic acid equivalents (Miller. 2009)
    The data in Table 1 does yet also show you that "dark chocolate", which is probably what most people who have at least some brains left in spite of a life of SAD dieting, is not really much healthier than conventional milk chocolate. Yes, it has twice as much polyphenols in that's still more than 50% less than you would get from baking chocolate and thus probably eventually so low that it's questionable whether the often-cited health benefits will eventually be realized.

    Table 1: Study Examples - Cocoa and Cardiovascular Risk Factors (Minor. 2014). Impressive as they may be, all these beneficial effects were observed when "real" chocolate was tested against "regular" chocolate.
    In the end, this may also depend on whether the chocolate is eaten instead of the common SAD junk-food diet or on top of it. The overall beneficial health effects on blood pressure Hensen and Deborah S. Minor summarized in their latest paper in the Journal of Clinical Hypertension, for example, were all observed in trials where a flavenol / polyphenol rich chocolate was compared to a regular milk or low polyphenol dark chocolate.

    Impressive as they may be, there is little doubt that the increases in HDL, flow-mediated dilitation (FMD), insulin sensitivity, and beta cell function, and the corresponding decreases in total cholesterol, LDL, blood pressure & co (see Table 1) will not occur in the average press release reader who picks up the next best super-size pack of chocolate at the supermarket after reading how healthy chocolate eventually is for him / her.

    Against that background it's even more important to raise the awareness of often-voiced, but rarely published concerns and reservations respectable scientists have advanced with respect to the constant pimping of chocolate as a health food. Six of them have been aptly compiled by F. Willford Germino in a 2013 comment on the previously referenced article by Minor & Minor (2013):
    • Publication bias. Positive results of studies get published while negative results are relegated to the back of the file cabinet, never to see the light of day or word in print. This is particularly an issue with studies that may be investigator-generated and not registered.
    • Limited enrollment. Generally, only small numbers of patients were included in the study populations, with enrollees usually numbering in the low double digits. The largest study included in this review comprised only 152 patients, perhaps enough to suggest some statistical benefit, but insufficient to convince most.
    • Short duration. The studies are typically short-term, lasting hours to days, with the longest study period lasting 18 weeks. Recommendations regarding long-term therapy require longer-term studies to demonstrate that efficacy continues with extended usage.
    • Soft endpoints. The studies often incorporated surrogate soft endpoints (effects on nitric oxide, flow-mediated dilation, and platelet aggregation), with the assumptions that there may be a correlation with hard cardiovascular endpoints. These studies, although provocative, have often failed to demonstrate universal clinical correlation. Even modest BP reductions, when found and reported, have been seen in only a small number of patients for short periods. Additionally, the only metric used to determine BP were readings performed in the office.
    • Double-blind issues. Challenges exist in the investigation of chocolate to achieve a true double-blind test. Chocolates have various tastes, colorations, and textures and any attempt to investigate the properties of one vs another must control for this. The value of single-blind studies needs to be proven.
    • Translation. Flavanols are the putative active compound in chocolate that results in possible health benefit, but chocolate formulations are more varied than coffee. Broadly speaking, dark chocolates, bitter and less creamy and smooth, are of far greater benefit that the more pleasing to the American palate milk chocolate. Yet, patients will often attribute possible benefit of one to the other. Additionally, there is little in the way of standardization among chocolates to know the actual content of active compound in each sold product.
    Even as a SuppVersity reader it's possible that you have not heard about all of these objections before. No wonder, there is after all, as Minor & Minor point out, certainly not the same degree of interest among patients as to whether or not 8 daily Brussels sprouts might provide similar cardiovascular protection as chocolate.
    Already available brussel sprout chocolate.
    "Chocolate is often associated with special occasions, holidays, and festivities. It is often displayed in boxes, wrapped, and meant to be something special, and, as such, evoke warm feelings in many, harkening back to earlier, happy times as a comfort food.

    Certainly this bears little resemblance to the 'charms' of Brussels sprouts." (Minor. 2013)
    Well, if only they knew that you can already buy "brussel-sprout chocolate" ... ok, agreed, I doubt it will offer the allure of pure chocolate, the satisfaction as the melting of the fats and cocoa on the tongue release the full flavor upon the taste buds and send a message of satisfaction to the brain... and then: the blatant taste of brussel sprouts? *shocker*

    So, it it really any wonder that press releases with titles such as "Why dark chocolate is good for your heart", "Key chocolate ingredients could help prevent obesity", "Chocolate may help keep brain healthy",  or "Regular chocolate eaters are thinner, evidence suggests" drives people to hope that chocolate may provide health benefits far beyond the satisfaction we derive with its consumption. A satisfaction neither brussel sprouts, nor real cacao have to offer.
    Figure 2: Mean scores (mm) on visual analogue scale for hedonic and other perceptual responses to chocolate puddings varying in sugar and fat content; 100 = extremely pleasant (Geiselmann. 1998)
    It is, after all. the perception of sweetness of chocolate that determines the hedonic and other perceptual responses we are looking for in this and other "comfort" foods (Geiselman. 1998). Which is why I am not sure, if consuming"organic cacao powder" and "baking chocolate" instead of milk chocolate and he accompanying decrease your diabetes and heart disease risk is actually going to make you happy.
    Eating Frequency, not amount, is what counts! Well, that's at least what a recent study from the University of California, San Diego, would suggest. Unlike the frequency of chocolate consumption, which is inversely associated with BMI, "the amount of chocolate eaten was not related to BMI, favorably or adversely (eg, per medium chocolate serving or 1 oz [28 g], =0.00057 [P=.97] in an age- and sexadjusted model" (Golomb. 2012).
    Beware of the being lied to: If you look closer, there is absolutely zero reliable evidence that eating more of the brown stuff, of which most people assume it was chocolote, entails any health benefits. It has become an unfortunate practice among press-release writers and even reviewers to overlook the experimental design (regular chocolate or other sweets vs. extremely high polyphenol chocolate) to make sure their pamphlet sends the previously cited message, we all want to hear: "Doing what you love to do, in this case eating chocolate is not bad for you."

    As the previous elaborations should have made clear, though, this statement lacks an asterisk and a dagger, to inform readers that (*) this statement is only valid if you are eating high polyphenol (="real") chocolate instead of other sweet, and that (†) even if it's "real" chocolate it will make you fat and sick, when it's eaten in excess. In moderation, on the other hand, chocolate can but certainly doesn't have to be a part of everyone's diet from Biggest Loser to Olympian athlete.
    References:
    • Chobanian, Aram V., et al. "The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report." Jama 289.19 (2003): 2560-2571.
    • Farhat, Grace, et al. "Dark chocolate low in polyphenols increases BMI in normal weight and overweight adults (121.3)." The FASEB Journal 28.1 Supplement (2014): 121-3.
    • Ford, Earl S., David F. Williamson, and Simin Liu. "Weight change and diabetes incidence: findings from a national cohort of US adults." American journal of epidemiology 146.3 (1997): 214-222.
    • Geiselman, Paula J., et al. "Perception of sweetness intensity determines women's hedonic and other perceptual responsiveness to chocolate food." Appetite 31.1 (1998): 37-48.
    • Germino, F. Willford. "Chocolate Is Good for Me, Right?." The Journal of Clinical Hypertension (2013). 
    • Golomb, Beatrice A., Sabrina Koperski, and Halbert L. White. "Association between more frequent chocolate consumption and lower body mass index." Archives of internal medicine 172.6 (2012): 519-521.
    • Latham, Laura S., Zeb K. Hensen, and Deborah S. Minor. "Chocolate—Guilty Pleasure or Healthy Supplement?." The Journal of Clinical Hypertension (2013). 
    • Miller, Kenneth B., et al. "Survey of commercially available chocolate-and cocoa-containing products in the United States. 2. Comparison of flavan-3-ol content with nonfat cocoa solids, total polyphenols, and percent cacao." Journal of agricultural and food chemistry 57.19 (2009): 9169-9180.
    • Stevens, J., et al. "Associations between weight gain and incident hypertension in a bi-ethnic cohort: the Atherosclerosis Risk in Communities Study." International Journal of Obesity & Related Metabolic Disorders 26.1 (2002).

    Study Identifies Caffeic Acid Induced AMPK-α2 Activity Behind the Fat Burning, Insulin-Sensitizing & Life-Extending Effects of Coffee. Plus: Why Creatine & Coffee Don't Mix!

    Image 1: I've got news for you: Real coffee does not come in brown sterophome cups ;-)
    Ever since Starbucks came out with the "McDonald's version" of what used to be the drink of the popes and kings, coffee has gotten sort of a bad reputation. It is supposed to "burn out your adrenal glands" (I bet most people who support this hypothesis don't even know where the adrenal glands are situated), derive you of  vital nutrients and water, reduce insulin sensitivity, give you palpitations and high blood pressure, ... I guess, you know the whole litany. If we take a closer look at the contemporary scientific consensus, many of these arguments against your 2-3 cups of coffee per day lack any scientifically verified basis. Others apply only if you (ab-)use the uber-potent high-caffeine, high sugar, low polyphenol Starbucks brew as "rocket fuel" on your mission not to mars, but to your first (or next?) heart attack.

    Live longer, live leaner and live diabetes-free with...coffee!

    I guess, some of you will probably remember my pre-Christmas blogpost on the "Anti-Diabesity Effects of Coffee", in which I elaborated on the results of a recently published paper by Matsuda et al. who observed significant reductions in weight gain in rodents receiving either diluted coffee or pure caffeine in addition to a fattening high fat (+high carb) diet. Contrary to the body weight gain, which was ameliorated about equally effective by both treatments, the "whole coffee" treatment had a much more pronounced effect on the particularly unhealthy visceral fat in the epididymal area (cf. previous news, figure 2).

    Figure 1: Molecular structure of chlorogenic and caffeic acid, two of the major phenolic compounds in coffee beans (adapted from Tsuda. 2012)
    Although these results clearly indicate that there is more to coffee than the world's most popular recreational drug, caffeine, they cannot answer the question what exactly this "more" would be. The most likely candidates obviously are the two major plant phenols in coffee beans, caffeic acid and its ester, cholorogenic acid (cf. figure 1). Both, caffeic, as well as cholorogenic acid have already been studied for their antihyperglycemic (=blood glucose lowering) effects in animal models (e.g. Rodriguez de Sotillo. 2002; Bassoli 2008), but the molecular mechanism by which they perform their blood sugar reducing magic had not been fully elucidated until Satoshi Tsuda and his colleagues from the Laboratory of Sports and Exercise Medicine at the Graduate School of Human and Environmental Studies of the University of Kyoto in Japan conducted an experiment which identified the AMPK-pathway about which you have already learned so much, here at the SuppVersity, as one, if not the underlying cause of the beneficial health effects of coffee.
    In view of the fact that cacao, just like coffee contains both chlorogenic and caffeic acid (Duke. 2000), it is almost certain that the health benefits which have been ascribed to the consumption of phenol rich dark chocolate within the last couple of years can be traced back to increases in skeletal muscle AMPK-phosphorylation, as well.
    To prove their hypothesis that caffeic acid and / or chlorogenic acid act directly on the AMPK-pathway in skeletal muscle,  the scientists incubated isolated rat epitrochlearis muscles with different amounts of the coffee phenols and measured the phosphorylation of AMPKα Thr172 and ACC Ser79
    Figure 2: Relative AMPK-phosphorylation in isolated rat epitrochlearis muscles in response to incubation with 0.01, 0.1 and 1mM of chologenic and caffeic acid (left); relative increase in AMPK-phosophorylation after incubation with 1mM of caffeic acid for 5, 15, 30 and 60 min (right; data adapted from Tsuda. 2012)
    As you can see, caffeic acid, but not chlorogenic acid lead to dose- and time-dependent increase in skeletal muscle AMPK-phosphorylation (cf. figure 2). A similar response was observedfor its downstream target (data not shown in figure 2), Acetyl-CoA carboxylase (ACC), an enzyme that is directly involved in the regulation of mitochondrial fatty acid oxidation.
    Figure 3: Relative increase in AMPK isoform phosophorylation (left) and increase in glucose transport measured with 3O-methyl-glucose as a marker (right) in skeletal muscle of rats after incubation with 1mM of caffeic acid for 30 min ( data adapted from Tsuda. 2012)
    And while it does not come as a surprise that the increase in AMPK went hand in hand with the previously observed increase in glucose uptake the underlying mechanisms of which the scientists tried to uncover (cf. figure 3), it is of particular importance for physical culturists and anybody else who is interested to burn fat, while maintaining / building muscle that this effect was mediated by the alpha 2, not the alpha 1 isoform of AMPK. As I hope those of you who have been following my dissertations on AMPK in the Intermittent Thought (Part 1, Part 2, Part 3) will be aware of, the former, i.e. AMPK-alpha-2 is also expressed in response to exercise and does not reduce muscle protein synthesis by compromising the mTOR response (note: due to the isoform-specificity of caffeic could be called a true exercise mimetic).
    Figure 4: Relative amounts of ATP and phosphocreatine (PCr) and phosphorylated AKT in skeletal muscle after incubation with 1mM of caffeic acid for 30 min (data adapted from Tsuda. 2012)
    That you do not have to be afraid of losing muscle, if you ramp up your skeletal muscle AMPK expression by caffeic acid, is also supported by the absence of any detrimental effects on skeletal muscle protein kinase B (AKT) expression and the adenosin-triphosphate (ATP) levels in the skeletal muscle samples (cf. figure 4). What is intriguing, though, is the statistically significant decrease in the amount of phosphocreatine, a phosphorylated creatine molecule your muscle (and brain) tissue uses as a rapidly mobilizable energy reserve.

    Caffeic acid won't decrease protein synthesis, but could reduce the effectiveness of creatine

    And while Tsuda et al. mention the detrimental effect caffeic acid exerts on intra-muscular phosphocreatine stores in the discussion of the results, they are not able fully explain this observation which reminds me of the old "myth" that the caffeine in coffee would compromise the beneficial effects of creatine supplementation... I guess we have just found why some studies did in fact support this hypothesis. If the caffeic acid induced increase in AMPK-phosphorylation goes hand in hand with a reduction in the amount of stored creatine phosphate (PCr), this could mean that you would need more creatine to achieve and maintain "maximal" levels of this high-performance energy reserve.

    As you can see, it is always the same, with every question we answer a new one arises. What did Socrates say? Yeah: "I know that I know nothing!" I suppose this is a good concluding word for today's blogpost. Come back tomorrow if you want to know what else you do not know ;-)