Lemon Juice, Resistant Starch, Coffee, Blueberries, Chili, Ginseng, Ginger, Mate, Gymnema Sylvestre, Bitter Melon. Supplements to Improve & Restore Insulin Sensitivity #4

Lemon Juice, Resistant Starch, Coffee, Blueberries, Chili, Ginseng, Ginger, Mate, Gymnema Sylvestre, Bitter Melon - they are all in this fourth serving of the insulin sensitizing supplements series and they are all in this collage. Can you identify all of them?

First of all, let me thank you for flooding me with good suggestions for supplements that should be discussed in this last installment of the series. It's Friday now that I start writing this post and it is probably going to be Sunday, before I find the time to finish the last of your suggestions; and that despite the fact that I am going to try to cut the infos short when I can foresee that it is not worth going into more details, anyway.

Not worth going into details? Yep, one of the supps, where this is clearly the case was suggested by Colby who wants me to address sodium-R-lipoic acid, which is nothing else but R-ALA and in my mind a scientifically unsupported spin-off of ALA that may in fact be inferior to the regular racemic form of lipoic acid which contains both the R- as well as the purportedly pro-inflammatory S-form of ALA (more about the benefits of inflammation in the context of hormesis).

Before we start, just a brief reminder: Do not consider spending your money on any of these supplements before you've not made / begun to make the lifestyle changes described in episode one of this series. Otherwise all of these supplements are nothing but a crutch supporting you on your journey along the Royal Road to Diabesity.

Ok, enough of the finger wagging for today; let's get to "your" supplement wishes. Let's see, what have we got?

• Lemon juice (citric acid) - This is another of Colby's suggestions (also asked for by "anonymous" who just missed his chance of becoming semi-famous). Colby says, he read about lemon juice in Tim Ferriss' Four Hour Body (a fascinating book, by the way; the only problem is that people forget that it's an N=1 experiment and few things that worked for Tim will work for you or anyone else, as effectively).
  
  

  

  Not citric acid specific enough, but worth mentioning: In a study where citric acid (the purported active ingr. in lemon juice) was admin. w/ thiamine, arginine and caffeine it lead to FAT GAIN in normal weight individuals (Muroyama. 2003) - this should remind you of the smart rules of supplementation, right?

  Ferris claims that in his experiments only lemon juice, but not vinegar, which happens to work by the same mechanism, i.e. slowing down the absorption of carbs, did actually lower his postprandial blood glucose levels. Unfortunately there is no research to support this claim and thus lemon juice is at best of as limited use as vinegar (see previous post).
  
  Using lemon juice for cooking purposes, on the other hand, has been shown to reduce the formation of pro-diabetic glycation end products during cooking.
  
  Using a marinade with lemon juice for example will reduce the production of AGEs in beef by 10%  (Uribarri. 2010)
  
  Overall, lemon juice is thus another "C" as in "you C-an try it if you are looking for yet another C-rutch", but certainly nothing that is going to solve any of your problems.
• Resistant Starches - Starches that cannot be broken down in the small intestine and will thus not release any glucose are a no-brainer, as far as improvements in insulin sensitivity are concerned. Think of them as fat, because that is what the "really resistant" starches, i.e. those that make it almost unharmed to the long intesine (RS-3 for the natural ones and RS-4 for the artificial ones). Once they have arrived there they are metabolized to short chain fatty by the bacteria in your gut.
  
  

  

  WMHDP pancakes are not good for you, but maybe better than regular ones.

  Now, the one thing that renders this starches still interesting is the fact that the fatty acids the gut bacteria produce are "short chain fatty acids" (SCFA) . These are, as the name implies "short" and thus easier digested than their nasty long-chain brethren that make up the lion's share of regular keto diets. Moroever, the SCFA have direct (receptor mediated) effects on the production of the "satiety hormone" GLP-1 that has positive effects on both glucose and lipid metabolism (Yadav. 2013).
  
  It is thus the conversion to SCFA and not the resistant starches which come in the varieties RS1 (=physically inaccessible or digestible resistant starch, such as that found in seeds or legumes and unprocessed whole grains),  RS2 (=resistant starch that occurs in its natural granular form, such as uncooked potato, green banana flour and high amylose corn), RS3 (=resistant starch that is formed when starch-containing foods are cooked and cooled such as in legumes, bread, cornflakes and cooked-and-chilled potatoes, pasta salad or sushi rice) and  RS4 (= starches that have been chemically modified to resist digestion, e.g. WMHDP), due to which RS1-4 get a "B" as in "B-etter than regular starches or sugars, B-ut no quick fix for sure". They are useful only in conjunction with the previously mentioned life-style changes from episode I (no, I will never tire of repeating this ;-).

• 

  From an anti-diabetes perspecitve more coffee appears to help more; in view of its effects on the central nervous system you still better limit your intake to max. 3-4 cups per day (Matusheski. 2012)

  Coffee (caffeine & other stuff) - Is certainly too extensive to be treated in detail, so I will refer you to the numerous previous posts on coffee at the SuppVersity, as well as "Warding Off Holiday Weight Gain 2.0: The Anti-Diabesity Effect of Coffee Goes Beyond its Caffeine Content" | read more.
  
  In addition, I would like to invite you to take a look at the image to the right that shows quite clearly that the anti-diabesity effect, of which you have learned that it could mediated by the benefits of caffeine on the liver (cf. "Diabetes & the Liver - Chicken vs. Egg" | read more) are reversed when you are already obese, diabetic & hyperlipidemic.
  
  While I refuse to officially rank coffee, I can tell you that most of the negative side effects are dose-dependently brought about by its caffeine content, and that I personally have a "never consume more than 500mg caffeine or 2-3 cups per day" rule in place and regret it deeply whenever I defy my rule for more than 2-3 days in a row - not on the diabetic side of things (I am rather a low blood glucose guy), but as far as overall well-being and energy levels are concerned. 

• 

  SuppVersity suggested read: "Want to Relieve Insulin Resistance? Eat your Blueberries!" | read more

  Blueberries (real food) - Let me first tell you that I do not intend to give you an overview of the myriad of proven and purported health benefits of blueberries. If that's what you are looking for, I suggest you take a peak at the latest review by Noerberto et al. 2013 (see references).
  
  What I want to give you instead is a real world example: A 2010 study by Stull et al. who found that the provision of isocaloric smoothies with and without 22.5 g blueberry bioactives to 32 obese, nondiabetic, and insulin-resistant subjects for 6 weeks led to a significant improvement of insulin sensitivity in the absence of changes in adiposity.
  
  According to the scientists the same effects could be achieved with 2 cups of fresh blueberries (or 45g of the powder they used to prepare the study) that makes blueberries an "A" as in "A must, but A bit expensive to have them every day". That does not change that consuming blueberries on a regular basis is going to help you improve or maintain you insulin sensitivity.
  
  Thanks for reminding me of including such a reasonable whole food in the series, Erik - ah and Ian, if you want pterostilbene, just eat your blueberries.

• 

  MCT + Chili a fat loss duo that will reduce your insulin sensitivity. That does not matter while you are dieting or low-to-no-carbing, but is a no go when you are doing neither of that.

  Chili (capsaicin) - Capsaicin is another suggestion from Erik, of which I am not quite sure, where he picked it up. Being mislabeled as "fat burner" capsaicin is just like caffeine a substance that increases the efflux of fat from the fat cells and will thus increase the serum level of free fatty acids. This will promote, not inhibit, insulin resistance. Against that background it is not surprising that Islam et al. report that capsaicin had no hypoglycemic, but insulinotropic (more insulin, but same amount of glucose in the blood = decreases insulin sensitivity) effects in a rodent model of type II diabetes (Islam. 2008).
  Note: If you are wondering why I am so bold to state that MCTs reduce your insulin sensitivity (see caption of the image), here is the study (Marcal. 2013) and this is the explanation: Fast fats = increase in FFA in the blood = insulin resistance. At least in an "average" = non-low carb + non-calorically restricted scenario it's as easy as that. When you replace the "Atkins fats" (= long chain fatty acids) with MCTs, on the other hand, you will obviously see benefits from medium chain triglycerides (cf. De Vogel-van den Bosch. 2011).
  In other words, if it's not used to cut body fat (in conjunction with diet and exercise) it's unlikely that capsaicin will help with insulin sensitivity, which is why it gets a "D" as in "D-on't use". And that would be the case even if capsaicin did not have some dubious effects on the Langerhans cells in the pancreas Gram. 2007). It's weight loss effects are totally overblown (see today's Facebook news) and it has been shown to blunt the beneficial effects of the "satiety hormone" cholecystokinin two decades ago (Ritter. 1985). If you want a "hot" alternative, you should thus go for plain onions (Babu. 1997).
• Ginseng (purported active ingredient ginsenoside Rh2): While there are plenty of rodent studies available, Cho et al. were the first to investigate the effect of Korean red ginseng in human beings and the results of their study which has been published in March this year are not exactly impressive.
  
  

  

  It's easy to see: Ginseng doesn't help healthy people. While the reduction in insulin sensitivity in response to 6g ginseng was not significant, it's obvious that healthy individuals won't benefit (Cho. 2013)

  The Korean researchers administered 6 g of  Korean red ginseng rootlets (n=34) or a placebo to a group of 68 participants (average BMI 26kg/m², average body fat 30.7%) for 12 week period and observed that
  

  "Korean red ginseng had no significant effect on improving the insulin sensitivity over time." (Cho. 2013)

  This is significant, because you can safely assume that its effects on individuals with lower body fat percentages (like you?) are probably bordering zero.
  
  Other studies report a physiologically irrelevant improvement in postprandial glycemia, when ginseng (in this case American) was administered exactly 40min before an oral glucose challenge (Vuskan. 2001). And the (non-significant) reduction in insulin sensitivity in the healthy but chubby subjects of the Cho study (see figure on the top right of this paragraph) is a perfect example of the previously cited imperative of applying the selectivity and specificity principles, when you select and buy your dietary supplements (learn more).
  
  In view of the fact that there is some allegedly inconclusive and "not convincing" (Kim. 2011) scientific support for the usefulness of ginseng in sick people, it still qualify for a "C-" as in "C-ould be useful for those who are already suffering from what we call the "metabolic syndrome". Of these, especially those who suffer from high blood lipids (e.g. Mucalo. 2012) could benefit and in these individuals you will probably also observe downstream improvements in glucose metabolism. These are however secondary to the reduction in blood lipis and will not occur in people like yourself, people who work out regular and lead the lives of someone who has found his / her way to physical culture.

• 

  Suggested read: "Beyond Warding Off Holiday Weight Gain: 250-1000mg of Freeze-Dried Ginger Reduce Visceral Fat In Rodents on High Fat Diet" | read more
  

  Ginger - SuppVersity readers will remember ginger from the list of "20+ Anti-Obesity Agents That Have the Potential to Inhibit Fat Gain Right at the Cellular Level" (read full article). If you do remember this article, you may also remember that the anti-obesity effect is brought about by ginger's ability to inhibit the pro-adipogenic peroxisome proliferator-activated gamma receptors (PPAR-gamma).
  
  Ginger has also been shown to exhibit appetite suppressant effects (Mansou. 2012), to improve the thermic effect of food (ibid.), to hold potential as an anti-NAFLD (non-fatty liver disease) "drug" (Sahebkar. 2011), to ameliorate the negative side effects of diabetes (Li. 2012), and to improve glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients (Mahluji. 2013)
  
  For whole ginger (i.e. not ginger extracts) the dosages are usually in the 2-4g range. And while this is probably not going to hurt anyone, there is simply too little evidence that the beneficial effects of ginger are not "solely" mediated by its potent anti-inflammatory action to award an "A"-level recommendation with respect to its insulin sensitizing effects.
  
  So, assuming that its usefulness is more or less limited to individuals with underlying inflammatory problems ginger gets a "B" as in "there are few B-etter general health foods out there, B-ut its benefits in lean individuals are probably not glucose specific". If you are looking for general anti-obesity effects, on the other hand, I'd suggest you go and grab a couple of ginger roots right now ;-)
• Mate tea (Ilex paraguariensis): The evidence from human studies for or against the usefulness of the last supplement on Erik's wishlist is not exactly what I would call extensive. A study by Klein et al. from 2011 is probably as good as it gets and, as it was to be expected, the results suggest that we are once more dealing with an anti-inflammatory agent that will have the greatest impact on people who already suffer from diabetes / the metabolic syndrome.
  
  

  

  SuppVersity suggested Read: "The Leptin-Ilex!? Does Yerba Mate (Ilex Paraguariensis) Restore Leptin Sensitivity or Does it Just Help You Lose Body Fat by Curbing Your Appetite?" | read more, but don't forget that fat loss and glucose sensitivity are not one and the same. While The former usually entails the latter, it does not always work the other way around.

  Contrary to the diabetic patients in the Klein study, the pre-diabetic mate-tea consumers (3x330ml of tea made from roasted mate tea) in his study, did not register any benefits in glucose metabolism and the improvements in lipid parameters may well be a mere consequence of the concomitant dietary changes Klein et al. observed (Klein. 2011).
  
  Just like many other purported "insulin sensitizers", Mate is thus another food / supplement that has only secondary effects on blood glucose. It's another "C" supplement with "C as in C-an be used by the obese diabetic". Drinking liters of mate, even if you don't like it, just to increase your glucose sensitivity does however seem to be pretty useless for anyone who ain't suffering from abnormal lipid levels and increased whole body inflammation.
• Gymnema Sylvestre - While there are a couple of human studies on gymnema their significance suffers from heavy sponsoring and / or the co-administration of other supplements. If you plod through the research that's out there you will however find some evidence for its usefulness in full-blown type II diabetics (500mg/day; Kumar. 2010) and some interesting effects on the sweet taste receptors (Sigoillot. 2012). The latter are blocked by gymnemic acid and could, at least when we are talking about the glucose receptors in the gut, modify both the absorption kinetics and hormonal response of / to glucose.
  
  In the end, the said effects on the sweet taste receptors may also be involved in the effects Shanmugasundaram et al. describe in a 1990 paper. In their study, the administration of 400mg of an GS extract lead to significant improvements in glucose management in 27 patients with insulin-dependent (=severe) diabetes. Since we do not really know that, and in view of the occasional reports of adverse reactions to gymnema supplements (e.g. a case-report by Shiyovich et al. (2010) that links the consumption of gymnema supplements to toxic hepatitis), I will still rank it as "D" as in "D-o wait until there is more and better research available".
  
  I personally consider the risk of consuming corresponding supplements very low, but the same goes for any potential benefits ... and one thing is certain, it's not "a potential panacea for the management of diabetes" which is what MJ Leach writes to attract attention to his 2007 review of the literature in the Journal of Alternative Complementary Medicine (Leach. 2007)

• 

  Suggested Read: "Purported Health Supplement Bitter Melon Induces Oxidative Damage in Rat Testes and Reduces Testosterone Levels by >50%" | read more

  Bitter melon (Momordica charantia): While the hype has already abated, the marketing guys did a pretty damn good job in pimping bitter melon as the goto panaceum for whatever health problem may have befallen you. With respect to it's insulin sensitizing effects Basch et al. wrote about a decade ago:
  

  "Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring." (Basch. 2003)

  Did that change over the course of the past 10 years? Of course not.
  
  So unless Google and sensationalist advertisements that are supposed to look like real journal articles are your main sources of "information" about dietary supplements you will probably have to concede that
  

  "[...] clinical trial data with human subjects are limited and flawed by poor study design and low statistical power [and] the clinical data regarding the anti-diabetic potentials of M. charantia and calls for better-designed clinical trials to further elucidate its possible therapeutic effects" (Leung. 2009)

  and conclude that
  

  "[t]here is insufficient evidence on the effects of momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice." (Ooi. 2013)

  That does not necessarily mean that it does not work, at all, but as a direct comparison with metformin shows, it's not a real alternative for type II diabetics (Fuangchan. 2011), whose HbA1c levels declined by meager 0.24% after being treated with a bitter melon supplement three times a day for three months (undisclosed amount of active ingredients in the caps; cf. Dans. 2007). I hope I do not have to point out that it is unrealistic to expect that you would see better effects in non-diabetics.
  
  I guess, it's probably not necessary to say that, but bitter melon is a bitter pill that gets a "D" as in "D-on't fall for the hype".
  

No block buster supps in this serving: Ok, I have to admit this last installment of the series had a couple of supplemental non-starters in it. Honestly, Ginger is the only one of the items listed above that stands a chance to make it into the insulin sensitizing protocol that's about to conclude this series next Sunday.

Until then, I hope all of you enjoy the rest of this weekend and come back for your daily dose of SuppVersity news tomorrow (all muscle heads listen up, you will like tomorrows news ;-)!

References:

• Babu PS, Srinivasan K. Influence of dietary capsaicin and onion on the metabolic abnormalities associated with streptozotocin induced diabetes mellitus. Mol Cell Biochem. 1997 Oct;175(1-2):49-57. 
• Fuangchan A, Sonthisombat P, Seubnukarn T, Chanouan R, Chotchaisuwat P, Sirigulsatien V, Ingkaninan K, Plianbangchang P, Haines ST. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. J Ethnopharmacol. 2011 Mar 24;134(2):422-8.
• Islam MS, Choi H. Dietary red chilli (Capsicum frutescens L.) is insulinotropic rather than hypoglycemic in type 2 diabetes model of rats. Phytother Res. 2008 Aug;22(8):1025-9.
• Kim S, Shin BC, Lee MS, Lee H, Ernst E. Red ginseng for type 2 diabetes mellitus: a systematic review of randomized controlled trials. Chin J Integr Med. 2011 Dec;17(12):937-44. 
• Kumar SN, Mani UV, Mani I. An open label study on the supplementation of Gymnema sylvestre in type 2 diabetics. J Diet Suppl. 2010 Sep;7(3):273-82.
• Leach MJ. Gymnema sylvestre for diabetes mellitus: a systematic review. J Altern Complement Med. 2007 Nov;13(9):977-83. Review.
• Leung L, Birtwhistle R, Kotecha J, Hannah S, Cuthbertson S. Anti-diabetic and hypoglycaemic effects of Momordica charantia (bitter melon): a mini review. Br J Nutr. 2009 Dec;102(12):1703-8. doi: 10.1017/S0007114509992054. Epub . Review.
• Li Y, Tran VH, Duke CC, Roufogalis BD. Preventive and Protective Properties of Zingiber officinale (Ginger) in Diabetes Mellitus, Diabetic Complications, and Associated Lipid and Other Metabolic Disorders: A Brief Review. Evid Based Complement Alternat Med. 2012;2012:516870.
• Mansour MS, Ni YM, Roberts AL, Kelleman M, Roychoudhury A, St-Onge MP. Ginger consumption enhances the thermic effect of food and promotes feelings of satiety without affecting metabolic and hormonal parameters in overweight men: a pilot study. Metabolism. 2012 Oct;61(10):1347-52.
• Marçal AC, Camporez JP, Lima-Salgado TM, Cintra DE, Akamine EH, Ribeiro LM, Almeida FN, Zanuto RP, Curi R, Boldrini SC, Liberti EA, Fiamoncini J, Hirabara SM, Deschamps FC, Carpinelli AR, Carvalho CR. Changes in food intake, metabolic parameters and insulin resistance are induced by an isoenergetic, medium-chain fatty acid diet and are associated with modifications in insulin signalling in isolated rat pancreatic islets. Br J Nutr. 2013 Jun 28;109(12):2154-65. doi: 10.1017/S0007114512004576.
• Matusheski et al. Coffee and Type 2 Diabetes Risk. In "Coffee: Emerging Health Effects and Disease Prevention" edited by Yi-Fang Chu.John Wiley & Sons, Mar 27, 2012.
• Mucalo I, Rahelić D, Jovanovski E, Bozikov V, Romić Z, Vuksan V. Effect of American ginseng (Panax quinquefolius L.) on glycemic control in type 2 diabetes. Coll Antropol. 2012 Dec;36(4):1435-40. Review.
• Muroyama K, Murosaki S, Yamamoto Y, Ishijima A, Toh Y. Effects of intake of a mixture of thiamin, arginine, caffeine, and citric acid on adiposity in healthy subjects with high percent body fat. Biosci Biotechnol Biochem. 2003 Nov;67(11):2325-3.
• Norberto S, Silva S, Meireles M, Faria A, Pintado M, Calhau C. Blueberry anthocyanins in health promotion: A metabolic overview. Journal of Functional. Foods, Available online 21 September 2013.
• Ritter RC, Ladenheim EE. Capsaicin pretreatment attenuates suppression of food intake by cholecystokinin. Am J Physiol. 1985 Apr;248(4 Pt 2):R501-4. 
• Sahebkar A. Potential efficacy of ginger as a natural supplement for nonalcoholic fatty liver disease. World J Gastroenterol. 2011 Jan 14;17(2):271-2. doi: 10.3748/wjg.v17.i2.271. 
• Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol. 1990 Oct;30(3):281-94.
• Shiyovich A, Sztarkier I, Nesher L. Toxic hepatitis induced by Gymnema sylvestre, a natural remedy for type 2 diabetes mellitus. Am J Med Sci. 2010 Dec;340(6):514-7.
• Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J Nutr. 2010 Oct;140(10):1764-8. doi: 10.3945/jn.110.125336.
• Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010 Jun;110(6):911-16.e12.
• Yadav H, Lee JH, Lloyd J, Walter P, Rane SG. Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion. J Biol Chem. 2013 Aug 30;288(35):25088-97.

Going Nuts On Berries: Ellagic Acid in Rasp- and Blueberries, Pecans, Walnut & Co Protects Against Visceral Obesity

Image 1: I hope you are not one of the guys who spits the tiny seeds of the raspberries out. That is not just disgusting, you would also spit away ~90% of their ellagic acid content.

Nuts and fruits, once hailed as healthy superfoods have been under serious scrutiny within the sometimes overtly "health-conscious" blogosphere. Yeah, consumed in excess both will make you fat; but I would venture the guess that it would be easier to kill yourself by drinking too much water, than by eating too many almonds and bananas... well, before I get derailed here, let's take a look at the data from a recently published study on the effects of ellagic acid, a dilactone of two gallic acid molecules that is found in a wide variety of - guess what? - nuts (pecans, walnuts, cashews, brazil nuts, etc.) and fruits (raspberries, pomegranates, grapes and blackcurrants, plums, grapes, cherries and the list goes on)!

Good for your heart, good for your gut, good for your metabolism, ... but bad for you belly fat

In previous studies ellagic acid has already been identified as a potential heart protectant (Kannan. 2011a, 2011b); it has been shown to ameliorate the progress of cancer (Losso. 2004), to protect from Staphylococcus aureus biofilm formation (Quave. 2012), to exert potent anti-inflammatory effects (Umesalma. 2010), to protect the gut (Gonzalez-Sariaz. 2010),... an open list of health benefits, on which the anti-visceral fat effect Panchal et al. observed in their 16-week rodent trial is probably not going to be the last health-benefit to be added.

Figure 1: Ingredient (g/kg) and macronutrient (% of total energy) composition of the control and the HCHF diet (diet according to Pudjal. 2010, which was used as a reference diet by Panchal. 2012).

In the study at hand Sunil K. Panchal, Leigh Ward and Lindsay Brown kept 8-9 week old male Wistar rats on regular (extreme high carbohydrate, cf. figure 1) or high carbohydrate + high fat (the scientists even state that explicitly and don't mislabel their diet as simply being "high fat"!) diets either with or without 0.8g ellagic acid per kg chow.

Figure 2: Ellagic acid (µg/g dry weight) content of methanol extract of selected nuts and fruits (based on Daniel. 1989)

In view of an average food intake of 30g and 22g in the control and HCHF diet groups and given an average weight of 400-450g per rodent, the animals thusly consumed roughly 40-60mg ellagic acid per kg body weight per day*:

• control: 60mg/kg per day - human equivalent ~ 10mg/kg
• HCHF: 40mg/kg per day - human equivalent ~ 6mg/kg
  
  *note: I calculated those myself, Panchal et al. provide an estimate of 50mg/kg, as a reference

If we take the data from a 1989 study by Daniel et al. as a reference (figure 2) and assume that you weigh ~80kg and that your stomach is about as effective in extracting the ellagic acid from the dry part of the fruit (it is interesting to note that in strawberries >90% of the ellagic acid is in the pulp, while in raspberries 87% is in the seeds) as the laboratory equipment of the scientists was, and if we further take into account that most fruit are ~90% water, you would have to eat ~3,200g of raspberries or blackberries to get your daily dose of 6mg of ellagic acid; or, due to the lower water content (most nuts have ~5% moisture; cf. Beuchat. 2006) 2,181g pecans or 1,220g walnuts.

Note: The above calculation is by no means scientifically valid. In addition to that, the ellagic acid content of fruits and nuts vary according to season, origin, storage, etc. So, don't blame me, if - despite adding a bag of walnuts and a huge basket full of raspberries to your pizza, cola, pasta, twinkies, hamburger, fries, etc - you still gain weight on your high fat high carbohydrate (=standard American diet), ok?

No matter how (in-)accurate the above calculations may be (as I noted, they are probably not very accurate), I am not as confident as Panchal et al. that the average diet with its ~1g of total polyphenols would more or less 'automatically' contain the required 480mg-800mg of ellagic acid, "if the majority of polyphenols in the diet are taken from the fruits and nuts containing ellagic acid".

A cup of blueberries and a handful of nuts a day keep the doctor away?

Although it would seem that Panchal et al. have not done their homework as far as the real-world implications are concerned (and as I will argue in the conclusion - mishaps like these are at the heart of the "superfood myths"), the results of their experiments suggest that ellagic acid could be one of the rare cases, where it may be worth helping nature along, by extracting and capping a polyphenol that is, at least in some cases - such as pomegranate, for example, where large amounts are contained in the leaves (Lei. 2003) - not even necessarily contained in the edible part of the fruit / plant.

Figure 3: Body weight gain, food intake, water intake and energy intake (left); body composition data (right) of rodents fed either a standard high carbohydrate (regular corn starch) or an energetically dense high carbohydrate high fat diet with or without 0.8mg/kg chow ellagic acid for 16-week (data adapted from Panchal. 2012).

If you take a look at the ameliorative effect the lower ellagic acid dosage ('lower' simply due to the lower intake of the energetically more dense high carbohydrate high fat chow) exerted you will see that its effects are surprisingly depot-specific: Contrary to the total body fat mass, which is (within the statistical margin) virtually identical in all groups, the allegedly dangerous abdominal fat was reduced by -33% and -36% by the treatment in both the control (remember >90% of the energy from cornstarch ;-) and the HCHF group, respectively (the reduction was similar in all visceral fat depots; data not shown).

Figure 4: Basal glucose, AUC glucose after 2 g/kg body weight glucose load, triglycerides, total cholesterol, non-esterified fatty acids, c-reactive protein, uric acid and urea levels in rodents fed the supplemented control and the unsupplemented and supplemented high carbohydrate high fat diets; data expressed relative to unsupplemented control diet (data calculated based on Panchal. 2012).

These profound reductions in the amount of inflammatory visceral body fat, stand in line with the statistically significant improvements in glucose and lipid metabolism (cf. figure 4). As you can see the diet-induced increases in glucose, NEFA, triglyceride, cholesterol, CRP and uric acid, as well as the reduction of its counterpart, urea were completely blunted in the high carbohydrate + high fat group that received the ellagic acid enriched chow, an effect, the researchers attribute to...

• an increase in fatty acid oxidation, indicated by increased CPT1 activity and
• reduced inflammation, indicated the reversal of diet-induced increases in Nrf2 and NF-kappaB 

... in heart and liver of the rodents. That the addition of ellagic acid to the diet also minimized the necrotic damage to the liver of the animals, is thusly not surprising.

"So, shall I embark on the fruit and nuts diet?"

Despite those scientifically 'proven' benefits I should yet not have to tell you that it would not be particularly wise to take this study as an opportunity to ransack Trader Joe's dried fruit and nuts warehouses... As unreasonable as the contemporary condemnation of real (not dried!) fruit and (non-rancid!) nuts may be, it did not come out of nowhere, but has its roots in the detrimental overconsumption of both, nuts and fruits in the media-driven believe that adding tons of those healthy "superfoods" to your diet would allow you to live into your late 90s without ever having to worry about any of the ailments of the Western society. Both, nuts and fruit are yet only two "superfoods" within a "superfood diet", ... ah pardon, a whole foods diet, where neither of them is a "treat" or "cheat", but simply nutrition!

On a side note: Can you imagine that your ancestors sprouted a handful of nuts after all the work they had to shell them? They must have been nuts, if they did - don't you think so?

 Contrary to the impression you may get, when you follow the discussion on certain bulletin boards, eating healthy does thus not imply that you have to restrict your dietary repertoire to meat, fish, butter, eggs and the occasional sweet potato; this is all the more true, since ellagic acid is only one example for the myriad of already known and still to be discovered micronutrients with beneficial health effects, of which you would be depriving yourself, if your list of "allowed foods" contains no more than 5-10 items.

Think about it: Just as the FDA-approved food additives are "harmless" if you consume only one of them and potential hazardous, when you eat the whole variety that is present in the fast-food laden SAD diet, it is the synergy of all those ellagic acids and whatever their names may be that makes a varied whole-foods diet so healthy - don't miss out on that!