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marylin monroe
Showing posts with label adipocyte size. Show all posts
Showing posts with label adipocyte size. Show all posts

Get Lean & Stay Lean with Emedin, Galangin & Antibiotics. Plus: Breakfast & Morning Glucose Metabolism. Diet Once, Never Eat to Satiety Again? Adipocyte Size & NAFLD

Instead of making excuses for posting yet another "short news" collection instead of the next installment of the Athlete's Triad series, I will honestly tell you that I simply wasn't in the mood. Moreover, I have the feeling that I have already outlined what is going to work, i.e. train less, eat more and don't get all psyched up about being lean and looking good. Live your life! Against that background my gut tells me that any further details would just get you off track and back into the viscous cycle of overtraining, overdieting and overthinking why things don't work out for you by evoking the impression that as long as you take supplement X you could get away with doing a little bit 'less less' and eat a little bit 'less more'.

This would be about as counter-productive as the eternal quest for the ultimate body fat blocker or fat burner of which today's Get lean and Stay Lean Quickie does actually feature three. While the temporary use of all of them as a crutch or 'afterburner' to a reasonably planned diet and workout regimen certainly makes sense, it's not like anyone of us got fat, because he or she was "fat burner deficient". A fat burner is not an essential nutrient and only an adjunct to diet and exercise! Keep that in mind not just when you read the following short news items, but also whenever you enter a supplement store (real or on the Internet) and find a new "revolutionary fat burner" on sale -- regardless of whether it has Dr. Oz or Mr. O on the packaging it won't actively, i.e. on its own and in the absence of a dialed in nutritional regimen, make you lose body fat.
  • Cassia tora (Leguminosae) seed, yet another "next big thing" to get rid of the blubber?  (Tzeng. 2012 --) The results the scientists from the Department of Internal Medicine, at the Pao Chien Hospital in  Ping Tung City will be publishing in the January 2013 issue of Food Chemistry do at at least look intriguing.  Although - and this goes to show you that SuppVersity readers always (well "almost always" ;-) are the first know first - at least one of the active ingredients in Cassia tora, which is also known as Senna tora and is, besides its use in Ayurveda medicine, also used in Sri Lankan cousin, is an old friend: Emodin! The stuff that gives rhubarb the fat burning prowess you read about in not  too long ago, here at the Suppversity.

    CSEE  had dose dependent ameliorative effects on body weight gain and visceral body fat levels that were - ad the highest dose - identical to those of the thiazolidinedione (TZD) drug pioglitazone (Tzeng. 2012)
    After fattening them for 2 weeks with the notorious high fat diet, the Koreans assigned their now obese lab rats to groups who received either
    • Cassia seed ethanol extract (CSEE) by oral gavage, once per day for 8 week with CSEE doses of 100, 200, and 300 mg/kg in a volume of 2 ml/kg distilled water,
    • the diabetes drug pioglitazone dosed at 20mg/kg/day, or
    • a placebo, containing just the distilled water.
    Without any effects on the amount of food the animals consumed, the Cassia seed ethanol extract totally blunted the HFD induced weight gain (weight gain was identical to control group on normal chow, see figure to the right).

    In that. the highest dosage had the greatest effect on both body weight gain, as well as plasma lipid levels and epididymal WAT sizes in HFD-fed rats. These effects were probably mediated by CSEE's beneficial effect on the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase. In addition, the researchers found that the cassia seed extract directly increased genes that are responsible for fatty acid oxidation and down-regulated their fat synthesizing counterparts in the visceral white adipose tissue of the animals.

    Whether CSEE is going to be a go-to supplement of the future cannot be said, now. What is certain, however, is that it constitutes yet another example of a potentially highly effective natural alternative to the established pharmacological 'treatment' (or rather management) of the diabesity epidemic.
  • Obese, once and forever, unless you diet for the rest of your life? (Kirchner. 2012) -- A paper that's been published in the latest issue of the Journal of the American Diabetes Association, clearly suggests that the ravenous appetite of "reduced-obese" individuals, i.e. people who have been dieting for weeks and months to shed they weight they have accumulated over years is not (solely) psychologically induced gluttony.

    Suggested read: "Longterm 5% Calorie Restriction & Longterm Dieting Make You Fat and Insulin Resistant." (read full article)
    When Kirchner et al. put their diet-induced obese mice were on a  food restricted for 5 weeks, they did in fact reach the same body fat levels as age-matched rodents who had never received anything but the standard chow. Their  blood glucose levels normalized and their insulin sensitivity increased, but the "reduced-obese" mice also showed markedly increased fasting-induced hyperphagia. In fact, when they given ad libitum access to their beloved high fat diet, they ate like there was no tomorrow and ended up gaining weight at a much faster pace than their never-obese peers, who were likewise allowed free access to the HFD.

    And it gets even worse, as the conclusion the scientists draw based on their results says that despite the fact that "caloric restriction on a HFD provides metabolic benefits", it may actually require a previously obese dieter to continue on the path of caloric restriction (i.e. never eat to 'satiety') for the rest of his/her life!
  • Morning to evening decline in insulin response to carbs suggests breakfast is the time where your body reacts most sensitive to carbs (Saad. 2012) -- Likewise published in the latest issue of Diabetes is a study by Ahmed Saad and colleagues from the Mayo College of Medicine in Rochester and the the University of Padova in Italy, which does at first not really sound like it was revolutionary new. Two definitive advantages of the study at hand were yet that the scientists used healthy individuals as subject and gave them regular mixed meals instead of a glucose solution in order to confirm the existence and identify the characteristic features of the diurnal pattern of glucose tolerance most people take for granted.

    The implications of this study for intermittent fasting are not as clear as you may think and certainly don't imply that you must break your fast in the morning (read more about breaking the fast, here)
    Overall 20 healthy volunteers with normal fasting glucose (4.8 ± 0.1 mmol/L) and HbA1c (5.2 ± 0.0%) participated in the study. They were provided with identical mixed meals during breakfast, lunch, or dinner at 0700, 1300, and 1900 h in a random order on 3 consecutive days. Physical activity was held constant so that e.g. muscle glycogen depletion and subsequent increases in AMPK induced GLUT-4 expression  would not skew the results.

    What Saad et al. fonud was that the postprandial glucose excursion was significantly lower (P < 0.01) at breakfast than lunch and dinner. At the same time the β-Cell responsivity to glucose was higher. This means there was more insulin released per unit of glucose, than during lunch or dinner.

    The time the hepatic insulin extraction was also lower at breakfast; although the difference reached statistical significance only in comparison to the dinner condition. Since the overall meal glucose appearance did not differ between meals and that the suppression of endogenous glucose production "tended to be lower (P < 0.01) and insulin sensitivity tended to be higher (P < 0.01) at breakfast than at lunch or dinner" (Saad. 2012), it is no wonder that the spike in blood glucose was largely augmented, when the subjects consumed the standardized meal for breakfast.
  • Adipocyte size is a determinant of non-alcoholic fatty liver disease (NAFLD) risk (Petäjä. 2012) -- One thing scientists still have not really understood is how some obese people seem to be way better off than others, although their BMIs, fat and lean mass appears to be identical. In view of the latest paper by a group of researchers from Finland and Sweden on the association between the average fat cell size and the occurrence of NAFLD, it could well be that ratio of the total adipose volume to the total fat cell number, which obviously is the adipocyte size, may be providing at least another piece to the puzzle that holds the answer to this question.

    In a previos post on the yoyo effect, I already discussed some aspects of adipocyte morphology - read more
    The scientists have studied 119 non-diabetic subjects in a cross-sectional study. The participants had a median age of 39 (26-53) years, and a mean BMI of 30.0±5.7kg/m2. Subcutaneous abdominal fat cell size, as well as the total amount of liver fat were measured by proton magnetic resonance spectroscopy, intra-abdominal (IA) and abdominal subcutaneous adipose tissue (SC) volumes by magnetic resonance imaging (MRI) and an additional gene analysis yielded information about the genotype (susceptible or not susceptble to metabolic syndrome) of the individuals.

    Simply based on a multiple linear regression analysis, age, gender, BMI, the intra-abdominal to subcutaneous fat ratio and the subject's PNPLA3 genotype, the results were only able to explain 42% of the variation of the liver fat. The inclusion of the adipocyte sizes increased the predictive value by 11%, so that "21% of the known variation in liver fat could be explained by adipocyte size alone" (Petäjä. 2012) This does yet also mean that once we are up to a 90% explanation  (which is unrealistic, by the way) the adipocyte size will only be able to explain "of the known variations".
  • Antibiotic that's commonly used in animal fattening kills body fat (Szkudlarek-Mikho, 2012) -- Reserachers from the College of Medicine at the University of Toledo in Ohio have found that polyether ionophoric antibiotics including monensin, salinomycin, and narasin, which are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming have toxic effects on adipose cells.

    Whether eating the chicken that ate antibiotics is going to make  you lean does still have to be established. Based on the results of the study at hand, it does however appear likely that eating antibiotics could - I do however doubt that they will achieve that without potentially serious side effects.
    Although previous studies suggest that salinomycin has anti-carcinogenic effects (Huczyński. 2012), the sharp increase in poultry consumption over the last decade(s) and the increased use of these "growth promoting" antibiotics by veterinaries and poultry farmers has often been suspected to be involved in the increase in metabolic and autoimmune diseases.

    At least in view of the former, i.e. metabolic diseases in general and obesity, in particular, it may therefore be surprising that the scientists from the University of Toledo discovered that the tested ionophoric antibiotics did not just inhibit the differentiation of cancer, but also that of preadipocytes into adipocytes:
    "The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ." (Szkudlarek-Mikho. 2012)
    Now, I would fully subscribe to the scientists suggestion that these "ionophoric antibiotics can be exploited as novel anti-obesity therapeutics", but until that has been done and we know which other cells' differentiation they may inhibit, as well, I'd strongly discourage anyone from 'supplementing' with the antibiotics from his or her poultry farmer next door. After all, you may well end up not just with less body fat, but with less brain tissue, as well... what? You don't care? Oh I see. The doctor must have inserted the cannula into your ears instead of your belly on your last liposuction, right?
  • Alpinia officinarum, a plant in the ginger family, stops fat gains in its tracks (Jung. 2012) -- Jung, Jang, Ahn and the rest of the researchers from the Korea Food Research Institute in Seongnam, report in their latest paper that an ethanol extract from Alpinia officinarum, a plant in the ginger family that's cultivated in Southeast Asia and is also known as lesser galangal, is yet another mainstay of traditional medicine with significant anti-obesity effects.

    It looks almost like ginger and works almost like ginger, but A. officinarum contains galangin, not gingerol and works via the PPAR-gamma pathway, as well. That's something gingerol doesn't do (Huang. 2012)
    Originally used throughout Asia in curries and perfumes, A. officinarum contains a dietary flavenol called galangin, which has already been shown to exert profound anti-cancer effects (Kapoor. 2012), whether it is solely responsible for the in vitro and in vivo inhibitory effects on lipid accumulation during the differentation of 3T3-L1 adipocytes is not certain, but appears to be likely.

    Via its effects on the fat synthesis and breakdown and PPAR-gamma activity the A. officinarum extract (AOE) lead to dose-dependent decreases in body weight gains of mice who were fed a high fat diet. It also reduced the visceral and liver fat deposition and partially restored the abnormally elevated insulin and leptin levels of the rodents.
    "Collectively, these results suggest that AOE prevents obesity by suppressing adipogenic and lipogenic genes. AOE has potential for use as an antiobesity therapeutic agent that can function by regulating lipid metabolism." (Jung. 2012)
    Certainly another nice find, but let's be honest, what's the real value of all this herbs? I mean yeah they work almost as effectively (in some cases even better) than pharmacological drugs, but both share a detrimental downside, that's not mentioned under "side effects" on the package insert or supplement bottle: They will only manage a problem the root course of which is the net result of a totally messed up diet.
That's it and since you've gotten the bottom line in advance and another time, just to make sure nobody can over-read it, in the last paragraph of the last news item, I just want to remind everyone that there are a couple of other interesting science news and links, for example about ...
  • the pro-carcinogenic effects of shift work and to a lesser degree constantly working at night (read),
  • the connection between high GI carbs and prostate cancer (read), or
  • the idiocy of battling the high GI carb induced decline in cognitive performance with even more sugar (read)
waiting for you on Facebook. Have a nice day and get lean and stay lean ;-)

References
  • Huang TH, Teoh AW, Lin BL, Lin DS, Roufogalis B. The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome. Pharmacol Res. 2009 Sep;60(3):195-206. Epub 2009 Apr 7.
  • Huczyński A, Janczak J, Antoszczak M, Wietrzyk J, Maj E, Brzezinski B. Antiproliferative activity of salinomycin and its derivatives. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7146-50.
  • Jung CH, Jang SJ, Ahn J, Gwon SY, Jeon TI, Kim TW, Ha TY. Alpinia officinarum Inhibits Adipocyte Differentiation and High-Fat Diet-Induced Obesity in Mice Through Regulation of Adipogenesis and Lipogenesis. J Med Food. 2012 Nov;15(11):959-67.
  • Kapoor S. Galangin and its emerging anti-neoplastic effects. Cytotechnology. 2012 Oct 25.
  • Kirchner H, Hofmann SM, Fischer-Rosinsky A, Hembree J, Abplanalp W, Ottaway N, Donelan E, Krishna R, Woods SC, Müller TD, Spranger J, Perez-Tilve D, Pfluger PT, Tschöp MH, Habegger KM. Caloric restriction chronically impairs metabolic programming in mice. Diabetes. 2012 Nov;61(11):2734-42. doi: 10.2337/db11-1621.
  • Petäjä EM, Sevastianova K, Hakkarainen A, Orho-Melander M, Lundbom N, Yki-Järvinen H. Adipocyte size is associated with NAFLD independent of obesity, fat distribution and PNPLA3 genotype. Obesity. 2012. Ahead of Print.
  • Saad A, Dalla Man C, Nandy DK, Levine JA, Bharucha AE, Rizza RA, Basu R, Carter RE, Cobelli C, Kudva YC, Basu A. Diurnal pattern to insulin secretion and insulin action in healthy individuals. Diabetes. 2012 Nov;61(11):2691-700.
  • Szkudlarek-Mikho M, Saunders RA, Yap SF, Ngeow YF, Chin KV. Salinomycin, A Polyether Ionophoric Antibiotic, Inhibits Adipogenesis. Biochem Biophys Res Commun. 2012 Oct 31.
  • Tzeng TF, Lu HJ, Liou SS, Chang CJ, Liu IM. Reduction of lipid accumulation in white adipose tissues by Cassia tora (Leguminosae) seed extract is associated with AMPK activation. Food Chem. 2013 Jan 15;136(2):1086-94. doi: 10.1016/j.foodchem.2012.09.017.

Rhein, PPAR-Gamma Antagonist from Rhubarb, Blunts Diet Induced Weight Gain, Increases Thermogenesis, Blocks Fat Storage, Improves Glucose Metabolism & More!

With 2lbs of rhubarb in the self-made syrup base, this Rhubarb Mojito (img +recipe metropochris.com) could be a real "fat loss drink"... well, if you sweetened the syrup with stevia and used it all at once with just a tiny amount of alcohol  ;-)
Allegedly, autumn it is not exactly rhubarb season, but it is the season where we usually begin to assemble our share of winter fat and that is, as you will probably understand after having read today's SuppVersity post, actually reason enough to turn it into "rhubarb" season. Chinese rhubarb, to be precise. The same rhubarb that has been used 2700BC already and is still one of the mainstays of TCM that's being hailed for its purging effects, as well as its ability to suppress feverish conditions, to cure stomach ailments and as a “cathartic” (an agent used to relieve severe constipation). According to a review by Steven foster, da-huang, as it is called by TCM practicioners, also has antibacterial effects and has been used to treat shingles, fevers, hypertension, burns, acute appendicitis, acute infectious hepatitis, conjunctivitis, swelling and pain of gums, and sores of the mouth or tongue (Foster. 2006).

Yet though many of these effects could come handy for anyone who is looking to make it through the coming winter season in good health, none of them tailors so directly to the aforementioned nasty winter fat as one of the less known "side-effects" of da-huang: its ability to suppress diet induced weight gain!

Rhein from Chinese rhubarb could keep (seasonal) weight gain at bay

According to Zhang et al. the ability of Rhein, one out of six potentially bioactive constituents of Rheum palmatum (see figure in the bluish infobox at the end of this article for a detailed analysis), which has not only recently been shown to directly inhibit the differentiation of 3T3-L1 adipocyte in vitro (Liu. 2011), has...
Figure 1: Molecular structure of Rhein (Zhang. 2012)
"[...] also been reported to have pharmacological and biochemical effects on the inhibition of liver fibrosis and insulin sensitizing and prevent hepatic steatosis through LXR inhibition in a high-fat diet-induced obese mouse model." (Zhang. 2012)
What still has to be elucidated, though, is whether these effects of Rhein, many of which have been observed in the petri dish, only, can provide protection against diet induced obesity in the "real world" (in this case first of all in the real world of rodents).

To be assess the in-vivo efficacy of Rhein as an anti-obesity supplement, the scientists from the Shanghai University of Traditional Chinese Medicine conducted an 8-week experimental trial, in the course of which two groups of obesity prone DB/DB and normal mice were fed a high fat diet (20% protein, 20% carbs, 60% fats; relative to total energy) with or without 0.1% Rhein in it and compared that to the effects of a species-appropriate low fat diet containing 20%, 70% and 10% of the total energy from proteins, carbohydrates and fats, respectively.
Figure 2: Effect of control, high fat(HF) and high fat + Rhein (HF + RH) on body weight, adipocyte size, and body temperature after cold exposure (4°C) of C57BL/6 (=normal) mice. Mice were fed a high-fat diet for 8 weeks and Rhein was powdered and mixed in the diet at 0.1% (Zhang. 2012).
I guess, even if it was not for the data in figure 2, you probably won't be surprised, when I am telling you now that the results of the 8-week dietary intervention were more than just promising for both the obesity prone, but also the normal mice (I guess, otherwise the study would not have made it into the SuppVersity news, anyways, right?). In fact the addition of no more than 3mg of Rhein /day (see blueish infobox at the end of the article for a calculation of the human equivalent dose) effectively ...
  • reduced fat weight in db/db mice from 45.2 ± 1.4 g to 40.8 ± 1.4 g, while the lean and fluid weights remained unaffected between all groups (data not shown, since less relevant)
  • blocked the weight gain and increase the energy expenditure in normal mice on a high fat diet, who had similar food intake as the control mice, but still remained as lean as the mice on the regular diet (see figure 2)
Yet despite the fact that it's always nice to have a supplement help the "geneticall disadvantaged" among our hairy friends - in other words the leptin mutants, scientists refer to as "obesity proe DB/BD mice - for you (probably no DB/DB human, right?) the weight stability of the normal mice, which was brought about at least in part by an increase in thermogenesis and uncoupling protein expression in the brown adipose (BAT) tissue of the rodents are is probably of greater relevance.

The significance of BAT and UCP-activity measures in mice remains questionable

Figure 3: There is more to the weight loss effect of Rhein than its effects on UCP expression in BAT - mRNA levels of selected hepatic genes involved in the metabolism of fatty acids (top, right), and glucose response to intravenous glucose load (bottom, left; Zhang. 2012).
That said, it is unfortunately, whether and to which extend these effects will observed in human beings. After all, the amount of brown adipose we have on our frame appears to be highly very low, and way less active that that of the critters in the study at hand.

However, even if the direct fat burning effects won't translate 1:1 or even 10:1 from mice to men, we may still be left with improved triglycerides and LDL-C levels (data not shown) and, maybe even more importantly, an improved glucose disposal (see figure 3, top); two factors that certainly won't hurt your health and/or ability to lose body fat, specifically since they come hand in hand with increases in LPL (= fat breakdown), and decreases in FAS (= lipid synthesis) in the livers of the animals that consumed the Rhein enriched chow.

And if that's not yet reason enough to look with different eyes on the allegedly somewhat sour rhubarb stalks you have certainly seen at the super, farmers, or whatever market you are shopping, its
  • antagonistic effect on the PPAR-gamma receptor (data from test with rosiglitazone in white adipose tissue not shown), by which it blocks fat storage and induces weight loss (cf. Huang. 2006; Gong. 2009), as well as the ...
  • distinct drop in hepatic fatty acid translocase CD36 activity (see figure 3, top right) that could offer at least some protection against NAFLD and subsequent insulin resistance even in the presence of a the sugar and fat overload of the standard American diet (Miquilena-Colina. 2011), 
may eventually convince you that this stuff is not so bad - in the end, some stevia will turn even the sourest rhubarb shake or stew into a nightmarishly sweet treat ;-).
"I guess eating rhubarb won't suffice, right?" Wrong!


How much do I have to take? The human equivalent of 0.1% Rhein at a daily food intake of 3g/mouse and a mean body weight of 45g (at the beginning of the study) would be ~5.4mg/kg body weight. And what's best, with a Rhein content of 0.96 mg/g and 1.12mg/g in regular raw rhubarb and Mongolian rhubarb, respectively (see figure above with data from Shang. 2003). You could theoretically get your daily dose of 300-550mg of Rhein from 300-550g of rhubarb per day. Whether your digestive tract will like that, remains to be seen, though ;-)
Apropos, rhubarb, I guess you will probably be expecting that this is another instance, where the "fat burner" may be "naturally occuring", but only in so minuscule amounts that you will have to wait for some supplement producer to read this post and come up with a "standardized extract" in a product carrying an imaginative name like RhubaLean(TM).

Now the good news is: If we assume that (a) none of the six other ingredients interferes with the effects of Rhein (in the study at hand, Zhang et al. tested whether Emodin would have similar weight loss effects - it did not; however, that does not mean that it would negate the effects of Rhein) and (b) you'd simple need the dose equivalent of the ~3mg the mice in the study consumed, an extract is not really necessary. According to my calculations (see blueish info-box to the right), approximately 300-500g of rhubarb per day would be enough!

Well, I know, that's plenty, but if we assume that the Rhein in the rhubarb stalks is not extremely susceptible to heat, mechanical processing etc., there are countless ways for you to incorporate it into your diet. And once you are fed up of rhubarb shakes, cakes, salad dressing, ice cream, etc. you could theoretically still create your own extract.

An important note of caution: Making your own or buying an extract would also have the advantage of being able to avoid the potentially toxic oxalic acid overload, you could get if (a) your rhubarb is of the high oxalic acid variety (500-750mg/100g; the lower end would be 150-250mg/100g) and you consumed so much of it that you got in the "danger zone" of >5g/day of oxalic acid. That said, most of the oxalic acid is contained in the leaves which have once been recommended as a replacement for spinach, while the edible part, i.e. the petioles of rhubarb leaves are just that, i.e. edible, because of the low oxalate content (Barceloux. 2009)

References:
  • Barceloux DG. Rhubarb and oxalosis (Rheum species). Dis Mon. 2009 Jun;55(6):403-11.
  • Foster, Steven. Desk Reference to Nature's Medicine. Washington, D.C.: National Geographic Society. 2006. 104–105.
  • Gong Z, Huang C, Sheng X, Zhang Y, Li Q, Wang MW, Peng L, Zang YQ. The role of tanshinone IIA in the treatment of obesity through peroxisome proliferator-activated receptor gamma antagonism. Endocrinology. 2009 Jan;150(1):104-13.
  • Huang C, Zhang Y, Gong Z, Sheng X, Li Z, Zhang W, Qin Y. Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochem Biophys Res Commun. 2006 Sep 22;348(2):571-8.
  • Liu Q, Zhang XL, Tao RY, Niu YJ, Chen XG, Tian JY, Ye F. Rhein, an inhibitor of adipocyte differentiation and adipogenesis. J Asian Nat Prod Res. 2011 Aug;13(8):714-23.
  • Miquilena-Colina ME, Lima-Cabello E, Sánchez-Campos S, García-Mediavilla MV, Fernández-Bermejo M, Lozano-Rodríguez T, Vargas-Castrillón J, Buqué X, Ochoa B, Aspichueta P, González-Gallego J, García-Monzón C. Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C. Gut. 2011 Oct;60(10):1394-402.
  • Shang X, Yuan Z. Determination of hydroxyanthraquinoids in Rhubarb by cyclodextrin-modified micellar electrokinetic chromatography using a mixed micellar system of sodium dodecyl sulfate and sodium cholate. J Pharm Biomed Anal. 2003 Feb 5;31(1):75-81.
  • Zhang Y, Fan S, Hu N, Gu M, Chu C, Li Y, Lu X, Huang C. Rhein Reduces Fat Weight in db/db Mouse and Prevents Diet-Induced Obesity in C57Bl/6 Mouse through the Inhibition of PPARγ Signaling. PPAR Res. 2012;2012:374936. doi: 10.1155/2012/374936. Epub 2012 Sep 25.

Whey or Casein, Pulse or Spread Evenly Across the Day? Does it Even Make a Difference in Terms of Fat Loss and Lean Mass Retention on a Diet? New + Old Empirical Data!

Image 1: Instinctively right? Milk contains soluble (=whey) proteins and casein. Are we overthinking things, when we rip them apart and does it even make a difference? Or is timing all that counts?
It's funny "overthinking", right next to overtraining and overdieting, has become one of the most common problems among the health and fitness enthusiasts who spend equal (or even more) time online as in the gym. "Would it be better if I take my BCAAs at a 3:1:1 or 2:1:1 ratio?", "Does it matter if my protein powder is 10% hydrosolate, 50% isolate and 40% concentrate or has a 30/50/20 ratio?" All that may well make a difference, but let's be honest: Look at the things 80% of these people are eating day in and day out and the way they throw the weights around in the gym and contrast that to a question like "Will my post-workout protein synthesis be 5% greater, when I switch from concentrates to hydrosolates?" ... enough of the ranting, though. After all this post is actually about one of the more sensible among these world-shattering questions:

Q
Will it make a difference, whether I use casein or whey protein on a diet and... what's the significance of having my daily allotment of protein spread evenly across the day vs. mostly (80%) in one sitting, when I am dieting?

In order to find the answer to this question a group of French scientists recruited 41 healthy, but chubby subjects (BMI ~32kg/m²; age ~33y) and put them on a relatively moderate caloric deficit that was calculated based on their basal energy requirement (what you would need lying around all day). In all four arms of the study, the macro-nutrient composition (25% as proteins, 25% as lipids, and 50% as carbohydrates) and energy content per pound of lean body weight (average energy intake 5.87 MJ per day) of the meals, which were prepared according to personalized menus the subjects received from trained dietitians, were identical.
Figure 1: It did not make a difference if the protein was ingested either spread equally across the day or as a pulse mostly (80%) in one sitting (top), fat and weight loss after the 6 week study period were virtually identical (data based on Adechian. 2012)
The little information on the exact menu choices the scientists offers includes a list of stable foods, such as various proportions of spinaches, broccoli, lentils, or green beans, butter, bread, fruits, soy yogurt, rice cakes and gingerbread and suggest that we are dealing with the typical "your dietitian recommends diet", here. With one exception, of course, the main protein source of all four experimental diets were dairy proteins (~80g; >80% of total protein). Casein and whey aka "milk soluble protein"* (see red box above), which were to be ingested either spread equally across or in a "pulsed" fashion (see figure 1, left):
*Note: the scientists refer to whey as "milk soluble protein, I stuck to the terminology in the graphs, but in essence these are mainly β-lactoglobulin, α-lactalbumin, as well as serum albumin, immunoglobulins, lactoferrin, and other minor fractions and thus the same you would find in your average whey concentrate which is, as you may have notices "more soluble" than casein (cf. Lacroix. 2006)
  • casein spread- subjects consumed ~20g of a casein protein supplement 4x a day
  • milk spread - subjects consumed ~20g of milk protein supplement 4x a day
  • casein pulse - subjects consumed the lions share, i.e. 80% of their ~80g of casein, as part of their 2nd meal, so that the protein intake over the day was 6.4g / 64g / 3.2g / 6.4g (see figure 1)
  • milk pulse - same as above, but with milk instead of casein protein
In view of the overemphasisze nutrient timing has gotten as of late withing the physical culture and the assumption that you would expect to see profound differences based on when you consume how much of fast or slow, high (milk) or average (casein) leucine protein etc., it may be disappointing that the weight loss was absolutely identical in all four arms of the study (-7.5 ± 0.4 kg).

Differences are few and far between: Weight loss, fat loss, muscle loss - NOT different! 

What may yet surprise even you, a seasons SuppVersity veteran, who will probably already have expected the non-significant (in fact non-existent) differences in terms of weight loss, could be surprised that the changes in body composition (see figure 1, bottom), i.e. -5.1 ± 0.2 kg reduction in body fat mass and -2.2 ± 0.2 kg reduction in lean body mass, were identical.

Since the same goes for the changes in the fat "liberating" proteins lipoprotein lipase (LPL) and adipose triacylglycerol lipase (AGTL), the fat "forming" protein fatty acid synthase (FAS), and three of the usual subjects, i.e. leptin, the adipoQ gene which is responsible for encoding adiponectin, of which recent research suggests it may be even more important than leptin for your metabolic health (Li. 2012; Hickman. 2012), and the reduction in the pro-inflammatory monocyte chemotactic protein-1  (MPC-1), the slightly more pronounced meal-induced postprandial protein synthetic response in the casein group at the end of the study period is actually the only difference based on which you could argue for one over the other protein source:
Figure 2: While the changes in LPL, AGTL, FAS, leptin, AdipoQ and MCP expression were identical (left); the post 6-week protein synthetic response to identical meals was slightly more pronounced in the casein group (right), the overall significance of this finding is yet questionable in view of identical lean mass losses - it could yet become important on a diet + exercise regimen as in the Demling study discussed in the bottom line box  (data based on Adechian. 2012).
Whether the measurable advantage of casein during this test (the evaluation was carried out by leucine tracer infusion, by the way) is just an experimental artifact or
Adherence is the key to success: While there was no difference in terms of the hunger the subjects felt when they were on the diet, the fact that only 23 of the initially 41 subjects did make it through the 6- week on ~ 1,500kcal/day is quite telling, also in view of the perceived inability to lose weight - if you can't stick to a by no means crazy caloric restriction for 6 weeks, how can you expect to get lean and stay lean, when the inevitable prerequisite for the latter is that you totally revamp your dietary habits for the rest of your life not just six, eight, or twelve weeks.
  • maybe something like "leucine resistance" in response to the higher leucine concentrations after the ingestion of the milk protein supplement in the course of the study period, or
  • alternatively, the greater IGF-1 response to casein (cf. Hoppe. 2009, a study which compares whey vs. casein, but would obviously suggest an advantage of casein over milk = whey + casein, as well); unfortunately IGF-1 wasn't measured, but the insulin levels which were minimally higher in the casein group could support that hypothesis,
... is questionable. Since the same is true for the practical relevance of the ~10-13% larger leucine balance during the postprandial phase of the post-diet whole body protein metabolism test in week 6, I would not fret about this difference too much, though.

Maybe, just maybe, the adipocyte morphology could make a difference

What I would consider significant, though it did not reach that status (probably due to the low number of participant that actually made it to the end of the study, see red box on the right), is the slight but in my eyes potentially important superiority of the equally spread protein ingestion in terms with respect to the before vs. after adipocyte diameter in the casein group:
Figure 3: The difference did not reach statistical significance, but if we take for granted that greater reductions in adopcyte sizes are associated with healthier metabolic profiles, you would be better advised to take your casein protein equally spaced across (15% reduction in adipocyte size vs. 7%, only, for pulsed casein intake) the day... for whey, aka "milk soluble protein", on the other hand it does not seem to matter (data calculated base on Adechian. 2012)
Now, even if we assume that this made a difference and a greater reduction in adipocyte size was a significant advantage, which it probably is from a health perspective, as Skurk et al. state that there is
"[...] a differential expression of pro- and antiinflammatory factors with increasing adipocyte size resulting in a shift toward dominance of proinflammatory adipokines largely as a result of a dysregulation of hypertrophic, very large cells." (Skurk. 2006)
and a recently conducted human trial, by Rizkalla et al. the main message this study should be sending out is not that it does not make a difference whether you use casein or milk protein as your main protein source on a diet, but that a high protein diet with a mediocre caloric reduction of ~20-25% and supplemented with high quality dairy protein (whey or casein) works: After all, more than -1kg of weight loss per week, 68% of the weight loss from fat in the absence of exercise is more than your average celebrity XYZ diet will do for you ;-)
Whey or casein? It's high cysteine content that can help to replenish your glutathione (=the master antioxidant) pools would be another factor that speaks in favor of whey. Whether normal-weight individuals on an already optimized dietary regimen would benefit to the same extend as the obese young men in the 6-week whey supplementation trial, Vatani et al. describe in the August issue of Appetite, is however questionable. After all, the increases in HDL the total antioxidant capacity and glutathione is as questionable as any possible negative influence of the starchy placebo the researchers used in that study (some of you may have seen the link on the SuppVersity Facebook Wall, already).
Figure 4: Fat loss and lean mass gains in formerly overweight police officers after 12 weeks of training and dieting with or without casein / whey hydrosolate (Demling. 2000)
Moreover, one of the few long-term (=non acute protein synthesis) studies investigating the differential effects of concomitant whey vs. casein hydrosolate protein supplementation, found statistically significant higher body fat reductions and lean mass gains in those 33-34 year-old police officers who supplemented their 12-week diet + strength training regimen with 2x37g of casein hydrosolate (8h apart; for the exact data see figure 4; Demling. 2000).
Note: since both the whey (Pro-Score Champion Nutrition) and the casein protein (MET-Rx USA) in this study were hydrosolates the differences in lean mass gains and fat loss are depend primarily on the amino acid composition of the proteins, and not, as it would be with micelle casein vs. whey, the absorption kinetics!
Bottom Line: Against that background the study at hand supports previous findings of the importance of a threshold intake of protein. Interestingly, it did not confirm the notion that this threshold intake should be spread equally across the day, which is something most commenters (me included) read into the seminal paper by Loenneke et al., which found a statistically significant negative correlation not between total protein intake, but between the number of meals with 10g or more essential amino acids in them and abdominal obesity (Loenneke. 2012). So, does timing matter, or does it not? 
  1. It does matter, when you work out, there is ample evidence to support that the ingestion of protein in the vicinity of the workout cannot just amplify the protein synthetic response but will also results in an increase in real world muscle gains.
  2. It appears that it does not matter, when you are dieting (only), though; not just the study at hand, but also the success many people report on intermittent fasting regimen, would support the notion that the more sustained anabolism you may be able to achieve by ingesting say 4x25g of protein instead of 1x80 + 2x10g has, compared to the total amount of protein you eat, relatively little influence on the conservation of lean body mass, when you are dieting.
And as far as the choice between casein and milk soluble protein, aka whey (see first red box), is concerned (see box on the right, as well), it would appear prudent to assume that a combination of both - just like nature intended it - would be the best choice as a "standalone" protein source (cf. "Whey and Casein Work Hand in Hand for Protein Anabolism, but Scientists Overlook Fat, When They Reassemble Milk"), while the higher leucine content and faster digestibility render whey the better candidate for classic "supplementation", as in having an additional shake before you start preparing your whole-foods post-workout meal, which should - and I hope it's not really necessary that I say that - obviously include a significant amount of protein (fish, eggs, meats, and if you will even more dairy ;-), as well. The usefulness (again, not necessarily the superiority!)  of slow digesting protein is something you should be aware of, anyway, right? If not re-read the "3.2kg of Lean Mass Over Night W/ 40g of Slow Digesting Protein 30min Before Bed!?" post from February 22, 2012.

References:
  • Adechian S, Balage M, Remond D, Migné C, Quignard-Boulange A, Marset-Baglieri A, Rousset S, Boirie Y, Gaudichon C, Dardevet D, Mosoni L. Protein feeding pattern, casein feeding or milk soluble protein feeding did not change the evolution of body composition during a short-term weight loss program. Am J Physiol Endocrinol Metab. 2012 Aug 14.
  • Demling RH, DeSanti L. Effect of a hypocaloric diet, increased protein intake and resistance training on lean mass gains and fat mass loss in overweight police officers. Ann Nutr Metab. 2000;44(1):21-9.
  • Hickman IJ, Whitehead JP. Structure, signalling and physiologic role of adiponectin - dietary and exercise-related variations. Curr Med Chem. 2012 Aug 9.
  • Hoppe C, Mølgaard C, Dalum C, Vaag A, Michaelsen KF. Differential effects of casein versus whey on fasting plasma levels of insulin, IGF-1 and IGF-1/IGFBP-3: results from a randomized 7-day supplementation study in prepubertal boys. Eur J Clin Nutr. 2009 Sep;63(9):1076-83. 
  • Lacroix M, Bos C, Léonil J, Airinei G, Luengo C, Daré S, Benamouzig R, Fouillet H, Fauquant J, Tomé D, Gaudichon C. Compared with casein or total milk protein, digestion of milk soluble proteins is too rapid to sustain the anabolic postprandial amino acid requirement. Am J Clin Nutr. 2006 Nov;84(5):1070-9.
  • Li FY, Lam KS, Xu A. Therapeutic perspectives for adiponectin: an update. Curr Med Chem. 2012 Aug 9.
  • Loenneke JP, Wilson JM, Manninen AH, Wray ME, Barnes JT, Pujol TJ. Quality protein intake is inversely related with abdominal fat. Nutr Metab (Lond). 2012 Jan 27;9(1):5. 
  • Rizkalla SW, Prifti E, Cotillard A, Pelloux V, Rouault C, Allouche R, Laromiguière M, Kong L, Darakhshan F, Massiera F, Clement K. Differential effects of macronutrient content in 2 energy-restricted diets on cardiovascular risk factors and adipose tissue cell size in moderately obese individuals: a randomized controlled trial. Am J Clin Nutr. 2012 Jan;95(1):49-63.
  • Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007 Mar;92(3):1023-33.
  • Vatani DS, Golzar FA. Changes in Antioxidant Status and Cardiovascular Risk Factors of Overweight Young Men after Six Weeks Supplementation of Whey Protein Isolate and Resistance Training. Appetite. 2012 Aug 10.

Nasty Insights into the Yo-Yo-Effect: Lower Body Fat Sticks and From Fit2Fat There's no Easy Way Back! Plus: Why It's Easier to Get 6-Pack Abs Than Striated Glutes & Hams.

Image 1: The person in the middle was probably once morbidly obese. How I know? Lower body adipose tissue sticks.
After yesterday's first installment of "On Short Notice", which by the way appears to have pleased most of you (thanks for the feedback, everyone!), we are going back to an in-depth analysis of another cherry-picked study, today. Don't worry, though, I believe even those who are more into the "rumpy pumpy" news will like this one. After all, it could provide some more insights into why your upper body and lower body don't match each other and - what's even more important it puts another emphasis on the primer to never ever let yourself go for too long.

The fat you gain today, will not be gone tomorrow!

In the scientific version of "from fit2fat2fit" (click here to watch the ABC report on the "experiment"), Prachi Singh and his colleagues from the Mayo Clinic in Rochester, UK, fed 23 volunteers (15 men and 8 women; BMI 23.6 6kg/m², mean age 30y), who were sedentary, but normal-weight and free of chronic disease, standardized diets with a macronutrient composition of 20% protein, 40% carbs and 40% fat. In addition each of the participants, who were weighed at least 5x per week had to eat 1-3 of the following snacks
  • ice-cream shake (402 kcal),
  • chocolate bars (a king-size Snickers bar, 510 kcal), or
  • an energy drink (Boost Plus, 360 kcal/8 oz)
in order to gain ~5% of body weight within the initial 8-week weight gain phase. By dropping the extra snacks, dietary counseling from and an increase in overall activity the participants had shed those extra pounds in a subsequent 8-week weight loss phase, again - and, somewhat to my surprise, this did actually work quite well, as the data in figure 1 goes to show you:
Figure 1: Body composition and fat depot weight at baseline and after weight gain and loss (based on Singh. 2012)
But despite the fact that it looks as if they were more or less exactly back to baseline a more detailed statistical analysis of the data revealed that only the total body weight, total fat mass and total fat free mass of the subjects (figure 1, left) , as well as their visceral and upper body subcutaneous (UBSQ) fat loss showed statistically significant correlations with the initial weight gain (p < 0.0001, p =0.001, respectively), or as a non-scientist would say it: Only for the aforementioned parameters everything was in fact back to baseline - the lower body fat gains, on the other hand stuck.
Figure 2: Correlation of changes in lower-body fat mass and femoral fat cell size (men: squares, women: circles; Singh. 2012)
Is lower body fat not a female problem? No, according to the study at hand which was however not not adequately powered to provide any definitive answers to this question, there were "no sex differences in fat distributions during weight gain and weight loss" (Singth. 2012). And while the actual actual data in figure 2 (taken directly from the original study) does confirm that, there is still a non-negligible difference in the total amount of body fat gained and lost, which reminds me of a previous post of mine on "Busting the 3,500kcal = 1lbs Weight Loss Myth! Plus: Women Need More, Men Less Than the Rule Predicts", it only confirms the scientists observation.
Due to the limited number of subjects and relative scarce data Singh et al. can only speculate about the exact underlying reasons for this phenomenon, stating that it is most likely related to the "differential triglyceride storage capacity or lipolysis rates of lower- and upper-body adipocytes". An assumption that does appear very likely, though, also because the reverse, i.e. the increased ability to rapidly store meal triglycerides of upper body fat cells (Marin. 1990; Jenson. 2003) and their overall increased susceptibility to to lipolytic stimuli (e.g. your average caffeine based lipolytic "fat burner") had been established in previous studies already (Gui. 1997; Martin. 1991; Nielsen. 2004).

Faster in faster out ain't the whole explanation, though.

Image 2: You can ask any bodybuilder, a six-pack is easier to get than striated glutes & hamstrings. And the difference between upper - and lower body fat storage could well explain this phenomenon!
Unfortunately, Singh et al.'s study does also suggest that the "faster in - faster out" mechanism is not the only physical / physiological reason for the persistence of lower body fat... when I come to think about it, you may yet well argue that it is in the end the reason that another phenomenon takes place. One, the scientists had observed in a previous study, already (Tchoukalova. 2010), namely that "UBSQ [upper body subcutaneous] and lower-body subcutaneous fat respond differently at the cellular level to accommodate increased energy storage" (Singh. 2012). While the former simply increases in size, the latter "reproduces", or to say it in medical terms:
  • upper body subcutaneous fat mass increases (mainly) by cellular hypertrophy
  • lower body subcutaneous fat mass increases (mainly) by cellular hyperplasia
You have encountered this difference in the "Intermittent Thoughts on Building Muscle" already (specifically in "Intermittent Thoughts on Building Muscle: The Skeletal Muscle Hypertrophy 101 - Part 1: What is Hypertrophy?") and may remember that it is essentially not much different from inflating a given number of balloons (hypertropy) vs. adding more balloons until the few large or the many small balloons eventually occupy the same total volume or, in this case, the fat depots (=sum of many small or few large fat cells) can hold the same amount of triglycerides.

Hypertophy vs. hyperplasia - the latter sticks!

In fact previous research suggests that as soon as the storage ability of the individual fat cells is exceeded, hyperplasia becomes the predominant way to increase the bodies fat storage capacities (usually this is also when the overflowing existing adipose tissue stores begin to "burn down" the house by releasing copious amounts of inflammatory cytokines; cf. Skurk. 2007). Consequently,
[a]fter weight loss, obese people have smaller adipocytes than do people with a similar percentage of body fat and stable weight [though] it is unknown whether those obese adults had more adipocytes before they became obese [...] evidence has suggested that postobese adults have a larger number of fat cells, which could be a long-term consequence of adult weight gain on adipose tissue cellularity. (Singh 2012)
And in fact, these changes in "adipose tissue cellularity" became obvious in the study at hand after no more than 8 weeks of weight gain and loss - life long body fat accumulation or weight gain in the double digit range may not even be necessary...
Limitations of the study: Taken on it's own the Singh study does yet fail to prove the hypothesis that weight gain is associated with increases in fat cell number while weight loss is not, simply because the scientists did take biopsies only at the end of the study - in my eyes a major design flaw, irrespective of the fact, whether the data they would have elucidated would have been "statistically non-significant", as they point out. I did therefore decide against plotting the respective data on adipocyte size and number because without appropriate knowledge of where the subjects were coming from it is worthless anyway.
In this context, it is also noteworthy that the amount of leptin that's released by a given fat cell appears to (non-linearly!) increase with it's size. Against that background the "adipocyte abundance" (many now almost empty fat cells with a very low leptin secretion) in formerly obese subjects could even explain why most of them are having a very hard time to keep the weight off, let alone shed those pounds that still cover their abs, buttocks, etc. After all, on the individual cell level, their body fat stores are in fact almost empty - regardless of the fact that these people still carry 20+ more pounds of body fat on their frame than someone who has not gotten obese in the first place.

Bottom line: NEVER go from fit2fat!

Video 1 (click here to watch): Don't do the "Drew Manning" - making money and becoming famous with being fat is not going to work out another time - after all, Ozzy has already had it on the show... well, maybe if you used Ozzy's Rasberry product (see previous post) to shed the weight again ;-)
Unless Spalding et al. are right and obese individuals must have developed their entire compliment of adipocytes before reaching adulthood (Spalding. 2008; studies such as Löfgren et al. suggest the exact difference, by the way) the results of this study do thus suggest that you better not do the Drew Manning (see video 1) - after all, your chances to cause a similar media stir like Drew (who by the way appears to be a nice guy), are invited by Dr. Oz and make it into the main news on almost all global television channels are close to zero. And with the profoundly reduced leptin expression, from your emptied fat cells you are going to have a very hard time to get rid of any of those new fat cells which may have formed while you were bulking (regardless of whether they are sitting in your upper or lower body), because an abundance of circulating leptin appears to be the crucial signal for your body to send those nasty storage cells into the fat cell nirvana (Della-Fera. 2001).

There are studies that suggest that supplements like CLA could help accelerate this process (Tsuboyama-Kasaoka. 2000). Unfortunately, the data comes from rodent studies, many human trials on the other hand did not elicit any beneficial results, in parts certainly due to lower dosages, which are however a safety measure to prevent side effects such as the profound insulin resistance and hyperinsulinemia Tsuboyma-Kasoaka et al. observed in their study. It appears only logical that the latter would be a direct consequence of the combination of triglyceride release profoundly reduced leptin levels in response to the sudden death of the fat cells, which was in fact so pronounced that the scientists do speak of "lipodystrophy", a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue.

In the end, the only feasible option left appears - once again - to turn your life inside out and wait until the pendulum will have swung back into the right direction.

References:
  1. Della-Fera MA, Qian H, Baile CA. Adipocyte apoptosis in the regulation of body fat mass by leptin. Diabetes Obes Metab. 2001 Oct;3(5):299-310.
  2. Dilzer A, Park Y. Implication of conjugated linoleic acid (CLA) in human health. Crit Rev Food Sci Nutr. 2012;52(6):488-513.
  3. Guo Z, Johnson CM, Jensen MD. Regional lipolytic responses to isoproterenol in women. Am J Physiol 1997;273:E108–12.
  4. Jensen MD, Sarr MG, Dumesic DA, Southorn PA, Levine JA. Regional uptake of meal fatty acids in humans. Am J Physiol Endocrinol Metab 2003;285:E1282–8.
  5. Löfgren P, Andersson I, Adolfsson B, Leijonhufvud B, Hertel K, Hoffstedt J, Arner P. Long-term prospective and controlled studies demonstrate adipose tissue hypercellularity and relative leptin deficiency in the postobese state. J Clin Endocrinol Metab 2005;90:6207–13.
  6. Marin P, Rebuffe-Scrive M, Bjorntorp P. Uptake of triglyceride fatty acids in adipose tissue in vivo in man. Eur J Clin Invest 1990;20:158–65.
  7. Martin ML, Jensen MD. Effects of body fat distribution on regional lipolysis in obesity. J Clin Invest 1991;88:609–13.
  8. Nielsen S, Guo ZK, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest 2004;113:1582–8.
  9. Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007
  10. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, et al. Dynamics of fat cell turnover in humans. Nature 2008;453:783–7
  11. Tchoukalova YD, Votruba SB, Tchkonia T, Giorgadze N, Kirkland JL, Jensen MD. Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proc Natl Acad Sci USA 2010;107: 18226–31.
  12. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes. 2000 Sep;49(9):1534-42.

Instant Coffee, Glycemia & Caffeine Powered Post-Workout Glycogen Repletion. Fish Oil, Arachidonic Acid Release & Prostaglandin Modulation. Adipocyte Sizes & Yoyo Dieting

Judged by the way they are looking at each other they don't care about their differential glucose / insulin response too coffee, but if you do, I suggest you scroll down and read the pertaining news item.
7.3% and 21.4%, those are the SuppVersity figures of the week. Figures that stand for the 2011 youth- and 2010 adult obesity rates in Colorado and they represent the nationwide "optimum" - at least according to CDC data from the respective years. Now, it was already hard to find US states with obesity rates below the nationwide average of 13% (youths) and 27.6% (adults). What is yet even harder or rather impossible is to dig up studies which try to elucidate why Colorado is the "leanest" of the 50 US states. Non-exhausting physical activity, for example, would be a candidate, but according to Wyatt et al. the "[e]ven in Colorado, one of the leanest states, very low levels of physical activity are seen in much of the population." (Wyatt. 2005).

Wouldn't it be worth taking some time to try to elucidate what the citizens in Colorado may be doing, their fellow Americans in Mississippi (highest adult obesity rate of 34.5%) or Alabama (highest youth obesity rates of 17%) ain't doing? Are they maybe having more or less fish oil or drinking only half the amount of caffeine? I don't know, but based on today's installment of "On Short Notice", you should be able to answer whether or not it is likely that factors like these could make a difference ;-)



Coffee, Sex and Your Physique (Gavrieli. 2013) -- The latter two, i.e. sex and your physique are what determines your postprandial glucose and insulin concentrations after escalating dosages of caffeinated coffee. That's at least what Anna Gavrieli from the Harokopio University in Athens and her colleagues from overseas write in a soon-to-be-published paper.

To examine the effects of different amounts of coffee on blood glucose and insulin concentrations in the postprandial phase (after a meal) the scientist recruited thirty-three volunteers [16♀/17♂, 16 normal-weight and 17 overweight/obese, 27.3 ± 7.2 (19–44) y] who came to the lab fasted and obviously without having  had a "wake up coffee" early in the morning. When they arrived, the subjects received a standardized meal, i.e. a slice white bread, 5 g of butter and 10 g of white sugar, providing 142 kcal (6.5% of energy from proteins, 62.5% from carbohydrates and 31.0% from lipids) along with 200 mL of water or instant coffee containing either 3 or 6 mg of caffeine/kg body weight on three different occasions.
Figure 1: Usual and experimental caffeine intake in the subjects (left); effects on glucose metabolism after standardized "breakfast" (=sugar binge) + water or different dosages of instant coffee (Gavrieli. 2013)
As you can see in figure 1, the blood samples the scientists obtained before, immediately after and in regular intervals over the remaining 3 hours after the ingestion of the "breakfast" do support the hypothesis that men and women, light and heavy weights react very differently to the ingestion of 200-500mg.

So what's the verdict then? Is coffee the way to go?


Post workout caffeine supplementation?! Just like dieting, working out is one of the confounding factors which render results like the one at hand valid only in certain scenarios. Against that background it is not surprising that a 2008 study by Pedersen et al., the results of which I have plotted for you in the figure above (Pedderson. 2013), found statistically significant improvements in glycogen resynthesis w/ 8mg/kg caffeine being coingested with 4mg/kg glucose after a workout. Whether this will yield real world benefits is obviously another story ;-)
While coffee delayed the rise of insulin in response to the standardized meal and the fall of glucose concentrations from its maximum levels in the entire study sample, the glucose incremental area under the curve (IAUC) was not just different between the interventions (with both coffee amounts inducing a greater area compared to water, p = 0.009), but also varied according to the sex and body weight of the subjects:
"Secondary, subgroup analysis at the nominal level showed that this might be more evident among females (PIAUC = .05) and overweight/obese participants (PIAUC = .03). Furthermore, coffee, mainly the 6 mg dose, could be lowering insulin concentrations the first 30 min after its consumption compared to water in men and overweight/obese participants." (Gavrieli. 2013)
So what do we make of these results, now? Well, first of all, even if your breakfast does not deserve the name food, having a single regular sized cup of coffee is unlikely to to any harm. Reversing the ratio of breakfast to coffee on the other hand and having a "Sex & The City" breakfast with a croissant and a large cup of breakfast will have you run the risk of having high blood sugar afterwards (esp. if you drink that 400mg+ pot of coffee with tons of sugar).



The tissue incorporation of regular triglyceride based fish oils is inferior to their phospholipid bound brethren. Want to learn more? Check out my article on that matter from June 2012 (learn more)
3g of fish oil modulate the eicasonoid production from omega-6 fatty acids in young men (Zulyniak. 2013) -- 2g of EPA and 1g of DHA that was the dosage the 10 young healthy males (23.4 ± 1.7 years) had to consume on every day of the 3-months supplementation period in Zulyniak et al.'s experiment which was designed to "better understand the potential health benefits of fish oil supplementation in young healthy males" (Zulyniak. 2013).

What the researchers observed were the expected decreases in serum triglycerides (-38%), a significant increase in the proportion of HDL-c relative to total cholesterol, as well as - and this is the actual news - an increase in eicosanoids production, namely prostaglandin-F2α (P < 0.0001) and thromboxane-B2 (P = 0.0296), after fish oil supplementation.

The latter two are products of omega-6 metabolism and confirm the replacement of arachidonic acid (AA, the long-chain omega-6 fatty acid and the quasi-analogon to DHA) in the cell membranes of the erythrocytes by EPA and DHA. This process must have triggered the increase in PGF2α and TXB2 production of which the scientists state that
On a side note: The results of this study don't change my opinion as far as the usefulness, let alone necessity of fish oil supplementation in healthy, athletic, fish eating SuppVersity readers is concerned. I don't see any.
"[...]previous work by both Boughton-Smith et al. and Scott et al. suggest that PGE2, PGF2α, TXB2, and 6-keto-PGF1α are the primary products of the COX2 pathway when AA is in abundance. Furthermore, Scott and colleagues suggested that with chronic elevation of AA, PGF2α and TXB2 production is more likely to be up-regulated due to their vasoconstrictive qualities, which would prevent the efflux of AA and other more-damaging eicosanoids from cells into circulation." (Zulyniak. 2013)
Whether this is actually a good thing does yet appear at least somewhat questionable to me and even Zulyniak et al. have to admit that future research was necessary to confirm "the production of eicosanoids capable of regulating vasoconstriction" and thus "substantiate this hypothesis" (Zulyniak. 2013). As you can see, we are still learning new stuff about things of which every disciple of Dr Oz believes he already knew everything.



Study supports hypothesis that regression in adipocyte size during weight loss could be reason for fat loss plateaus and "walls" (Verhoef. 2013) -- As a seasoned SuppVersity veteran, you are probably aware of the possible influence the size of your fat cells could have on weight loss success, failure or stagnation (learn more).

In a previous post on the Yoyo effect, I already discussed some aspects of adipocyte morphology - including the way lower body fat tends to be more stubborn than upper body fat (read more)
A recent study from the Maastricht University does now offer further support for my previously expressed hypothesis that the reduction of adipocyte size that comes with profound weight loss in then formerly obese individuals could be at the heart of the weight loss plateaus and over-pronounced metabolic downregulation formerly obese individuals experience at way higher body fat levels than someone who has never been obese in his / her whole life. Verhoef et al. put a group of twenty-eight overweight (BMI 28-35kg/m²) healthy subjects on a very low energy diet for 2 months. The 500kcal/day period (50g carbs, 52g protein, 7g fat + multi-mineral supplement delivering the RDA of all nutrients) was followed by a 10-month period of weight maintenance.

Over the course of the low energy diet intervention period, the adipocyte size decreased by -16.7%, the body fat level, on the other hand dropped by only 4.7%. Still, the leptin levels plummeted from 20.3 to 13.1 µg/L and did not return to baseline in the course of the "weight maintenance" phase.
Figure 2: Relative changes (compared to baseline) in body composition, adipocyte volume and leptin after the dieting intervention and the miserable weight maintenance phase (Verhoef. 2013)
In how far the suppressed leptin levels were actually responsible for the fact that the "weight maintenance" phase turned out to be a very dirty, fat only bulking phase cannot be said, but we know from previous studies, that the process of shrinking in itself
"has been reported to generate cellular stress and the more [the adipocytes] shrink, the higher will be the resistance against increasing mitochondrial beta-oxidation via HADHsc [hydroxyacyl-Coenzyme A dehydrogenase] during follow-up." (Verhoef. 2013)
And as if that was not enough the slight increase in ATGL (lipolytic protein) and HADHsc in the "weight maintenance" phase are, as the scientists point out, indicative of the appearance of newly differentiated adipocytes that are are metabolically active contribute to an "improved physiological status", but could potentially make future weight loss (esp. the aesthetic one) even more difficult.

"Empty" adipocytes <> lower leptin <> more glucose-to-fat conversion <> rapid fat gain

If CLA worked in humans as it does in rodents, it could solve the "small adipocyte" problem (learn why)
Moreover, the glycolyctic and thus potentially glucose-to-fat conversion promoting enzyme Aldolase-C did not just distinguish the successful weight maintainers (low Aldolase-C) from the yoyo dieters (high Aldolase-C), it also correlated with the leptin production of the fat cells, of which we know from previous studies that it is in turn negatively correlated to their size (Skurk. 2007)... too complicated?

Ok, let's express it the other way around. The "emptier" your adipocytes are (=smaller size), the less leptin they will produce and the more likely they are to convert glucose to fat and stash that away in their empty "tummies".

Suggested read for those who want to dig further into the purported underlying effects of weight regain: Maclean PS, Bergouignan A, Cornier MA, Jackman MR. Biology's response to dieting: the impetus for weight regain. Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R581-600.



That's it for an allegedly too lengthy installment of "On Short Notice"... about as much a misnomer as the "weight maintenance" phase in the Verhoef study, I guess. Maybe some of today's Facebook news can make up for that? In the end news like
    Want to make HIIT a hit for you? Not a problem, the SuppVersity holds all the information you need. Start out with the respective two post article series and descend into the archives, where you are going to find more about HIIT, how it compares to LISS and which different regimen have shown some promise in peer-reviewed research (learn more)
  • High fat dieting reduces the beneficial effects of resistant starch - Reduction in abdominal obesity with 42% fat diet = zero (read more)
  • HIIT hits home in 8 young, untrained men - 12 HIIT sessions lead to increased V02 kinetics (read more)
  • Ice slurries are the new energy gels - Scientists observe significant increases in cycling performance (read more)
  • Physical therapy as effective as surgery for a meniscal tear and osteoarthritis - Unfortunately patients are too lazy and the revenue for the doctors too small to be used more often (read more)
  • Evolution is to blame for inflammatory disease - At least that's what the latest "paleo" research would suggest (read more)
are eventually the reason that the saturdaily short news are always so lengthy. The really short stuff is already on Facebook ;-)

References:
  • Gavrieli A, et al. Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized, controlled, clinical trial. Metabolism.2013 [ahead of print]
  • Pedersen DJ, Lessard SJ, Coffey VG, Churchley EG, Wootton AM, Ng T, Watt MJ, Hawley JA. High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine. J Appl Physiol. 2008 Jul;105(1):7-13.
  • Verhoef SP, Camps SG, Bouwman FG, Mariman EC, Westerterp KR. Physiological response of adipocytes to weight loss and maintenance. PLoS One. 2013;8(3):e58011.
  • Wyatt HR, Peters JC, Reed GW, Barry M, Hill JO. A Colorado statewide survey of walking and its relation to excessive weight. Med Sci Sports Exerc. 2005 May;37(5):724-30.
  • Zulyniak MA, et al. Fish oil supplementation alters circulating eicosanoid concentrations in young healthy men. Metabolism. 2013 [ahead of print]