Saturday, November 30, 2013

Science Round-Up Seconds: How Colostrum Turns the Oxidative Downsides of Endurance Exercise into Benefits and Why Cacao is so Much More Than Just Delicious

Looking for a delicious and more creative way than colostrum powered chocolate milk to combine today's seconds? What about Linda Wagner's Chocolate Cherry Bomb Smoothie with Colostrum, Caco, Maca, Acai, almond milk & more?
By now you will probably have listened to yesterday's installment of the SuppVersity Science Round-Up either via the Super Human Network live stream, or after downloading the podcast (the Round-Up starts in the 2nd hour) that has now been available for ~20h. In case you did not have the chance to listen live or listen to the podcast, but have a vested interest in erectile (dys-)function, optimal testosterone levels, the connection between testosterone, DHT, estrogen, insulin resistance, obesity, the health of your liver and longevity or you are simply eager to learn more about the latest research on high intensity interval training, steady state cardio,  everyday activity and the fallacy of the "exercise just makes you hungry hypothesis" (additional suggested read: "Dr. Oz Was Right: Exercise Does not Just Make You Hungry") and their effects on your metabolic health, conditioning and physique there is no way, you want to miss listening to this show, either before or after you devour this week's installment of the SuppVersity Science Round-Up Seconds.
  • Colostrum supplementation blunts exercise induced reduction in endogenous anti-oxidants and potentiates its beneficial effects (Appukutty. 2013) --Published on November 22, this paper by Appukutty et al. is only the latest in a long line of articles on the effectiveness or ineffectiveness of colostrum as an ergogenic aid (suggested read: "Ask Dr. Andro: Are Colostrum and Milk Healthy Muscle Builders?). We will get to these differences in a minute, but let's first take a look at the effects the provision of 50mg/kg body weight (human equivalent: 2.4mg/kg) had on the total antioxidant status, lipid oxidation, xanthine oxidase and super oxide dismutase levels in treadmill exercised (30min per day) mice.
    Figure 1: Relative levels of total antioxidants, xanthine oxidase and super oxide dismutase in supplemented (COL), exercised (EX) and exercised + supplemented (EX + COL) mice expressed relative to sedentary non-supplemented control (Appukutty. 2013)
    It's not difficult to see that the effects of the colostrum supplement go beyond the mere amelioration of the exercise induced decrease in total anti-oxidant enzymes and super oxide dismutase levels. The human equivalent of only 2.4mg/kg body weight per day did - after 14 days of supplementation the total antioxidant status in the exercised + supplemented rodents was already 5% greater, after 21 days whopping 11% greater than in the supplement only group.

    In view of the previously reported benefits of supplemental colostrum you could certainly argue that the obvious parallels to the difference between "training" and "overtraining", with the former having promotive and the latter having compromising effects on the endogenous anti-oxidant system of your body are no coincidence. In view of the about as many studies which found no or at least no significant factually or potentially ergogenic effects in response to supplemental "beast milk", we still have to answer the question I invoked in the introductory paragraph of this sub/item of today's installment of the SuppVersity Science Round-Up Seconds: "How come it works in some, but by no means all studies?" The answer could actually be way more straight forward than you think and reads "Simply because he scientists used different supplements!"

    Even the dairy industry has realized that the way they feed their cows and post-process their colostrum, before they eventually feed it to their offspring, renders almost 60% of the maternal colostrum from US dairy farms "inadequate" so that "a large number of calves are at risk of failure of passive transfer or bacterial infections, or both." (Morrill. 2013)

    Not all colostrum is made the same and the beneficial effects of each and every individual product - specifically with respect to the integrity of the intestinal wall - will necessarily depend on its bacteria content and the latter depends on the feed the cows receive as well as the processing the colostrum undergoes.
    If you do still remember my post on the etiology of exericse-induced increased intestinal permeablity and the beneficial effects 'intact' colostrum has on the integrity of the gut you just have to put two and two together and you have your explanation: Just like the efficacy of any artificial supplement depends on he chemicals the producer puts into it, the effectiveness of a food supplement will vary due do both natural (e.g. seasonal, feed dependent, stress andhealth related...) and 'unnatural' fluctuations in its ingredient profile. Heat treatment, which is applied to almost all commercially available colostrum supplements, for example, may leave most of the IgG content intact, but it will reduce not just the total count, but also the diversity of the microbiota in colostrum (only the heat resistant bacteria, mostly gram-positive, will survive; cf. Hayes. 2013) 
  • Study shows, cacao phenols protect your gut from inflammation, but there is much more cacao can do for you (Rodríguez-Ramiro. 2013) -- As a recent paper by scientists from the Ciudad Universitaria in Madrid (Spain) goes to show you, colostrum and bacteria are not the only naturally occuring supplements that are good for your gut health. Cacao has just been shown to do a pretty decent job, as well.

    Table 1: Nutritional content of the experimental diets the rodents were fed for 8 weeks with the carcinogen being injected in week 3 and 4 (Rodríguez-Ramiro. 2013)
    In an in-vivo the Spanish observed that a diet that was enriched with 12% cacao powder had astonishing anti-inflammatory effects in a rat model of azoxymethane (AOM)-induced colon carcinogenesis. The rodents had been fed the 12% cacao diets (composition see table 1 to he right), for 8 weeks. In weeks three and four, the scientists injected the procarcinogenic drug azoyxymethane in order to induce intestinal inflammation that would potentially lead to the development of colon cancer.

    Compared to the animals on the regular chow, the rats in the cacao group exhibited highly significant decreases the nuclear levels of  NF-κB and the expression of pro-inflammatory enzymes such as cyclo-oxygenase-2 and inducible NO synthase, all of which were profoundly upregulated in response to the AOM injections in their peers on the regular diet.

    In a subsequent in-vitro experiment on Caco-2 cells, the scientists were also able to confirm that cocoa the cacao polyphenols effectively down-regulate the levels of inflammatory markers induced by TNF-α by inhibiting NF-κB translocation and JNK phosphorylation.

    Now, it does not really appear feasible to eat a 12% cacao powder diet, right? Well, based on the data from table 1 the average food intake and body weigh of the rodents and some mathematical shenanigan, it's actually not difficult to calculate that the human equivalent dose, which would be 150g of cacao powder per day conains no more than 3g of polyphenols and could theoretically be achieved by supplementing with ~15g of chocamine every day. Ok, that would be hilariously expensive, but I assume you don't inject 3.25mg/kg azoyxymethane on a regular basis, right? Well, I guess this would mean that you won't need 15g of chocamine or 150g of cacoa powder to protect your gut either, right?

    Moreover, I suspect that most if not all of you will have heard or read about one of the dozens of epidemiological studies which show associations between very moderate intake of dark chocolate and cardiovascular, neuronal and metabolic health. Apropos "metabolic" did I mention that the animals in the cacao group were also 10% leaner than their peers on the regular - probably not a fair comparison with the differences in the macronutrient make-up but it would still be worth adding another bulletin point to a pretty impressive list of scientifically proven health-benefits of cacao consumption (or supplementation with respective extracts), which comprises among other things
      Guess how she got in shape? Right! The EDC Program ! EDC? Yeah: "The Female Weight-Loss EDC: The Fat Burning, Waist Reducing Synergy of Exercise, Diet and Dark Chocolate" - click here to  learn more
    • high antioxidant activity
    • improved insulin sensitivity, beta cell function & carbohydrate metabolism
    • improved HDL/LDL ratios
    • inhibition of detrimental byproducts of the arachidonic acid metabolism
    • induction of NO-mediated, endothelium-dependent relaxations
    • reduced incidence of stroke due to hypotensive effects
    • anti-CVD effects via TGF-β1 and decreased tendency of blood to clotting
    • local and systemic TNF-alpha modulation and VGEF suppression => anti-cancer efects
    • immune effects that can protect you from tooth decay
    • protection against UV radiation and rejuvenating effect if its applied to the skin
    • suppressive effect on fatty acid synthesis
    • increases in mitochondrial respiratio
    • ability to boost serotonine (5-HT), improve mood and lower appetite and cravings
    • [...]
    I am not intending to make an all-encompassing list, here. Instead I will conclude with the astonishing insight from one of the most recent meta analysis that the daily consumption of the polyphenol equivalent of 100g of dark chocolate (at least 60-70% cacao content; 500-1,000mg polyphenols) would prevent 85 cardiovascular events per 10,000 capita every year (Zomer. 2013).

    Don't get me wrong I am with you with respect to the absurdity of cost-analyses when we are talking about health, but that's unfortunately the way the health business is operating and therefore I won't simply ignore the 50,000$, which is the saving the scientists estimate for every saved life and the corresponding 40$ of which Zomer et al. suggest that they should be spent "per person per year could be devoted to advertising, educational campaigns, or potentially subsidisation of dark chocolate in this high risk population." (Zomer. 2013)

That's  it for this week - at least as far as the SuppVersity Science Round-Up goes

Since Maxim asked "And what about garlic?", here is an addendum summarizing what I maybe did not get across very well at the end of the show, when I was flabbergast that the show was already over: The researchers took 20 male non-athletes (aged 22-26 years, body fat 16-20% and VO2max 38-42 ml/kg/min) randomized them to 700mg garlic or dextrose control  for 14 days and had them work out at 75% VO2max on the treadmill for 30 minutes at the end of the intervention period. Afterwards they analyzed the blood samples and found that (a)the 14 day supplementation alone reduced the basal triglyceride and increased the high density lipoprotein-cholesterol (HDL) increase (P<0.05) and (b) increased the beneficial effects of the exercise bout on acute reductions in LDL and triglycerides (Zekril. 2013)
I hope you enjoyed listening to the show (click here to download the podcast in case you still haven't done so) and satisfied your cravings for more with this installment of the SuppVersity Science Round-Up Seconds: In case you haven't I suggest you browse over to the SuppVersity Facebook Wall and check out the latest news on
  • The connection between MS an impaired blood-brain barrier: A leaky brain and the intrusion of fibrinogen (a coagulation protein from the blood) could be the cause of multiple sclerosis (read more)
  • Fishing for Omega-3s in Milk: One cup of fish oil enhanced milk yields 432mg of DHA + EPA... and it does not taste or smell fishy (read  more)
  • Heart disease may begin even before you are born: Prenatal stress will turn the "probably" before "develop heart disease" into a "most likely" (read more)
When you are done with that and still hungry for more, you may want to check out my, as well as Patrick Arnold's, Kurtis Frank's (examine.com) and Willem Koert's (ergolog.com) contributions to a round-table discussion on the more or less recent ban of DMAA (aka geranium oil) in Australia - I have been so busy that I totally forgot about having done the respective interview weeks ago. Sorry for letting you know so late ;-)


References:
  • Appukutty M, Radhakrishnan AK, Ramasamy K, Ramasamy R, Abdul Majeed AB, Ismail MN, Safii NS, Poh KB, Chinna K, Haleagrahara N. Colostrum supplementation protects against exercise - induced oxidative stress in the skeletal muscle in mice. BMC Res Notes. 2013 Nov 22;5(1):649.
  • Hayes MM, Hughes TA, Greene AK. Bacterial diversity in dried colostrum and whey sold as nutraceutical products. J Food Sci. 2013 Jul;77(7):M359-63.
  • Morrill KM, Conrad E, Lago A, Campbell J, Quigley J, Tyler H. Nationwide evaluation of quality and composition of colostrum on dairy farms in the United States. J Dairy Sci. 2013 Jul;95(7):3997-4005.  
  • Rodríguez-Ramiro I, Ramos S, López-Oliva E, Agis-Torres A, Bravo L, Goya L, Martín MA. Cocoa polyphenols prevent inflammation in the colon of azoxymethane-treated rats and in TNF-α-stimulated Caco-2 cells. Br J Nutr. 2013 Nov 28:1-10. 
  • Zekri1 R, Jafari A, Dehghan G.  The concurrent effect of one bout aerobic exercise and short-term garlic supplementation on the lipids profile in male non-athletes. J Shahrekord Univ Med Sci. 2013; 14 (5) :34-41
  • Zomer E, Owen A, Magliano DJ, Liew D, Reid CM. The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model. BMJ. 2013 May 30;344:e3657.

Friday, November 29, 2013

Human Study: OTC Supplement Doubles T-Levels & Boosts Erections More Than Tadalafil - Too Good to Be True?

Just to make sure you don't suffer from withdrawl symptoms until Adelfo posts the next update on his current contest prep, I thought I'd share a photo that shows where he is currently at - not bad for someone of whom a handful of you have been shocked to hear that he eats at least 200g carbs per day and ice-cream almost every evening, right?
It's Thursday and before I'll get to a question on a very recent study I received via the SuppVersity Facebook page, I will brief you on the line-up of today's installment of the SuppVersity Science Round-Up on the Super Human Radio Network. By now, most of you should actually be familiar with the modus operandi: In case you cannot listen live at 1PM EST, you can always download the show ~2h later either from the "Physical Culture for Your Ears" menu in the sidebar of the SuppVersity, or right over at www.superhumanradio.com - obviously, you can also wait for tomorrow's SuppVersity Science Round-Up Seconds, in which I am providing some additional information on things we have discussed and post selected topics that did not make it into the show.

Apropos topics, the first topic we are going to address does actually pertain to the second part of this post and revolves around a recently published paper by Fabrizio Iacono et al. whose results do - just as SuppVersity reader Mark, who pointed me towards this article, says - look "too good to be true".

    Now, upon closer scrutiny it turns out that they may well be "true", but are not just as "good" as they may initially look like. From this testosterone-laden topic we are then going to proceed with topics revolving around male and female longevity, optimal workout types and intensities for different trainees,the health effects of garlic, colostrum and chocolate and related topics.

    I could mention more, but am afraid that this will just increase the risk of rushing through the items too quickly. Optimally, you just tune in live and pick up the rest in "print" in tomorrow's SuppVersity Science Round-Up Seconds!

    200% increase in total and 130% increase in free testosterone

    Just a reminder: Taurine has also (rodent) data showing up to 180% increases in testosterone and that's not exclusively in the sick and old.
    This subheading sounds as if I was to pimp the "revolutionary new testbooster" by "whatever company" that will get you muscular and ripped in no time, right? Well, in the end it could well be the text of an advertisement, yet not one from any of the usual suspects but rather one for TRADAMIX®, a blend of "three natural substances with an 'anti-aging' effect on the tissues of the male genitourinary apparatus" (Tradapharma Sagl. 2013) - I know, without the usual "-bols", "-diols", or at least some indirect references to illegal anaobolic substances in the product name, this does not sound like it would work, but the +200% increas in total and +130% increase in free testosterone are for real and documented in a peer-reviewed study involving seventy patients (67.3± 3.7 years) with stable marital relations and reduced libido, with or
    without erectile dysfunction who received either the infamous PDE-5 inhibitor Tadalafil (5mg/day) or two servings of the aforementioned 'testicular anti-aging supplement' (Iacono. 2013).

    But before we even get to the testosterone levels, let's tackle the main problem of these guys and the actual research interest of the scientists from the University “Federico II” of Naples in Italy first. After all, the main outcome of the study at hand were the improvements in sexual desire and erectile function and those were almost identical in both groups - from 16 to 33 and 16 to 31, in the supplement vs. drug groups, respectively. If you go by the results of the international index of erectile function (IIEF) questionnaire (see figure 1, left), on the other hand, the dietary supplement yielded actually outperformed the blockbuster prescription drug by almost 10%:
    Figure 1: Results of international index of erectile function (IIEF) questionnaire and RigiScan (device to measure penile tumescence and rigidity continuously that's used to differentiate vascular from psychogenic erectile dysfunction) before and after 2 months of treatment with Tradamixina and Tadalafil (Iacono. 2013).
    What's probably even more impressive, though, are the differential effects of Tradamixina vs. Tadalafil on the RigiScale values (see figure 1, right). The RigiScale is an etablished means to differentiate psychogenic from organ-related (vascular) erectile dysfunction (Basar. 2001) and the fact that there was a significant reduction of RigiScale positive subjects in the Tradamixina group does already suggest a possible reason for the initially mentioned 200% increase in total and 130% increase in free testosterone (see figure 2).
    Figure 2: Total and free testosterone levels before and after the administration of Tradamaxine (2 servings per day) or Tadalafil (2mg/day) to Seventy patients (67.3± 3.7 years) with stable marital relations and affected by reduced libido for 2 months (data based on Iacono. 2013)
    What this underlying reason is? Well, probably reduced systemic inflammation, which leads to reductions in cortisol, blood glucose, insulin resistance, oxidative damage to the testes etc. and thus simply facilitates the restoration of normal testosterone levels.

    If you know how google works, it'll take you maybe 5 minutes and a credit card and you'll have a couple of pounds of the ingredients right on the way to your doorstep.
    Yep, you heard me right: A boost of +200% just brought those guys who started with 10ng/dl below the already way too broad normal range from 260-1080ng/dl (values may vary from lab to lab) in a quasi hypogonadal state, back to midrange levels of 680ng/dl.
    Real world implications for healthy young men: The chance that a healthy, fit individual with normal testosterone levels would see a boost of 200% in his total or 130% in his free testosterone levels is not low, it is simply ZERO!
    Notwithstanding, Tradamixina (or rather its ingredients) is actually more than just a cilialis alternative. While the latter is a short term solution to get rid of the symptoms of an underlying disease, the combination of Ecklonia Cava, tribulus, and d-glucosamine + n-acetyl-d-glucosamine could actually tackle the most frequent cause of erectile dysfunction, which is the triad of inflammation, insulin resistance and arteriosclerosis (for more details see info-box to the right).

    So how does this stuff work? Although investigations into the mechanism by which the provision of Tradamaxine did work its magic was actually not part of the study, it's actually not difficult to hypothesize what may be the underlying cause of these unquestionably astonishing results. Firstly, the brown algae Ecklonia Bicyclis (better known as Ecklonia Cava!)of which each serving has 150mg has a very high content of sterols, polyphenols and tannins and is probably the main active ingredient of a formula which includes 396mg of tribulus and 144mg of d-glucosamine and n-acetyl-d-glucosamine as a 'support'. The phlototannins 7-phloro eckol and 6,6′-bieckoll that have been isolated from Ecklonia, a marine brown algae which has been used for centuries in traditional medicine in Asia, are more or less unique with respect to the potency of their antioxidant activity (Li. 2009). In conjunction with tribulus, d-glucosamine and n-acetyl-d-glucosamine, which also exhibit a certain degree of anti-inflammatory activity, a decrease in systemic inflammation is the most likely cause of the profound pro-sexual and pro-hormonal effects of this blend, which is yet by no means as unique as the producers would have it.
    Bottom line: It is no coincidence that erectile dysfunction has been identified as a "harbinger of cardiovascular clinical events" (Thompson. 2005) and "a sentinel event for CAD [coronary artery disease]" (Irekpita. 2009). So if you are in the unlucky situation to suffer from vascular (and not physogenic) erectile dysfunction, and had the choice between a drug that will ameliorate the symptoms, i.e. Tadalafil, or a supplement that will treat the underyling cause, the decision for the supplement and against the lifestyle drug should be obvious, right?

    Still, there is one, ... no, actually there are two things I would like to ask you, before you run all spiked up to the next best supplement shop: Firstly, how accurate would you say is the authors' claim that there was "no conflict of interest", if no one else, but the lead author of the study, has been granted a patent on the formula on April 4th, 2013 (US2013/089722 A1)? And secondly, do you really believe that it is a mere coincedence that the researchers deliberate use the hardly known appellation Ecklonia Bicyclis for a brown algae all of you probably know as Ecklonia Cava (see "Ecklonia Cava Polyphenols Help Shed Weight Even in The Presence of a Slight Caloric Surplus") throughout the whole paper without mentioning once that it is better known as "Ecklonia Cava"? I am well aware that studies are expensive and need to be financed and I am by no means suggesting that the results are - as Mark suspected - "too good to be true" (remember. the men were hypogonadal to begin with), but this paper does still have a somewhat peculiar aftertaste.

    References:
    • Basar MM, Atan A, Tekdogan UY. New concept parameters of RigiScan in differentiation of vascular erectile dysfunction: is it a useful test? Int J Urol. 2001 Dec;8(12):686-91.
    • Iacono F, Prezioso D, Illiano E, Romeo G, Ruffo A, Amato B. Sexual asthenia: Tradamixina versus Tadalafil 5 mg daily. BMC Surg. 2013 Nov 15;12 Suppl 1:S23.
    • Irekpita E, Salami TA. Erectile dysfunction and its relationship with cardiovascular risk factors and disease. Saudi Med J. 2009 Feb;30(2):184-90. 
    • Li Y, Qian ZJ, Ryu B, Lee SH, Kim MM, Kim SK. Chemical components and its antioxidant properties in vitro: an edible marine brown alga, Ecklonia cava. Bioorg Med Chem. 2009 Mar 1;17(5):1963-73.
    • Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA. 2005 Dec 21;294(23):2996-3002. 
    • Tradapahrm Sagl. Tradamix. 2013 < http://www.tradamix.com/en/ > retrieved on 11/29/2013.

    Thursday, November 28, 2013

    Probiotics + Green Tea - Synergistic Superstack or Sciency Non-Sense? Green Tea Alone Totally Blunts HFD Induced Weight Gain, L. Plantarum Does Not Add to Its Effects

    L. plantarum may metabolize green tea phenols, but don't add to their anti-diabesity effects 
    Green tea has actually never seized being all the rage and probiotics are the sexy new kid on the block right around the corner of the supplement shops and and science laboratories of the western hemisphere. Against that background I guess that the title of a paper that's been published ahead of print on Monday will probably suffice to catch your interest: "Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice." (Axling. 2013) - and that despite the fact that "mice are no little men" ;-)

    '1 + 1 =4' the synergism of green tea and probiotics could make it possible

    I guess, the idea sounds logic: Take one thing that has been proven to ameliorate diet induced obesity, namely green tea, and combine that with another one, of which it appears as if it would also exhibit beneficial effects into an even more potent stack. In fact, the scientists' rationale was yet slightly different:
    "The species Lactobacillus plantarum (L. plantarum) has the ability to metabolize phenolic acids  and to split up tannins. The metabolites are presumably more easily absorbed and distributed into the tissues where they can act as antioxidants and electron scavengers. Phenolic compounds can also have antimicrobial effects that may affect the composition of the gut microbiota, in favour of polyphenol-metabolizing components of the microbiota. Also, green tea extracts have been shown to selectively inhibit the growth of pathogenic bacteria while either enhancing or not affecting the growth of beneficial bacteria like lactic acid bacteria. To the best of our knowledge, the impact of green tea powder as a prebiotic compound to promote lactobacilli or other health promoting components of the microbiota has not previously been evaluated."
    In other words, the expected benefits of providing both green tea and probiotics in conjunction were (1) an increased bioavailability of the phenols and tannins from the green tea that would be induced by the probiotics and (2) an increase in the probiotics' survival and ability to modify the gut microbiome that would be brought about by the addition of the green tea.

    What looks good on paper does not necessarily work out in a complex organism

    Figure 1: Ingredient total amount of Flavan-3-ol, Phenolic acid and Flavenol in water and methanol extracts from the green tea leaves that have been used in the study (Axling. 2013); as you can see the total quantity and the ratios of the bioactive ingredients of the extract actually depend on the extraction method.
    Apropos green tea, you can see the exact ingredient profile of the green tea supplement that has been used in the study at hand in figure 1. In view of the fact that the C57BL/6J mice received no extract, but simply powdered green tea leaves, it may not be important in this context, but could be relevant for your future purchases that methanol and water extracts differ not only in terms of the total amount of Flavan-3-ol, Phenolic acid and Flavenol they contain, but also with respect to the ratio of the respective phytochemicals. I guess, those of you who have been around in September 2011, already, will remember that I have discussed the impact these ostensibly negligible differences can have more than a year ago in "-20% Reduction in Serum Testosterone by 5 Cups of Green Tea. Endocrine Effects Depend on Catechin Composition". In case you are one of the many newcomers or have simply forgotten (let alone missed ;-) this post, I suggest you go back and read that up, as it may help you get a better understanding of the underlying reasons due to which quality and quantity of the health effects of green tea (supplements) wary from study to study... but let's now get back to the experimental setup of the Axling study.

    Green tea alone already blunts HFD induced weight gain

    As mentioned before the extracts were simply mixed with the high fat diet, the mice were consuming in the course of the 22 week study period. With the probiotic supplement that was administered with the drinking water (L. plantarum at 1.5% (v/v) or roughly 3 × 10^9 cfu/ml) we are thus dealing with four different groups:
    • Control: High fat chow + no supplement
    • LP: High fat chow + L. plantarum
    • GT: High fat chow + green tea
    • GT + LP: High fat chow + green tea + L. plantarum
    If you focus solely on the initially quoted hypothesis about the synergistic effects of green tea + L. plantarum, the actual study outcomes - at least as far as the blood markers in figure 2 are concerned  - are certainly disappointing.
    Figure 2: Glucose insulin, fructosamine, cholesterol, triacylglycerol, non-esterified fatty acids and adiponectin levels in the blood of the mice in week 11 and week 22 of the study (Axling. 2013)
    It's not like '1+1 would equal 4', but rather like '1 + 1' would just be sufficient to yield '1' not just '0.9' or even less. The in fact, the addition of the probiotics, alone, did very little within the first 11 weeks as far as it's ability to th reduce the diet-induced insulin resistance is concerned and it's addition to the green tea supplement did not improve blood glucose and lipid management, but did in fact diminish the impressive effects the green tea supplement brought about.
    Figure 3: Relative change (compared to control) in bacterial diversity and lactobacilli count in response to the supplement regimen (Axling. 2013)
    That the probiotic was basically useless, is actually no wonder if you take a closer look at the changes of gut microbiome in figure 3. Aside from an intermediate increase in lactobacilli, it could not boost the amount of these supposedly healthy bacteria in the long term. Rather than that it did induce an allegedly statistically non-significant decrease in the overall diversity (figure 3, left).

    Minor differences with quasi-nonexistent real-world effects

    At the mRNA level, the addition of L. planatrum counter-acted the anti-obesity effects of green tea, as evidenced by
      Figure 4: Body weight and fat levels of the mice (Axling. 2013)
    • 20% higher fatty acid synthase levels, an enzyme that's responsible for the synthesis of fatty acid
    • the reversal of the statistically significant reduction in acetyl-CoA caroxylase (ACC), an enzyme that's one step ahead of FAS in the cascade of which you could say that it supplies the raw material for fatty acid synthesis, and
    • minimally higher PPAR-gamma levels (responsible for fat storage) 
    in the LP + GT vs. GT group, respectively. The net effects on body weight and fat mass, on the other hand were negligible. In essence the bulk of the beneficial effects of the green tea extract remained intact. Moreover, the addition of L. plantarum did have two distinct effects, that were not observed in the GT only group:
      Figure 5: Liver cholesterol and HMG-CoA-R after 11 (top) and 12 (bottom) weeks (Axling. 2013)
    1. a statistically non-significant -20% reduction in the mRNA expression of the inflammatory marker TNF-alpha, and
    2. a whopping and surprising increase in HMG-CoA reductase of +50% and +70% increase in HMG-CoA reductase mRNA compared to the green tee only and the control group, respectively
    And while there is nothing in the study that would suggest that there were any beneficial effects from the TNF-alpha reduction, the increase in HMG-CoA reductase is in fact an oddity. After all, despite statistically significant increases in the enzyme that's responsible for the synthesis of cholesterol and the main target of statin drugs (Stancu. 2001), the cholesterol levels dropped by 64% and 39% compared to the control group, in weeks 11 and 22, respectively.

    What do these Jerusalem artichokes, agave, bananas, burdock, camas, chicory, coneflower, costus, dandelion, elecampane, garlic,jicama, Leopard's-bane, mugwort, onion, wild yams, yacon and a whole host of other foods have in common? Right! They contain inulin. which has only recently been shown to have the ability to ameliorate body weight gains by up to 50%! Intriguing? Go back to my previous post and learn more about inulin, beta-glucans and their anti-diabesity effects.
    Bottom line: A non-statistically significant reduction in TNF-alpha and an elevation of cholesterol synthesis in the presence of lower liver cholesterol levels, which would be suggestive of an increased excretion of cholesterol (thus the increased synthesis to come up for the loss), are in my humble opinion nothing that would render the combination of green tea + L. plantarum superior to the provision of green tea alone. The latter on the other hand, appears to be a great tool to keep the damage of the energy-dense Western diet in check - with no added, let alone synergistic benefit of these particular probiotic.

    Maybe the provision of another probiotic or even another strain of L. plantaris would yield at least '1 + 1' results. This would yet be a research question for another study (one I would by the way not be willing to finance ;-) and does not change the fact that the original research hypothesis that there would be a potentiating effect due to the synergism of the two supplements is - even if the scientists don't openly acknowledge that - debunked for L. plantaris DSM 15313 and green tea.

    References:
    • Axling U, Olsson C, Xu J, Fernandez C, Larsson S, Ström K, Ahrné S, Holm C, Molin G, Berger K. Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL/6J mice. Nutr Metab (Lond). 2013 Nov 26;9(1):105.
    • Stancu C, Sima A. Statins: mechanism of action and effects. J Cell Mol Med. 2001 Oct-Dec;5(4):378-87.

    Wednesday, November 27, 2013

    Asparagus Extract Tops Anti-Diabetes Drug Glibenclamide. Plus: Dozens of Add. Health Benefits - From Aphrodisiac to Anti-Hangover & from Neuroprotection to Anti-Aging

    Coho salmon, shrimp and asparagus with melted butter - better than any diabetes drug ;-)
    Within the last couple of weeks, I have been moving news-items like this one into the "On Short Notice"  category, or simply totally discarded the dozen or so "herb XYZ" or "extract ABC ameliorates hypoglycemia in rodent model of type II diabetes" papers that are published on a weekly basis. The mere number of studies on whatever exotic, herb, spice or isolated polyphenol from the most remote areas (usually in Asia) the names of which I often even have heard about before, is simply too large to cover them all... and let's be honest: In the end, it's also downright boring to read about stuff that decreases blood glucose in a rodent model to a miniscule extend, when you already know that chances that you ever get your hands on a significant amount of that are zero, right?

    There are however, two good reasons, why Rahman Md. Hafizur, Nurul Kabir and Sidra Chishti most recent paper, which has been published on November 24 in the latest issue of the British Journal of Nutrition, has still made it not just into the short, but actually the 'official' SuppVersity news are twofold: Firstly, the effects of the Asparagus officinalis extract they administered at two different dosages to their rodents were just mediocre, but - as you are about to see - right on par with the diabetes drug glibenclamide, a sulfonylurea based medication that is often sold in combination with metformin (the respective drugs are called Glucovance and Glibomet). And secondly, briefly summarizing the main results of the study provided a nice incentive to dig somewhat deeper into the already established beneficial health effects of asparagus - and I can tell you, those are about as numerous as the aformentioned boring "herb XYZ"-studies ;-)

    From the scientists' petri dishes to the rodent cage and... onto your dishes?

    Asparagus officinalis L. is probably what the average Westerner would call "common asparagus". It's native to most European, African and Asian countries and its medicinal usage has been reported in the British and Indian Pharmacopoeias and in traditional systems of medicine such as Ayurveda, Unani and Siddha. Most of you will probably be aware of its mild diuretic effects and the distinct smell of your urine which will betray that you are someone who loves its delicate flavor in salads, vegetable dishes, soups and (if you are like me) poundwise with melted Kerrygold butter, some potatoes a decent amount of ham or some grilled meat during the asparagus season... but I am digressing here, let's get back to the facts.
    To get to the bottom of previously reported beneficial effects of asparagus in various inflammatory (metabolic) diseases, the initially conducted an in-vitro study, to test the radical scavenging ability of their Asparagus extract and found that ...
    "[...] A. officinalis at a concentration of 0·5 mg/ml exhibited 86·8 % radical-scavenging activity, as shown by a significant decrease in the absorbance of DPPH radicals. These results suggest that A. officinalis has potent antioxidant activity, as the positive control propyl gallate exhibited 91·4 % radical-scavenging activity. (Hafizur. 2013)
    Afterwards they injected a group of male and female Wistar rats with streptozotocin to induce diabetes. Subsequently, the rodents received either 250 or 500mg/kg body weight of an Asparagus officinalis (AO) extract or 5mg/kg body weight of glibenclamide (GIB) once daily via an oral syringe - the dosage was adapted once weekly according to changes in body weight.
    Figure 1: Fasting blood glucose and insulin levels, total antioxidant status (TAS was measured using the ABTS) and beta cell area / islet expressed relative to control at the end of the 29 day study period (based on Hafizur. 2013)
    A cursory glance at the data in figure 1 reveals: The initially betrayed anti-hypoglycemic effects (hypo[...] = ability to lower [blood sugar]) the high dose of Asparagus officinalis extract (AO500, figure 1) had on the fasting glucose levels of the animals were as potent as those of the diabetes drug glibenclamide.  Moreover, the treatment with AO500 had a slightly, but statistically significanty higher impact on the total antioxidant capacity and the same benificial effect on the morphology and function of the pancreas. Nevertheless, neither the A. officinalis extract, nor the glibenclamide treatment were able to restore the compromised insulin producton to more than ~70% of the value the non-streptozotocin-intoxicated animals.

    There is much more to asparagus than it's antidiabetic effects

    As impressive as these results may be, if we simply rely on the findings Hafizur, Kabir and Chishtiit present in this recent paper, we will actually miss not just half, but rather 95% of the potential health benefits the different genus and parts of asparagus have to offer.

    Figure 2: A. racemosis administered at a dose of 200mg/kg per day makes male rats about as horny (and able to perform) as bi-weekly injections of testosterone (Thakur. 2009) - not that you would need that, but it's nice to know anyways.
    Despite the fact that asparagus is a highly nutritious source of vitamin B6, calcium, magnesium and zinc, and a very good source of dietary fiber, protein (in at least in view of the fact that it's an almost zero calorie veggie ;-), vitamin A, vitamin C, vitamin E, vitamin K, thiamin, riboflavin, rutin, niacin, folic acid, iron, phosphorus, potassium, copper, manganese, selenium, highly bioavailable chromium, and even small quantities omega-3 fatty acids (Morales. 2013), so that the regular incorporation of asparagus alone into your diet will supposedly be beneficial for you, some of the more intricate health effects may in fact require the extraction of and supplementation with specific phytonutrients from Asparagus officinalis, A. racemosus, A. cochinensis and its various cousins.

    In order to give you an idea of what you can expect, I have compiled a comprehensive, yet by no means extensive list of benefits which have been ascribed to root, seed, and even leaf extracts of asparagus over the past decades
    • anti-cancer effects: Asparagus contains saponins that have in-vitro anti-(liver-)cancer effects (Ji. 2013); 
    • neuroprotective effects: Chinese asparagus contains pregnanes that sooth neuro-inflammation (Jian. 2013; compounds could be present in regular A. officinalis as well) and can protect your liver and brain from aging (Xiong. 2011); 
    • antiaging effects: A. contains enzymes that help with protein digestion (Ha. 2013); 
    • hypolipidemic effects: n-butanol extracts from A. officinalis exert anti-hyperlipidemic effects (Zhu. 2011); 
    • antimicrobial effects: A. has antibacterial activity against Escherichia coli, Shigella dysenteriae, Shigella sonnei, Shigella flexneri, Vibrio cholerae, Salmonella typhi, Salmonella typhimurium, Pseudomonas putida, Bacillus subtilis and Staphylococcus aureus (Mandal. 2000); 
    • allows for geno-typing at home ;-) A. allows you to do a personal gene analysis to find out whether you have a single nucleotide polymorphism at rs4481887, which would make it impossible for you to smell the distinct odor the urine acquires after eating asparagus (Pelchat. 2011); 
    • anti-hangover effects: A. helps your liver to metabolize alcohol and can even prevent a hangover (Kim. 2009); 
    • buttery taste: A. contains phytochemicals which generate the sensation of having butter in the mouth (Dawid. 2013); 
    • anti-stress effects: Ethanolic extracts from Asparagus racemosus have anti-stress activity and help your adrenals take a time out (Joshi. 2013)
    • carbblocking effects: Asparagus racemosus inhibits the digestion of carbohydrates and enhances insulin action (Hannan. 2011); in this context it is interesting to remark that the in-vitro essay of the the study at hand suggested that A. officinalis, or rather the specific extract the scientists used in their study "has a very little effect on delaying glucose absorption" (Hafizur. 2013)
    • immune promoting effects: A. racemosus ramps up natural killer cell activity (Thakur. 2013); AR also enhances memory and prevents amnesia (Ojha. 2013), 
    • profound aphrodisiac effects: A dried root extract likewise from A. racemosus more than doubled the 'desire' of male rodents within 29 days (Thakur. 2009; cf. figure 2)
    • MAO and acetylcholine breakdown inhibition: A. racemosus competitively inhibits acetylcholine and monoamine metabolizing enzymes (Meena. 2011)
    As this highly incomplete list goes to show you, the health benefits are numerous. Unfortunately, this does also apply to the different phytochemicals which trigger all these effects. The probability that the next best extract you may find on the shelves or virtual outlets of a supplement store is actually going to to yield the health benefits you may be looking for are therefore pretty slim.

    Although parts of it are edible as well, A. racemosus, is actually better known for its multitude of beneficial health effects that range from Antibacterial activity (some) antisecretory and antiulcer activity over mood enhancing and anti-depressive properties, and immunomodulatory effects to such profane things as libido enhancement or getting rid of superfluous water before a show or photo shoot.
    Bottom line: In view of the practical problems associated with spotting appropriate extracts, I guess it would be best you take the fact that a 2003 paper in scientific journal Nutrition (Pellegrini. 2003) ranked asparagus 7th among 34 fruits and vegetables with respect to its free radical scavenging abilities, as an incentive to simply incorporate asparagus into your diets more frequently.

    If, on the other hand, you are dealing with any specific health condition, it would certainly make sense to look for an extract that contains the proper genus of asparagus, is made from the right parts of the plant and - if possible - is even standardized for a specific compound: If you were interested in upping your estrogen levels, you would for example have to pick a whole plant extract of A. dumosus that would at best contain a standardized amount of 20-hydroxecysterone (Kaur. 1998). If it's rather the anti-ulcer effects you are after, your 'asparagus product of choice' should be made of the roots of A. racemosus ideally standardized for its Shatavairin content (Bhatnagar. 2005)... 

    And now, you tell me eating healthy was complicated and taking supplements was easy ;-)

      References
      • Bhatnagar M, Sisodia SS, Bhatnagar R. Antiulcer and antioxidant activity of Asparagus racemosus Willd and Withania somnifera Dunal in rats. Ann N Y Acad Sci. 2005 Nov;1056:261-78.
      • Dawid C, Hofmann T. Identification of Sensory-Active Phytochemicals in Asparagus (Asparagus officinalis L.). J Agric Food Chem. 2013 Nov 8.
      • Ha M, Bekhit Ael-D, Carne A, Hopkins DL. Characterisation of kiwifruit and asparagus enzyme extracts, and their activities toward meat proteins. Food Chem. 2013 Jan 15;136(2):989-98. 
      •  Hafizur RM, Kabir N, Chishti S. Asparagus officinalis extract controls blood glucose by improving insulin secretion and β-cell function in streptozotocin-induced type 2 diabetic rats. Br J Nutr. 2013 Nov;108(9):1586-95.
      • Hannan JM, Ali L, Khaleque J, Akhter M, Flatt PR, Abdel-Wahab YH. Antihyperglycaemic activity of Asparagus racemosus roots is partly mediated by inhibition of carbohydrate digestion and absorption, and enhancement of cellular insulin action. Br J Nutr. 2011 Sep 8:1-8.
      • Ji Y, Ji C, Yue L, Xu H. Saponins isolated from Asparagus induce apoptosis in human hepatoma cell line HepG2 through a mitochondrial-mediated pathway. Curr Oncol. 2013 Jul;19(Suppl 2):eS1-9.
      • Jian R, Zeng KW, Li J, Li N, Jiang Y, Tu P. Anti-neuroinflammatory constituents from Asparagus cochinchinensis. Fitoterapia. 2013 Oct 24.
      • Joshi T, Sah SP, Singh A. Antistress activity of ethanolic extract of Asparagus racemosus Willd roots in mice. Indian J Exp Biol. 2013 Jun;50(6):419-24. 
      • Kaur H. Estrogenic activity of some herbal galactogogue constituents. Ind J Anim Nutr. 1998;5:232–4.
      • Kim BY, Cui ZG, Lee SR, Kim SJ, Kang HK, Lee YK, Park DB. Effects of Asparagus officinalis extracts on liver cell toxicity and ethanol metabolism. J Food Sci. 2009 Sep;74(7):H204-8. 
      • Meena J, Ojha R, Muruganandam AV, Krishnamurthy S. Asparagus racemosus competitively inhibits in vitro the acetylcholine and monoamine metabolizing enzymes. Neurosci Lett. 2011 Sep 26;503(1):6-9.
      • Morales P, Ferreira IC, Carvalho AM, Sánchez-Mata MC, Cámara M, Tardío J. Fatty acids profiles of some Spanish wild vegetables. Food Sci Technol Int. 2013 Jun;18(3):281-90.
      • Ojha R, Sahu AN, Muruganandam AV, Singh GK, Krishnamurthy S. Asparagus recemosus enhances memory and protects against amnesia in rodent models. Brain Cogn. 2010 Oct;74(1):1-9.
      • Pelchat ML, Bykowski C, Duke FF, Reed DR. Excretion and perception of a characteristic odor in urine after asparagus ingestion: a psychophysical and genetic study. Chem Senses. 2011 Jan;36(1):9-17.
      • Pellegrini N, Serafini M, Colombi B, Del Rio D, Salvatore S, Bianchi M, Brighenti F. Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. J Nutr. 2003 Sep;133(9):2812-9. 
      • Thakur M, Chauhan NS, Bhargava S, Dixit VK. A comparative study on aphrodisiac activity of some ayurvedic herbs in male albino rats. Arch Sex Behav. 2009 Dec;38(6):1009-15. Epub 2009 Jan 13.
      • Thakur M, Connellan P, Deseo MA, Morris C, Praznik W, Loeppert R, Dixit VK. Characterization and in vitro immunomodulatory screening of fructo-oligosaccharides of Asparagus racemosus Willd. Int J Biol Macromol. 2013 Jan 1;50(1):77-81.
      • Zhu X, Zhang W, Pang X, Wang J, Zhao J, Qu W. Hypolipidemic effect of n-butanol Extract from Asparagus officinalis L. in mice fed a high-fat diet. Phytother Res. 2011 Aug;25(8):1119-24.

      Tuesday, November 26, 2013

      Magic Numbers: 1g Protein per 2g Carbs + Circuit Training = The #1 Formula for Weight & Fat Loss in Obese Women?

      If there is one thing about this study that's not debatable it is that eating whole foods, cleaning your diet from all sorts of junk and working out lifting weights and doing aerobics were the cornerstones of the weight loss success of these women, regardless of whether they consumed a low, medium or high amount of protein.
      Roughly two years ago, when the SuppVersity opened its doors, it was pretty rare to find a scientist who would be willing to "waste" (that's probably how he or she would have said it ;-) precious time and the limited funds of his institution to study the effects of "high protein diets". Over the past couple of months, things have been changing, though: I've just checked and according to Pubmed, the number of publications containing the exact phrase "high protein diet", alone,  has increased by ~32% in 2011 and has remained on the same comparably high level ever since. That said a recent study from the University of Guelph in Canada is only the latest in the line of a whole host of publications that deal with the beneficial effects of high(er) protein diets on weight loss in overweight, (pre-)diabetic subjects; exactly those people who have previously been advised to stay clear of all fats, ignore the proteins and focus on the "healthy and satieting" low GI carbs, by the way.

      Yet though the tides may be turning ...

      ... a paradigm shift within the scientific community usually doesn't come over night - a famous scientist and philosopher of science once said that it usually takes until the proponents of the old paradigm died out, before a new one is fully established. Since roughly two years and even two decades are hardly enough for this to happen, it is actually not surprising that Dawn. D. Campbell and Kelly A. Meckling, despite giving the high protein diet credit for having produced some promising results in the past, speculate that
      "the combined effects of a normal protein: carbohydrate ratio with cardiovascular and resistance training would be more beneficial and easier to comply with than either the low- or high-protein diets in this target population of women with risk factors for the MetS" (Campbell. 2013)
      In view of the fact that Rehm et al. conclude ther 2008 review of the literature with the statement...
      "Diets moderately increased in protein and modestly restricted in carbohydrate and fat, particularly saturated fat, may have beneficial effects on body weight, body composition, and associated metabolic parameters." (Rehm. 2008)
      ... and against the background that the evidence of the real-world benefits of a higher protein intake is accumulating, and pertinent reviews and editorials have been appearing on a monthly basis, ever since (e.g. Hession. 2009; Keller. 2011; Acheson. 2013), the research hypothesis of the study at hand sounds a bit 'last year', not to say 'last decade' to me.

      Do we have a bias here?

      Moroever, with the research hypothesis being a good indicator of a built-in bias, we will have to pay pretty close attention to distinguish the actual data Campbell and Meckling measured from their interpretations of the latter. After all, every "good" SuppVersity student should remember that we have seen time and again how the differences between facts and interpretations often become somewhat blurry in the conclusions of way too many (for my liking) papers as of late. So let's see if Campbell's and Meckling's conclusion that...
      "A diet with a 1:2 protein:carbohydrate ratio promoted better improvements than either the LP or HP diets, and may be superior in reducing long-term chronic disease risk in this population." (my emphasis in Campbell. 2013)
      What can be said right away is that the protocol the scientists used, specifically the way they are working with macronutrient ratios instead of paradigmatic percentages of the RDA, is actually pretty progressive.

      "Subjects were encouraged to consume whole foods as opposed to pre-packaged or processed foods and to restrict intake of whole-fat dairy, high-fat red meats, deep-fried foods, potato chips, cookies and refined sugar products. Instead, subjects were encouraged to choose whole-grain pro-ducts, lower-fat meats, fish, turkey, eggs, low-fat milk and cot-tage cheese, nuts, seeds, and a variety of vegetables, fruits and berries. Before beginning the study workout programme, subjects completed baseline fitness testing to assess muscular strength and cardiovascular fitness." (Campbell. 2013)
      Instead of simply upping the protein intake from the 0.8g/kg body weight the RDA suggest would be optimal, Campbell and Meckling put their obese (mean BMI ~35kg/m²) female participants (of which only 54 completed the study) on calorically restricted diets (supposedly -30% below their habitual energy intake which had been evaluated by the means of a 7-day food record) which contained an equal relative amount of fat (<30%), but had different protein-to-carbohydrate ratios:
      • low protein (LP) - 1g protein : 4g carbohydrates
      • medium protein (MP) - 1g protein : 2g carbohydrates
      • high protein (HP) - 1g protein : 1g carbohydrates
      To put that in perspectve, a women who may have been consuming a baseline diet containing 2,300kcal per day would have had to restrict her caloric intake to 1,610kcal. Of these 1,610kcal, <30% would come from fat (60g), while the rest would be ingested in the form either 56g protein and 225g carbohydrates (LP), 94g protein and 188g carbohydrates (MP), or 140g protein and 140g carbs (HP).

      There is no effective weight loss without exercise and a whole food diet!

      In addition to the dietary regimen the 117 participants who initially met the eligibility criteria were supposed to particpate in a  supervised 12-week circuit training program at the University of Guelph Athletic Centre.
      The 1 h study fitness programme was completed three times/week on Mondays, Wednesdays and Fridays at a consistent time assigned to each subject. Subjects had to sign in for their workout sessions, and all exercises were supervised by a study coordinator and/or personal trainer. Subjects began their workout with a 9 min warm-up using springboard pads where walking in place, jogging or dancing took place. Then, subjects completed a 30 min circuit alternat-ing between resistance training and cardiovascular exercise bouts. All main muscle groups of the body were targeted throughout the thirteen resistance training machines. Starting weight values on resistance training equipment were 65 % of their calculated maximum strength as determined by their modified 1 repetition maximum. Subjects were instructed to complete one set of eight to fifteen repetitions on each piece of equipment to reach muscle fatigue."
      The circuit training used a build-in progression with ~5% increases in weight, whenever the subject were able to complete 15 repetitions on a given exercise. The same goes for the aerobic parts of the workouts, where the
      Subjects began exercising at 65 % of their maximum heart rate for the first 3 weeks and gradually increased the intensity by 5 % every 3 weeks to a maximum intensity of 80 % by week 12. 
      As far as the aerobic part of the workouts was concerned, they alternated between a step, springboard pad and stationary bike. All workouts closed with some ab training (including a standard crunch, oblique crunch and a core-strengthening exercise called the plank, done to failure) and stretching.

      "Hey, exercise is good for me!"

      Other than you may have expected the 35 dropouts (which were equally distributed across all dietary groups) were not brought about by laziness or the unwillingness to get up and move. On the contrary, many subjects recorded that they had "more energy and felt better than before the study began" (Campbell. 2013). Aside from minor constipation (the scientists don't mention in which group this occured) and some minor shedding in one of the subjects in the low protein group (probably coincidence, by the way), the intervention went fine for those who had the guts, time and discipline to stick it and yielded - as the data in figure 1 goes to show - favorable results in all three arms off the study:
      Figure 1: Changes in antroprometric data, blood pressure and heart rate after 12 weeks (based on Campbell. 2013)
      If we were stupid enough to focus solely on the BMI reductions, we could even say that all diets were equally effective. Upon closer scrutiny and the use of some statistical shenanigan, it does however become clear that the scientists' initial hypothesis that the normal protein diet with a 1:2 protein to carbohydrate would have a small edge over both, the low protein diet (in terms of body fat loss and lean mass retention; p < 0.05) and the high protein diet (solely in terms of body fat loss; p < 0.05) seems to hold true. What's more, this trend in DXA measured improvements in body composition stands in line with noteworthy reductions in waist circumference (7.9, 11.6 and 8.6 cm in the LP, NP and HP), of which Cambell and Meckling write:
      "Again, the decrease in the NP group was greater than that in the LP group. Further-more, hip circumferences decreased similarly (P < 0·05) in response to each diet with reductions of 7·4, 8·8 and 8·4 cm in the LP, NP and HP groups, respectively. Waist:hip ratios declined significantly (P < 0·05) after 12 weeks by 0·01, 0·04 and 0·01 in the LP, NP and HP groups, respectively, but reductions were greater in the NP v. LP (P=0·020) and HP (P=0·025) groups." (Cambell. 2013)
      No group specific diet effects were observed for the reductions in blood pressure and heart rate. Now, this obviously raises the question, whether the existent changes may have been brought about by non-compliance.

      "So maybe the protein eaters just didn't eat their protein?"

      Non-compliance is, as SuppVersity students know, one of the major problems with all of these relatively uncontrolled dietary interventions (see "High Carb vs. High Fat: What Really Happens When Science Meets the Real World"). And in fact, with average caloric intakes of 3641, 3729 and 3633 kJ/d  in in the low, medium and high protein groups, the subjects were actually consuming 10% less energy than they were supposed to.

      Suggested read for everyone who can't or doesn't want to believe that you can easily eat 157g of carbs (which is what the women in the normal protein group did) and still lose fat while retaining all your precious lean muscle mass: "Carbohydrate Shortage in Paleo Land: New Data for A Scientific Outlook at the Low-to-No Carb Paleo Confusion. Will More Than 125g of Carbs Make You Fat?" (read more)
      Despite the fact that this type of non- or rather 'over-compliance' can also have detrimental effects on someone's weight loss efforts, there were no intergroup differences which would skew the ultimate comparison; and much to my surprise the majority of the subjects did even manage to come close to their macronutrient goals by adapting their previously almost identical protein to carbohydrate ratios of  1:3.5, 1:3.2 and 1:32 at baseline to 1:3.5, 1:2.1 and 1:1.3 by week 12. With respect to the total protein intake, this equals
      • significant decreases in protein intake (82 and 88 g/d to 55 and 75 g/d) for the low and normal protein groups and
      • significant increases in protein intake (from 84 to 100 g/d) in the high protein group
      This does also mean that the percentage of subjects who met the 0.8g/kg RDA for dietary protein intake at the beginning of the study had dropped to zero in the low protein group by week 12.

      The subjects in the normal protein intake group were about as close as you can get and those in the high protein group consumed significantly more protein than the 'well-meaning' authors of the dietary recommendations feel would be good for them ;-) Other changes the scientists observed were:
      • a significant declines in carbohydrate intake in the normal and high protein group
      • a decreased sugar intake in all groups (most pronounced in the HP group)
      • a decreased fat intake in all groups (p<0.001)
      • significant decreases in sodium intake in all groups 
      • non-significant decreases in calcium, zinc and vitamin D intake
      I guess, I don't have to tell you that none of the few existing inter-group differences discussed above appears to provide any reason to question the small, but statistically significant superiority of the normal protein diets compared to either the low protein or the high protein diets. And despite being the only study participants who were in a positive nitrogen balance, the subjects in the HP group did not see more beneficial effects on the retention of lean mass than the normal protein group.

      So what?! Normal protein rules?

      No matter how you look at the results of the study at hand, based solely on the data Campbell and  Meckling presented here, there is not a single argument to brought forward in favor of the 1:1 vs. the 1:2 protein to carbohydrate ratio. Moreover, the single most important determinant of (long-term) dietary success that is the ease with which dieters feel they can adhere to a given nutritional protocol also speaks in favor of the normal, not the high protein diet. The answer to the initially raised question, whether the scientists' conclusion that.. 
      "[a] diet with a 1:2 protein:carbohydrate ratio promoted better improvements than either the LP or HP diets, and may be superior in reducing long-term chronic disease risk in this population" (my emphasis in Campbell. 2013)
      ...was biased by their own research hypothesis would therefore be "NO! It wasn't." -  Now, that does not change the fact that I personally am biased and would therefore have liked the ladies to get past the 90g of quality protein / day margin. This would incidentally not have been difficult, if these wannabe overachievers had not reduced their caloric intake from ~2,300kcal/day to ~1,360kcal, but had contended themselves with the planned -30% reduction. The difference of 230kcal/day would left more than enough room for two additional protein shakes per day!

      Figure 2: Fat loss and lean mass gains of the police officers in the Demling study (Demling. 2000)
      That a similar regimen consisting of an even milder -20% reduction in calorie intake and the consumption of 70-75g of whey or casein hydrolysate can produce magnificent results, when it is combined with regular strength training (4days per week 30-35min of liftin), has been shown by Demling and DeSanti 12 years ago, already (see figure 2).

      It should be said, though that the 'success ratio' of carbs to protein in the Demling study was likewise ~1:2 (!) - the sole difference was that the obese police officers in the Demling study simply ate twice as much protein and twice as much carbs with a baseline fat intake of ~35g per day.

      References:
      • Acheson KJ. Higher-protein diets for health? European Journal of Clinical Nutrition. 2013; 66, 763–764.
      • Brehm BJ, D'Alessio DA. Benefits of high-protein weight loss diets: enough evidence for practice? Curr Opin Endocrinol Diabetes Obes. 2008 Oct;15(5):416-21. 
      • Campbell DD, Meckling KA. Effect of the protein:carbohydrate ratio in hypoenergetic diets on metabolic syndrome risk factors in exercising overweight and obese women. Br J Nutr. 2013 Nov;108(9):1658-71. 
      • 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.
      • Hession M, Rolland C, Kulkarni U, Wise A, Broom J. Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Obes Rev. 2009 Jan;10(1):36-50.
      • Keller U. Dietary proteins in obesity and in diabetes. Int J Vitam Nutr Res. 2011 Mar;81(2-3):125-33.

      Monday, November 25, 2013

      Shedding Some Light on the Leaky Gut <> Exercise Connection. Plus: 20+ Things You Should or Shouldn't Do to Protect and Restore the Integrity of Your Intestinal Wall

      Have you ever felt nauseated after a workout? Or does your protein supplement gives you diarrhea only if you take it right after a workout? Both can be related to the toll  exercise can take on the integrity of your intestinal tract.
      To be honest, I was quite surprised that I did not get a hell lot of hatemail in response to the the 'MSG heals the gut study' I posted last Sunday... Be that as it may, I feel sort of awkward to have opened Pandora's box without proving you with some betters tools than mono-sodium glutamate (MSG) to seal the box, or rather your leaky gut, again. Therefore I decided to post this mini-feature on a particular issue all of us will be dealing with: An exercise induced increase in gut permeability. As you are going to see, there are a lot of similarities to the 'classic' leaky gut, which is often implicated in the etiology of chronic inflammatory bowel diseases. In order to understand these similarities, but also the few, yet important differences, we will have to lay some theoretical groundwork.

      "What exactly is a leaky gut?"

      The easiest way to answer this question would be to say: "That's what everybody and his mama is talking about these days". This definition as concise (and precise) as it may be, is yet about as productive as the talk that's at its heart. So, instead of relying on hearsay, let's rather briefly recap how intestinal wall actually works.

      Since the intestines are meant to let nutrients and fluid pass, a certain degree of leakiness is absolutely natural. Problems arise only, when the self-regulatory system is broken and/or the permeability exceeds a normal / healthy threshold (img. by Mariana Ruiz).
      The mucosal layer of the intestinal tract is made up of epithelial cells, so-called enterocytes which are connected to one another by specialized proteins. These proteins form the tight junctions (TJ) - a term, you will probably have encountered numerous times before. The main constituents of this kit in between the enterocytes are proteins such as occludin, zona-occludens and claudins. Together, the array of enterocytes and the tight junction form the the intestinal barrier, which allows the absorption of nutrients and water, while preventing the translocation of harmful substances from the gut into the bloodstream.

      The integrity of this barrier is influenced by the phosphorylation state of the proteins within the tight junctions.The exact interactions are compilcated and can be looked up elsewhere (Banan. 2005). What's important for you to realize is that during prolonged exercise which is necessarily accompanied by an increase in core temperature, cardiovascular and thermoregulatory responses compromise intestinal blood flow.

      With the core temperature usually being lower than the temperature in your intestines, the temperature of your gut can easily approach 41°C during a workout.That's more than your epithelial cells can handle and can lead to structural damage of the 'patches' in the tight junctions + epithelial cell layer (Lambert. 1985).

      HIIT veterans or weight lifters are not off the hook

      Now, the last paragraph may have sounded as if only long endurance workouts like 10k-runs or marathons could entail damage to the intestinal cells. That's however not the case, since the redirection of the blood away from the splanchnic arteries and to the working muscle that's even more pronounced in high(er) intensity exercise, will initiate an ischaemia reperfusion cycle which can entail oxidative damage not during, but interestingly after the the workout, when the blood rushes back into the intestines (Wijck. 2011).

      Take home message: There are two distinct pathways that contribute to the leaky gut during and after a workout (a) heat and (b) ischaemic/reperfusion stress. Both influcne the phosphorylation state of the proteins in the tight junctions and will thus increase the permeability of the gut lining.

      It stands to reason that the combination of high intensity and long durations, as you will find it in an ultra-marathon runner, for example, is particularly detrimental to the integrity of the intestinal wall, so that it is not exactly surprising that (ultra-)endurance athletes have the highest prevalence (60-90%) of gastrointestinal distress that which manifests in the form of diarrhoea, nausea, stomach problems, bloating and intestinal cramps (Worobetz.1985; Peters.1999; Jeukendrup.2000)

      There is more than one thing you can to to protect, heal and restore your gut integrity

      The fact that a "leaky gut" is like an open door not just for exogenous toxins or live bacteria, but also for their 'endotoxic poop' is probably no news for you. In fact, it is also the reason why you want to either prevent the pathological increases in gut permeability, in the first place, and/or (re-)seal the gut as soon as possible after your workouts. In this regards, there are three fundamental and easily implementable strategies that should always be employed before you even think about using specific supplements:
      • Figure 1: HSP 70 offers protection against endotoxins (LPS) in vivo (top) and in vitro (bottom; Dokladny. 2010)
        Despite the possible ischaemic / reperfusion stress short high intensity exercise bouts like sprinting are generally less taxing on the integrity of the tight junctions than longer duration medium intensity aerobic workouts. Avoiding these particularly gut-stressing workouts and/or taking special precautions before and after marathons and other endurance events would thus be strategy #1 to keep the epithelial cell layer intact and pathogens and toxins from entering the circulation.
      • The natural intracellular expression of heat shock proteins (HSPs) can protect the tight gut junctions during and/or help their restoration after a workout. Just like all our endogenous protection systems the production of HSPs can be trained. Giving your body the time it needs to accommodate by making small, but consistent steps towards longer and/or more intense workouts would therefore be strategy #2.
      • That leaves us with strategy #3, of which I hope all of you will be using anyway - even if you have not been aware of its gut protective effect, yet: The provision of adequate fluid supply before, during and after a workout (Lambert. 2008).
      As the workout durations become longer and longer and/or the respective intensities higher and higher, solely relying on your bodies self-healing capacity and adequate hydration may seize to work, though. Despite the fact that our bodies accommodate to the ever increasing demand for intracellular protection against heat stress by upregulating the HSP expression (athletes have higher HSP expression to a standardized endurance training protocol than normal individiuals; cf. Fehrenbach. 2000), there is - just as with about every adaptive response - a certain threshold, when hormesis, i.e. the beneficial adaptation to a manageable amount of stress, is no longer an option.

      From "A" as in arginine to "Z" as in zinc - a list of things to keep the gut lining intact

      While there has been quite a lot of research as of late into which dietary supplements and even regular foodstuff would be able to modulate the heat shock proteins in order to prefer the desired downstream benefits on gut integrity, the number of compounds of which it is reasonable to assume that they can actually make a difference is still very small:
      • Colostrum supplementation to cell cultures has been shown to increase the expression of HSP-70 in human epithelial cells; studies with human subjects are rare and ambiguous:  While Marchbank et al., have been able to show that bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes (Marchbank. 2011), Buckley et al. actually observed detrimental effects of 8 weeks of bovine colostrum supplementation on the exercise induced gut permeability in runners (Buckley. 2009).The explanation for these discrepencies is not clear, but may be related to the longer duration / different intensity of the exercise protocols, or differences in the immunoglobolin, peptide or amino acid composition of the supplements.
      • Zinc in general and specifically polaprezinc, a zinc based anti-ulcer drug, which has primarily been used in Japan as a means to seal leaky Japanese guts, show some promises, as in the treatment and prevention of increased intestinal permeabilty (Zhang. 2009). It is thought that zinc is critical for tight junction assembly and has been shown to be critical in the protection of the gut lining from the chronic toxic assault of alcohol (Zhong. 2010). That being said, you should keep in mind that alcohol will deplete your bodies zinc stores, so that it cannot be said, if someone with an adequate zinc intake would benefit to the same degree as a zinc deficient alcoholic. Moreover, as "natural" as they may be, even essential minerals like zinc don't come without potential side effects (cf. "After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome", read more).
      • Glutamine has been used as treatment for patients suffering from irritable bowel syndrome and Crohn’s disease and has been shown to actively increase the expression of HSP70 in critically ill patients (Jonas. 1999; Ziegler. 2005).  
      • Berberine could be an ideal addition to glutamine (thx to Maxim Okhrimenko for pointing that out in the comments); berberine does not only modulate the TNF-alpha response in the intestines and increases AKT, but has also been shown to maintain / rescue intestinal glutamine transport and glutaminase activity (Gu. 2009; Amasheh. 2010; Li. 2010; Niu. 2011)
      • Probiotics are still an 'under-researched' newcomer and though there is some preliminary evidence pointing to the efficacy of probiotic therapy as a means of improving gut function and enhancing the integrity of the intestinal tight junctions, the ideal supplement regimen, as well as its long-term effects will still have to be elucidated in human studies. Studies by Ewaschuk et al. have yet already shown that the impact factors released from Bifidobacteria infantis can offer a certain degree of protection against experimentally induced colitis in rodents (Ewaschuk. 2008). As far as exercise specific studies are concerned, a recently published paper by Lamprecht et al. is probably the first peer reviewed human study to report allegedly "borderline significant" beneficial effects on gut permeability (measured only indirectly by quantifiying the zonolin conent of the feces) and TNFalpha expression in response to a multi-species probiotics (1010 CFU/day, Ecologic®Performance orOMNi-BiOTiC®POWER) in 23 trained men (Lamprecht. 2013; the study was partially funded with a grant from Winclov, the manufacturer of the respective supplements).
      • Butyrate, yet not all short chain fatty acids, have recently been found to decrease gut permeability (Ferreira. 2013). Both data from human studies, as well as exercise specific data is yet still absent.
      • Hydroxypropyl methylcellulose (HPMC), which is a non-fermentable fiber, has been shown to protect rodent guts from a high fat diet induced increase in gut permeability (Kim. 2013), as in the case of butyrate its efficacy (and when you think about athletes, tolerability) will yet still have to be confirmed in human trials.
      • L-Arginine (and AAKG) as a source of nitric oxide, which is necessary to protect the gut barrier from invaders could have a protective effect, as well (Quirino. 2013); and though this effect is not exercise specific, we know that arginine requirements increase in states of chronic stress, it would therefore be logical that supplementation with l-arginine, or even better AAKG, which comes with a precursor to glutamine will have beneficial effects on the tightness of the guts of intensely training athletes, as well (suggested read: BCAAs, glutamine and ammonia detox) .
      • Oats, maybe due to their beta glucan content and their ability to increase the production of short-chain fatty acids in the large intestine, oats offer protection against alcohol induced increases in tight junction permeability (Tang. 2009); exercise specific studies have yet to be conducted, though.Personally I would yet not be surprised if this would turn out to be very effective (note: as long as they are not cross-contaminated, oats are 100% gluten-free)
      • Goats milk (powder) has been shown to be equally effective as colostrum in reducing heat and thus most likely exercise induced gut permeability (Prosser. 2004)
      • Lactoferrin, a multifunctional protein of the transferrin family that is present in milk may have protective effects against LPS-mediated intestinal mucosal damage and impairments of the barrier function in intestinal epithelial cells (Hirotani. 2008)
      • Vitamin A in adequate amounts is necessary to maintain gut integrity; it is likely that this is all the more true if gut integrity and immune function are additionally challenged by strenuous exercise (Quadro. 2000)
      I guess, I could find even more supplements (and foods) that may help you protect or restore your gut lining, but let's be honest: As important and beneficial eating and supplementing the right things may be, all your efforts would be foiled if you eat foods and supplements that will have the opposite effect on your gut lining. So here is the complementary and likewise non-exhaustive list of stuff you'd better avoid (at least in high doses) if you want to keep your tight junctions intact and your gut from becoming leaky:
      Figure 2: Gliadin peptides induce the release of zonulin which in turn interacts with the tight junctions and increases the diffusion of small molecules (∼350 Da) across the cell membrane. Whether the tight junctions open up wide enough to allow for free diffusion of whole gliadin peptides, whose molecular weight is at least 2000 Da, remains to be determined, though (Heyman. 2011)
      • Alcohol will wreak havoc on the permeability of your intestines; probably in consequence of its depleting effect on ileal zinc concentration (Zhong. 2010).
      • Gliadin (in wheat/gluten) does actively promote the release of zonolin and the widening of the tight junctions (see figure 2); whether you will notice that or not, depends on the occurrence and extent of an immune response as it is characteristic for Celiac patients. I guess, it's actually not necessary to say that all sorts of other allergens, respectively the ensuing inflammatory response to being exposed to them will have detrimental effects on the integrity of your gut, as well, right?
      • ALA, EPA and DHA the dietary omega-3 fatty which may help sooth tight junction permeability in states of chronic inflammation will actually increase it, when the baseline inflammation is already low or they are consumed in excess (Usami. 2001; Roig-Pérez. 2010)
      • Copper and iron increase tight junction permeability of caco-2 cells via distinct mechanisms (Ferruzza. 2002)
      • Capsaicin, piperine and other hot spices do not only cause a burning sensation in your mouth, it literally burns your intestinal cell lining, as well (Johri. 1992; Tsakura.2007)
      • Quercitin by blocking the increase in HSP-70 will increase the suceptibility of your gut to exercise induced increases in permeablity (Kuennen. 2011)
      • NSAIDs like aspirin and ibuprofen increase the permeability of the gut ad amplify the potentially detrimental effects of exercise (Lambert. 2007)
      Obviously, only few of the last mentioned offenders are exercise specific, but if you start working out with already compromised gut integrity, you can hardly complain if a couple of grams of glutamine, or whatever else you may have picked from the previous list, don't effectively protect your intestinal wall from damage. What's even more important though is that you understand the Janus-faced nature of anti-oxidants and anti-inflammatory compounds. As beneficial as they may be in situations of chronic or acute pathologic inflammation, NSAIDs, quercitin and even your beloved omega-3 can eventually extinguish the 'controlled fire' your body needs to keep all immune and metabolic functions simmering along nicely (suggest reads: "Are you stressed enough for a longer life?" and "Inflammation is a True Fat Burner").

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