Monday, April 29, 2013

Dietary Zinc & Copper Improve Glucose & Lipid Metabolism. High Cortisol Amplitudes Counter Belly Fat. Hypoxic Hearts Love Creatine + Ribose. Apples Counter Cancer & Obesity

I guess this is about as close as we have hitherto gotten to understand why we got fat. Wrt to the hilarious pace at which we got fat and are still getting fatter, we are much better informed though.
After you've learned about the general importance of exercise for your health and a couple of tweaks that may or, as in the case of sugary "energy drink", may not help you maximize the benefits and performance gains on Saturday. The focus of today's SuppVersity article is on the results of non-exercise related studies that highlight non-exercise related confounders of your health.

Before we get to the actual news, I would yet like to invite all of you to take a look back at the increasingly obese history of the US... I suppose those of you who have not yet seen the link on my Facebook wall, will enjoy the animated obesity map in the Atlantic article from April 11. I mean, even if we still don't have anything but over-simplistic cookie-cutter "explanations" of why we get fat, the map shows that we do at least know how fast we got fat!

You don't feel knowing about how fast we got fat is good news? Ok, maybe you'll like one the following results from recent studies better:

  • Dietary zinc & copper influence glucose & lipid metabolism in women (Shab-Bidar. 2013) According to a recent study from the Obesity Research Center at Shahid Beheshti University of Medical Sciences in Tehran, Iran, there is a gender specific effect of copper and zinc in the diet on glucose and lipid metabolism of men and women in Iran - statistical significant effects were observed only in women with...
      Odds ratios for the MetS and low HDL across quartiles of copper intake (Shab-Bidar. 2013)
    • higher zinc intakes being associated with higher HDL-C, lower triglycerides (TG) and lower 2-hour blood glucose, and 
    • higher copper intake correlating with higher HDL-C, lower fasting blood glucose (FBG), significantly lower TG and a huge 81% reduction in the risk for suffering from metabolic syndrome (highest vs. lowest copper intakes)
    These observations stand in contrast with the current notion of the "bad" copper and the "good" zinc and reamphasize the importance of both nutrients for metabolic health.
    Remember: Two questions that will still have to be resolved pertain to (a) the gender-specificity of the effects and (b) confounding effects of food quality / choice and thus whether the same beneficial effects would be observed with the standard American diet.
    For both, but espicially for copper a little more than the RDA does not appear to hurt: What's particularly interesting, is that contrary to the zinc intakes in quartile 4 (>14mg/day; RDA 9mg/day) the copper intake in quartile 4 was more than 3x higher than the current RDA for women (0.9 mg). In fact, even the copper intake in the lowest quartile ~1.5mg/day was way above the RDA. If that's something we have to be surprised about is yet questionable, after all, there is not exactly much research on "optimal copper nutrition" (much contrary to zinc, by the way) and the RDA is based on age-old depletion-repletion studies and will thus probably reflect the absolute minimum to maintain "normal" serum levels.

  • Evidence from human study: Flat cortisol profile not averages or spikes are associated with increased adiposity and visceral obesity (Sharp. 2013) In their most recent paper that's soon going to be published in the American Journal of Human Biology Dan S. Sharp and his colleagues from the Center for Disease Control and the State University of New York provide conclusive evidence for the irrelevance of mean cortisol levels with respect to the purported negative effects of cortisol on visceral obesity.
    Associations between sextiles of within-subjects cortisol standard deviation (SD) in 217 Buffalo policemen and adjusted lean-mass trunk index (Sharp. 2013)
    As the data in the figure above clearly shows, the police officers with the greatest cortisol fluctuations (spikes and troughs) had the highest ratio of lean body mass to trunk mass. It is thus, as the scientists phrase it,
    "not the average level of salivary cortisol among 18 specimens on each officer that drives the association; it is the variation among specimens."
    The oral cortisol measures were taken on 3 subsequent days in standardized procedures that involved a venipuncture and a standardized high protein meal as "challenges", on day 1, six measures that were taken by the police officers over the course of the day, on day 2, and series of tests that was taken after a dexamethasone challenge after waking on day 3 (the subjects had ingested 0.5mg of dexamethasone the night before).
    Bottom line: While the scientists are careful in pointing out that it will still have to be established that the results translate to other populations. The results corroborate the uselessness (if not potential detrimental effects) of "cortisol blockers", I've discussed in my previous in the Science Round Up Seconds on March 29, 2013 (read more).

  • Combination of creatine and d-ribose heals damaged, but unscarred rodent-hearts (Caretti. 2013) While the many of the "daggered" claims* on the boxes of various "advanced" creatine products (learn more about their uselessness) are probably a little overblown (*the dagger refers to the "not verified by the FDA"), that's nothing compared to the absolutely disappointing results trainees had with d-ribose. Meanwhile, it seems as if even the last jerk knew that the unbearably sweet simple sugar is nothing worth spending his/her money on.

    Ribose regulates the novo synthesis and restoration nucleotides, can relieve the energy toll of ischemia  and its usefulness in the context of CVD is backed by rodent and human studies (Shecterle. 2011)
    In view of it's physiological role in the recovery of ATP levels (Helsten. 2004), it was assumed that supplementatal D-ribose would ameliorate the ATP depleting effects on exercise and improve endurance in glycolytic and/or long endurance activities, yet...
    "[...s]tudies examining the effect of ribose on performance during intense intermittent exercise and rowing have not been able to demonstrate improved performance in humans." (King. 2012)
    Other than the non-existence of side-effects, pertaining studies, which used up to ∼40 g/day, as well as acute and chronic supplementation regimen did  yet not yield any positive results

    Now, the aforementioned studies on the ergogenic effects of d-ribose were conducted in healthy individuals, in whom the ATP re-synthesis obviously does not depend (and not even benefit) from the provision of the monosaccharid that was discovered by Emil Fischer in 1891, when he analyzed the carbon structure of gum arabic (Prince. 2012). "Healthy" would yet not be the correct term to describe the rodents in the recently conducted study by Caretti et al. who observed that five week-old mice who were exposed to an atmosphere containing 10% O2 for 10 days in order to induce right ventricle hypertrophy and left ventricle apoptosis did not show any signs of cardiac damage, when they were gavaged creatine + D-ribose, every day.

    And while both phenotypes, i.e. the hypertrophy of the right and apoptosis of the left ventricle, were blunted to a certain degree by creatine or d-ribose, only their reversed the pathogenic changes to the heart muscle "almost" completely, by normalizing the expression of AMPK and Akt signaling in the hearts of the rodents.
    Light micrograph of representative nuclear pro-files (background, red = atypical, green = normal nuclei; my emphasis) and volume (%) of atypical cardiac cells in anterior left ventricle of rodents on caffeine + nicotine + ephedrine combo (learn more)
    Bottom line: While they may not be beneficial for the average trainee, people "on" the literally heart-breaking combination of nicotine + caffeine and ephedrine, could be able to reduce their detrimental effects on the heart (learn more), by adding this combination of proven (creatine) and disproven (d-ribose) ergogenics to their supplement regimen. People with sleep-apnea and other conditions which will leave the heart poorly oxygenized for longer time-periods should obviously benefit, as well.

    Based on the likewise promising results of previous studies in (human!) subjects with congestive heart failure (e.g. Omran. 2003), a daily dose of 5g d-ribose, along with the tried an proven chronic ingestion of 5g of creatine appears to be a good starting point, until respective human trials have been conducted.

  • Further evidence for the "An apple a day..." theory (Rago. 2013) In an allegedly methodically complicated, but very comprehensive analysis of the effects of raw, whole apples on the plasma metabolome of rodents, researchers from the University of Copenhagen found
    Total antioxidant activity (µmol vitamin C equivalents/g) of various fruits (Boyer. 2004)
    "that the intake of fresh apple in rats has a considerable and specific impact on the plasma metabolite profile, reflecting altered gut microbial metabolism, retarded lipid- and protein catabolism, and lowered metabolic, oxidative and steroid-related stress". (Rago. 2013)
    These results stand in line with the recent observations a group of Spanish researchers made, when they added a polyphenol extract from apples to the chow of rodents on an obesogenic high-fat + high sugar (HFS) diet:
    "Our results from histological studies demonstrated that supplementation of HFS with AP markedly reversed the enlargement of adipocyte volume induced by HFS diet intake in the epididymal fat pad, reducing it by almost 28% [...it also] reversed the increase in the population of large epididymal adipocytes, especially with diameters higher than 130m." (Boqu. 2013)
    The visceral specific effects of the apple polyphenols in the Boqué study could thus be interpreted as supportive evidence for the real-world significance of the metabolomic changes Rago et al. observed in the afore-cited study.
    Bottom line: No reason to be scared of the "high fructose fruit" apple. It comes with all HFCS sweetened beverages don't have. Polyphenols, vitamins, minerals and most importantly a flesh from which the fructose is extracted only slowly. Still, I have to warn you: Apple consumption can have profound beneficial effects on your health, such as (random examples)
    •  - 17% colorectal cancer risk (Michels. 2006)
    •  - 37% wheeze risk in your offspring (Willers. 2007)
    •  - 21% reduced risk for cancers of the oral cavity and pharynx (Gallus. 2005)
    •  - 25% reduced risk for oesophagus (Gallus. 2005) 
    •  - 18% / -15% / -9% risk red. for breast / ovary / prostate cancer (Gallus. 2005)
    and obviously the - 15% reduced breast cancer risk, the if you want to avoid these, you should thus better keep obsessing about the high fructose content of apples and stick to sausages and lard ;-)

References:
  • Boqué N, de la Iglesia R, de la Garza AL, Milagro FI, Olivares M, Bañuelos O, Soria AC, Rodríguez-Sánchez S, Martínez JA, Campión J. Prevention of diet-induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns. Mol Nutr Food Res. 2013 Mar 25.
  • Boyer J, Liu RH. Apple phytochemicals and their health benefits. Nutr J. 2004 May 12;3:5.
  • Caretti A, Bianciardi P, Marini M, Abruzzo PM, Bolotta A, Terruzzi C, Lucchina F, Samaja M. Supplementation of creatine and ribose prevents apoptosis and right ventricle hypertrophy in hypoxic hearts. Curr Pharm Des. 2013 Apr 10. [Epub ahead of print]  
  • Gallus S, Talamini R, Giacosa A, Montella M, Ramazzotti V, Franceschi S, Negri E, La Vecchia C. Does an apple a day keep the oncologist away? Ann Oncol. 2005 Nov;16(11):1841-4. 
  • Hellsten Y, Skadhauge L, Bangsbo J. Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. Am J Physiol Regul Integr Comp Physiol 2004;286:R182–8.
  • Michels KB, Giovannucci E, Chan AT, Singhania R, Fuchs CS, Willett WC. Fruit and vegetable consumption and colorectal adenomas in the Nurses' Health Study. Cancer Res. 2006 Apr 1;66(7):3942-53. PubMed PMID: 16585224.  
  • Omran H, Illien S, MacCarter D, St Cyr J, Lüderitz B. D-Ribose improves diastolic function and quality of life in congestive heart failure patients: a prospective feasibility study. Eur J Heart Fail. 2003 Oct;5(5):615-9.  
  • Price, NPJ. The Name of the–ose: An Editorial on Carbohydrate Nomenclature. J Glycobiol. 2012; 1(e105).
  • Rago D, Kristensen M, Gözde G, Federico M, Morten P, LarsOve D. LC–MS metabolomics approach to investigate the effect of raw apple intake in the rat plasma metabolome. Metabolomics. 2013; 1573-3882.
  • Shab-Bidar S, Hosseini-Esfahani F, Mirmiran P, Mehran M, Azizi F. Dietary intakes of zinc and copper and cardiovascular risk factors in Tehranian adults: Tehran Lipid and Glucose Study. Nutrition & Dietetics. 2013
  • Sharp DS, Andrew ME, Fekedulegn DB, Burchfiel CM, Violanti JM, Wactawski-Wende J, Miller DB. The cortisol response in policemen: Intraindividual variation, not concentration level, predicts truncal obesity. Am J Hum Biol. 2013 Apr 20.
  • Shecterle LM, Wagner S, St Cyr JA. A sugar for congestive heart failure patients. Ther Adv Cardiovasc Dis. 2011 Apr;5(2):95-7.
  • Willers SM, Devereux G, Craig LC, McNeill G, Wijga AH, Abou El-Magd W, Turner SW, Helms PJ, Seaton A. Maternal food consumption during pregnancy and asthma, respiratory and atopic symptoms in 5-year-old children. Thorax. 2007 Sep;62(9):773-9. Epub 2007 Mar 27.