Curcumin, Genistein, Pomegrenate & Co. - A Dirty Dozen of Supplements & Foods to Keep Your Prostate Cancer Free

Which of the dirty dozen of supplements and foodstuffs in today's SuppVersity review can really help you to make sure, you're not the one out of those nine men who develops prostate cancer?

Supplements that are supposed to protect you from developing prostate cancer and/or agents that may help patients with existing prostate issues are - obviously - in high demand. And as W. Merkle points out in a recent article in the German science journal Urologe using them - even if they may not be as effective as some patients may believe - makes sense: from a psychological perspective, alone (Merkle. 2014).

Taking a pill with selenium, for example, has been shown to alleviate some of the side effects of chemotherapy. General protective effects against prostate cancer, on the other hand, have not been established. In fact, the most recent studies rather suggest that "supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status" (Kristal. 2014).

Supplements are nice, but without exercise you are missing 50% of the anti-cancer equation!

Tri- or Multi-Set Training for Body Recomp.?

Alternating Squat & Blood Pressure - Productive?

Pre-Exhaustion Exhausts Your Growth Potential

Full ROM ➯ Full Gains - Form Counts!

Battle the Rope to Get Ripped & Strong

Hula Hooping to Spot Reduce in the Midsection

Luckily, there are other supplements with more promising data. Supplements that will actually complement, a healthy diet and active lifestyle, the two pillars of all (not just prostate) cancer protection. Supplements like...

• Curcumin - As a SuppVersity reader you've probably already expected to see the curcumin on the list. Its potent anti-inflammatory effects and more specifically its ability to target multiple inflammatory pathways, which include NF-KappaB, COX2, STAT3 and high levels of CRP, Prostaglandins and TNF-alpha make it a particularly valuable anti-tumor agent of which Guo et al. observed in a recent study that it will induce cell cycle arrest and apoptosis of prostate cancer cells by regulation the expression of IkappaBalpha, c-Jun and androgen receptor (Guo. 2013)
• Genistein - Just like curcumin, genistein acts on NF-KappaB (Adjakly. 2013). In addition it will upregulate a protein called miR-574- 3p that will have cancer cells "kill themselves" (go into apopotosis; Chiyomaru. 2013). In addition scientists have found genistein to support the efficiacy of Cabazitaxel which is used for the treatment of hormone-refractory prostate cancer.
• Pomegranate - Pomegranate extracts or rather its ingredients, i.e. ellagic acid, caffeic acid, luteolin and punicic acic, have been shown to inhibit the proliferation and induce apoptosis in prostate cancer cells (NCI. 2013).

  

  Figure 1: If you look at the actual increase in apoptotic cancer cells in response to the pomegranate treatment, it is obvious that some patients (e.g. #53) benefited more than others (Pantuck et al. 2006)

  A clinical trial by Pantuck et al. (2006) was also able to show that the time it takes for the PSA levels, an albeit debatable marker of prostate cancer risk, to double decreased significantly, when the subjects, men with rising PSA after surgery or radiotherapy, were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Unfortunately, a more recent study by Stenner-Liewen et al. (2013) could not confirm these effects. 
• Brassica vegetables (cruciferous vegetables) - While general vegetable intake is already associated with a -39% reduced risk of developing extraprostatic prostate cancer (cancer, eating tons of cruciferous vegetable, it was the intake of broccoli and cauliflower that made the biggest impact in a 2007 study by Kirsh et al.
  
  

  

  Even if they don't protect you from prostate cancer broccoli & co will inhibit myostatin and could help you to grow more muscle... well, at least theoretically, you know about the difference between the petri dish and the real world, so don't expect monster gains | more.

  As it is usually the case the evidence is yet ambiguous. In a 2002 review of the evidence, Kristal, et al. found that of the six studies they could clearly interpret, only three reported statistically significant reduced risks (P < 0.05), while one reported a borderline significant reduced risk (P = 0.06). Against that background Verhoeven et al. are right, when they say: " Further epidemiological research should separate the anticarcinogenic effect of brassica vegetables from the effect of vegetables in general" (Verhoeven. 1996).
  
  More recently, Joseph et al. found that the existing differences in the epidemiological data may be due to genetic polymorphisms due to which only men with a certain genetic polymorphisms in glutathione S-transferases M1 and T1 will benefit from eating tons of cruciferous veggies (Joseph. 2004).
• Green tea - Green tea is good for everything, right? Well unless it's not loaded with toxic molecules (see previous SuppVersity article) this may in fact be right. Convincing evidence from human trials is albeit scarce. What we do have are rodent studies like the ones that were conducted with TRAMP mice, which model closely mirrors the pathogenesis of human prostate cancer.
  
  In these mice EGCG, one of the main catechins in green tea, decreased the proliferation of prostate cancer cells and reduced the PSA levels. Scientists believe that these effects are mainly mediated by the effects EGCG has on the growth promoting proteins ERK1/2. Unfortunately, the same rodent studies also suggest that it is probably too late for many of you to start drinking green tea, now, because said beneficial effects are only observed in young, not in old TRAMP mice (Donald. 2012).

• 

  Coffee is for the ladies, too! Studies show significantly reduced risks of breast cancer with 5+ cups of coffee. Tee and cacao help, as well | more

  Coffee - Obviously I am biased, when it comes to coffee. I still hope you believe me when I say that drinking 5+ cups of coffee per day has been associated with significantly reduced risk of prostate cancer in what is probably the most large-scale meta-analysis of the topic today.
  
  In their meta-analsis of 12 peer-reviewed case-control studies, Lu et al. calculated a 4% risk reduction for Europeans who consumed five or more cups of coffee and Americans who consumed 4 or more regular cups of coffee (equ. to approximately 400-500mg of caffeine). Moreover, the scientist found "a significant inverse association in all categories of prostate cancer except Gleason <7 grade" in both the "fixed-effects model" and the "random-effects model" (Lu. 2014).
  
  Wilson et al. also report an inverse association between coffee consumption and the incidence of highly malignant prostate cancer (Wilson. 2013). This means that drinking coffee is not only going to reduce your overall risk of developing prostate and other cancers (Geybels. 2013), it will also increase your chance that in the unfortunate case you still develop cancer, it's going to be a benign and treatable form of prostate cancer.
• Lignans (e.g. from flaxseed) - While many of you will probably know them as "bad anti-androgens", there is little doubt that lignans from flax and other foodstuff inhibit cancer growth. What is particularly interesting about these agents is that they don't work via the "regular" NF-kappaB pathway but inhibit the expression of the vascular endothelial growth favtor (VEGF; cf. Azrad. 2013).
• Lycopene - It's the bright red carotene and carotenoid pigment and phytochemical that gives tomatoes and other red fruits and vegetables, such as red carrots, watermelons, gac, and papayas, although not in strawberries, red bell peppers, or cherries their color.
  
  Based on the currently available evidence it appears to help not just with prostate, but also with pancreatic, intestinal and lung cancer (Giovannucci. 1999). In that, it makes a particularly effective adjunct to classic cancer therapy (Tang. 2011).

  

  Figure 2: Prostate cancer risk w/ high vs. low intakes of the given antioxidants according
  to XRCC1 genotype (Goodman. 2006)

  Unfortunately, the data is ambigious... as usual. Unlike for other agents, it does yet appear as if scientists have already identified a certain gene, i.e. XRCC1, which appears to determine whether you do or do not benefit from the consumption of increased amounts of tomato lycopene (Goodman. 2006).
  
  In view of the fact that certain genotypes actually increase their prostate cancer risk specifically if they are consuming both, a high amount of lycopene and vitamin E (alpha-tocopherol), the latest Cochrane Review on the protective effects of lycopene against prostate cancer considers the evidence for "preliminary" and "insufficient" (Ilic. 2011).
• Fish oil / omega-3 - In spite of the fact that the media jumped at the finding of the SELECT trial (learn more) that claimed that selenium would be bad, while a high fish consumption or rather a high amount of omega-3s in the blood would protect you against prostate cancer, a close re-analysis of the data you can read up on at the website of the Life Extension Foundation indicates that this was all media hype.
  
  With a de facto difference of only 0.18% the difference was... well, you'd say a joke, scientists would say "within the margin of statistical error" and thus by no means significant. If you take an even closer look at the data, it would even seem as if omega-3 fatty acids would increase the risk of prostate cancer.
• Resveratrol - If you look at the existing evidence you will be surprised to find studies that indicate that resveratrol increases (Klink. 2013) and studies that show that it inhibits prostate cancer growth (Iguchi. 2012; Kai. 2011).
  
  Again, it took a closer look at the data and another experiment to find out what really was going on: a dose-dependent effect with increased risk with low and decreased risk with high doses of resveratrol (Benitez. 2007). Bad news: With the current low biovailable oral resveratrol preparations you're likely to end up in the "increased risk" resveratrol exposure zone.
• Selenium - While I have mentioned it in the introduction already, it's certainly worth taking a closer look at what selenium is actually supposed to do.
  
  In their 2011 review of the literature, Rizky Abdulah et al. didn't just highlight the many different molecular pathways, by which selenium could protect you from developing cancer, they also point out that the type of selenium supplement used could be of critical importance with respect to the success of your efforts to avoid the development of cancer. In that,...

  

  In rodents selenium acts as corrosion inhibitor in the brain | learn more

  "[...] methylselenol is believed to be the critical metabolite in selenium chemoprevention. Since methylselenol is highly reactive, methylselenol precursors such as Semet and Se-mSC are important both in in vitro and in vivo experiments. Semet and Se-mSC conversion to methylselenol, however, requires enzymatic conversion by the enzyme β-lyase, which is 800 times less prevalent in human tissues than in mouse tissues.

  This may explain why the results of Semet and Se-mSC anticancer studies in humans were not as impressive as in vivo experiments. Although researchers have now turned to other Se compounds such as mSeA, which do not need enzymatic conversion to methylselenol, or selenite, which does not need to be converted to methylselenol for its anticancer properties, more substantial research on selenium compound metabolism in human tissues is necessary." (Abdulah. 2011)

  In other words, as of now, we don't know which form of selenium we actually have to use in human trials to generate similar impressive results as they have been observed in rodents.
  
  And as if that wasn't already "bad" enough, a meta-analysis of intervention studies by Hurst et al. (2012) indicates that there is a very narrow "band" of serum concentrations, where selenium is actually good for you! When your selenium level passes 170 ng/ml the tumor-protective effect disappears and - worst case scenario - your risk increases. So remember: More does certainly not help more!
• Silibin (from milk thistle) - You probably think of milk thistle as a "liver supplement". In fact, its main active constituent will yet also reduce the efficacy of osteoclast cytokines and reduce the concentration of RANKL-ligands. Thus it will regulate the NF-κB und AP1 levels in cells and inhibit the proliferation, invasion and migration of metastatic prostate cancer (Ting. 2011; Chen. 2012) 
• Vitamin D - Believe it or not: There are things vitamin D3 cannot do! One of this things is to protect you prostate cancer. That's the prerogative of active vitamin D aka calciferol. In rodent studies and studies on human cell lines calciferol and multiple analogs of active vitamin D have shown to be promising drugs for prostate cancer protection, though (Tokar. 2005).
  
  

  

  Underestimated Vitamin D Sources: Eggs, Chicken, Pork, Fish & Dairy Contain Ready-Made 25OHD | more

  Since simply popping tons of vitamin D3 is (luckily) without effect on the levels of calciferol (otherwise you would run the risk of being calcified from the currently prevalent abuse of vitamin D3 supplements), using vitamin D3 is less effective, but not useless.
  
  In 2010, for example, Woo et al. observed that the time it took for the PSA levels of prostate cancer patients to double was significantly reduced, when the subjects received 2,000 IU of vitamin D3 per day (Woo. 2005) - an effect of which previous in vitro studies suggest that it could be due to the local conversion of D3 to active vitamin D in prostate cancer cells (Tokar. 2005).
• Vitamin E - Needless to say that vitamin E has gotten a bad rep ever since scientists observed an increased risk when they gave the subjects of the SELECT trial vitamin E (learn more). Still, as long as you stay away from "classic" vitamin E and buy one of the still expensive tocotrienol supplements (or eat red palm oil), you can expect an anti-proliferative effect of the vitamins E (Conte. 2004; Srivastava. 2006)

It's never too late to make a change! In September 2005, researchers from the University of California-San Francisco pub- lished a study that shows that intensive lifestyle changes (i.e. changin the way you eat, the amount of exercise you get, etc.) may affect the progression of prostate cancer in a highly beneficial way (Ornish. 2005) - with PSA reductions of -4%, reduced glucose levels (-70%!) improved blood lipids and higher, not lower testosterone levels.

Bottom line: While all of the above supplements and food constituents will help, nothing beats a healthy lifestyle with a balanced whole foods diet, stress control and regular exercise.

Overweight (+20% risk for BMI >25.38, already), gaining 5-10% weight after your 20s (+30%; Putnam. 2000), being self-employed (+170%) and thus probably stressed, having a family history of prostate cancer (father +140%, brother +420%), being a "former drinker" (beer +20%, wine +20%) or a current liquor drinker (+40%) and consuming more than 96g of alcohol per week (+50%), on the other hand, will - for most of the variables unnecessarily - increase your prostate cancer risk (Andersson. 1996) | Comment on FB!

References:

• Abdulah, Rizky, et al. "Molecular targets of selenium in prostate cancer prevention (Review)." International journal of oncology 39.2 (2011): 301-309. 
• Andersson, Swen-Olof, et al. "Lifestyle factors and prostate cancer risk: a case-control study in Sweden." Cancer Epidemiology Biomarkers & Prevention 5.7 (1996): 509-513.
• Azrad, Maria, et al. "Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer." Journal of medicinal food 16.4 (2013): 357-360.
• Benitez, Dixan A., et al. "Mechanisms Involved in Resveratrol‐Induced Apoptosis and Cell Cycle Arrest in Prostate Cancer—Derived Cell Lines." Journal of andrology 28.2 (2007): 282-293. 
• Chen, Rongxin, et al. "The significance of MMP-9 over MMP-2 in HCC invasiveness and recurrence of hepatocellular carcinoma after curative resection." Annals of surgical oncology 19.3 (2012): 375-384.
• Chiyomaru, Takeshi, et al. "Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer." PloS one 8.3 (2013): e58929. 
• Conte, Carmela, et al. "γ‐Tocotrienol Metabolism and Antiproliferative Effect in Prostate Cancer Cells." Annals of the New York Academy of Sciences 1031.1 (2004): 391-394.
• Donald, J. L. "Plasma metabolic profiling reveals age-dependency of systemic effects of green tea polyphenols in mice with and without prostate cancer." Molecular BioSystems 6.10 (2010): 1911-1916.
• Geybels, Milan S., et al. "Coffee and tea consumption in relation to prostate cancer prognosis." Cancer Causes & Control 24.11 (2013): 1947-1954. 
• Giovannucci, Edward. "Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature." Journal of the National Cancer Institute 91.4 (1999): 317-331.
• Guo H, Xu YM, Ye ZQ, Yu JH, Hu XY. "Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of IkappaBalpha, c-Jun and androgen receptor." Pharmazie 68.6 (2013):431-4.
• Hurst, Rachel, et al. "Selenium and prostate cancer: systematic review and meta-analysis." The American journal of clinical nutrition 96.1 (2012): 111-122.
• Iguchi, Kazuhiro, et al. "Antiandrogenic activity of resveratrol analogs in prostate cancer LNCaP cells." Journal of andrology 33.6 (2012): 1208-1215. 
• Joseph, Michael A., et al. "Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk." Nutrition and cancer 50.2 (2004): 206-213.
• Kai, Li, and Anait S. Levenson. "Combination of resveratrol and antiandrogen flutamide has synergistic effect on androgen receptor inhibition in prostate cancer cells." Anticancer research 31.10 (2011): 3323-3330.
• Kirsh, Victoria A., et al. "Prospective study of fruit and vegetable intake and risk of prostate cancer." Journal of the National Cancer Institute 99.15 (2007): 1200-1209.
• Klink, Joseph C., et al. "Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell‐line specific manner, through paradoxical effects on oncogenic pathways." The Prostate 73.7 (2013): 754-762.
• Kristal, Alan R., et al. "Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk." Journal of the National Cancer Institute 106.3 (2014): djt456.
• Lu, Yu, et al. "Coffee consumption and prostate cancer risk: an updated meta-analysis." Cancer Causes & Control 25.5 (2014): 591-604. 
• Merkle, W. "Prostatakarzinomprophylaxe durch Nahrungsergänzungsmittel." Der Urologe (2014): 1-7.
• NCI (2013) Pomegranate: prostate cancer, nutrition and dietary supplements (PDQ). NCI, Bethesda. http://www.cancer.gov
• Ornish, Dean, et al. "Intensive lifestyle changes may affect the progression of prostate cancer." The Journal of urology 174.3 (2005): 1065-1070.
• Pantuck, Allan J., et al. "Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer." Clinical Cancer Research 12.13 (2006): 4018-4026.
• Putnam, Shannon D., et al. "Lifestyle and anthropometric risk factors for prostate cancer in a cohort of Iowa men." Annals of epidemiology 10.6 (2000): 361-369.
• Stenner-Liewen, Frank, et al. "Daily Pomegranate Intake Has No Impact on PSA Levels in Patients with Advanced Prostate Cancer-Results of a Phase IIb Randomized Controlled Trial." Journal of Cancer 4.7 (2013): 597. 
• Srivastava, Janmejai K., and Sanjay Gupta. "Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells." Biochemical and biophysical research communications 346.2 (2006): 447-453.
• Tang, Yaxiong, et al. "Lycopene enhances docetaxel's effect in castration-resistant prostate cancer associated with insulin-like growth factor I receptor levels." Neoplasia 13.2 (2011): 108-119. 
• Ting, Harold, Gagan Deep, and Rajesh Agarwal. "Molecular mechanisms of silibinin-mediated cancer chemoprevention with major emphasis on prostate cancer." The AAPS journal 15.3 (2013): 707-716. 
• Tokar, Erik J., and Mukta M. Webber. "Chemoprevention of prostate cancer by cholecalciferol (vitamin D3): 25-hydroxylase (CYP27A1) in human prostate epithelial cells." Clinical & experimental metastasis 22.3 (2005): 265-273.
• Verhoeven, Dorette T., et al. "Epidemiological studies on brassica vegetables and cancer risk." Cancer Epidemiology Biomarkers & Prevention 5.9 (1996): 733-748.
• Wilson, Kathryn M., et al. "Coffee and risk of prostate cancer incidence and mortality in the Cancer of the Prostate in Sweden Study." Cancer Causes & Control 24.8 (2013): 1575-1581.
• Woo, Tony Choon Seng, et al. "Pilot study: potential role of vitamin D (cholecalciferol) in patients with PSA relapse after definitive therapy." Nutrition and cancer 51.1 (2005): 32-36.

Low Vitamin D & Insulin Resistance; Ghrelin Response to Overfeeding; Glutamine for the Elderly; 5g/Day Creatine for Women; MSM for GH Activity in Bone; Curcumin for Burns

Vitamin D research hyper-inflation - unfortunately few of the papers will ever be printed, otherwise we could at least use them to heat our homes, in case the price for oil gas and other fossil energy keep rising ;-)

The SuppVersity Figure of the Week is "1614"! That's the number of studies with the exact phrase "vitamin D" in their title that have been published in the past 9 months and 14 days of the year 2012 (more than five papers per day!). Compared to 1,453 papers in the year 2011 and 1,169 papers in 2010. Projected onto the rest of the year that's going to be a +40% increase in mostly redundant papers! I mean, let's be honest, we have not made any significant scientific progress in the area of vitamin D research over the past months: We have still no idea where the associations end and the causations begin and are more or less clueless as to why vitamin D supplementation simply does not yield any of the beneficial results it is supposed to.

And as if that was not already bad enough, due to the advent of an infinite number of second-class online journals that made the vitamin D paper hyperinflation only possible, most of these papers will never be printed. Otherwise I'd suggest we put them to some good use and burn them like the woman in the image on the right was burning paper money during the days of monetary hyperinflation, over here in Germany in the years 1922 - 1923 ;-)

Vitamin D and insulin resistance 

Having low levels does only make a difference, if you are obese. That's the result of the most recent analysis of data from the MONICA10 cohort consisting of 2656 participants (men and women aged 41–71 years) who participated in a 10-year follow-up examination during 1993–1994 as part of a population-wide survey in Denmark (cf. figure 1; data adjusted for sex, season of blood collection, history of CVD, family history of diabetes, physical activity during leisure time, healthy food index, fish intake, supplement use, smoking status, alcohol intake and educational level):

Figure 1: Risk of incident diabetes associated with serum 25(OH)D and waist circumference categorized as normal, overweight and obese (data based on Husmemoen. 2012).

"Low serum 25(OH)D was associated independently with incident diabetes. The inverse association was only found in overweight-obese and not in normal weight individuals, suggesting that obesity may modify the effect of vitamin D status on the risk of diabetes." (Husmemoen. 2012)

These results stand in line with previous research you've read about here at the SuppVersity suggesting that rather than the absolute 25-OHD levels, which are indicative of your "vitamin D reserves", an obesity induced disruption in the management / metabolism of the "sunshine vitamin" appears to be the real culprit that's behind the associations (not causations!) between low vitamin D levels and the metabolic syndrome.

That this problem can't be solved by simply adding more vitamin D to the equation stands to reason and would also explain why the few controlled vitamin D3 supplementation trials in non (morbidly) obese, highly vitamin D deficient individuals that exist did not bring about any of the metabolic benefits the researchers had expected.

Supplemental glutamine prevents non-sarcopenic age-induced weight loss 

We usually think of being overweight, when we talk of "weight problems". For older people it is yet often rather the opposite. Many are losing weight and start to literally wither away. And while glutamine does not help with the muscular aspect (strength training and at least 20g of EAA-rich proteins with every meal), it could at least help with making the most of the food you eat and the supps you take.

While the mechanism is not yet fully elucidated, the results of a recent study by Meynial-Denis et al. clearly suggest that the provision of supplemental glutamine effectively prevents the loss of body weight. A possible mechanism my be related to its concomitant (or upstream?) effects on the integrity and function of the enterocytes in the gut lining of the very old rats the researchers used as a model (Meynial-Denis. 2012).

Therefore I am not convinced that the researchers hypothesis that these effects are brought about by

1. the ameliorative effects of glutamine on the age-induced CO(2)/glutamate ratio, and
2. the role of glutamate as a precursor for glutathione, arginine and proline biosynthesis,

fully explain the observed effects. And even if they are, the additional (maybe in that case downstream) improvement of nutrient absorption subsequent to the conservation or restoration of a healthy/-ier gut lining can hardly be underestimated. After all, it is becoming increasingly clear that much of the age-induced loss of body weight is at least promoted, if not causally related to the decreased absorption of various essential nutrients.

Unexpected ghrelin response during 7-day overfeeding experiment in obese subjects

"Confusing" would in fact be a better term to describe the surprising finding that 7-days on a diet containing 70% more energy than the 68 healthy young, normalweight, overweight and obese men usually consumed did not reduce, but increase the amount of the acylated form of ghrelin (often touted as the "active" = hunger promoting form of ghrelin), in the blood of the study participants (Wadden. 2012). Moreover, ...

• there was no significant difference in fasting acylated ghrelin between normal weight, overweight, and obese men at baseline and
• the amount of acylated ghrelin was negatively correlated with weight and BMI for normal weight and with BMI in overweight men.

Yet while ghrelin also correlated with the changes in body weight and BMI the study participants experienced in the course of the one-week intervention. It was negative (which is obviously what you should expect) only in he normal- and overweight subjects. In the obses study participants, on the other hand, the correlation was positive, i.e. more weight gain = more ghrelin.

Illustration of the global obesity epidemic (WHO. 2005). The study at hand makes it pretty clear that a pathological dysregulation of energy intake is at least part of the problem.

In other words: While there were no differences at baseline an increase in acetylated ghrelin was associated with lower body weights and weight loss in normal- and overweight subjects, while the obese (=pathologically overweight subjects) showed increases in acetylated ghrelin, when they gained weight.

If we stick to the fundamental hyptothesis that ghrelin is in fact a "hunger hormone" and the acylation, i.e. the addition of an acyl functional group to the basic molecule, works like an "on switch" that activates the appetite increasing effects of ghrelin, this means nothing else than overeating and gaining weight makes obese men hungrier. This finding provides further evidence for the hypothesis that the natural regulation of food intake is not simply impaired, but totally out of whack in obese individuals.

MSM turns out to be a local GH booster and bone builder 

MSM? That's the stuff in the joint supplements, right? Correct! Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound with well-known anti-oxidant properties and anti-inflammatory activities that is a longstanding standard ingredient in joint supplements (next to glucosamine sulfate and chondroitin sulfate - you notice the sulf... ah, pattern here, right?).

I guess you knew all that already, but I would be surprised if you had also been aware of the fact that MSM exerts direct anabolic effects on the bone by increasing the expression of GH-related proteins including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and mesenchymal stem cells.

"MSM increased IGF-1R and GHR mRNA expression in osteoblastic cells. The expression of MSM-induced IGF-1R and GHR was inhibited by AG490, a Jak2 kinase inhibitor. MSM induced binding of STAT5 to the IGF-1R and increased IGF-1 and IGF-1R promoter activities. Analysis of cell extracts by immunoprecipitation and Western blot showed that MSM enhanced GH-induced activation of Jak2/STAT5b. [...] Furthermore, MSM increased ALP activity and the mineralization of MSCs." (Joung. 2012)

Unfortunately, in vitro studies like these don't provide any information on appropriate dosages, but a study that was published in August 2012 reports that dosages up to 10-fold higher than the dose equivalent of the 300-400mg/day, which are at the upper end of the spectrum of the dosage recommendations of currently available MSM supplements, lead to "dose dependent" decrease in the degeneration of the cartilage in the knee joints in a mouse model of osteoarthritis (Ezaki. 2012). The hilariously high dose of 30-40g (100x the recommended amount), on the other hand, led to significant losses of body, liver, and spleen weight.

So, even with an acute fracture you better keep your MSM intake within reasonable limits - specifically, because we do not even know if oral methylsulfonylmethane will help with either bone-healing or bone strength in humans, at all.

If muscle is metabolic currency, creatine is the cash machine

"Ehhh! This will make me hold water? No thanks I already got enough of that! And muscle, not thanks..." Shut up! Muscle is metabolic currency and gaining muscle and strength is equally beneficial for the health of men and women, alike.

Against that background you may want to print the results from a recently published paper by Andreo Fernando Aguiar from the North University of Paranay and his colleagues and put the print out somewhere where all, not just the older ladies at your gym will see that taking 5g of creatine /day helped eighteen healthy ladies in their best years (64.9±5.0 years) to

If looking gorgeous and being strong & healthy is your goal, creatine is your supplement of choice, ladies...and gents! Changes in body fat percentage and muscle mass in response to 12-week strength training expressed relative pre value in control group (calculated based on Aguiar. 2012)

• train at a more than 2-fold higher volume,
• make 5.1, 3.9, and 8.8% greater progresss in bench press, leg extension, and biceps curl performance
• gain 3.2% more fat-free mass and 2.8% more muscle mass, and
• be more efficient in performing submaximal-strength

...than the nine women in the placebo group (Aguiar. 2012). With a somewhat higher overall training volume and maybe three instead of just 2 sets of 10-15 reps of

• vertical bench press, lat pulldown, 
• biceps curl, triceps pushdown, 
• knee extension, leg curls, 
• seated calf raises, and abdominal crunches

three times per week and a reduced carbohydrate intake (carbs down by 20% to 45% and protein up by 20% to 40% of the total energy intake) I am pretty sure the ladies in the creatine group would also have been able to turn the hitherto non-significant 2% reduction in total body fat into a significant one.

"Strong is the new sexy" and creatine can help you to get there!

About time to pull the emergency break strength train eat and take creatine?!

In a way it's unfortunate that the ability to promote weight loss is an almost necessary prerequisite for an ergogenic to  be attractive to women. If you can't answer the question "Will it make me lose weight... ah, I mean fat?" with a definitive "Yes, ma'am!", they won't buy it. That said, even with the current training and dietary regimen, the women in the creatine group dropped 1.6% total body fat and, due to the increase in lean mass, decreased their body fat percentage by -2.8%, while the ladies in the control group gained 1.2% body fat (total), so that their body fat percentage effectively did not change at all (+0.4%). Stronger, leaner and healthier! What more can you ask for in a dietary supplement?

Topical curcumin improves wound healing (plus tips how to prepare it)

In view of its profound anti-inflammatory effects it is actually not straight forward that curcumin would improve wound healing - at least not in the early, inflammatory phase of the process. Accordingly the researcher from the Department of Dermatology at the Faculty of Medicine of the Namik Kemal University in Tekirdag, Turkey, divided their burned rodents into 3x2 groups who were scheduled to be anesthetized on day 4 (A), day 6 (B) or day 8 (C) after after they had been burned with an aluminum branding iron that had been placed without pressure for 30s on the back of the rats (Kulac. 2012).

Histopathological scores for inflammatory cells, collagen, deposition, angiogenesis, granulation tissue formation, and epithelialization in each group (based on Kulac. 2012); group A (4th day post burn), group B (8th day post burn), group C (12th day post burn)

The rats in the three treatment groups who had received 200 µl of curcumin at a concentration of 100 mg/kg body weight, topically, once daily, showed increased wound healing during all the critical steps of tissue regeneration, i.e. inflammation, collagen deposition, angiogenesis, development of granulation tissue, and the repair of epithelium.

Interestingly, the inflammatory cell infiltration was significantly increased in curcumin groups and that regardless of when the tissue samples were analyzed. Collagen deposition, angiogenesis and granulation tissue formation were likewise higher in curcumin compared to the placebo group, with the earliest squamous epithelial re-epithelialization being observed on the 4th in treatment subgroup (figure 2, Group A).

Self-made curcumin band-aids / pastes

And in case you don't want to waste money or support Johnson and Johnson by buying the tumeric laced bandages they apparently sell in India, here are two ways to prepare a bandage and a tumeric paste that will probably help with sorts of inflammatory skin conditions (Hinkle. 2012):

In India people use tumeric + honey facial masks; also to treat acne, by the way.

• tumeric wrap / band-aid: Combine one teaspoon of dried turmeric powder with two teaspoons of either dried or fresh ginger. Spread the mixture over a cloth, then wrap around the affected area and seal it with a plastic bandage.
• tumeric paste for burns: Combine one teaspoon of turmeric powder with one teaspoon of aloe vera gel and apply it directly to the burned / inflamed part of your skin (make sure not to apply it directly onto open wounds, though!)

Be careful, though! Tumeric is also a powerful dye that's not easy to wash off again. So whatever towel you may be using as a wrap may therefore be ruined and in case the paste gets in contact with your shiny new white shirt, hot pants or whatever those are likely to be ruined, as well.

---

Have you ever listened to the to the SuppVersity Science Round Up on Super Human Radio? If not, check out the podcasts

That's it for today, folks. I am not sure whether you feel this is sad or good, but I hope for you, and in a way me and the SuppVersity, that it is the latter, because it may well be that I will increase the frequency of these On Short Notice. In that I will be trying to get even further away from the lengthy items from last week and make them actually short, again ;-)

A pros pos short, those who like these news updates, may also enjoy the weekly SuppVersity Science Round Up that airs live every Thursday at 12.30 or 1.00PM EST, And if you can't tune in live, you can simply have google show you the links to the podcasts of the latest shows.


References:

• Aguiar AF, Januário RS, Junior RP, Gerage AM, Pina FL, do Nascimento MA, Padovani CR, Cyrino ES. Long-term creatine supplementation improves muscular performance during resistance training in older women. Eur J Appl Physiol. 2012 Oct 7.
• Ezaki J, Hashimoto M, Hosokawa Y, Ishimi Y. Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model. J Bone Miner Metab. 2012 Aug 10.
• Hinkle, Lynette. Homemade Remedies With Turmeric. eHow.com - Herbs & Botanicals for Health J-Z. < http://www.ehow.com/way_5402326_homemade-remedies-turmeric.html > retrieved on Oct 13, 2012.
• Husemoen LL, Skaaby T, Thuesen BH, Jørgensen T, Fenger RV, Linneberg A. Serum 25(OH)D and incident type 2 diabetes: a cohort study. Eur J Clin Nutr. 2012 Oct 3. doi: 10.1038/ejcn.2012.134. 
• Joung YH, Lim EJ, Darvin P, Chung SC, Jang JW, et al. MSM Enhances GH Signaling via the Jak2/STAT5b Pathway in Osteoblast-Like Cells and Osteoblast Differentiation through the Activation of STAT5b in MSCs. PLoS ONE. 2012; 7(10): e47477.
• Kulac M, Aktas C, Tulubas F, Uygur R, Kanter M, Erboga M, Ceber M, Topcu B, Ozen OA. The effects of topical treatment with curcumin on burn wound healing in rats. J Mol Histol. 2012 Oct 2.
• Meynial-Denis D, Bielicki G, Beaufrère AM, Mignon M, Patureau Mirand P, Renou JP. Glutamate and CO(2) production from glutamine in incubated enterocytes of adult and very old rats. J Nutr Biochem. 2012 Aug 13.
• Wadden D, Cahill F, Amini P, Randell E, Vasdev S, Yi Y, Zhang W, Sun G. Serum acylated ghrelin concentrations in response to short-term overfeeding in normal weight, overweight, and obese men. PLoS One. 2012;7(9):e45748.

Cinnamon, Curcumin (Turmeric), Licorice (Glycyrrhizin), Melatonin, Milk Thistle (Silymarin). Supplements to Improve and Restore Insulin Sensitivity - Serving #3

Sleep hygiene was part of the lifestyle tips in the first episode of this series, with this episode you get a tool that can help you get back into the groove: melatonin.

This is Sunday number three with supplements that may help you improve / maintain your glucose sensitivity and I can already tell you it's going to be the last one. In other words, if there are any compounds that have not yet been covered in this series - just a reminder

• Alpha Lipoic Acid, GABA, Taurine, Green Tea, Gooseberry & Fenugreek were addressed in detail as part of supplement list #1
• Berberine, Banaba (Corosolic Acid), Rauwolfia Serpentina, (Apple Cider) Vinegar, Chromium were addressed in detail on supplement list #2 

- this is your last chance to make a wish! So, if you have something special in mind, use the comment section at the end of this article and tell me which agents you want to see in issue #4 on next Sunday.

Ah, ... it should be obvious that none of the following agents qualifies: Cinnamon, Curcumin (Turmeric), Licorice (Glycyrrhizin), Melatonin, Silymarin - why? Well those are the ones you can read about in the paragraphs below :-)

• Dosages for cinnamon supplements range from 1-6g+ of pure real cinnamon (cinnamomum vera) to 150-500mg of extracts (depending on their quality). You should be aware though that "fake" cinnamon (cinnamomum cassia, which is sold in the US simply as "cinnamon") contains (highly variable amounts) of coumarin a liver toxic and carcinogenic substance w/ an upper intake limit of 0.07mg/kg body weight that may easily be exceeded by eating common foodstuffs like oatmeal with cinnamon in small children (Fotland. 2012).
  

  According to Fotland et al. this can lead to toxicity reactions within weeks. So don't be cheap and better make sure not to buy "fake cinnamon" (=cassia) for you or your kids and loved ones.
  Cinnamon (Cimmomium verum!) [B]: Cinnamon is unquestionably one of the best known supplements for diabetics. "High blood sugar? Have some cinnamon in your sugar-laden Starbucks coffee!"... and this is exactly where the problem is. Everyone knows that cinnamon works - acutely(!), because he or she can measure his blood glucose after the ingestion of the said Starbucks coffee with and without cinnammon, but...
  1. according to the latest meta-analysis the long-term benefits of using cinnamon to manage blood glucose levels in type II diabetics are zero - the most important measure of their overall glycemic status, i.e. HbA1c, does not change significantly; or I should say: it reacts formidable in studies lik Lu et al. (2012; 120 or 360mg/day treated alongside standard diabetes drug) and deteriorates in others (Mang. 2006; Wainstein. 2011; etc.)
  2. studies in healthy individuals suggest that the blood glucose lowering effects are a mere results of an inhibition of the digestion and absorption of high GI carbs (6g regular cinammon w/ rice or pudding; Hlebowicz. 2007)
  There is however recent evidence that some of the secondary plant material, i.e. the proanthocyanidins you will find in cinnamon water extracts exert a direct protective effect on stressed pancreatic beta cells.
  Just a note for those who feel I am a "supplement hater": I am not the only one displaying a healthy degree of skepticism towards the hoopla that surrounds the use of cinnamon as an anti-diabetic. The "gold standard" review from the Cochraine Foundation says: "There is insufficient evidence to support the use of cinnamon for type 1 or type 2 diabetes mellitus. Further trials, which address the issues of allocation concealment and blinding, are now required. The inclusion of other important endpoints, such as health-related quality of life, diabetes complications and costs, is also needed" (Leach. 2013)
  Overall, cinnamon is thus a "B" as in "one of the B-est agents to protect yourself from developing insulin resistance and diabetes": It can also be interesting for type II diabetic looking to improve his blood lipids, but this is a different topic (cf. Khan. 2003). So, if you can't keep away from the sweet stuff of which you know ever since episode 1 of this series that you are not supposed to eat it, some cinnamon won't hurt - if you hate the taste, though, don't force it down. It's not really worth gagging.

• 

  In healthy human beings the administration of 6g of curcuma longa before a 75g glucose tolerance test does just one thing: It spikes insulin without improving the glucose uptake. Technically this is a decrease - not an increase in insulin sensitivity, which would have to be observed if curcumin was an insulin-sensitizer.

  Curcumin (Turmeric; curcuma longa) [C] - Curcumin is probably among the hottest supplements out there. Everybody appears to know exactly what it does and obviously everything is ueber-potent and super-healthy. It does therefore appear almost unquestionable that curcumin is going to help with insulin resistance, as well... right? Well, unquestionable as it may apper, the mere assumption that it would do so is not just unwarranted, but downright misleading.
  
  While there is evidence that its anti-inflammatory effects can help restore normal insulin sensitivity in diabetic individuals and animals, such as the streptocitozin-induced diabetic rodents in a 2011 study by Na et al., the important evidence from human studies is not there. In fact, in a 2010 study from the Skåne University Hospital in Sweden, Wickenberg, Ingemasson and Hlebowicz were able to show that curcumin worsens the insulin sensitivity of fourteen healthy subjects.
  
  Being first and foremost and anti-inflammatory agent, it is at imho not surprising that curcumin is not the ideal insulin sensitizer. In view of the fact that the obese and inflamed may need a little help to get their baseline inflammation back in check, before any "anti-diabesity" agent may even start working curcumin does however still qualify as a "C" as in "take in C-ombination" with other agents, but only if you're actually dealing with inflammatory problems (e.g. high CRP-1 value in serum; type 1 diabetes and problems with heme oxygenation, cf. Aziz. 2013). After all, the emerging role of reactive oxygen specimen in muscule- and thus tissue- and anti-obesity-specific glucose uptake clearly suggest that the suffocation of all inflammatory signals is not going to help, but hinder glucose uptake (Merry. 2012).
• Licorice (glycyrrhizin) [D] - While it has a bad rep as a "cortisol increasing" agent that puts you at risk of developing high blood pressure glycyrrhizin does actually have the ability to reverse diet-induced insulin resistance and get the GLUT-4 glucose transporters back out on the cell surfaces. Sil et al., for example report that they observed corresponding improvements of insulin sensitivity in a rodent model of high frutcose feeding (which is actually not much different from the average victim of the American diet; dosage was 50mg/kg or 600-750mg/day for a human being; Sil. 2013)

  

  Table 1: Analysis and comparison of active ingredients in Radix Glycyrrhizae (licorice) from Europe and China by capillary-zone electrophoresis (Rauchensteiner. 2005)

  As you can see in the table above the glycyrrhizin content of different forms of licorice is somewhere between 2-3mg/100mg (Rauchensteiner. 2005). In other words, to hit the 600-750mg you will necessarily need an extract - unless you want to consume kilograms of licorice.
  
  

  

  What about testosterone? A larger scale 4-week trial with 100g/day of licorice containing 0.15% glycyrrhizic acid could not find any significant changes in sex steroid hormones (Sigurjonsdottir. 2005)

  Whether that's a smart thing to do is however questionable, as licorice does not just have the potential to increase blood pressure, but is also a relatively unpredictable agent. Most of the glycyrrhizin will never even make it through the gut and into your blood, but rather be converted to other metabolites by your gut microbiome. Injections on the other hand appear to be possible, but the example of a 72-year old subject of a case report from the year 2000 goes to show you that in some cases the anti-diabetic effects may be a tad bit to potent. The subject did after all end up being profoundly hypoglycemic after the injection of 80mg of glycyrrhizin (Motoo. 2000).
  
  Despite potential anti-diabetic effects (read more) and the potent anti-obesity effects (3g of licorice per day = 2% body fat reduction in normal weight volunteers w/out dietin → learn more) you have read about here at the SuppVersity licorice does therefore get a "D" as in "D-on't take", because it seems as if the margin between 'enough to elicit beneficial effects' and 'so much that you are risking side effects' is pretty narrow.

• 

  Melatonin has also been shown to have beneficial effects on glucose uptake and glycogen synthesis after exercise and scientists speculate that it could play a major (facilitative) role in skeletal muscle adaptation to exercise (learn more)

  Melatonin [C]- I know, I know, it's a "dangerous hormone" ... well, nobody will propose that, when we talk about prescribing verifiably more dangerous oral contraception to women. I wonder how that is!? After all, this "dangerous hormone" could, mitigate the negative side effects many of the oral contraceptive appear to exert on the glucose metabolism of young, previously healthy women (for an in-depth discussion see Lopez. 2012). Ah, I am digressing, once again. So let's get back to melatonin.
  
  Assuming you follow all the recommendations from installment 1 of this series you should not be in dire need of melatonin supplementation. Sometimes, however, life comes in the way - for me that happened in the course of the last weeks. Oftentimes it's not even necessarily the "bad things" in life that keep you from getting enough sleep and producing a truckload of endogenous melatonin. It is in these situation, where some supplemental help in pill- or capsule-form may in fact come extraordinarily handy as an acute treatment that will work by its beneficial effects on skeletal muscle glucose uptake (Ha. 2006), leptin expression in response to insulin (Alonso-Vale. 2005) and 24h glucose homeostasis (la Fleur. 2001)
  
  In view of its many-fold effects on the mammalian metabolism and the age-related decline in melatonin production, it is actually not surprising that the provision of melatonin to aging rodents (0.4μg/ml in drinking water) was able to restore plasma insulin and leptin levels to youthful levels and continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels without any effects on plasma corticosterone and total thyroxine (T4),  testosterone, insulin-like growth factor I (IGF-I) and total triiodothyrone (T3) compared to placeo (Rasmussen. 2002)
  
  That being said, for young(er) individuals, it may be sufficient to restore a normal circadian rhythm by strategically supplementing at the right times. In conjunction with a consequent "lights out strategy" (learn more), this should get you back on track and your insulin resistance up. Melatonin is thus a classic "C" as in "C-an be used by everyone"; a "C" that does however need some basic information about when you want to take the 1-10mg of melatonin to derive the greatest benefits (learn more about phase shifting your circadian rhythm) .
• Silymarin (Milk thistle) - Not exactly one of the agents you would expect on a list like this, but contrary to many better known anti-diabetic agents milk thistle can - just like cinnnamon, by the way - inhibit the accumulation of human islet amyloid polypeptide in the pancreas and the subsequent development of the end stages of diabetes (=the inability to produce insulin). In a 2006 study from Iran the provision of milk thistle to type II diabetics (200mg silimarin, 3x daily) lead to significant reduction in acute (blood glucose) and long-term measures of (HbA1c) of glucose management, as well as improvements in insulin levels (see figure below).

  

  Changes in fasting blood sugar (FBS), long-term marker of FBS (HbA1c) and insulin levels in randomized controlled trial w/ 51 type II diabetics; data expressed relative to median values across all groups (Huseini. 2006)

  In view of the results from the randomized controlled human study depicted in the figure above and based on the fact that silybin / silymarin / milk thistle helps controlling NAFLD, of which you learned earlier this week that it may as well be the cause not the consequence of insulin resistance (learn more). Milk thistle deserves a "B" as in "B-etter than many more specific agents". Dosages range from 500-1,500mg per day and you should make sure you get a standardized product and not an extract with non-disclosed amounts of active ingredients in it.

I know there are more agents, but I do also know that I cannot address each and every herb that may have the potential to reduce your blood glucose levels by 1pt. So unless you want me to make the last five picks, take your chance and let me know which agents you are still missing in the comments.

References:

• Allen RW, Schwartzman E, Baker WL, Coleman CI, Phung OJ. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann Fam Med. 2013 Sep-Oct;11(5):452-9.
• Alonso-Vale MI, Andreotti S, Peres SB, Anhê GF, das Neves Borges-Silva C, Neto JC, Lima FB. Melatonin enhances leptin expression by rat adipocytes in the presence of insulin. Am J Physiol Endocrinol Metab. 2005 Apr;288(4):E805-12.
• Aziz MT, El Ibrashy IN, Mikhailidis DP, Rezq AM, Wassef MA, Fouad HH, Ahmed HH, Sabry DA, Shawky HM, Hussein RE. Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy. Diabetol Metab Syndr. 2013 Mar 12;5(1):13.
• Fotland TØ, Paulsen JE, Sanner T, Alexander J, Husøy T. Risk assessment of coumarin using the bench mark dose (BMD) approach: children in Norway which regularly eat oatmeal porridge with cinnamon may exceed the TDI for coumarin with several folds. Food Chem Toxicol. 2012 Mar;50(3-4):903-12. 
• Ha E, Yim SV, Chung JH, Yoon KS, Kang I, Cho YH, Baik HH. Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells. J Pineal Res. 2006 Aug;41(1):67-72.
• Hlebowicz J, Darwiche G, Björgell O, Almér LO. Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects. Am J Clin Nutr. 2007 Jun;85(6):1552-6. 
• Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res. 2006 Dec;20(12):1036-9.
• Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003 Dec;26(12):3215-8.  
• la Fleur SE, Kalsbeek A, Wortel J, van der Vliet J, Buijs RM. Role for the pineal and melatonin in glucose homeostasis: pinealectomy increases night-time glucose concentrations. J Neuroendocrinol. 2001 Dec;13(12):1025-32.
• Lopez LM, Grimes DA, Schulz KF. Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus. Cochrane Database Syst Rev. 2012 Apr 18;4:CD006133.
• Lu T, Sheng H, Wu J, Cheng Y, Zhu J, Chen Y. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Nutr Res. 2012;32(6):408-412.
• Mang B, Wolters M, Schmitt B, Kelb K, Lichtinghagen R, Stichtenoth DO, Hahn A. Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2. Eur J Clin Invest. 2006 May;36(5):340-4. 
• Merry TL, McConell GK. Do reactive oxygen species regulate skeletal muscle glucose uptake during contraction? Exerc Sport Sci Rev. 2012 Apr;40(2):102-5. 
• Motoo K et al. Non-insulin-dependent Diabetes Mellitus in an Elderly Patient with Hypoglycemic Attacks Induced By Glycyrrhizin Administration. Journal of the Japan Diabetic Society. 2000; 42(8).
• Na LX, Zhang YL, Li Y, Liu LY, Li R, Kong T, Sun CH. Curcumin improves insulin resistance in skeletal muscle of rats. Nutr Metab Cardiovasc Dis. 2011 Jul;21(7):526-33. doi: 10.1016/j.numecd.2009.11.009. 
• Rasmussen DD, Boldt BM, Wilkinson CW, Yellon SM, Matsumoto AM. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology. 1999 Feb;140(2):1009-12. Erratum in: Endocrinology 2002 Apr;143(4):1269.
• Rauchensteiner F, Matsumura Y, Yamamoto Y, Yamaji S, Tani T. Analysis and comparison of Radix Glycyrrhizae (licorice) from Europe and China by capillary-zone electrophoresis (CZE). J Pharm Biomed Anal. 2005 Jul 15;38(4):594-600.
• Sigurjonsdottir HA, Axelson M, Johannsson G, Manhem K, Nystrom E, Wallerstedt S. Liquorice in moderate doses does not affect sex steroid hormones of biological importance although the effect differs between the genders. Horm Res. 2006;65(2):106-10.
• Sil R, Ray D, Chakraborti AS. Glycyrrhizin ameliorates insulin resistance, hyperglycemia, dyslipidemia and oxidative stress in fructose-induced metabolic syndrome-X in rat model. Indian J Exp Biol. 2013 Feb;51(2):129-38.
• Wainstein J, Stern N, Heller S, Boaz M. Dietary cinnamon supplementation and changes in systolic blood pressure in subjects with type 2 diabetes. J Med Food. 2011;14(12):1505-1510.
• Wickenberg J, Ingemansson SL, Hlebowicz J. Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects. Nutr J. 2010 Oct 12;9:43.

2.1kg Muscle From Fast Food Supplement; No Prolactin, No Fat; Oleic Acid Counters CLA's Inflammatory Effect; Spicy Marinades vs. Salmonella; Flaxseed, Estrogen & Penis Size; TTA in the Emergency Room; Alcohol & Binge Eating

Image 1: Scientifically proven muscle builder - 2.1kg lean mass in 3 months, no post-cycle therapy necessary!

I was just about to write another one of my artistic introductions, trying to incorporate all the exciting On Short Notice news I've piled up for you into a brief narrative, when I realized that you probably don't really appreciate those introductions (I guess, I would skip them myself, so don't worry, this is more of an objective assessment than an accusation). So, I listened to my gut and decided to skip this part of this series, today, and rather spend the time to edit another item I did actually not want to post today. It's the one on the "IIFYM slightly gone wrong fast food bulk" in the Hambre study, to be precise; and I would venture the guess that you won't mind taking that instead of a longer introduction, once you've read and digested the impossible: You cannot only gain muscle with "fast food supplements", you won't even get fatter than you would if you just used a classic whey protein... oh my, I see, you are already scrolling down: What I said, I would have been wasting my time, had I written a longer introduction. But dare you, if you don't at least read the other items, as well!

• 

  Figure 1: Food intake (top, lef) and energy expenditure (bottom, left) as well as body fat % (top, right) and body weight development of the normal vs. prolactin negative mice after 14 weeks on standard chow (SC) or high fat diet (HFD; Auffret. 2012); btw: taking super-doses of vit. B6 will induce nerve damage, not fat loss!

  Without prolactin mice can't get fat! If that is true for humans as well, this would mean that Julien Auffret and his colleagues would have made a very important finding that could help us solve at least part of the diabesity pandemic, if we found a way to mimick the effects the "beigening" (=making white adipose tissue behae similar to the fact burning brown adipose tissue) effect the genetic ablation of the prolactin receptor on the fat cells of the mice in the Auffret study had on their susceptibility to diet induced obesity (Auffret. 2012).
  In particular, the scientists found that the ablation of the prolactin receptor gene in the mice results in profound increases in the expression of master genes controlling brown adipocyte fate (PRDM16) and mitochondrial function (PGC1α, UCP1), which allow - and this is the actual caveat,, here - for an inrease in thermogenesis.
  The latter, in turn, allows the rodents to burn off a major part of the fat they would otherwise store and thus keeps them relatively lean despite HFD feeding. Aside from the fact that the hyperphagic rodents on the high fat diet were still fat (there is no debating that!), you may savely assume that the effects will be way less pronounced in human beings, where 9/10 "thermogenic" agents that have been successfully tested in rodents do nothing at all, anyway. Against that background the hunger-promoting effects of the prolactin recetor ablation would suggest that it is almost as likely that a drug that block prolactin completely would make obese individiuals even fatter, since that's usually what happens if you eat more - like the mice in the prolactin (-/-) group did (see figure figure 1), without burning more.

• 

  Figure 2: Comparison of MUFA : CLA ratios in steak and mince from grass fed or conventional beef and milk from mares, sows, women (human milk ;-), goats and cows (based on Dhiman. 1999; Jahreis. 1999; McAfee. 2011); higher values indicate more MUFA per unit of CLA, but more must not necessarily be better - in fact too much MUFA could completely block the fat loss effects of CLA and thus maybe explain why it rarely works in humans - our diets are pretty high in oleic acid and thus the ratio will be much lower, than in the high dose CLA rodent trials

  Conjugated linoleic acid needs oleic acid to work without side effects. That's the main take-home message from a recent study conducted by researchers at the at the University of North Carolina at Greensboro, who found that oleic acid, the mono-unsaturated fatty acid from olive oil & co, does prevent the expression of inflammatory genes in adipocytes treated with the "anti-fat fat CLA"..
  So, until my friends from the supplement industry read this post and come out with yet another SuppVersity science powered product with CLA in olive oil* you simply make sure to have a spoon of the liquid gold from time to time, when you feel that you need to take CLA to burn more fat. Unfortunately, this could not just mean that you can rid yourself of the nasty side-effects as discussed in "CLA Destroys Body Fat! But at Which Costs?", but also that the "body fat destruction" will at least be ameliorated if not totally absent :-(
  * I had hardly written this post, when I browsed the web and found that a certain newcomer and as of late very succesful "yellowish green" company has already a CLA + Olive Oil + Avocado Oil combination on the market, for them this would mean that they didn't even have to change their formula

• 

  Image 2: It's funny how so many things people (or at least chefs) have been doing forever, here marinating meats, simply make sense, isn't it?

  Antibacterial marinades for your meat! Don't worry this is not yet another dysfunctional functional food that's going to make you sick, but an all-natural mixture of green tea, lemon and turmeric you will have to smear onto your chicken meat if you want to make sure to get rid of the C. jejuni and S. enteritidis it may be contaminated with.
  All it takes are 24h of "incubation", but that's nothing else than leaving your meat lying in the marinade in your fridge and thus something you would do anyway, right? That's what I would call a convenient, effective and above all totally natural and healthy way of gettting rid of Samonella and Campylobacter :-)
• Tons Flaxseed flour in your diet will increase estrogen, but won't decrease the size of your penis, well at least not visible ;-) That's probably the most straight-forward summary of the results, Ludmila Ferreira Medeiros de França Cardozo and her colleagues present in the latest issue of Food and Chemical Toxicology after analyzing the effect of a flaxseed flour containing diet on the expression of hormone levels and penis morphology of male rats (de Franca. 2012)

  

  Image 3: Flaxseed bread won't turn you into an hermaphrodite overnight, don't worry.

  While the rats that were maintained on a diet containing 25g of flaxseed flour per 100g for 250days had significantly elevated estrogen levels in the blood 39.5 vs. 32.5 pg/mL (+22%), the minor drop in testosterone did not reach statistical significance and the reduced diameter of the corpus spongiosum, which helps to maintain the urethea as a viable channel for the ejaculation was obviously no problem for the fertility, either - at least the scientist don't mention anything in this regard; unfortunately, they did not really test it, either, as the poor male Wistar rats that were abused in this experiment were bachelors against their will.
  In view of the fact that flaxseed ain't the best source of omega-3s, anyway, and there appears no other good reason (for men and women!) why you would eat them in large quantities (I am not talking about the occasional tablespoon of flaxseed, here), I would still suggest to stay away from it.

• 

  Image 4: In farm-raised salmon chronic TTA administration has been shown to improve cardiac function and immune activity; it does however also lead to cardiac growth during viral infections, so that the benefits of chronic administration are still by no means certain (Grammes. 2012a & 2012b); long-term human studies, on the other hand, are not yet available.

  Acute TTA administration soothes the flames and keeps the coronary vessel open You will unquestionably remember my previous posts about the fat burning fatty acid tetradecylthioacetic acid (TTA) and how it's ability to accumulate in various tissues of your body could potentially become problematic. In the short term however, it's anti-inflammatory effects can come very handy. So handy, in fact, that the a recently published study by Pettersen et al. would suggest that we are soon going to see TTA balloons being inserted into coronary vessel walls, in order to deliver the sulfur-containing fatty acid right to an obstructed vessel that's being operated on, in order to suppress the local expression of inflammatory cytokines, as well as the subsequent macrophage infiltration and the unwanted collagen formation, which would precipitate restenosis (=further clogging) of the very heart vessel that has only just been opened operatively.
  You may now rightly ask yourself what this has got to do with you? Well, if it works locally, it could work similarly systemically and other studies such as Bjørndal (2012) do confirm just that: 0.4% TTA reduce TNF-α, IL-1β, and IL-6 in an experimental model of colitis and render the rodents guts more of less bullet..., ah, pardon, dextran sulfate sodium (DSS; a chemical used to induce cholitis) proof. The long-term effects of the continous consumption of ~3g of TTA, which would be the human equavalent of those 0.4% TTA in the rodent diets is yet still not fully established (re-read: "TTA & Fish Oil" and "TTA & Fish Oil - Revisited").

• 

  Figure 3: Alcohol overrides the inhibitory control over food intake (Chapman. 2012)

  Of TV watching, sleep deprivation and alcohol consumption, booze has the most pronounced negative effect on reward saliency and inhibitory control of food intake! That's the conclusion Colin Daniel Chapman, Christian Benedict, Samantha Jane Brooks, and Helgi Birgir Schiöth mkae based on their latest meta-review of pertinent studies from pubmed (N=23). With an impact factor of 1.03 on a scale from -4 to 4, alcohol is by far the worst the greatest effect on food intake and shows the highest correlation with obesity (Chapman. 2012).
  Compared to booze, both sleep deprivation (50% less) and TV watching (20% less) appear almost harmless. Their contribution in the non-drinking part of the population may yet still not be underestimated, also because the urge to do the latter, i.e. watch TV, when you ought tho sleep, precipitates the former and subsequent derangements in the circadian rhythm (suggested read: "The SuppVersity Circadian Rhythm Series").
• IIFYM was yesterday, ROWFYM is today, but what's going to be tomorrow? If that's all Greek to you, let me first bring you in the loop on the acronyms. While IIFYM designates "If It Fits Your Macros", implies (in the most extreme case) that you give a sh*t about what you eat, as long as you hit your macronutrient ratios for the day ("Carbs? Gimme that pizza!") and is getting increasingly popular among those who are fed up with broccoli and chicken breast and either unwilling or unable to see that those are not the only, and I would say, by far not the most healthy foods you can eat, ROWFYM is my own invention, means "Regardless Of Whether It Fits Your Macros" and would probably end up for way too many trainees in a protocol similar to the one 12 of the 24 subjects in a recent study from the Linköping University in Sweden were following for 12 weeks (Hambre. 2012).

  

  Image 5: "WTF do you want, I am doing ROWIFYM, here! That's serious bulking, man. Scientifically validated." If you want to follow his example, go ahead... but 3 months really is the absolute max and only if you are still healthy - regardless of whether the blood markers return to normal in the course of your next diet.

  While those lucky (?) twelve healthy young men (aged 19–32 years) in what I will from now on call the "fast-food arm" of the study had to add a delicious (???) fast food menu (1350 kcal, 41 g protein) on top of their diets, the other twelve participants had to contend themselves with a blatant protein shake (33g of whey) as their bulking supplement of choice. The reasoning behind this at first sight unquestionably highly questionable experiment was that the Swedish scientists wanted to elucidate, whether it would really make a difference whether you are eating "clean" (=adding a whey protein shake) or simply stuffing yourself with the next best, allegedly protein-laden fast food you can find during a 3-months bulking cycle (at least three lifting sessions per week) and the results were, ... well, let's say surprising.
  As you would expect, subjects in both groups managed to gain some weight. The first surprise is that subjects in both groups gained identical amounts of weight, namely 3.6kg. That's not all, however. Even the lean mass increases 2.1kg did not differ between the groups (measure by DEXA scans) and the sophisticated (compared to a similar calories in vs. calories out calculation) measurement of the resting metabolic rate, the scientists had conducted yielded that both groups had compensated for the overeating by a statistically highly significant (p < 0.0001!) + 10% increase in resting metabolic rate!

  

  Figure 4: Kaplan-Meier plots indicating the percentage of patients that made it to time-point X (see horizontal axes) without adverse event after their first coronary event - patients w/ (thin line) vs. w/out (bold line) metabolic syndrome (top), patients with high (thin line) vs. low (bold line) ApoB leves (bottom; based on Corsetti. 2005); ApoB turns out to be a way better risk predictor than having metabolic syndrome

  Before you do now jump into your car and head for the next drive-in "restaurant" with a big yellow "M" in front of it, you may want to take into consideration that this extended ROWIFYM version of the IIFYM approach, where you may hit the protein but overshoot on the carbs and fats (and certainly not  the good ones), did lead to statistically significant increases in fasting insulin and ApoB, a building block of LDL that has been associated with increased risk of arterial plaque formation (Gebel. 2008), compared to the "clean bulk" (= whey only) group. And while those changes (as well as the increase in RMR) were reversed on the 12 months follow-up, I am not sure if especially those people, who are most fond of bulking approaches like that, i.e. men (and very rarely women) who have been following a junk food diet for way too long already, should take the results of this study as an incentive to do a 3-month fast food bulk during the winter. After all, it could be that one additional LDL molecule that nests in the already existent arterial plaque which will eventually break the camel's, no your neck - or for those who like it more explicitly, which won't let the next mini blood clot pass by and causes a stroke, which could, in the worst case, end deadly!

That's it as far as the official On Short Notice items go, for today. If you don't have enough yet, I suggest you take a glance at the 6-10 news-items I've piled up on the SuppVersity Facebook Wall for you to review. Maybe you've read that sleeping with wife and children in a room would decrease your testosterone levels? False! Maybe it decreases the intellectual capacity of the reporter who wrote the respective news-item you may have read, but what really happens, is an increase in the amplitude of the circadian pattern with higher morning and lower evening testosterone levels (click here to read more). And if you neither have or plan to have children or don't care about your or your significant other's testosterone levels, you may be interested in a study that debunks the use of a "slim belt" for weight loss purposes, the idiotic idea to counter BPA toxicity with soy, the way working out can make depressed old people happy again, and more... ah, I almost forgot, there will also be an exercise special of On Short Notice very soon - and I am not talking about next Saturday, here - so stay tuned, it could be published anytime (Tip: If you subscribe to the SuppVersity Facebook Page you won't miss it ;-)

 References:

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• Bjørndal B, Grimstad T, Cacabelos D, Nylund K, Aasprong OG, Omdal R, Portero-Otin M, Pamplona R, Lied GA, Hausken T, Berge RK. Tetradecylthioacetic Acid Attenuates Inflammation and Has Antioxidative Potential During Experimental Colitis in Rats. Dig Dis Sci. 2012 Aug 2.
• Chapman CD, Benedict C, Brooks SJ, Birgir Schiöth H. Lifestyle determinants of the drive to eat: a meta-analysis. Am J Clin Nutr. 2012 Sep;96(3):492-7. Epub 2012 Jul 25.  
• Corsetti JP, Zareba W, Moss AJ, Sparks CE. Apolipoprotein B determines risk for recurrent coronary events in postinfarction patients with metabolic syndrome. Atherosclerosis. 2004 Dec;177(2):367-73.
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• Gebel E. Meet LDL's partner in plaque. ApoB puts the "bad" in bad cholesterol. Diabetes Forecast. 2008 May;61(5):39-40.
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• Grammes F, Rørvik KA, Thomassen MS, Berge RK, Takle H. Genome wide response to dietary tetradecylthioacetic acid supplementation in the heart of Atlantic Salmon (Salmo salar L.). BMC Genomics. 2012n May 11;13(1):180.
• Hambre D, Vergara M, Lood Y, Bachrach-Lindström M, Lindström T, Nystrom FH. A randomized trial of protein supplementation compared with extra fast food on the effects of resistance training to increase metabolism. Scand J Clin Lab Invest. 2012 Aug 30.
• Jahreis G, Fritsche J, Möckel P, Schöne F, Möller U, Steinhart H. The potential anticarcinogenic conjugated linoleic acid, cis-9,trans-11 C18:2, in milk of different species: Cow, goat, ewe, sow, mare, woman. Nutrition Research. October 1999; 19:10. 1541–1549.
• McAfee AJ, McSorley EM, Cuskelly GJ, Fearon AM, Moss BW, Beattie JA, Wallace JM, Bonham MP, Strain JJ. Red meat from animals offered a grass diet increases plasma and platelet n-3 PUFA in healthy consumers. Br J Nutr. 2011 Jan;105(1):80-9.
• Murali N, Kumar-Phillips NS, Rath NC, Marcy J, Slavik MF. Effect of Marinating Chicken Meat with Lemon, Green Tea and Turmeric Against Foodborne Bacterial Pathogens.International Journal of Poultry Science. 2012; 11(5): 326-332.
• Pettersen RJ, Salem M, Rotevatn S, Kuiper KK, Larsen TH, Bohov P, Berge RK, Nordrehaug JE. Effects of local delivery of Tetradecylthioacetic acid within the injured coronary vessel wall. Scand Cardiovasc J. 2012 Aug 30.
• Reardon M, Gobern S, Martinez K, Shen W, Reid T, McIntosh M. Oleic Acid Attenuates trans-10,cis-12 Conjugated Linoleic Acid-Mediated Inflammatory Gene Expression in Human Adipocytes. Lipids. 2012 Sep 2.