Get Lean & Stay Lean Quickie: Add Cinnamon to Cereals. NPY Detrimental? Melatonin Beneficial! 50,000IU Vitamin D3 Useless. Phtalate DHEP Dangerous! PPAR, AKT & GLUT-4 Agonist From False Black Pepper Surprisingly Potent!

In 1998 the Consumer Union wrote a letter to the FDA complaining about the occurrence of DEHP and other "endocrine disrupting chemicals" in cheese and dairy of which they suspected that they were partially emitted from the plastic wrappings (read more)

Those of you who are following the SuppVersity news on Facebook very closely, will be aware that I announced yesterday, already that there was going to be another installment of On Short Notice, today... another "Quickie", so to say with a couple of selected news on getting and staying lean. Something I know is pretty much a pain in the a** of most of us and if you take a closer look at the news about phtalates it is actually no wonder. I guess on their own those nasty plasticizers would probably not even be a problem, but together will all the other byproducts of our convenient lives, they form a perfect storm.

And you know what's worst, simply wrapping all those plastics that 'infect' even organic foods with the 'P-Virus' around your waist while you're working out will probably make things worse, not better.

Let's get down  to business ;-)

Enough of that! Are you ready for today's quickie -- Note: The next installment of the Athletes' Triad is scheduled for next week. I am honestly sorry for these delays, but I just have "real" work to do on the weekends at the moment and no time to do the respective research that would be necessary to provide you with not just any, but actually useful information. In the mean time I hope you like this post, as well.

• 6g of cinnamon stretch postprandial glucose response to cereals over more than 2h. That's the result of the latest study from the Ball State University in Muncie (Magistrelli. 2012). Interestingly the effects of 6g of ground Cassia Cinnamon were independent of the body weight and metabolic health of the thirty-seven 18 to 30 year-old normal-weight and obese study participants.
  
  

  

  Figure 1: Postprandial blood glucose with plain cereal containing 50g  carbs and the same cereal with cinnamon in all subjects, normal-weight and obese; by the way if you go by the AUC I doubt there is a benefit, after all the glucose does not drop base to baseline within 120min (Magistrelli. 2012).

  There is however one slight downside to this study: The scientists measured the blood glucose response for only 120min. If you take a look at the graph in figure 1 you will immediately notice that the co-ingestion of 75g of "Cream of Wheat", an instant farina cereal, with 6g of regular cinnamon did lead to a 24% reduction in the area under the glucose curve, but only if you discard what happened after the 120-min period the scientists used to measure. After all, the co-administration of Cassia cinnamon did not do anything that could not be ascribed to a mere reduction in glucose uptake - there is no evidence for an improvement of insulin sensitivity here. On the other hand, the absence of spikes in blood glucose will protective effects against the development of type II diabetes, esp. in the presence of a diet that's overall high in carbohydrates where one blood sugar spike chases the other.
  

  "To date, no study has documented cinnamon's influence on postprandial blood glucose after a mixed meal. Although preliminary in nature, the available research suggests cinnamon supplementation can significantly reduce short-term glycemic response in healthy adults." (Magistrelli. 2012)

  The last information is actually pretty surprising. Personally I expect the effects to be less pronounced with mixed meals, but since we still don't really know the underlying mechanism it's difficult to predict what exactly is going to happen, when you eat a spoon full of cinnamon right before your steak with rice. This as well as the previously discussed prolonged elevation of blood glucose (see figure 1)  actually raise some doubts about the real-world usefulness of eating tons of cinnamon if you don't actually like it, just as a way to manage blood glucose - specifically if you are not a type II diabetic (or on your way to become one) and avoid "food" like cereals and similar junk, anyways.
• Neurpeptide Y (NPY) does not protect against obesity -- Based on the results of a recent rodent study from the University of Turku in Finland, it seems that the exact opposite is the case. In that it does not seem as if it would fail to make you satiated and happy. Rather than that it appears to put your metabolism in "high efficacy" mode, so that you gain weight despite the fact that you are not eating more.
  
  The Finish researchers exposed two strains of mice to a typical Western type diet (high energy, high fat, high carbohydrate) for seven weeks. One strain, the OE-NPY(DBH) mice, had 'naturally' high amounts of NPY in the noradrenergic neurons of the brain, the other were normal wild type mouse. Actually, the scientists had expected that the high NPY expressing mice would gain less weight than their wild-type peers, but much to their surprise, the exact opposite was the case.
  
  

  

  In 1990 Kaye et al. conducted post-mortem analyses on the brains of patients with anorexia nervosa and found highly elevated levels of NPY. These results do actually stand in line with those of the study at hand, after all anorexic patients don't feel any exuberant hunger (in the later stages of the disease) and their bodies are running in a mode that is meant to conserve even the smallest amount of energy they consume.

  And as if that was not already strange enough, the scientists also found that female OE-NPY(DBH) were much more prone to gain significantly more weight and larger white and brown fat depots with no difference in UCP-1 levels, hyperphagia (=overeating) or decreased activity. And the weight gain was not without consequence, as these mice
  

  "...also displayed impaired glucose tolerance and decreased insulin sensitivity. OE-NPY (DBH) and WT males gained weight robustly, but no difference in the degree of adiposity was observed." (Ruohonen. 2012)

  Now what's interesting is that similar effects were only observed in 40% of their male counterparts and in exactly none of the wild type males on the Western type diets. These observations lead Ruhonen et al. to the conclusion that ...
  

  "[...] increased NPY release may predispose females to a greater risk of weight gain under high caloric conditions." (Ruhonen. 2012)

  And if you asked me this must be mediated by whatever gender-specific direct effect on feed efficacy and the changes in brown adipose tissue morphology the researchers observed in the NPY overexpressing mice. This would be good news, since brown fat figure much less in human beings than in rodents. Unfortunately, with identical body temperatures and UCP-1 expression in all animals that is at best one of the causative factors. It can hardly explain all the profound weight and fat gains in the non-hyperphagic (not overeating) OE-NPY mice.
  
  Now, at least for me this raises the question if this is not yet another instance, where the artificially increased NPY levels in the absence of the natural confounding factors, such as increased GLP-1 levels, for example (click here to learn more about GLP-1), couldn't be the actual reason and any conclusions with respect to pro- or anti-obesogenic effect of NPY based on the results at hand would be as unwarranted as the usage of drugs that target this and other neuropeptides in isolation.

• 

  Just in case you have missed the Circadian Rhythm Series, this would be the right time to read about how to boost / not hamper melatonin, live by your internal clock and get healthy and lean (and stay the same) - light and foods timing are key, here (learn more).

  Thiazolidinediones + melatonin, a dynamic duo vs. insulin resistance -- A group of researchers from the Indira College of Pharmacy in Tathawade, India, have just published a study on the combined effects of PPAR agonists and melatonin as a means to ameliorate dexmethasone (artificial cortisol) induced insulin resistance in rodents (Ghaisas. 2012).
  
  The data of the study casts a particularly good light on melatonin which does, contrary to the potentially fattening PPAR agonists pioglitazone and rosiglitazone, not entail a simple increase in glucose storage within the adipose tissue. The combination treatment did also normalize the levels of superoxide dismutase, catalase, glutathione reductase and lipid peroxidation in liver homogenates, an effect the scientists partly ascribe to the antioxidant effects of melatonin , as well (the reduced blood glucose is obviously another factor) 
• 50,000 IU of vitamin D per week improve 25OHD in previously vitamin D deficient subjects but don't produce the expected improvements in insulin sensitivity. Contrary to one of the most underrated dietary supplement, namely melatonin (see previous news item), the most overrated, namely vitamin D3, does not do anything for insulin sensitivity -- even when the subjects are deficient to begin with and their 25OHD levels do actually respond to supplementation (Simha. 2012).
  
  Despite a weekly dose of 50,000 IU of vitamin D3 and a + 42% increase in 25-OHD levels (to be fair it must be said that the levels were still relatively low and nowhere near where some experts want to see it), the researchers from the Department of Internal Medicine at the Texas Tech University Health Sciences Center at Permian Basin did not observe any improvements in glucose uptake after 8 weeks of supplementation in their 12 healthy subjects with baseline plasma 25-hydroxy vitamin D (25OH-D) levels of less than 20 ng/mL.
• More about DEHP and its occurrence in your environment: Prepackaged foods are among your best sources to get your detrimental dose of DEHP every day. Belgian children have been shown to get up to 80% of their DEHP and other phtalates from school lunch. And bread was the worst offender (Sioen. 2012) - probably because it's packed 'sandwich style' in plastic containers of which Cirillo et al. were able to demonstrate that these and other plastic packagings leech the phtalates right into the food (Cirillo. 2011). It is therefore no wonder that the packaged hopsital foods are full of it (Teresa. 2012).
  

  Apropos, having a venyl flooring in either schools or hospitals will only increase the DEHP load due to the emission of the plasticizer into the air (Yu. 2012) and the DEHP content of the bags with blood transfusions are so high that the anti-doping agencies use it as a marker of illegal blood transfusions (Monfort. 2012). Moreover, phtalates leech into milk and dietary products fat-enriched food such as cheese and cream during processing and storage (Kappenstein. 2012); vegetable oils in plastic containers are likewise full of it (Wu. 2012).

  Cooking seems to remove some of the phatalates, but that does not work for vegetables for example (Fierens. 2012). No wonder foods are still the #1 source, followed by bottled water and indoor air of phatalate exposure in Westerners (Martine. 2012).
  

  Unfortunately, the negative effects of DEHP and its metabolites are not restricted to obesity or the prenatal period, they also induce insulin resistance and metabolic syndrome later in life (Rajesh. 2012) - effects which can be ameliorated by increased vitamin C + E intakes. DEHP has also been shown to reduce progesterone and lead to apoptosis of the ovarian granulosa cells and subsequent infertility (Li. 2012a). Similar detrimental effects have been seen in male rodents (Li. 2012b).
  Natural metabolite of ubiquitous plasticizer DEHP sets you and your unborn kids up for obesity DEHP is used in a wide range of soft PVC products ranging from lifesaving medical devices such as medical tubing and blood bags, to footwear, electrical cables, packaging, tarpaulins for lorries, flooring, stationery and roofing. According to a recent study that's been published in Bioscience Reports its natural metabolite MEHP [mono-(2-ethylhexyl) phthalate] has the potential of turning you into a fat, sick slob:
  

  "In the present study, we show the dose-dependent effects of MEHP on adipocyte differentiation and GPDH (glycerol-3-phosphate dehydrogenase) activity in the murine 3T3-L1 cell model. MEHP induced the expression of PPARγ as well as its target genes required for adipogenesis in vitro. Moreover, MEHP perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to a low dose of MEHP significantly increased b.w. (body weight) and fat pad weight in male offspring at PND (postnatal day) 60. In addition, serum cholesterol, TAG (triacylglycerol) and glucose levels were also significantly elevated. These results suggest that perinatal exposure to MEHP may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders." (Hao. 2012)

  In the latest risk assessment of the EU and the DEHP Information Center it is of course 100% save... which bags the question, whether the guys working there simply consider being obese normal, so that anything that makes you even fatter is "save" and does not pose any more of a health threat than life in general, or if they just deliberately ignore that molecules rarely go in and out of our bodies unmetabolized and thus settled for a set of totally meaningless petri dish experiments, before they concluded:
  

  "The use of DEHP has been carefully considered by EU scientists and it is already well regulated by European legislation relating to toys and childcare articles, cosmetics, food contact materials and medical devices." (DEHP Information Center. 2009)

  Hallelujah! Unfortunately it's metabolite MEHP [mono-(2-ethylhexyl) phthalate] obviously is not such a nice guy :-/  

• 

  Figure 2: Serum markers and adiposity, as well as mRNA expression in adipose tissue of male and female mice after 14 weeks on "high fat" diets (based on Estrany. 2012)

  High fat diets (Western style) for women only? I know, this is once again a rodent study, but it is still intriguing that scientists from the Universitat de les Illes Balears in Palma de Mallorca and the Instituto de Salud Carlos III in Madrid, Spain, found that male rodents become insulin resistant and obese, when they are fed a high fat diet (30% fat, in other words high fat + high carb), the female rodents, on the other hand, switch to a 'fat burning mode' or as the scientists state they ...

  "[...] counteract excessive fat intake by improving their ability to use lipid fuels, which limits adiposity and maintains insulin sensitivity." (Estrany. 2012)

  Just as in a previous study neither the male nor the female rats showed the usual symptoms of hyperphagia (overeating), and the body weight gains in all groups were normal.
  
  "Normal" body weight gain and insulin resistance? That should actually ring a bell. Correct! "Normal-weigh obesity" or being skinny fat! And in fact, the underlying reason for Estrany et al.'s observations seems to be that the diet increased the inflammation in the male rats, while it did not do so in the female rodents. What exactly it was that made the difference here, will yet still have to be elucidated, but my best bet is estrogen, which is by no means just the bad guy as which it is portrayed within the fitness community.
• Molecule in false black pepper aka Embelia ribes turns out to be natural GLUT-4 + PI3K/AKT activator, PPAR-gamma agonist and anti-diabetic. What's particularly exciting about the embelin the active ingredient in Embelia ribes Burm, a member of the species Myrsinaceae, which is widely distributed in India and and has a documented history of being used as a diabetes 'medication' in the Ayurvedian traditional medicine system, is that it increases insulin sensitivity without predisposing to further weight gain and adiposity, as the standard Thiazolidinediones (TZDs) such as rosiglitazone and pioglitazone do.
  
  Using the same streptozotocin (STZ) induced rodent model of type II diabetes you have encountered in numerous other studies that have been covered here at the SuppVersity a group of researchers from the Loyola College in Chennai and the University of Madras (Gandhi. 2012), have found that 50mg/kg body weight of embelin that had been extracted from fresh E. ribes fruits by drying and eluting the raw material in benzene...
  

  • 

    Figure 3: Effects of embelin vs. rosiglitazone on insulin levels and rel. expression of antioxidant enzyme activity (Gandhi. 2012)

    reduced body weight gain, blood glucose and plasma insulin in treated diabetic rats,
  • modulated the altered lipid profiles and antioxidant enzymes,
  • exerted cytoprotective effects on the β-cells of the pancreas,
     
  • increased the PPARγ expression in epididymal adipose tissue,
  • inhibited adipogenic activity (=fat gain),
  • mildly activated PPARγ levels in the liver and skeletal muscle, and
     
  • regulated insulin mediated glucose uptake in epididymal adipose tissue through translocation and activation of GLUT4 in PI3K/p-Akt signaling cascade.
  And best of all, contrary to most natural anti-diabetes, these effects were no mere downstream effects of the antioxidant effects of Embelin, but can be ascribed to direct receptor binding: The active ingredient from false black pepper does not only show a high binding affinity for PPARγ, in the experiments Gandhi et al. condcted, it also had stable binding affinities for the active sites of PI3K, p-Akt and GLUT.
  
  
  Embelia ribes in Ayurveda The false black pepper is no newcomer to the scene of natural medicine / health supplements. Embelia ribes has been used in Ayruveda for centuries as an appetiser, laxative, carminative, anti tape-worm cure, to ameliorate / protect from snake bites, against skin deseases, bronchitis and urinary discharges, versus dyspepsia, liver ailments, jaundice, and glatulence.
  The results certainly are exciting, specifically in view of the fact that emeblin could be interesting not just for type II diabetics and individuals with insulin resistance, but also for lean mean women who are looking for a tool that would optimize their insulin sensitivity without the pro-obesogenic effects that render most other "insulin sensitizer" at best useless. And if we assume that similar effects on PI3K and p-AKT do occur in skeletal muscle, as well (this was unfortunately not measured in the study at hand), embelin could even help you build some muscle. Just as its general efficacy in human beings the last hypothesis does of course still require experimental verification... but don't worry, you know that I will keep you posted on any future studies!

That's it! What? You want more? But that's what a quickie is supposed to be it's the frequency that makes it worthwile not the length... ah, I guess I better wish everyone a happy Sunday before I am starting to go into further details here ;-)


References:

• Cirillo T, Fasano E, Castaldi E, Montuori P, Amodio Cocchieri R. Children's exposure to Di(2-ethylhexyl)phthalate and dibutylphthalate plasticizers from school meals. J Agric Food Chem. 2011 Oct 12;59(19):10532-8.
• DEHP Information Center. DEHP Fact Sheet (revised). June 14, 2012. <  www.dehp-facts.com/upload/documents/webpage/ECPI%20-%20factsheet%20DEHP%20revised%20-%20140609.pdf > retrieved on Nov. 03, 2012.
• Estrany ME, Proenza AM, Gianotti M, Lladó I. High-fat diet feeding induces sex-dependent changes in inflammatory and insulin sensitivity profiles of rat adipose tissue. Cell Biochem Funct. 2012 Oct 30.
• Fierens T, Vanermen G, Van Holderbeke M, De Henauw S, Sioen I. Effect of cooking at home on the levels of eight phthalates in foods. Food Chem Toxicol. 2012 Sep 14;50(12):4428-4435.
• Ghaisas MM, Ahire YS, Dandawate PR, Gandhi SP, Mule M. Effects of Combination of Thiazolidinediones with Melatonin in Dexamethasone-induced Insulin Resistance in Mice. Indian J Pharm Sci. 2011 Nov;73(6):601-7.
• Gandhi GR, Stalin A, Balakrishna K, Ignacimuthu S, Paulraj MG, Vishal R. Insulin sensitization via partial agonism of PPARγ and glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway by embelin in type 2 diabetic rats. Biochim Biophys Acta. 2012 Oct 24. doi:pii: S0304-4165(12)00302-9.
• Hao C, Cheng X, Xia H, Ma X. The endocrine disruptor mono-(2-ethylhexyl) phthalate promotes adipocyte differentiation and induces obesity in mice. Bioscience Reports. 2012; 32:619–629.
• Kaye WH, Berrettini W, Gwirtsman H, George DT. Altered cerebrospinal fluid neuropeptide Y and peptide YY immunoreactivity in anorexia and bulimia nervosa. Arch Gen Psychiatry. 1990 Jun;47(6):548-56.
• Li N, Liu T, Zhou L, He J, Ye L. Di-(2-ethylhcxyl) phthalate reduces progesterone levels and induces apoptosis of ovarian granulosa cell in adult female ICR mice. Environ Toxicol Pharmacol. 2012 Sep 1
• Li XW, Liang Y, Su Y, Deng H, Li XH, Guo J, Lian QQ, Ge RS. Adverse effects of di-(2-ethylhexyl) phthalate on Leydig cell regeneration in the adult rat testis. Toxicol Lett. 2012 Oct 11. 
• Martine B, Marie-Jeanne T, Cendrine D, Fabrice A, Marc C. Assessment of Adult Human Exposure to Phthalate Esters in the Urban Centre of Paris (France). Bull Environ Contam Toxicol. 2012 Oct 23.
• Magistrelli A, Chezem JC. Effect of ground cinnamon on postprandial blood glucose concentration in normal-weight and obese adults. J Acad Nutr Diet. 2012 Nov;112(11):1806-9. 
• Monfort N, Ventura R, Balcells G, Segura J. Determination of five di-(2-ethylhexyl)phthalate metabolites in urine by UPLC-MS/MS, markers of blood transfusion misuse in sports. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Sep 21. doi:pii: S1570-0232(12)00560-0.
• Rajesh P, Sathish S, Srinivasan C, Selvaraj J, Balasubramanian K. Exposure to diethyl hexyl phthalate (DEHP) to adult male rat is associated with insulin resistance in adipose tisssue: Protective role of antioxidant vitamins (C & E). J Cell Biochem. 2012 Sep 18.
• Ruohonen ST, Vähätalo LH, Savontaus E. Diet-induced obesity in mice overexpressing neuropeptide y in noradrenergic neurons. Int J Pept. 2012;2012:452524. doi: 10.1155/2012/452524. Epub 2012 Oct 18. 
• Simha V, Mahmood M, Ansari M, Spellman CW, Shah P. Effect of Vitamin D Replacement on Insulin Sensitivity in Subjects With Vitamin D Deficiency. J Investig Med. 2012 Oct 29.
• Wu P, Yang D, Zhang L, Shen X, Pan X, Wang L, Zhang J, Tan Y, Feng L, Ying Y. Simultaneous determination of 17 phthalate esters in edible vegetable oils by GC-MS with silica/PSA-mixed solid-phase extraction. J Sep Sci. 2012 Nov;35(21):2932-9.
• Xu Y, Liu Z, Park J, Clausen PA, Benning JL, Little JC. Measuring and Predicting the Emission Rate of Phthalate Plasticizer from Vinyl Flooring in a Specially-Designed Chamber. Environ Sci Technol. 2012 Oct 23.

Ceylon Cinnamon as Metformin Alternative? Combined Rodent + Human Study Yields Promising Results, But Do You Actually Need Another Expensive Carb Blocker?

What you need is original Ceylon Cinnamon, not the cheap Cassia Cinnamon, which is often loaded with potentially toxic coumarin.

The mechanism by which cinnamon and metformin work may be completely different, the net outcome, on the other hand, is very similar: Both reduce the blood sugar excursions in insulin resistant individuals.

In contrast to metformin, of which I can only repeat that it is pointless to use it (unless you want the AMPK overexpression to leave you hypoglycemic and hungry all day), if you are lean and healthy, cinnamon may yet also offer benefits to normal-weight, normo-glycemic individuals like the 18 subjects (11 men, 7 women) in a recent study from Dialpha SAS in France (Beejmohun. 2014).

You can learn more about protein intake at the SuppVersity

Maintain and Improve Your Insulin Sens.

5 Tips to Improve Your Insulin Sensitivity

ALA, Gaba, Taurine & Co to Improve IS

Berberine, Banaba & Co to Improve IS

Curcumin, Licorice & Co to Improve IS

Lemon Juice, Res. Starch, Coffee to Improve IS

The combined rodent + human study, Beejmohun et al. conducted is, to the knowledge of its authors, the first study to check the acute effect of cinnamon extracts (specifically a hydro-alcoholic Ceylon
cinnamon extract) in a randomized, placebo-controlled, cross-over clinical trial in healthy subjects.

Figure 1: Alpha-amylase inhibitory effect of CCE.Values represent mean of triplicate measures (Beejmohun. 2014).

The first thing the scientists did was to assess the in vitro inhibition of the pancreatic α-amylase enzyme activity, or, as the bros would say: Its carb-blocker quality (if you block α-amylase, you block the breakdown of complex carbohydrates).

As you can see in Figure 1 the "carb blocker" activity of the Ceylon Cinnamon extract was similar to that of acarbose, an anti-diabetic drug used to treat type 2 diabetes mellitus and, in some countries, prediabetes (in the US it's sold by Bayer as Precose in Europe and China as Glucobay). As you probably already guessed, acarbose was specifically designed to inhibit enzymes (glycoside hydrolases) needed to digest carbohydrates - enzymes like the alpha-amylase enzyme.

The Type of Cyelon Cinnamon Extract Matters: The scientists compared the effects of their hydro-alcoholic to regular aqueous cinnamon extracts and found the hydro-alcoholic to be 8% more potent. Keep that and the fact that plain cinnamon from the supermarket will in 99% not be Ceylon cinnamon in mind, when you shop for natural blood glucose managers. Eventually, the cheaper Cassia Cinnamon is probably not just going to work less effectively, it may also push you across the maximal tolerable intake level for coumarin (0.1 mg/day/kg of body weight; 7 mg/day for a person of 70 kg), of which the Ceylon Cinnamon extract (CEE) in the study at hand containes less than 0.2 mg per serving and thus only 2.8% of the tolerable intake level.

It is thus not very surprising that the rodent study revealed that he quick and significant rise in glycemia (73.5 ± 2.8 mg/dL above the pre-STT value (T0)) that occurred 30 min after the starch load with 1.5 g/kg of body weight of starch in rats after an overnight fast was reduced by 20.4%, when the rodents received an additional 50 mg/kg (650mg for a human being) of the Ceylon Cinnammon extract with their starch load.

Figure 2: There is a logarithmic dose response effect w/ increasing dosages of CEE (Beejmohun. 2014).

As Beejmohun et al. point out, the beneficial "effect is particularly significant during the peak of glycemia at 30 min (Student’s t-test P < 0.001)." (Beejmohun. 2014). And as the data in Figure 2 shows, it increased logarithmically with increasing dosages (this means more is only a little better and more than 150mg/kg or ~1.8g for a human being are probably useless due to the ceiling effect).

We are interested in human studies, right?

So, let's leave the rodent data an take a look at the blood sugar levels of the 18 human subjects, who consumed 1g of the extract before a standardized meal.

Figure 3: Effect of 1 g CCE on blood glucose and insulin response after a standard meal in humans (Beejmohun. 2014).

I assume I don't have to explain the data in Figure 3. What we see is the expected reduction in blood sugar response of which previous studies suggest that it is mostly produced by a reduction in glucose uptake from the digestive tract (Hlebowicz. 2007) and further promoted - at least in insulin resistant individuals (Kim. 2006) - by minor increases in cellular glucose uptake.

One thing that we may want to keep in mind, though, is the fact that the ameliorative effect on the blood sugar response was more pronounced in the first 60 minutes after the meal (-21.2% vs. -14.8% area under the curve). An observation that should remind you of the fact that the temporary inhibition of alpha-amylase and thus the slower digestion of carbohydrates may influence the glycemia, but not (necessarily) the total energy, let alone the total amount of sugar your tummy is going to squeeze out of the digesta in the hours after your meal.

There are dozens of supplements which can help you to improve your insulin sensitivity. Many have more promising mechanisms of action than the overhyped carbohydrate blocker cinnamon | more.

Bottom line: I am still 100% not excited about the use of Cinnamon in healthy individuals. For someone with blood sugar issues, on the other hand, it may be worth to postpone the influx of sugar into the system by using 1g of a hydro-alcoholic Ceylon Cinnamon extract.

But let's be honest: Wouldn't it be better to change your diet? People who use carb or fat blockers always remind me of that idiot who wears a helmet, when crashing his head against a wall infinitely - So, why don't you simply stop eating tons of pasta and rearrange the macro composition of your meals from high to moderate carb, if you don't work out and can't afford eating carbs | Comment on Facebook.

References:

• Beejmohun, Vickram, et al. "Acute effect of Ceylon cinnamon extract on postprandial glycemia: alpha-amylase inhibition, starch tolerance test in rats, and randomized crossover clinical trial in healthy volunteers." BMC Complementary and Alternative Medicine 14.1 (2014): 351.
• Hlebowicz, Joanna, et al. "Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety in healthy subjects." The American journal of clinical nutrition 85.6 (2007): 1552-1556.
• Kim, W., et al. "Naphthalenemethyl ester derivative of dihydroxyhydrocinnamic acid, a component of cin-namon, increases glucose disposal by enhancing translocation of glucose transporter 4." Diabetologia 49.10 (2006): 2437-2448.

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.

Science Round-Up Seconds: Does the Paleo Diet Ruin Your Lipid Profile? Plus: Liver Health & Hepatitis - Milk Thistle & Beyond. Libido Boosters & Real PDE-5 Inhibitors. "Fake" Cinnamon, Coumarin, Bloodthinning & Carcinogenic Cereals.

Is the Paleo Diet unhealthy for healthy individuals? A recent thesis would suggest just that. Learn more about and make up your mind based on the last installment of the Science Round-Up and today's Seconds (img informedhealth.com.au)

I hope you did not miss that the SuppVersity Science Round-Up will as of now always be starting early(-ier) at 12PM EST. If so, don't worry, you can still download the show and listen to Carl and me talking about the things you may be missing, the ones you get extra and those you would rather not have in your supplements and foods. Let's take silymarin, for example, as you have learned on the show, not all "liver assist", "liver clense" or "liver health" products are created equal. Most intriguingly, their ability to scavenge free radicals, as measured by the trolox assay, is not singularly dependent on the actual silymarin content, but will - as the data from the study Anthony et al. conducted (Anthony. 2013) - vary largely, depending on where the milk thistle was grown, how it was processed and thus what else, aside from the purportedly active ingredient is in it.

There is more to natural products than a single active ingredient

If you will, the "there is more to it" was a golden thread that ran through the whole show, but before we follow it up to the next topic, I want to provide you at least an excerpt from the actual data Anthony et al. produced.

Table 1: Selected products tested in the study ordered by their anti-oxidant activity in the TROLOX essay; products with highest TROLOX and anti hepatitis C viral activity highlighted in green and violet, respectively (Anthony. 2013)

As you can see my selection of the 45 products, the scientists bought and tested, reflects what you have already heard on the show: The silymarin content varies largely. In essence, the actual silymarin content may yet not even be that important. If you focus solely on their TROLOX equivalents (TROLOX is a vitamin E like antioxidant and it is used to quantify the anti-oxidant activity in a standardized way - more or less like the meter is used to quantify the length of an object or seconds are used as a standard timespans are expressed in).

More about Liv-52: Actually, the Himalaya(R) product is one of the few OTC supplements with not just one, but more than 20 studies to back its hepatoproctective and antioxidant effects. One thing to keep in min about the research is though that it was - despite being mostly published in peer-reviewed journal - in large parts conducted by scientists who work either for or with the company. As I've pointed out previously, this does not mean that the data is flawed, but it puts observations such as the improved glucose uptake (213%) , the 50% reduction in triglyceride content (anti-NAFLD effect), the 790% increase in glutathione, as well as the decreased TNF-α (-51%) and IL-8 (-550%) and concomitant -65% and -69% reductions of lipid oxidation and DNA fragmentation, respectively, Vidyashankar et al. observed in a recent in-vitro study somewhat into perspective (Vidyashankar. 2012).

If you are looking for the most potent among the readily available products in my selection the most potent "liver protectant" would actually be the PED user's first choice Liv-52, which does not even contain silymarin but is based on an undisclosed amount of  capers (Capparis spinosa), wild chicory (Cichorium intybus), arjuna (Terminalia arjuna), negro coffee (Cassia occidentalis), yarrow (Achillea millefolium) and tamarisk (Tamarixgallica). Bio Silymarin by Advanced Beta Glucon Therapy, on the other hand, is a close second with an almost identical TROLOX value (9.4 vs. 9.5 for Liv-52), is based on silymarin; plus, it exerts 77% more pronounced hepatitis C virus (HCV) antiviral activity than the Himalaya product which lists "viral hepatitis" as the #1 indication on the corresponding website.

As far as these anti-HCV effects, which were standardized against the results the scientists observed in cultures that were treated with 100 U/mL interferon-α, are concerned another Source Natural's Silymarin Plus, emerged as the most potent product. With the "plus" signaling the addition of choline, inositol, vitamin C+E, this observation confirms that antioxidant activity and anti-viral activity are two pairs of shoes - even when the active ingredient (silymarin) is the same.

Apropos active ingredient

You are yet by no means at the mercy of milk thistle and silymarin, when you want to protect your liver from harm. Spices like

• Tumeric (curcumin)
• Coriander

• Garlic
• Red chili
• Black pepper

bust also coffee and green tea, and fruits and vegetables such as

• carrots
• ivy guard
• sweet corn
• soy (for the glycine in it)

• grapes
• custard apples
• Indian gooseberries
• pomegrenade
• sea buckthorn

have potent anti-oxidant and antiproliferative activities (Shukla. 2013)

OTC libido boosters - more than just an alternative

Now that we are talking about alternatives, let's get straight to the next one: The "alternative" to viagra, cialis & co. Honestly, I would hope that you will never have to use one of these (I suggest you take a peak at yesterday's post "The '20 / 30 Principle' Sheds 15% Body Fat in 6 Months, Boosts Testosterone & Sexual Performance in Overweight Men. Plus: Six Signs You're Doing Too Much, Already."; read more), but in the unfortunate case you do, you may be surprised how effective the majority of them actually is.

Figure 1: Categorial breakdown of the adulterated majority of the 91 products from the Campbell study (Campbell. 2013)

A brief glance at the data in figure 2 does yet suffice to see that this is not another case of the "nature knows best principle", but simply a consequence of the fact that the majority of these products do contain either sildenafil and/or taldalfil or some sort of molecular cousin ("analogs" in figure 2). Moreover, in 18 out of these products the dosage was >110% of what would be legit on a per serving base for the prescription varieties (I suspect this is 20mg).

Also mentioned in this context: Saw palmetto is a PDE-5 inhibitor (cf. Yang. 2013). Although the evidence is from a rabbit study, it's pretty likely that there will be at least some discernible effects of saw palmetto on PDE-5 activity an iNOS activity in the human corpus cavernosum, as well.

Coumarin: Carcinogenic & blood thinning cereals

Table 2: Coumarin content in mg/100g of the samples from the Wang study

As unfortunate as it may seem, the chance that the cinnamon you consume with pre-packaged food is "real" (=verum) and from the inner bark of Cinnamomum verum are close to zero. Since this is however the only variety, where you can be almost 100% sure that you don't consume blood thinning and pro-carcinogenic coumarin, it does actually not come as a surprise that cinnamon apple sauce or a cinammon roll bought from the local supermarket contain 0.64 and 2.1mg of this agent on a per serving basis.

If you take a closer look at the rest of the data Wang et al. collected for their latest study (Table 2; cf. Wang. 2013), you may be surprised to see that regular bread, generally unsuspicious oats and purportedly healthy granola bars contain coumarin in amounts that will have you easily surpass the daily uptake limit of 0.1 mg/kg body weight, which was established by the European Food Safety Authority (EFSA) right after it became clear that coumarin is a potential carcinogen... *yamyoll*

Nedless to say that the consumption of respective supplements, which are currently heavily marketed as healthy anti-diabesity agents, could do more harm then good, when the producers play it cheap and put the next best "Cinnamomum XY" they can get their hands on into the caps.

Neither viagra nor cinnamon caps are "paleo", yet still...

E. Trexler titled his recently published thesis "Paleolithic Diet is Associated With Unfavorable Changes to Blood Lipids in Healthy Subjects", which would suggest that the paleo diet is similarly unhealthy as the consumption of "fake", coumarin-loaden cinnamon or high amounts of isolated cholorogenic acid (story is discussed in detail in the podcast; cf. Mubarak. 2013).

Figure 2: Lipid profile (left; values expressed in % of reference levels), fitness and body fat level (right) before and after the Paleo + Crossfit interention (calculated based on Traxel. 2013)

If you take a closer look at the abstract and the actual "side effects" (figure 2), the 10-weeks of paleo dieting + CrossFit-based, high-intensity circuit training exercise program had on the body composition and fitness levels, I personally cannot but ask the following question:

 "What is the significance of the elevations in LDL and minor reductions in HDL in a scenario that produces exactly what has just been shown to be at the heart of the 'Obesity Paradox' and lipid values that are still within the ever-narrowing 'normal' or 'optimal' range?"

I'll leave it up to you to answer this question and decide whether it can really be so bad to rid yourself of all modern, processed foods including any form of processed sugar, soft drinks, and coffees, while fueling your life and workout related energy by increasing your consumption of lean meat, fish, eggs, nuts, fruit, and vegetables. Have a nice weekend!

References:

• Anthony K, Subramanya G, Uprichard S, Hammouda F, Saleh M. Antioxidant and Anti-Hepatitis C Viral Activities of Commercial Milk Thistle Food Supplements. Antioxidants. 2013; 2(1):23-36.
• Campbell N, Clark JP, Stecher VJ, Thomas JW, Callanan AC, Donnelly BF, Goldstein I, Kaminetsky JC. Adulteration of Purported Herbal and Natural Sexual Performance Enhancement Dietary Supplements with Synthetic Phosphodiesterase Type 5 Inhibitors. J Sex Med. 2013 May 1. 
• Mubarak A, Hodgson JM, Considine MJ, Croft KD, Matthews VB. Supplementation of a high-fat diet with chlorogenic Acid is associated with insulin resistance and hepatic lipid accumulation in mice. J Agric Food Chem. 2013 May 8;61(18):4371-8. 
• Shukla SK, Kumar V. Bioactive Foods and Supplements for Protection against Liver Disease. In: Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease. Elsevier. 2013. 
• Trexler, E. Paleolithic Diet is Associated With Unfavorable Changes to Blood Lipids in Healthy Subjects Honors Research Thesis. Ohio State Univeristy. May 2013.
• Vidyashankar S, Sharath Kumar LM, Barooah V, Sandeep Varma R, Nandakumar KS, Patki PS. Liv.52 up-regulates cellular antioxidants and increase glucose uptake to circumvent oleic acid induced hepatic steatosis in HepG2 cells. Phytomedicine. 2012 Oct 15;19(13):1156-65.
• Yang S, Chen C, Li Y, Ren Z, Zhang Y, Wu G, Wang H, Hu Z, Yao M. Saw Palmetto Extract Enhances Erectile Responses by Inhibition of Phosphodiesterase 5 Activity and Increase in Inducible Nitric Oxide Synthase Messenger Ribonucleic Acid Expression in Rat and Rabbit Corpus Cavernosum. Urology. 2013 Apr 23. doi:pii: S0090-4295(13)00169-6.