Ask Dr. Andro: Are Vitamin Supplements Bad For Me (1/2)? The "wrong" Vitamin E Supplements Increase Cancer Risk.

Figure 1: This is where you, my American friends (and most Europeans), should and would get your "E's" from - it's called "food" (Eitenmiller. 2004)

With the recent publication of two studies on increased all-cause mortality in older women (Bjelacovic. 2011; Mursu. 2011) who took multivitamins (+2.4%), vitamin B6 (+4.1%), folic acid (+5.9%), iron (+3.4%), magnsium (+3.6%), zinc (+3.0%), and the "killer" copper (+18%) and increased risk of prostate cancer due to selenium and/or vitamin E supplements (Klein. 2011) on a regular basis and the huge media attention these studies,

• "Certain Dietary Supplements Associated With Increased Risk of Death in Older Women, Study Suggests"
• "Vitamin E Supplement May Increase Prostate Cancer Risk, National U.S. Study Finds"

have received, I got interested in taking a closer look at what I would usually have discarded as epidemiological guesswork and scare tactics, anyway.

How can a vitamin be bad for you? It's supposed to be a vital nutrient, goddammit!  

In that, I want to start with the 2nd of the two studies, i.e. the one on Vitamin E, which also happens to be a "true" Ask Dr. Andro question. After all, Steven Acerra posted a whole bunch of related questions on my Facebook page (remember you can always send in questions you want to have answered in this column!)

Image 1: Conflicts of interest, as declared in the paper by Klein et al.

Are medical studies "objective"? Being a scientist (in a whole different area of research, though), myself, I am well aware that financing expensive cutting edge science with the meager support from national agencies is impossible, these days. Therefore, I refuse any rash prejudgements based on the openly stated potential conflicts of interest (cf. image 1), as Steven put them forward in a follow-up comment on my facebook page. If you want to blame someone, blame the influential editors of the large journals, including the JAMA, where Klein's paper was published. Their acceptance of a paper determines whether a study appears on the SuppVersity, "only", or is taken up by a journalist from a major popular scientific magazine or, as in this case, even the Health Podcast of Time Magazine.

Other than Steven suspected, the study by Klein et al. that was published in the latest issue of JAMA (the Journal of the American Medical Association which is not particularly well know for being independent of the pharma lobby, cf. red box ;-) - despite its size - actually is a "controlled" trial... Well, as controlled as a study with 34 887 men who were randomly assigned to receive selenium (n= 8752), vitamin E (n=8737), vitamin E + selenium (n=8702) or placebo (n=8696), can be. It is part of, or  I should say, the final outcome of the so called SELECT trial, a large scale intervention that was conducted in the United States, Canada, and Puerto Rico. Data acquisition started on August 22, 2001 and ended three months ago, on July 5, 2011. The fact that the study is over is good news for all participants, because, as the bold headlines would have it, all treatments increased the participants' risk to develop cancer. Yet, what mainstream media didn't tell you is that (I quote directly from the detailed results in the paper; Klein. 2011):

The rate of prostate cancer detection was greater in all treatment groups when compared with placebo* but was statistically significant only in the vitamin E alone group. After adjustment for the marginal effects of vitamin E and selenium, the interaction between vitamin E and selenium was statistically significant (P=.02), indicating no increased risk of prostate cancer when vitamin E and selenium were taken together. The risk of Gleason 7 or greater disease was higher for all 3 interventions [vitamin E + 16%; selenium +21%; combination: +23%] but did not reach statistical significance for any group.

* I suspect this is probably about as far as most journalists read - if they even had the fulltext of the study, when they wrote their sensational and fearmongerish articles

If you compare the real findings to what you may have read in the course of the last week, it is quite obvious that half of the media reports got the results completely wrong. A quarter of the reporters obviously did not know the meaning and importance of "statistical significance" and the lousy rest does not care about information, anyway, as long as a headline could potentially increase sales or pageviews, it makes it into the magazine or onto the website.

No matter what the press says: You better know your vitamins E before taking the wrong one

Figure 2: Natural RRR alpha-tocopherol and synthetic SRR alpha tocopherol which is one of the isomers in the -50% less potent all-rac-alpha tocopherol, which is the "vitamin E" the 34,887 men in the large scale trial conducted by Klein et al. have received at a dose of 400IU per day  (figure from Traber. 2011)

This leaves us with just one "unexpected" result to be explained, i.e. a statistically significant increase in cancer risk with 400IU of supplemental "vitamin E" per day. In case you've noticed the quotation-marks before and after vitamin E, in the previous sentence, you already know where this is heading. After all, you would assume that the scientists would use the most potent weapons from their arsenal in their battle against prostate cancer - wouldn't you? Trial "S0000 Selenium and Vitamin E in Preventing Prostate Cancer" (clinical trials identifier: NCT00006392) sponsored by the Southwest Oncology Group, however, relied on the cheap all-rac-alpha-tocopheryl acetate of which Max K. Horwitt had shown back in 1980, already, that "all-rac-alpha-tocopheryl acetate may have no more than half the biological potency of d-alpha-tocopheryl acetate" (Horwitt. 1980). About, 19 years later Horwitt, then over 90 years old (!), was still fighting a fight against the medical establishment who maintained that the cheap synthetic form of vitamin E would have at least a 73.5% the activity of the naturally occurring form. In a letter to the editors of the American Journal of Clinical Nutrition he writes (Horwitt. 1999):

Now in my 90th y, I doubt whether I will ever see the proper correction made in the official values of the tocopherols. Having introduced the term equivalent as used by committees of dietary allowance, I prefer that this designation be used to describe the potency of the tocopherols. In the recommended dietary allowances, l mg RRR-a-tocopherol has a biological value of 1.0 a-tocopherol equivalents. Accordingly, in modified US Pharmacopoeia vitamin E units, RRR-a-tocopherol should have a value of 1.0, all-rac-a-tocopherol a value of 0.5, RRR-a-tocopheryl acetate a value of 0.91, and all-rac-a-tocopheryl acetate a value of 0.455.

Meanwhile, the USDA has changed their calculations in the USDA National Nutrient Database for Standard Reference, according to release #20 (USDA. 2008), the all-rac-alpha-tocopheryl acetate 
is now officially classified as -55% less potent than natural tocopherol. Now, the chance to pick the worst of the four vitamin E's was 25% and *bang* Klein et al. nailed it. Can this be coincidence - I guess if it was you could call it "bad luck".

Supplementation may offset the natural balance by exchanging natural gamma tocopherols for cheap synthetic alpha-tocopherols

"Bad luck", also because supplementation with high doses of alpha-tocopherol has been shown to hinder "normal" incorporation of gamma-tocopherols into VLDL particles, to increase hepatic clearance of gamma-tocopherols and, in the end, to deplete plasma gamma-tocopherol levels, as well (Jiang. 2011). Now, if you have a less potent type of vitamin E, you obviously have to supplement more (to achieve a potency equivalent to 400IU you obviously need +55% more all-rac than natural tocopherol!)... but does that really matter? Oh yes it does! As gamma tocopherol and not alpha-tocopherol is "the vitamin E" which inhibits cyclooxygenase activity and, thus, possess heart-healthy anti-inflammatory properties. No wonder that Jiang et al. report in a 2001 review that...

1. plasma gamma-tocopherol concentrations are inversely associated with increased morbidity and mortality due to CVD. 
2. serum concentrations of  gamma-tocopherol, but not of alpha-tocopherol, were lower in CVD patients than in healthy control subjects. 
3. in a concomitant cross-sectional study of Swedish and Lithuanian middle-aged men,  plasma gamma-tocopherol concentrations were twice as high in the Swedish men, but that the Swedish men had a 25% lower incidence of CVD-related mortality. In contrast, this inverse correlation was not observed with alpha-toco-pherol. 

... and the list goes on. Now, you will probably say "But Dr. Andro, those men got cancer from vitamin E, not cardiovascular disease!" and, as always, you are right, BUT the evidence that gamma- not alpha-tocopherol (or at least a "natural" mix of both) is cancer protective is even more conclusive than the one on the CVD-protective effect of the former.

What are normal ratios of alpha- to gamma-tocopherol? While we hardly can say which ratios are optimal, we know that the "normal" ratio of serum alpha- to gamma-tocopherol levels for Americans who do not take any supplements is 5:1 (alpha:gamma). According to Chopra and Baghavan his ratio further increases to greater than 20-fold in people taking vitamin E supplements (Chopra. 1999).

High gamma-tocopherol levels reduce risk of prostate cancer by -500% [no typo!]

In 2000 Helzlsouer et al. analyzed the blood of 10 456 male residents of Washington County and found that (Helzlsouer. 2000)...

For gamma-tocopherol, men in the highest fifth of the distribution had a fivefold reduction in the risk of devel-oping prostate cancer than men in the lowest fifth (Ptrend = .002).

With p = 0.002 the chance that this was "coincidence" is exactly  125x smaller (0.2%) than Klein et al.'s chance (25%) to pick the worst alpha-tocopherol variety there is for their large scale intervention. And while this is only an epidemiological study, we have more than enough in-vitro and animal data to confirm the anti-cancer effect of gamma-tocopherol:

Prostate cancer:
• Jiang. 2004:  "... gammaT and mixed vitamin E forms induce cell death by interrupting the de novo sphingolipid pathway in a prostate cancer cell line"
• Campbell. 2009: Growth arrest (40%) in PC-3 prostate cancer cells through the regulation of fatty acid metabolism and PPAR gamma mRNA and protein upregulation was achieved with gamma-tocopherol within 6 h.
• Jiang. 2011: Sphingolipid promoting effects of gamma-tocopherol induces apoptosis and autophagy in prostate cancer cells

Colon cancer:
• Campbell 2006: In-vitro study on human colon-cancer cell lines; "treatment with RRR-gamma-tocopherol resulted in significant cell death for all cancer cell lines tested, while RRR-alpha-tocopherol did not [...] RRR-gamma-tocopherol may aid chemotherapy without toxic effects to normal cells demonstrated by most chemotherapeutic agents"

Other cancers:
• Yu. 2009: Mouse model (human breast cancer) + in-vitro studies > "α-tocopherol not only failed to exhibit anticancer properties but it reduced anticancer actions of γ-tocopherol in vivo and γ-tocopherol and α-TEA in vitro."; what is important to note, though is that the all-trans-variety used in the Klein study did at least inhibit proliferation and increase apoptosis (programmed cell death) in vivo.
• Yang. 2010: "[I]nhibition of inflammation as well as of cancer formation and growth in the lung and colon in animal models" by tocopherol supplement with  57% gamma-T
• Ju. 2010a: "In cell culture, the growth of H1299 cells [lung cancer] was inhibited by tocopherols with their effectiveness following the order of delta-T > gamma-TmT > gamma-T, whereas alpha-T was not effective."
• Ju. 2010b: "... recent results have demonstrated that a gamma-tocopherol-rich mixture of tocopherols inhibits colon, prostate, mammary and lung tumorigenesis in animal models, suggesting that this mixture may have a high potential for applications in the prevention of human cancer"

And directly referring to the "partly negative" outcomes of studies into the potentially beneficial effects of "vitamin E" supplements (which were almost exclusively conducted with alpha-tocepherol-only products), Reiter el al. wrote in a 2009 review (Reiter. 2009):

As pointed out in this review, more and more evidence indicates that γT and other vitamin E forms than αT have unique bioactivities that may be important for maintaining and improving human health (Dietrich et al. 2006; Jiang et al. 2001). For example, γT is a stronger inhibitor of cyclooxygenase and possibly lipoxygenase than αT. Furthermore, γT traps reactive nitrogen species more efficiently than αT. Some of these in vitro effects are slowly being confirmed in vivo, but more studies are needed here. In addition, γT but not αT exhibits anti-proliferative and pro-apoptotic effects on cancer but not normal epithelial cells (Jiang et al, 2004). [...] Thus, despite the undisputed anti-inflammatory effects of α- and γT, the recent large-scale interventional studies aimed at reducing diseases associated with chronic inflammation have been disappointing, but may be explained by the complex interaction of the different vitamin E forms with inflammatory signaling, xenobiotic transformation, and as yet undefined pathways.

I think I do not have to point out that with what we know today about the necessary synergy of the vitamins E (including the tocotrienols, which I deliberately left out, in order not to overcomplicate things) and the results of a 2003 study by Huang (Huang. 2003), which showed that supplementation with 400IU of RRR-alpha-tocopheryl acetate (remember due to the fact that this is the more potent variety, the actual dose in µg was -50% lower than in the Klein study)

reduced serum gamma-tocopherol concentrations by a median change of -58% [95% CI = (51%, 66%), P < 0.0001], and reduced the number of individuals with detectable delta-tocopherol concentrations (P < 0.0001),

initiating a similar study as Klein et al. did 10 years ago, would border physical injury resulting from negligence, today. And although the use of isolated forms of vitamin E, which you will find in most of the cheap multivitamin tablets you can buy at the supermarket, could also be involved in the negative effect "certain dietary supplements" (including multivitamins) were reported to have on the health of "older women" in the 2nd study, I mentioned in the introduction, I will address this issue in an individual installment in a follow up to this post in the course of the next week. So stay tuned for more.

Creatine, DHT, Hair Loss & Prostate Cancer - Bro-Scientific Old Wives' Tales or Possible Side Effect? Plus: (Non-)Sense Creatine Loading, Exercise Induced 5-α Reduction & More

Poor guy! Must have taken too much creatine and treated his hair for muscle ;-) Ok, seriously, creatine may have helped a little that he was able to build this impressive physique, but the hair? Come on, seriously!?

If you have been around the bulletin boards of the fitness and bodybuilding community, I am pretty sure you will have heard about creatine induced increases in dehydrotestosterone (DHT). Probably you will also have had someone chime in who claimed that his hair started to fall out, when he started to use creatine supplements - right? Well, I guess in that case you will probably also remember how another guy chimed in and said: "Hold on does that mean that creatine will cause prostate cancer?"

Never heard something like that? I suggest you trust my word, then; and in case you want "scientific evidence" head over to www.pubmed.com and type in "creatine D" it will offer you "creatine DHT" as one of the typical search phrases people are looking for.

Cock-and-bull - right?

It is true that there is a study that supports the concept of increased DHT levels in athletes (20 collegiate rugby players to be precise) in response to 21 days of creatine supplementation. The athletes who participated in the said trial came from a Rugby Institute situated near Stellenbosch University in South Africa. None of the subjects had taken any supplements with their normal diet for 6 weeks before the trial in the course of which all had been randomized to one of the following groups:

• creatine: 25g creatine + 25g glucose for 7 days; 5g crea + 25g glucose for 14 days
• placebo: 50g glucose for 7 days; 30g glucose for 14 days
  

The subjects underwent standardized training, albeit for different player positions, during the whole study period. All subjects were residents at the institute and the ate the same food at the cafeteria. Moreover, all 20 were just coming back from a winter break and were "in similar condition as the start of the study and not fatigued from consecutive weeks of match play" (van der Merwe. 2009).

Instead of simply taking more you may rather want to "Super Charge Creatine W/ Baking Soda" | learn more

Creatine loading is neither necessary nor useful for the majority of athletes. Unless you have a meet close ahead there is no need to gobble down 25g+ doses of creatine - specifically not in one sitting. While the typical creatine supplementation protocol consists of a loading phase of 20 g creatine/d or 0.3 g creatine/kg/d that's followed by a 3-5 g/day (or 0.03g/kg) maintenance phase (Buford. 2007), it is also possible to use daily doses of ~3–6 g or between 0.03 to 0.1 g/kg per day (Willoughby. 2001; Hickner. 2010).

All subjects were lean (13-14% body fat and muscular 75kg muscle of 86-87kg total body weight) and thus way more representative of the average creatine guzzling gymrat than untrained average Joes whose beer bellies may well have messed up their endocrine system to an extend that could explain the DHT increases from 0.98 nmol/L to 1.53 nmol/L. The fact that the DHT levels in the control group did not change significantly in the course of the 7-day loading phase (in fact they dropped, but due to the high standard deviation the drop from 1.26 nmol/L to 1.09 nmol/L was non-significant), lends further support that the changes, the researchers observed must have been the result of the 25g of creatine the 10 subjects in the active arm of the trial had to swallow on during the first seven days of the study period.

Figure 1: Serum DHT levels total (left) and expressed relative to baseline levels in control group (right); data calculated based on van der Merwe et al. 2009

As you will probably already have read in-between the lines, I am not exactly impressed - let alone scared - by these results. Why? Well, the initial 56% increase in DHT was not only followed by a -10% decline during the maintenance phase, but this decline brought the DHT levels of the young men in the creatine group pretty close to where they had been in the placebo group at T0 (1.38nmol/L vs. 1.26 nmol/L for creatine vs. placebo, respectively).

The high DHT levels observed in the study at hand, were only midrange

If that does not comfort you, maybe it will help, if I tell you that the reference range for adult men ranges from 0.8-3.4 nmol/L (NHS Pathology. 2013 - please note that these reference ranges vary from lab to lab, in ng/dL the upper limit usually is 85ng/dL, which is 2.93nmol/L). Accordingly, the total DHT level of the subjects in the van der Merwe study did not even scratch the 50% mark on the reference range, when they maxed out at the end of the 7-day loading phase.

With a meager 9% difference to the baseline levels in the control group and a total DHT level of 1.38nmol/L in the "low DHT" zone of the reference range, I wouldn't say it is necessary (from a mere safety perspective) to investigate, as Green suggested it in a 2010 letter to the editor, whether the creatine supplement that has been used in the study may have been contaminated with androgenic compounds (Green. 2010). To answer the question about the why, i.e. "Why did the DHT levels in the creatine group go up, while those in the control group remained the same?",  it would yet in fact be nice to know if we were dealing with the side effects of androgenic compounds in the creatine supplement or the physiological effects of exercise, which has repeatedly been shown to be able to increase both intra-muscular and systemic DHT levels in men and rodent models (see the bottom line for selected references).

Want to learn how to modulate your DHT levels naturally? Rice, safflower, sorghum & Co. can help! learn more

In view of the fact that these increases are intensity dependent, but limited by the androgen suppressive effects of overtraining, The increased DHT levels may eventually have been a secondary response to increased training loads and the ameliorative effect creatine exerts on the androgen suppressive effects of overreaching (Volek. 2004).

And while I cannot tell you if this actually was the reason for the increase in DHT, I can tell you that the scientists assertion that what they observed was a "large increase in DHT rather than a marginal (possibly physiologically insignificant)"  (van de Merwe. 2009) is (at best) warranted if we look at the intra-group effect. In view of the broad "normal" range and the low baseline DHT levels in the creatine group, this relevance of this relative increase is yet more than questionable.

And the increasing DHT:Testosterone ratio?

Even at the risk of sounding like a smart ass, I do not want to forgot to mention that the "oh so dangerous" increase in DHT/T levels the scientists emphasize in their conclusion was found to be associated with a reduced risk of hair loss (-35% risk reduction) in 315 male subjects who were stratified with regard to age, race, and case-control (Demark-Wahnefried. 1997).

This and similar observations which have been made by Nomura et al. (1988), Hsing (1993) Shaneyfelt (2000) with respect to the non-significant impact of high(er) serum DHT levels on the occurance of prostate cancer and, more importantly, the increased risk that comes with higher T:DHT ratios, I seriously doubt that you have to be concerned about either your superb head of hair or your hitherto still pain and cancer free prostate when you are downing your daily dose of 3-5g creatine monohydrate.

No! Physical activity does not cause prostate cancer. I guess you will be surprised that I even address this issue, but due to several major shortcomings in previous prospective and epidemiological studies, you will easily find studies such as the one by Cerhan et al. which claims that men with a high physical activity have a 90%(!) increased risk of prostate cancer. What the abstract does not tell you, though, is that the researchers "forgot" to conduct a time lagged analysis to overcome the "I started to exercise yesterday, so I exercise vigorously every day" effect and did thus fail to measure consistent physical activity. Edward et al. did just that over a 4 year period and observed a -53% risk reduction for men aged 65+ to develop advanced prostate cancer.

Take home message: Despite being statistically relevant the absolute changes in the DHT levels van der Merwe et al. observed in the study at hand were neither physiologically relevant (DHT remained well within the reference range), nor totally inexplicable. Being afraid of hair loss, let alone prostate cancer, in response to the consumption of (untainted) creatine supplements is thus totally unwarranted.

And just in case you still want to freak out, I suggest you keep sitting on your ass for the rest of your life and refrain from ever playing football or any other sport again... why? Well according to Lupo et al., your DHT levels will double during a single football match. This and similar observations by Hawkins in a middle aged men on a 12-months aerobic exercise program (14.5% increase with moderate intensity cardio 6x per week; cf. Hawkins. 2008), as well as the results from Aizawa et al. who were able to demonstrate "that acute exercise enhances the local bioactive androgen metabolism in the skeletal muscle of both sexes" and not just men, do as bro-logic dictates suggest that any kind of physical activity will make you hair fall out and your prostate grow... now tell me how realistic is that?

References:

• Aizawa K, Iemitsu M, Maeda S, Otsuki T, Sato K, Ushida T, Mesaki N, Akimoto T. Acute exercise activates local bioactive androgen metabolism in skeletal muscle. Steroids. 2010 Mar;75(3):219-23.
• Buford T, Kreider R, Stout J, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J:International Society of Sports Nutrition position stand: creatine supplementation and exercise.J Int Soc Sports Nutr. 2007;4.
• Cerhan JR, Torner JC, Lynch CF, Rubenstein LM, Lemke JH, Cohen MB, Lubaroff DM, Wallace RB. Association of smoking, body mass, and physical activity with risk of prostate cancer in the Iowa 65+ Rural Health Study (United States). Cancer Causes Control. 1997 Mar;8(2):229-38. 
• Demark-Wahnefried W, Lesko SM, Conaway MR, Robertson CN, Clark RV, Lobaugh B,
  Mathias BJ, Strigo TS, Paulson DF. Serum androgens: associations with prostate
  cancer risk and hair patterning. J Androl. 1997 Sep-Oct;18(5):495-500. 
• Giovannucci EL, Liu Y, Leitzmann MF, Stampfer MJ, Willett WC. A prospective study of physical activity and incident and fatal prostate cancer. Arch Intern Med. 2005 May 9;165(9):1005-10.
• Hawkins VN, Foster-Schubert K, Chubak J, Sorensen B, Ulrich CM, Stancyzk FZ, Plymate S, Stanford J, White E, Potter JD, McTiernan A. Effect of exercise on serum sex hormones in men: a 12-month randomized clinical trial. Med Sci Sports Exerc. 2008 Feb;40(2):223-33
• Hickner R, Dyck D, Sklar J, Hatley H, Byrd P:Effect of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race.J Int Soc Sports Nutr 2010;7:26.
• Hsing AW, Comstock GW. Serological precursors of cancer: serum hormones and risk of subsequent prostate cancer. Cancer Epidemiol Biomarkers Prev. 1993 Jan-Feb;2(1):27-32.
• van der Merwe J, Brooks NE, Myburgh KH. Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players. Clin J Sport Med. 2009 Sep;19(5):399-404.
• Nomura A, Heilbrun LK, Stemmermann GN, Judd HL. Prediagnostic serum hormones and the risk of prostate cancer. Cancer Res. 1988 Jun 15;48(12):3515-7.
• Shaneyfelt T, Husein R, Bubley G, Mantzoros CS. Hormonal predictors of prostate cancer: a meta-analysis. J Clin Oncol. 2000 Feb;18(4):847-53.
• Van der Merwe J, Brooks NE, Myburgh KH. Three weeks of creatine monohydrate supplementation affects DHT to testosterone ratio in college-aged rugby players.Clin J Sports Med. 2009;19:399–404.
• Volek JS, Ratamess NA, Rubin MR, Gómez AL, French DN, McGuigan MM, Scheett TP, Sharman MJ, Häkkinen K, Kraemer WJ. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur J Appl Physiol. 2004 May;91(5-6):628-37.
• Willoughby DS, Rosene J:Effects of oral creatine and resistance training on myosin heavy chain expression.Med Sci Sports Exerc2001,33:1674–1681.

Pomegranate for Prostate, Rheuma, Breast Cancer, Aromatase, Obesity, Diabetes, Inflammation, HIV, Influenza, Herpes, Crohn's, Hepatitis, Infertility ... You Name It!

Image 1: This drawing from a German 1885 compendium on the flora in Germany, Austria and Switzerland shows that other than Acai & Co, pomegranate is no exotic (expensive and useless) discovery of some fly-by-night supplement vendor.

People are always all the rave, when some clever scientist (or should I say business man?) dug up another of those exotic fruit from a godforsaken valley somewhere in the African or South-American primeval forests. With the hype around ACAI & Co they often forget that there have been real Superfoods just around the corner, right in their local grocery store for years. Pomegranate, as it becomes increasingly evident from recent research, is one of these Superfoods - one that has even been mentioned in the Book of Exodus and has been part of the Ayurevedic tradition for centuries, now. While I have been following the research for some months now, the one mind-boggling study result has always been missing so that this is in fact the first blogpost in quite some time on the "seedy apple" ("pommum", lat. "apple" + "granatus", lat. "grain, seed").

To be precise, this is a post that was triggered by a Facebook message from Lothar, who informed me about the publication of the preliminary results of a phase II trial on the effects of pomegranate extract in prostate cancer prevention (Carducci. 2011).

In all of the 104 patients, whose PSA levels were on the rise after local therapy, the PSA doubling time, which, contrary to absolute PSA values, appears to be a more or less reliable indicator of cancer progression (Semenuik. 2006; Lee. 2005), lengthened by an average of +55% and that regardless of the dosage (1g vs. 3g) the patients received.

This result is unquestionably pretty impressive, it is, however, only part of the picture that has been emerging over the past years. Even if we only include selected studies from the last three months (!), we have to add at least the following health benefits

Image 2: If you consider this pomegranate seed trail long, then you will feel that the list of their health benefits is endless ;-)

• anti-rheumatic, anti-oxidant effect (Balbir-Gurman. 2011),
  reduction in the tender joint count by -62%; -25% reduced free radical-induced lipid peroxidation
• inhibition of glucose-uptake (Kim. 2011),
  -50% Na+-dependent glucose uptake at 424 μg/ml pomegranate extract
• anti-carcinogenic and pro-apoptotic effects (Dikmen. 2011),
  reduces profileration and induces apoptosis (programmed cell death) in breast cancer cells
• cardioprotective selective estrogen receptor modulator (Sreeja. 2011)
  the methanol extract of pericarp of pomegranate is an effective and cardioprotective SERM without some of the negative side effects of tamoxifen, such as increases in uterine weight and proliferation
• anti-obesity effect in diabetics (Gonzalez-Ortis. 2011)
  stops weight and fat gain in 20 obese diabetics
• potent anti-inflammatory (Faria. 2011)
  not limited, but specifically effective in suppressing the NFκ-B pathway
• promotes bone formation in fetus (Monsefi. 2011)
  when given as an extract to pregnant mice (no human data yet)
• antiviral properties (Su. 2011)
  against HIV-1, influenza, herpes, and poxviruses, and human noroviral surrogates
• protective effect against Crohn's disease (Rosillo. 2011)
  attributed to its ellagic acid content
• antioxidant and antiartherogenic effects (Haber. 2011)
  protects from hardening of the arteries due to plaque buildup
• ergogenic and anti-soreness effect (Trombold. 2011)
  pomegranate juice attenuates weakness and reduces soreness of the elbow flexor
• nephro- and hepaprotective effect (Cayir. 2011)
  pomegranate seed extract attenuates chemotherapy-induced acute nephrotoxicity and hepatotoxicity 
• protective against diet-induced obesity and diabetes (Vroegrijk. 2011)
  dietary pomegrenate seed oil ameliorates high-fat diet induced obesity and insulin resistance in mice, independent of changes in food intake or energy expenditure
• pro-fertility effect / protection against lead poisoning (Leiva. 2011)
  due to its antioxidant activity an ethanolic extract of pomegranate reversed the damage produced by lead acetate on spermatogenesis 
• oral antiplaque effect (Bhadhabe. 2011)
  pomegranate mouthrinse could be long-term antiplaque rinse with prophylactic benefits

to a still preliminary and yet already epic list of health-benefits of an ancient superfruit that is obviously not exotic and exciting enough to compete with the mostly useless, fancy-named herb and fruit extracts people are willing to spend millions of dollars on, year by year... ah, I forgot to mention: the ripe fruit also tastes damn good!

Eat Whole Foods! Lose Weight, Improve Your Blood Lipids, Reduce Estrogen, Protect Yourself Against Chromosomal Damage and Defeat Prostate Cancer With Cabbage.

Image 1: The magic ingredient is in the root not in the commonly eaten leaves of "bok choy". Chances that you will find a "whole" (including the root) chinese cabbage" (lat. brassica rapa) at your local supermarket, are yet very low... but wouldn't this be a good reason to start gardening really "whole" foods in your backyard? (img. Wikigardener)

If you are a student of the SuppVersity, you are probably already annoyed by my favorite slogan "Nature knows best!" Nevertheless, I will not tire to repeat that "eating your way to a leaner and healthier you" is probably the only sustainable alternative on a side-effect ridden life on drugs such as Xenical.

As Trisha Gura points out in a newsitem on sciencemag.com,

[t]he current trio of [weight loss] drugs on the market, endocrinologists say, is, at best, weak and, at worst, plagued by side effects. Hoffmann-La Roche's Xenical, for instance, blocks fat-digesting enzymes called lipases. That prevents the gut from digesting and absorbing fat. But lipids aren't the only molecules malabsorbed; Xenical also causes cramping and severe diarrhea in many obese patients because water molecules also fail to be taken up by the gut.

Thus, the study results of Sojin An and his colleagues from five different research centers in the Republic of Korea, which although they have been published back in 2009, landed in my inbox only recently, come along quite handy. In a 8-week controlled trial the scientists found that the addition of 50mg/kg of an ethanolic extract from Brassica campestris spp. rapa roots (human equivalent: 4mg/kg) to the high fat diet (+25% more calories than standard chow) of ICR (imprinting control region) mice did not only ameliorate the weight and fat gain, but even reduced both gains in body weight (-3%), as well as white adipose tissue weight (-8%) compared to the normal fed control group.

Figure 1: Weight gain, fat gain (white adipose tissues) and energy intake of mice on a hypercaloric high fat diet (HFD) supplemented with either 50mg/kg chinese cabbage root extract or Orlistat (Xenical); values expressed relative to control group on normal chow (data calculated based on An. 2009)

The cabbage root extract outperformed Xenical not only in terms of its effect on body weight and fat accumulation, other than the pharmacological fat-blocker, it also preserved the leptin sensitivity of the mice, which was profoundly compromised (as can be seen by the +25% increase in leptin) in the Orlistat group (cf. figure 2).

Figure 2: Relative changes in blood lipids and adipokines in mice on a hypercaloric high fat diet (HFD) supplemented with either 50mg/kg chinese cabbage root extract or Orlistat (Xenical); values expressed relative to control group on normal chow (data calculated based on An. 2009)

The underlying mechanism behind all that is probably related to the 2-fold increase in beta-3 adrenergic receptor and the 3-fold increase in hormone-sensitive lipase (HSL) gene expression the researchers measured in the white adipose tissue of the animals. Both of them are intricately involved in the breakdown and release of stored triglycerides and their expression in rodents is suppressed upon high fat feeding.

In case you are as annoyed as I would be by the branding in the figures, I suggest you tell my friend "The Press" over at Anabolic Minds that "copy + pasting" the work of others like that, instead of citing only parts of the article and linking back to the source, is not what one would expect of an "anabolic mind". Thanks!

Want to plant your own veggies, but don't know how? Listen to SHR #703 "Urban Gardening: Like Your Life Depends On It"

My repeated advice to "eat whole foods", gets a whole new meaning, however, when you further consider that

• fatty acids from the pollen of brassica campestris have been shown to have a "strong inhibitory" effect on aromatase (Yang. 2009),
• the leaves protect "against in vivo genotoxicity and oxidative stress" (Tiku. 2008), and
• the chloroform extract from its pollen kills prostate cancer cells (Wu. 2007),

doesn't it? There is yet one obvious caveat to this advice. Without a green thumb, as Carl Lenore's significant other, Alisa Profumo, has one, it will be hard to get your hands on a whole brassica campestris plant, i.e. its leaves, roots and the pollen-laden blooms... ah, and just in case you take this insight as an opportunity to start gardening, I suggest you go and check out episode #703 of Super Human Radio "Urban Gardening: Like Your Life Depends On It" - who knows, one day your life could actually depend on it ;-)

On Short Notice: PWO EAA Supps for Young & Old, Indoor Pools & Low Testosterone, Life-Savingly Low T3/rT3 Ratios, Copper-Zinc-Manganese, Lifting for Prostate Health +More

Image 1: It's neither just as much, nor just as serious, but I would still venture the guess that it will take you more than 30s to digest today's installment of "On Short Notice" - despite the fact that the new format has no lengthy "short news", anymore ;-)

For this installment of "On Short Notice" I have decided to go a somewhat different route than before: Originally, the first post you would have read after this short introduction would have dealt with the potential negative health effects of homogenized milk. What was intended as a "on short notice" item, did however become lengthier and lengthier, until it finally turned into an "almost full-length post" (a slightly extended version of this article is going to be published on Monday). This "incident" made me revisit the last installments of this series only to realize that the majority of the supposedly "short" On Short News items had become "almost full-length posts" and were thus either somewhat overblown or still to short for what the study / topic had to offer...

To cut a long story short, I decided to stick to the very short items, formerly known as "On Very Short Notice" from now on.  If you have any reasonable objections against this practice, feel free to use the comment area of this post to complain. Do not forget, however, that you can still request a longer article on any particularly interesting topic or simply discuss the blurbs with me and others here or on the SuppVersity Facebook wall... Ready? Let's roll!

• 

  Figure 1: Ratio of muscle intracellular leucine to blood leucine concentration in response to
  resistance exercise and ingestion of 20 g of essential amino acids in young and older men.

  Older physical culturists can't "eat to grow" benefit from EAA ingestion - at least not to the same extend younger lifters do. And while this alone would hardly qualify as "news", the, or I should say one of the underlying reasons Jared M. Dickinson and his colleagues discuss in a paper that's scheduled to be published in the next issue of the Journal of Clinical Nutrition certainly is (Dickinson. 2012).
  One hour after the 7 young (30 ±2yr) and 6 old (70 ±2yr) male "recreationally active" study participants had performed a standardized leg training program consisting of 8 sets of 10 reps on a Cybex leg extension machine at an intensity of 70%RM (3 min rest between sets) Dickinson et al. supplied them with a 500ml of a fluid that contained 20g of leucine enriched essential amino acids (EAA) (exact composition: histidine 8%, isoleucine 8%, leucine 35%, lysine 12%, methionine 3%, phenylalanine 14%, threonine 10%, and valine 10%). In the hours following the leg training the scientists measured the amino acid flux and took muscle biopsies from the vastus lateralis to quantify the amino acid transporter (the "shuttle" that carries the amino acids from the blood stream into the muscle) expression in the trained leg muscles of their subjects.
  Contrary to what happened in the younger subjects, the expression of the transporter proteins was not further augmented (over exercise alone) in response to the ingestion of the EAA supplement in the older study participants. Consequently, the restoration of the intra- to extracellular amino acid ratio which was complete after 5h in the young subjects took more time and was not completed, when the third biopsy was taken at T=5h in the older subjects (see figure 1). A result, which (re-)emphasizes the paramount importance of physical activity in older people not just to become stronger, but also to ward off sarcopenia (=muscle loss) and subsequent frailty!

• 

  Figure 2: Unadjusted (top, middle) and adjusted (bottom) testosterone levels in adolescent boys depending on their exposure to chlorinated indoor-pool water before the age of 7y (bottom) and 10y (top, middle) respectively.

  Michael Phelps & Co at high risk of low testosterone - That's at least what we'd have to conclude from a 2011 paper that was published in the International Journal of Andrology by Nickmilder et al. who found that there is a clearcut association with early life exposure to chlorinated indoor-pool water and low testosterone levels in adolescence (and probably later in life, although that was not part of the study; cf. Nickmilder. 2011)
  As the data in figure 2 shows, the association with lower testosterone levels is most pronounced (p < 0.01) when the data was adjusting for inhibin B, FSH, age, time of blood sampling and breastfeeding (figure 2, bottom). With p < 0.05 (=5% chance that this is just coincidence) even the unadjusted values for pool water exposures of >250h before the age of 7 years were however statistically significant and as the scientists point out probably a result of the prolonged exposure of the "highly permeable scrotum" (Nickmilder. 2011)  to chlorinated water.
  

  Intriguingly, Bob Weinhold mentions in his otherwise rather critical comment on the study that Shanna Swan, a professor of preventive medicine at the Mt. Sinai School of Medicine, did not just criticize the "paucity of evidence from other studies", but also her hint at "effects from bath water exposures" as potential confounding factors (Weinhold. 2012). Against that background I suggest you go and take a very close look at the label of whatever cosmetic products you pour into your (male) children's bathwater.

• 

  Image 2: The dreaded low T3/rT3 ratio appears to be life-saving for critical ill patients. And when you come to think about it, it could well be a "natural mini coma" by which your body diverts all available resources to the one thing that's certainly more important than having a six pack: SURVIVAL!

  Low T3/rT3 ratio protects critical ill from death! While 1000s of visitors of various bulletin boards and discussion groups on the Internet are whining about a too low ratio of the "active" to the "inactive" form of triiodothyronine, the observation Marijke Gielen and her colleagues made, when they studied the chance of critically ill patients to be released early and alive from hospital, would suggest that rT3 is way more than a nasty millstone around the neck of (over-)dieters. After all, Gielen et al. found that the patients with the best blood glucose control and lowest T3/rT3 ratios had a +19% increased chance of being released early and alive (Gielen. 2012). An increase in the T3/rT3 ratio, on the other hand, was independently of glucose management, associated with a -14% lower chance of being released early and alive!
  I guess that this should be reason enough to rethink the generally touted "uselessness of rT3", wouldn't you agree? After all, it could well be that it is the rT3 induced metabolic slowdown that allowed for optimal recovery - much similar to the artificial coma physicians will induce in burn victims or other critically patients to have them recover faster / at all. This would yet also imply that having a very low T3/rT3 ratio is - as I've previously mentioned, by the way - a good indicator of other, non-thyroid related pathologies you should better try to spot and take care of before they will eventually show up and turn you into a subject for a follow up study for Gielen et al. (related: "T4+T3 Combination Therapy Instead of T4 Mono-Therapy")

• 

  Figure 3 (Zhu. 2012): Vitamin D3 is converted to the active metabolite 1,25(OH)2D3 by sequential 25-hydroxylation and 1a-hydroxylation.

  Slow conversion of D3 to 25-OHD in the obese suggests: Low vitamin D is a result of obesity - not vice-versa! Within the past decade(s) many scientists have observed correlations between higher adiposity and lower vitamin D levels (e.g. Arunabh. 2003). Only within the last 5 years or so, however, those results have been interpreted as "scientific evidence" that low vitamin D levels play a causative role in the current obesity epidemic. First evidence for the opposite, i.e. a causative relationship between obesity and the occurrence of chronically low systemic vitamin D levels in obese individuals (90%+ of the obese women in the study had 25OHD level <50 nmol l⁻¹; Wamberg. 2012), does yet come from a study that has been published in the International Journal of Obesity a couple of weeks ago.
  According to the Wamberge et al. present in their paper, the occurence of low 25(OH)D levels in the sera of obese individuals is a direct consequence of the sluggish bioactivation of vitamin D3 in the subcutaneous adipose tissue of obese patients. The latter is due to the -71% and -49% reduced expression of the two of the enzymes from the cytochrome P450 enzyme cascade (25-hydroxylase and 1α-hydroxylase, to be precise, see figure 3), which are responsible for the conversion of dietary or skin-derived (after sun exposure) vitamin D3 to 25(OH)D, which is the form of "vitamin D" your doctor will usually measure, and the "active" form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3) aka calcitriol.

• 

  Image 3: That's what active prostate cancer prevention can look like - no vaccine necessary!

  Heavy lifting protects against prostate cancer! This is the result of yet another of a whole host of studies which finally acknowledge the value of weight training with respect to all sorts of health benefits that have previously been ascribed to aerobic training only (Teixeira. 2012). Published ahead of print in the online version of the Scandinavian Journal of Medicine & Science in Sports the paper by Teixeira et al. is the first one to report that strength training can reduce the risk of prostate cancer by (re-)establishing a healthy balance between natural cell death and growth.
  In the course of a 91-day period a group of rodents were exposed to a daily "weight lifting regimen" (=jumping, 4x10 jumps with 50–70% of their body weight strapped to the thorax and 60–s rests between sets). This torture lead to an increase in corticosterone (=cortisol), DHT and testosterone levels, and brought about a healthier ratio of cell growth to apoptosis in the prostates of the animals than it was present in the age-matched sedentary control.

• 

  Figure 4: Building muscle requires more than just pumping existing fibers full of protein (click on the image to read up on the details)

  Scientists confirm Intermittent Thoughts on Building Muscle: Myostatin allows cells to "blow up", but does not facilitate structural changes. What's funny though, is that Lee et al. obviously feel that this is a great thing; and while it may actually be in the context of sarcopenia (pathological muscle dystrophy), where agents that block myostatin could proof very valuable tools, it just confirms that these agents are of little use, if not counterproductive for athletes and physical culturists who would always have to be on the look-out not to outgrow the necessary (re-)construction process, of which I have argued in the Intermittent Thoughts on IGF-1 an Its Splice Variants, already that it is necessary to keep the ever-growing muscles functional.
  So, in case you have a few vials of a real myostatin inhibitor lying around (not the hilarious egg-derived supplement that was sold a couple of years ago by snake oil vendors), you better talk to your medical practitioner about some growth hormone, as well, if you don't want to end up huge, but so weak that you can't make it up the five stairs in front of your gym ;-)

• 

  Image 4: While some experts say otherwise it appears illogical that the increase in breast tissue density, that's characteristic of women with a non-android body fat distribution would increase breast cancer risk. The majority of studies still ascribes a much higher increase in cancer risk to abdominal obesity (=android fat).

  Silicon boobs? Not necessary if you stay in shape! While the overall size still is a matter of genetics, the density of the female breast shows such a strong negative association with the android : gynoid ratio in young women (one standard deviation up corresponds to a -20% reduction in dense breast tissue; Dorgan. 2012) that it would seem as if simply staying in shape and thus avoiding the accumulation of body fit in the "unfemale" android areas could would (other factors like breastfeeding etc. aside) save one or another woman from a still very much underestimated and by no means just monetarily costly operation (cf. Bolton. 2012). And let's be honest: What are those silicon balls worth anyway, when the blubber starts shortly beneath? What certainly is bad news for the adolescent obesity generation , though is that childhood obesity is an even stronger predictor of low amounts of dense breast tissue. Even after adjustment for adult obesity each BMI z-score, i.e. one standard deviation upwards, was associated with a -27% decrease in tender breast tissue.
  Against that background it appear dubious, whether or not the often touted association between dense breast tissue and breast cancer risk is by any means a causative one... after all Abu-Abid et al. report in their review on the literature that abdominal obesity, i.e. an android body fat pattern is one of the best predictors of increased risk for all cancers (Abu-Abid. 2002).
• Are manboobs a sign of intelligence? Could be if we put any faith into the relation between the size of your hippocampus and your intellectual capacity, the findings Janine Bayer and her mostly female colleagues (this could be important, who knows maybe this is a feminist conspiracy!?) report in their latest paper on the effects a certain genetic polymorphicism (rs700518) in the aromatase enzyme CYP19A1 will have on both systemic as well as hippocampal estrogen levels and had the volume of the posterior hippocampal gray matter (Bayer. 2012). Unfortunately most manboobs today are a simple result of overaromatization due to obesity and whether this is a hallmark feature of superior intelligence appears at least questionable to me (suggested read: "Chest Fat, Bitch Tits, Chesticles and How to Get Rid Off Them")

• 

  Image 5: 1x 1g of taurine = 1.5% faster 3k-times in trained middle distance runners - another benefit of the underrated sulfur amino acid, taurine

  Taurine works for 3k-runs as well that's the simple message of a recently published study by Balshaw et al. In the randomized, double-blinded crossover experiment the ingestion of 1,000mg of taurine immediately prior to a 3km run increased the time-trial performance of the eight trained middle-distance runners by statistically significant 1.5%, on average (Balshaw. 2012); this does allegedly not sound like much, but if you take into consideration that this was a single serving effect it is actually quite impressive compared to the the ~1% performance increment in the narrow range of 90-120s activities that has recently reported to come out of weeks of beta alanine supplementation.
  So, if the testosterone boosting, anti-diabetic effects of taurine (see "Up to 180% Increase in Testosterone & More From Taurine") did not already convince you to invest the ~$20 for a 500g batch of this sulfur amino acid, maybe these results and a couple of hours in front of the TV watching track & fields events at the Olympic Games '12 can ;-)

• 

  Figure 5: Glucose metebalism markers of oxidation and nitric oxide (top) calculated artheorscleortic risk (bottom, left) and body weight gain (bottom right) in the different groups

  Differential and common effects of zinc, copper and manganese supplementation on body weight gain, glucose metabolism and cardiovascular health have recently been reported by scientists from the Usmanu Danfodiyo University in Nigeria. In their paper that has been published in the Journal of Oxidative Medicine and Cellular Longevity Muhammad et al. report that the provision of high copper (4mg/kg), high manganese (10mg/kg) and high zinc (20mg/kg) diets or the addition of all three supplemental minerals to the diets of salt-loaded hypertensive male Wistar rats all offered at least some protection against the oxidative stress, dyslipidemia, and insulin resistance that's associated with hypertension.
  As the data in figure 5 goes to show, the provision of additional copper does yet appear to exert the most benefits. In view of the short duration of the study, it would yet be more than premature to recommend copper only supplementation regimens in the absence of proven and most importantly specific deficiencies. Rather than that those of you who are suffering from the triumvirate of elevated blood pressure, insulin resistance and dislipidemia would probably be better off if they increased their overall intake of these trace minerals.

• 

  Image 6: Sounds stupid, but if you are concerned about your dopamine receptor count, you better make sure to eat the bun and order an extra large coke (the original with tons of sugar, of course ;-)

  High fat / low carb = reduced striatal dopamine receptor availability this is the quintessence of a short communication that has been published in the International Journal of Obesity three days ago. According to E van de van de Giessen and his co-workers, rats on a high fat high fat diet (this is no typo but the way of the researchers to acknowledge that the "original high fat diet" as it is interpreted by most scientists is almost equally high in carbohydrates (calorie-wise) as it is in fat; not so for the "High Fat High Sugar High Fat" (HFHS hf) diet in the van de Giessen study. Compared to the regular high fat diet, the HFHS-hf diet ameliorated the increase in energy intake, but reduced the availability of D2 & D3 receptors in the nucleus accumbens.
  Overall, the ratio of fat to carbohydrate in the diet and not as it has previously been speculated the degree of adiposity or the total energy intake were the most and only significant correlate of the central dopamine receptor downregulation the researchers observed in their test animals (Giessen. 2012). In view of the fact that Fetissov et al. speculated in 2002, already, that "[l]ow D2 receptor expression may be causal for an exaggerated dopamine release observed in obese rats during food ingestion" (Fettisov. 2002) this is bad news - as it would indicate that the low carb induced reduction of dopamine receptor density could precipitate to reward driven episodes of overeating... an emphasis is on the conditional, here, as the majority of low-carb dieters will probably confirm my gut feeling that during the low carb diet, the exact opposite appears to be the case (at least as long as we are talking about even more fatty foods ;-).

• 

  Image 8: According to Hwang et al. it does not matter how you cook your broccoli, if you want to keep the glucosinolates intact. The main point is that you do it fast!

  Cooking your veggies without water reduces cholesterol oxidation and improves potassium status that's what a group of Japanese researchers who declare they do not have any affiliation with the producer of multi-ply cookware, Vita Craft Japan Ltd, found in a 2-week intervention study in the course of which both the "just eat your veggies" and the "eat your veggies, but cook them without water in multi-ply cookware(TM)" (the product reference is #5123) increased their beta carotene and vitamin C levels and decreased their LDL and total cholesterol levels, but only the "without water cookers" had significantly reduced oxidized LDL and profoundly improved (=lower) Sodium : Potassium ratios in their urin (Mori. 2012).
  Now, while this sounds as if it would make sense to buy this cooking "gear" things look somewhat different, when you take a look at the absolute differences and outcomes. While the oxidized LDL levels did in fact improve more in the muli-ply group this brought them just back into the exact same range where they were hovering in the other groups, as well. Similarly, the Na:K ratio was better, but it did improve in the "regular cooking" group as well and would thus probably end up in the same range, after another 2-6 weeks of vegetable eating - regardless of whether you cook them with water or not. Things would probably not be much different for the glucosinolate content of broccoli of which Hwang et al. report in the same issue of the International Journal of Food Sciences and Nutrition report that, they decreased significantly and time-dependently during boiling, steaming and microwaving (Hwang. 2012)
• Black tea, lemon and honey: Can you stack it? Yes, you can! Camellia sinensis, Citrus limon and Apis mellifera all have a record of being potent antioxidants, but according to a paper in the August issue of the International Journal of Food Sciences and Nutrition lemon-flavoured black tea becomes an even more potent health drink, when you "spike" it with honey (Pereira. 2012).
  Moreover, Pereira et al. found that the darker species of the different honeys from Lavandula stoechas, Erica sp. pl. and other indigenous floral species from north-east Portugal they tested were more potent than the light amber varieties.

• 

  Image 9: The powdery Matcha tea is not only already high in catechines, it will also release>130x more of it's EGCG content into the brewing water than most regular green teas! And as if that wasn't enough, it has a 64% higher caffeine concentration (6.4 vs. 3.9mg/g), as well.

  Matcha tea has an uber-potent 137x increased EGCG content! This is one of the "oldie but goldie" studies I hit upon when I did "colleteral research" in response to a Highbrow Paleo member complaining that the over-potent Matcha tea literally blew him away. Actually not very surprising in view of the fact that it contains 137x more EGCG than regular green tea (brand China Green Tips; cf. Weiss. 2003). And while the selection of a specifically catechin rich fraction will figure here, as well, much of the effect is probably simply a result of the increased surface area and thus the greater efflux of the bioactive ingredients into the brew the tea is steeped in.
  In view of the previously reported negative effects very high doses of green tea catechins can have on your testicular health all matcha lovers out there should better limit their daily consumption to one or two cups of the exclusive brew (see "20% Reduction in Testosterone with 5 Cups of Green Tea").
• Oral anti-oxidants restore glutathione in diabetic skin At least in rodents this works pretty damn well. According to Sokmen et al. all it takes to restore the natural antioxidant defense system in the skin of streptozotocin-induced diabetic rats (model of type II diabetes) are 250 mg/kg vitamin C, 250 mg/kg vitamin E and 0.2 mg/kg selenium (Sokmen. 2012). The human equivalent of these orally supplied antioxidants would be 40mg/kg vitamin C, 45 IU/kg vitamin E and 30µg/kg selenium - all much too high to benefit anyone who is not diabetic, by the way.

• 

  Image 10: Usually I am really enthusiastic about new technologies, but looking at how careful physicists handle nanomaterials, and how food designers and the cosmetic industry unleash them on the costumers, like the US and UDSSR unleashed the a-bomb radiation on their own soldiers, ignorant of the (un?)known dangers.

  Nano-sizing fish oil doubles absorption - This is the result of a recently conducted rodent trial by Tanmoy kumar Dey the results of which are soon going to be published in Food Research International (kumar Dey. 2012). The more than +50% increased absorption the scientists found for their nano emulsified fish oil in the small intestine of the lab rats is - at least in my humble opinion - somewhat frightening. Firstly, I am really not sure we really need the hilarious amounts of fish oil, where the use of respective products would make sense (it should be said, though, that this new formula has been developed for parenteral nutrition, specifically). We have, secondly, not the slightest idea if those nano-sized fish oil molecules behave anywhere similar to their fluffy large brethren - who tells us that they don't have the exact opposite effect on our health?
  And third and lastly, if nano-sized fish oil is absorbed 100% more efficiently, all other nanomaterials - especially those that are nor increasingly popular in the cosmetic industry - will have a similarly increased "bioavailability" and could thus not only reach places in our body they were never intended to reach, but do just that in very significant amounts!

References

• Abu-Abid S, Szold A, Klausner J. Obesity and cancer. J Med. 2002;33(1-4):73-86. Review.
• Arunabh S, Pollack S, Yeh J, Aloia JF. Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab. 2003 Jan;88(1):157-61.
• Balshaw TG, Bampouras TM, Barry TJ, Sparks SA. The effect of acute taurine ingestion on 3-km running performance in trained middle-distance runners. Amino Acids. 2012 Aug 2.
• Bayer J, Rune G, Kutsche K, Schwarze U, Kalisch R, Büchel C., Sommer T. Estrogen and the male hippocampus: Genetic variation in the aromatase gene predicting serum estrogen is associated with hippocampal gray matter volume in men. Hippocampus. 2012.
• Boulton TN, Malacrida C. Women and cosmetic breast surgery: weighing the medical, social, and lifestyle risks. Qual Health Res. 2012 Apr;22(4):511-23.
• Dickinson JM, Drummond MJ, Coben JR, Volpi E, Rasmussen BB, Aging differentially affects human skeletal muscle amino acid transporter expression when essential amino acids are ingested after exercise, Clinical Nutrition. 2012.
• Dorgan JF, Klifa C, Shepherd JA, Egleston BL, Kwiterovich PO Jr, Himes JH, Gabriel KP, Van Horn L, Snetselaar LG, Stevens VJ, Barton BA, Robson AM, Lasser NL, Deshmukh S, Hylton NM. Height, adiposity and body fat distribution and breast density in young women. Breast Cancer Res. 2012 Jul 16;14(4):R107.
• "Caffeine." Encyclopedia of Drugs, Alcohol, and Addictive Behavior. Ed. Rosalyn Carson-DeWitt. Vol. 1. Gale Cengage, 2001. eNotes.com. 11 Aug, 2012 <http://www.enotes.com/caffeine-reference/>
• Fetissov SO, Meguid MM, Sato T, Zhang LH. Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake. Am J Physiol Regul Integr Comp Physiol. 2002 Oct;283(4):R905-10.
• Gielen M, Mesotten D, Wouters PJ, Desmet L, Vlasselaers D, Vanhorebeek I, Langouche L, Van den Berghe G. Effect of Tight Glucose Control with Insulin on the Thyroid Axis of Critically Ill Children and Its Relation with Outcome. J Clin Endocrinol Metab. 2012 Aug 7.
• Hwang ES, Kim GH. Effects of various heating methods on glucosinolate, carotenoid and tocopherol concentrations in broccoli. Int J Food Sci Nutr. 2012 Jul 10.
• kumar Dey T, Ghoshb S, Ghoshb S, Koleyc H, Pubali, D. Comparative study of gastrointestinal absorption of EPA & DHA rich fish oil from nano and conventional emulsion formulation in rats. Food Research International. 04 Aug 2012.
• Lee SJ, Huynh TV, Lee YS, Sebald SM, Wilcox-Adelman SA, Iwamori N, Lepper C, Matzuk MM, Fan CM. Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway. Proc Natl Acad Sci U S A. 2012 Aug 6.
• Mori M, Hamada A, Mori H, Yamori Y, Tsuda K. Effects of cooking using multi-ply cookware on absorption of potassium and vitamins: a randomized double-blind placebo control study. Int J Food Sci Nutr. 2012 Aug;63(5):530-6. Epub 2012 Jan 9.
• Muhammad SA, Bilbis SL, Saidu Y, Adamu Y. Effect of Antioxidant Mineral Elements Supplementation in the Treatment of Hypertension in Albino Rats. Oxidative Medicine and Cellular Longevity, vol. 2012, Article ID 134723, 8 pages, 2012.
• Nickmilder M, Bernard A. Associations between testicular hormones at adolescence and attendance at chlorinated swimming pools during childhood. Int J Androl. 2011 Oct;34(5 Pt 2):e446-58.
• Oosting A, Kegler D, Wopereis HJ, Teller IC, van de Heijning BJ, Verkade HJ, van der Beek EM. Size and Phospholipid Coating of Lipid Droplets in the Diet of Young Mice Modify Body Fat Accumulation in Adulthood. Pediatr Res. 2012 Jul 31.
• Pereira C, Barros L, Vilas-Boas M, Ferreira IC. Potentiating effects of honey on antioxidant properties of lemon-flavoured black tea. Int J Food Sci Nutr. 2012 Aug 3.
• Sokmen B, Basaraner H, Yanardag R. Combined effects of treatment with vitamin C, vitamin E and selenium on the skin of diabetic rats. Hum Exp Toxicol. 2012 Aug 2.
• Teixeira GR, Fávaro WJ, Pinheiro PF, Chuffa LG, Amorim JP, Mendes LO, Fioruci BA, Oba E, Martins OA, Martinez M, Martinez FE. Physical exercise on the rat ventral prostate: Steroid hormone receptors, apoptosis and cell proliferation. Scand J Med Sci Sports. 2012 Jul 26. 
• van de Giessen E, la Fleur SE, Eggels L, de Bruin K, van den Brink W, Booij J. High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity. International Journal of Obesity. 7 August 2012.
• Wamberg L, Christiansen S, Paulsen SK, Fisker S, Rask P, Rejnmark L, Richelsen B, Pedersen SB. Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss. International Journal of Obesity. 17 July 2012.
• Weinhold B. Can indoor swimming alter hormones in boys? Environ Health Perspect. 2012 Jan;120(1):A18.
• Weiss DJ, Anderton CR. Determination of catechins in matcha green tea by micellar electrokinetic chromatography. J Chromatogr A. 2003 Sep 5;1011(1-2):173-80. 
• Zhu J, DeLuca HF. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet? Arch Biochem Biophys. 2012 Jul 1;523(1):30-6.

Androgen Threesome: BPA Exposure & Free Testosterone in Men. TRT Good For the Prostate. DHT, Allopecia (Hair Loss) & Monascus Fermentation. Plus: Mycotoxins in GCB Supps

Coffee and green coffee bean extracts are by no means the only way by which you are exposed to mycotoxins. Corn, for example, is likewise a favorite for the toxic mold. The same goes for almost all other grains. Common routes of exposure are, amongst others cereals, breads, wines, and even mils and meats (of swine ad turkey, not chicken; Duarte. 2010)

36%, 32%, 10%, and 16% these are the SuppVersity Figures of the week and the percentages of green coffee bean supplements (remember the chlorogenic acid news in Thursday's installment of the Science Round-Up) that were contaminated with Ochratoxin A, ochratoxin B, fumonisin B1 and mycophenolic acid, respectively.

"Mycotoxins occurred in the following concentration ranges: ochratoxin A: 2.7–136.9 µg/kg, ochratoxin B: 3.5–20.2 µg/kg, fumonisin B1: 110.0–415.0 µg/kg, mycophenolic acid: 43.1–395.0 µg/kg." (Vaclavi. 2013)

These poisonous substances are produced by fungi that form during (inproper) storage and are suspected to inhibit protein synthesis, damage macrophage systems, inhibit particle clearance of the lung, and increase sensitivity to bacterial endotoxins... ah, I almost forgot ochratoxins also wreak havoc on your hormones (Frizzell. 2013).

So far for the bad news, now the good one: According to the researchers calculations even with most contaminated of the 50 products they the average consumer who adheres to the suggested dosing protocol will still be well within the tolerable weekly intake (TWI) of 120 ng/kg body weight per week and tolerable daily intake (TDI) of 2000 ng/kg body weight per day for ochratoxin A and fumonisin B₁, respectively (these values were estimated by the EU Scientific Committee on Food (SCF) and the European Food Safety Authority (EFSA) - corresponding values of the "well-meaning" FDA or any other US government agencies are - as usual - not available).

Let's get to our androgen threesome

• 

  SuppVersity readers know: Tea is not only good for your prostate (learn more), it can also help you lose weight (read more)

  Testosterone replacement improves prostate issues (Ko. 2013) -- Contrary to what common "wisdom" will tell you scientists from the Yeungnam University College of Medicine in Korea can tell you that the 17 out of  46 patients who suffered from lower urinary tract symptom before they underwent TRT using intramuscular injection of 3 months bases injection of testosterone 1,000 mg undecanoate over a year achieved significant improvements (decrements) on the International Prostate Symptom Score (IPSS).
  
  Needless to say that "[d]uring the median follow up of 15.1 months, no patients experienced urinary retention, BPH-related surgery, or admission for urinary tract infection".

• BPA and low testosterone, you better know what to look at (Zhou. 2013) -- Talking about testosterone, there is finally some relatively reliable human data on the effects of BPA exposure on the hormone levels in men.

  

  Figure 1: Relative difference in free androgen index (FAI), androstenedione (AD), free testosterone (FT), SHBG, inhibin (INB), prolactin (PRL), follicle stimulating hormone (FSH), estrogen (E2) an total testosterone (T);  comparing the men with to the men without workplace exposure in the Zhou study

  As you can see in figure 1 the effects would go unnoticed, if you do not test for free hormones, but just checked the amount of total testosterone. How you can recognize that from the data? Well, the figures above the bars are the p-values. All that are >0.5 would suggest that this effect is statistically non-significant, so that every study not looking at things like the free androgen index (FAI) or the free testosterone levels (FT) will miss the 15% and 10% reduced levels of the latter and conclude: That it does not make a difference, if your serum contains 3.198 or 0.276mg/L as it was the case in the exposed and non-exposed subjects in this study from the Shanxi Medical University, because BPA won't harm you anyway.

• The fermented solution to all problems androgen?  (Chiu. 2013) Monascus bacteria that is used to ferment red mold rice, a traditional spice that is consumed throughout Asia could prevent androgenetic alopecia, benign prostate hyperplasia and prostate cancer.

  

  Figure 2: Changes in testosterone an DHT mice on TRT (control) w/w-out 0.2 & 0.5% Monascus extract in chow, corresponding images of the stained slices from the prostate and hair loss compared to standard treatment with finasteride (Chiu. 2013)

  The results of a recent study from the Department of Environmental and Occupational Health at the National Cheng Kung University Medical College clearly suggest that the way in which a monascus extract suppressed baldness in male B6CBAF1/j mice 

  

  Learn how to modulate DHT/T naturally.

  • decreased PSA levels  
  • decreased tumor volume and
  • decreased prostate cancer incidence, 
  • decreased dihydrotestosterone (DHT),
  • but left testosterone unchanged
  The effect was dose-dependent and was observed with 0.5-3% of the extract in the rodent diets. While it is not unlikely that the results will translate into human studies, it should be obvious that at least for the >0.5% doses, supplementation will be necessary.
  
  Irrespective of these latest study results, previous research indicates that Monascus-fermented products have many functional secondary metabolites, including monacolin K, citrinin, ankaflavin, and monascin and these have been shown to possess anti-inflammatory, antioxidative, cholesterol-lowering effect, and antitumor activities. Probably all of you will be familiar with at least one of them: Red Yeast Rice, the natural statin. And if you are not into spices or extracts, there are also other foods and even wines that are fermented with Monascus.

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That's it for today: I know ladies, with today's focus on the male hormones, I owe you (big time?). But don't worry, there are also a couple of Facebook News, you may be interested in

• 

  Suggested read: "Carbohydrate Shortage in Paleo Land" (read more)

  "Oldie but goldie: T3, rt3 and carbohydrate intake in hyper- and eucaloric scenarios - Something worth considering for those constantly battling low T3 an high rT3 levels (read more)
• Omnipresence of "healthy" Subway sandwiches correlates w/ obesity rates - "Countries with the highest density of Subway restaurants such as the USA (7.52 per 100,000) and Canada (7.43 per 100,000) also tend to have a higher prevalence of obesity in both men (31.3% and 23.2%, respectively) and women (33.2% and 22.9%, respectively)." (read more)
• Understanding the neurological side effects of statin drugs - US scientists observed unusual swellings within neurons, which the team has termed the "beads-on-a-string" effect (read more)
• DHEA supplementation at 25gm/day to restore female fertility - A recent study from Turkey would suggest that this could actually work (read more)

If that's still not enough, come back tomorrow for another serving of the latest news from the realms of exercise, nutrition and health sciences, here at the SuppVersity! In the mean time, enjoy your weekend, everone!

References:

• Chiu HW, Chen MH, Fang WH, Hung CM, Chen YL, Wu MD, Yuan GF, Wu MJ, Wang YJ. Preventive effects of monascus on androgen-related diseases: androgenetic alopecia, benign prostatic hyperplasia, and prostate cancer. J Agric Food Chem. 2013 May 8;61(18):4379-86.  
• Duarte SC, Pena A, Lino CM. Ochratoxin a in Portugal: a review to assess human exposure. Toxins (Basel). 2010 Jun;2(6):1225-49. doi: 10.3390/toxins2061225. Epub 2010 Jun 1. Review. 
• Frizzell C, Verhaegen S, Ropstad E, Elliott CT, Connolly L. Endocrine disrupting effects of ochratoxin A at the level of nuclear receptor activation and steroidogenesis. Toxicol Lett. 2013 Mar 13;217(3):243-50.  
• Ko YH, Moon du G, Moon KH. Testosterone replacement alone for testosterone deficiency syndrome improves moderate lower urinary tract symptoms: one year follow-up. World J Mens Health. 2013 Apr;31(1):47-52.
• Vaclavik L, Vaclavikova M, Begley TH, Krynitsky AJ, Rader JI. Determination of Multiple Mycotoxins in Dietary Supplements Containing Green Coffee Bean Extracts Using Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC-MS/MS). Journal of Agricultural and Food Chemistry. May 2013 [ahead of print].
• Zhou Q, Miao M, Ran M, Ding L, Bai L, Wu T, Yuan W, Gao E, Wang J, Li G, Li DK. Serum bisphenol-A concentration and sex hormone levels in men. Fertil Steril. 2013 May 4.