Science Round-Up Seconds: Vitamin E Succinate, How It's Extracted from Barley Leaves, Kills Cancer, Ramps up Growth Hormone & Spikes Prolactin. Plus: Testostosterone & Thyroid Hormone Decline Due To Plyometrics & HIIT

Regardless of all the hypocritical hoopla around his persona, Lance Armstrong has always been able to push himself like no one else. No wonder that intense plyometrics were part of his regimen.

If the SuppVersity Science Round Up was a meal, I guess you could say that Carl Lanore and I were sort of gluttonous, yesterday (click here to download the podcast, if you have not already done so). We almost raced from one topic to another and therefore all the good stuff from the list is gone already and I am a bit pressed on time to get some "private life" in, so that I am not psyched about the idea of writing about auxiliary stuff.

Against that background and in view of the fact that I felt that the pace of yesterday's show did not really leave enough room for some important details, I will stick to rehashing and expanding on the stories about Vitamin E succcinate and the detrimental effects of beating the crap out of yourself doing plyometrics or crazy HIIT workouts (too regularly), in today's installment of the SuppVersity Science Round-Up Seconds.

Let's see. Why don't we start at the end of yesterday's show?

• Vitamin E succinate the most potent anti-cancer tocopherol known to man. As you have heard on the show, vitamin E succinate attaches directly to a protein that's preferentially expressed in carcinogenic or pre-carcinogenic cells. It goes by the name α-Tocopherol-associated protein (TAP) and was found to be one of the major α-tocopherol binding proteins in serum, liver, brain and prostate. What has as of yet not been so clear, though, is that the expression of this protein increases with the malignancy of (breast) cancer (Tam. 2013). 
  
  

  

  Figure 1: Effects of alpha tocoperyl succinate alone (TOS), doxorubicin alone (DOX) or both (DOX + TOS) on cell viability in human MB231 breast cancer cells (my edits, original from Tam. 2013) - note: The effect was less pronounced in other cancer cells, so that it is reasonable to assume that the efficacy of the therapy will depend on the exact genotype of the cancer (for those tested in the study it was MB231 > SKBR3 > MCF 10A)

  When alpha tocopherol succinate binds to the protein on the cancer cells, this will either alone, or in combination with chemotherapy trigger apoptosis and cell death. It is as of yet not fully elucidated why vitamin E succinate is highly cancer-specific and leaves the healthy cells intact, but this could be related to the high metabolic rate and exuberant ROS production of cancer cells. There is however some research that would suggest that the cancer cells literally suffocate in their own radical oxygen specimen (ROS), which can no longer be cleared from the cell, due to the alpha-tocopheryl succinate induced displacement of ubiquinone from CII and the subsequent blockade of succinate dehydrogenase (SDH) activity (Dong. 2013).  If this hypothesis holds true it would therefore appear that long-term chronic supplementation with vitamin E succinate cannot be recommended until future studies on its general safety have been undertaken. As an adjuvant to chemotherapy, on the other hand, it could drastically reduce the dosage requirements during chemotherapy in specific types of cancer (see figure 1) and thus minimize side effects.
  
  You see, there is more to it than you can say in two minutes on the radio and this is why I will make sure we don't rush through the items that fast, in the next show. Ah,... of course the dietary source. I had almost forgotten about that one. As mentioned on the show, alpha tocopheryl succinate was originally extracted from Barley leaves. An while this may not be the first paper dealing with this "natural vitamin E analog", the one by Badamchian et al. is probably the one you will be most interested in.
  
  Published in the Journal of Nutritional Biochemistry the paper does not only describe the isolation of vitamin E succinate from green barley leaf extract (BLE)...
  

  "BLE [barley leaf extract] powder (50 mg/mL) was suspended in water and stirred for 1 hr at room temperature. The mixture was then centrifuged at 3000g for 30 minutes using a bench-top centrifuge. The pellet was discarded and the supernatant was pre-filtered through a Millipore DEPTH filter. The filtrate was then filtered through 0.45 I.tM mem- brane and stored at -20 ° C for HPLC or biological assays." (Badamchian. 1999)

  ... it does also shine another spotlight on its potential biological effects, as far as it's ability to increase growth hormone, but (unfortunately?) also prolactin in isolated anterior pituitary cells from female rodents:
  

  

  Figure 2: Prolactin and growth hormone release in anterior pituitary cells of female rodents after incubation with different amounts of green barley extract in which vitamin E succinate had been deterimed as the main ingredient before (based on Badamchian. 1999)

  It's really hard to estimate whether or not one of these effects would translate from a rodent cell in the petri dish to you or me popping a cap with vitamin E succinate everyday. That's particularly true in view of the fact that the underlying mechanism of the increase in GH and the imho more concerning increase in prolactin is neither mediated by increases in intracellular C-AMP, as it would be the case for GRF (old acronym for growth hormone releasing hormone), nor is it induced by the hydrolysis of polyhoshpoinositide, which is the underlying mechanism of the stimulative effect of TRH (thyrotropin releasing hormone). So basically we neither know how it works, nor do we know, whether the oral ingestion of vitamin E-succinate would be sufficient to produce serum concentrations in the pituitary that would be high enough concentrations to make any difference at all (note: the scientists excluded the influence of other components of the extract by testing alpha tocopherol succinate on its own in a separate trial)
  
  Bottom line: Based on roughly one dozen of in-vitro studies there is simply still to little evidence to decide who, outside of people with a history of cancer or someone who is just undergoing chemotherapy would benefit. Therefore, I suggest you wait before you add vitamin E succinate to your list of 'must have' supplements. Is it promising? Sure! Is it exciting, yeah! Is it save for a healthy being to be taken chronically??? I can't tell.
• The detrimental hormonal effects of pushing yourself beyond the tolerable threshold - Hardcore plyometrics and heavy HIIT and their impact on testosterone, cortisol, thyroid hormone and co: I guess you did already get the main message when you listened to the show, but just to give you an idea about the actual quantities, I thought it would be nice to provide you with two graphs as a reference.
  

  

  Figure 3: Comparison of the hormonal responses measured in the plyometrics (left) and the HIIT vs. LISS (right) study (based on Ozen. 2013 and Hackney. 2013)

  If you focus mainly on the differential cortisol responses in the two studies, it would appear likely that we are dealing with two very different forms of 'overtraining' here. While the HIIT protocol (90s at 100-110%, 90s active recovery at 40% matched for workload with steady state jogging at 60-65% of the VO2 max) probably wouldn't be a problem, if the athletes would get adequate rest and nutrition in the days after the session, the 6-weeks of plyometrics (15 session, increasing density, 90-195 reps per session) were enough to send the participants right into the vicious circle of the Athlete's Triad (if you have not done so already, I suggest you read up on that in the eponymous SuppVersity series).
  
  And you know what? Despite, or I should probably rather say due to their compromised hormone levels the guys in the plyometrics study did not lose a single gram of body weight. Good for their muscle, bad for the fat which was likewise preserved by the hormonal shut down, which affected both cortisol and testosterone in a similar way. So is that good or bad news? Well, let me say it this way:. Usually I see people training for a purpose and while the outcome often is stagnation and chronic fatigue, I would suspect that only few of you will have that on their mind, when they are hitting the gym, right?

Apropos viscous circle, and overtraining in order to avoid "overblogging" I will call it a day for today. Come back tomorrow for a couple of wholly new studies from the realms of exercise and nutrition sciences and in case you are planning to drink this evening, I highly suggest you check out the SuppVersity Facebook newspost on the effects of green tea extract on the uptake of alcohol. It may well be that those old fatburner caps of yours can be put to a way better use ;-)

References:

• Badamchian M, Spangelo BL, Bao Y et al. Isolation of a vitamin E analog from green barley leaf extract that stimulates the release of prolactin and growth hormone from rat anterior pituitary cells in vitro. Journal of Nutritional Biochemestry. 1994; 5: 145-150.
• Dong LF, Low P, Dyason JC, Wang XF, Prochazka L, Witting PK, Freeman R, Swettenham E, Valis K, Liu J, Zobalova R, Turanek J, Spitz DR, Domann FE, Scheffler IE, Ralph SJ, Neuzil J. Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II. Oncogene. 2008 Jul 17;27(31):4324-35. Epub 2008 Mar 31.
• Hackney AC, Kallman A, Hosick KP, Rubin DA, Battaglini CL. Thyroid hormonal responses to intensive interval versus steady-state endurance exercise sessions. Hormones (Athens). 2013 Jan-Mar;11(1):54-60.
• Ozen, SV. Reproductive hormones and cortisol responses to plyometric training in males. Biol Sport.2013; 29 (3).
• Tam KW, Ho CT, Lee WJ, Tu SH, Huang CS, Chen CS, Lee CH, Wu CH, Ho YS. Alteration of α-tocopherol-associated protein (TAP) expression in human breast epithelial cells during breast cancer development. Food Chemistry. 2013 [ahead of print]

Can 5 Cups of Coffee Boost Testosterone to Estrogen Ratio in Overweight Men Transiently by Almost 200%? Plus: SHBG Its Own Receptor and Its Role in Prostate & Breast Cancer

Testosterone booster in men and estrogen amplifier in women? As if there were not already enough good reasons to get your daily dose of the 'kingly' brew ;-)

You would not have to be a diligent student of the SuppVersity to know: Coffee is a truly remarkable brew. Even mainstream media has gotten wind of the multitude of beneficial effects a moderate intake of the former drink of the kings and popes can have on your health and if it was not for the authors and newscasters blind reliance on whatever the press release guys are telling them, it would probably not even have been necessary for me to broach the beneficial effects coffee can have on your metabolic health and overall well-being in posts like "Coffee - 3 Cups a Day Keep Insulin at Bay", "Pre-Workout Caffeine: Fat Liberator, Substrate Modulator, Trans-Fatty Acid Eliminator & Performance Upregulator!" and many more.

So what is it this time? What else can coffee do for you?

I guess something only few people others than SuppVersity readers will be aware of is the fact that caffeine  and therefore coffee makes a nice testosterone booster (Beavon. 2008; study was discussed briefly as part of a longer post on June 20, 2013 an mentioned previous times in other posts) -- at least if you stick to moderate doses of ~300-400 mg before a workout. So, unless you are a newbie or missed the respective news, you should not be surprised that a recent study from the Harvard School of Public Health (Wedick. 2013), which had actually been designed mainly to investigate the effects of 5x 6-ounze cups caffeinated and decaffeinated coffee (both instant coffees; brand: Nestlé’s Taster’s Choice) on serum levels of sex hormone-binding globulin (SHBG), found that the consumption of both 'real' and 'fake' (=decaffeinated) instant coffee did lead to increases in total and free testosterone and profound decreases in estradiol (bound and free).

Figure 1: Levels of SHBG, testosterone, free testosterone, estradiol, free estrogen, the testosterone to estrogen ratio and DHEA in the male participants of the study expressed relative to a caffeine abstinent control group (based on Wedick. 2013)

As the data in figure 1 goes to show these changes were unfortunately transient and the impressive +189% increase in the testosterone to estrogen ratio which occurred during the first month of treatment totally disappeared within the next four weeks. On the other hand, the effects on SHBG the scientists had expected based on the assumption that both SHBG and caffeine intake have been found to be associated with lower risk of type II diabetes in large epidemiological studies, was non-existent in the first and second 4 weeks of the study... at least in the male subjects who were all overweight, nonsmokers and habitually coffee consumers, who had been required to abstain from caffeine intake for at least 2 weeks before the study was conducted.

Figure 2: Levels of SHBG, testosterone, free testosterone, estradiol, free estrogen, the testosterone to estrogen ratio and DHEA in the female participants of the study expressed relative to a caffeine abstinent control group (based on Wedick. 2013)

If you take a look at the data from the female participants (likewise overweight non-smokers, habitual caffeine consumers and, at the beginning of the study, 'dried out'; see figure 2), a different image emerges, in the women we do in fact see a transient rise in SHBG, which goes hand in hand with a decrease in testosterone, de to which the T/E ratio drops by -36% and -54% in the groups drinking caffeinated and noncaffeinated coffee respectively. Just as in their male counterparts, the levels did go back up in the second part of the study so that all values, including the SHBG levels were back in to normal after 8 weeks (please note changes in the 20% range are irrelevant and could be due to having a meal before the test, bad sleep, whatever).

The relative data tells only part of the story

Figure 4: Absolute values of the testosterone to estrogen ratio after 4 and 8 weeks; baseline levels were 16.2, 15.8, 18.2 in the caffeinated coffee, decaffeinated coffee and control group respectively. The data clearly shows: Coffee needs a PCT ;-)

If we do now take a closer look at the actual data and discard the comparison to the control group the scientists the picture becomes even more complex. After all the data in figure 4 clearly indicates that we are dealing with a combined effect here. It is correct that the ingestion of the caffeinated beverage had pronounced effects on the T/E ratio especially in the male participants, what the data in figure 1 does yet not tell you is the fact that this effect was also so pronounced, because simply stopping to drink caffeine reduced the T/E ratio from 18.1 to 8.4, i.e. by 54%(!).

Now this certainly reduces the effect size, but it does not totally negate the effect. After all the 'real' coffee drinkers (w/ caffeine) did still increase their T/E ratio from 16.2 to 24.2 -- a certainly likewise noteworthy increase of +29% that is however still far away from the exorbitant +189% increase compared to the poor guys who did not just lose their coffee, but also their virility.

So what does this tell use?

How cares about SHBG anyways? You should! After all there is relatively conclusive evidence that normal (not exorbitantly high!) SHGB levels have a protective effect against breast cancer in women and mechanistic evidence that they increase the risk of prostate cancer in men. In both cases SHBG acts independently via the largely ignored SHBG receptor that modulates the action of estrogens. Co-activation of SHBG and estrogen receptor in the prostate induces similar effect on prostate specific antigen secretion as DHT (Nakhla. 1997). Since estrogen alone does not have this effect, it is no wonder that stinging nettle root (Urtica dioica), with its SHGB inhibiting effect is a viable tool in the treatment of benign prostatic hyperplasia (Hryb. 1995). In the female breast, on the other hand, SHBG seems to " trigger a 'biologic' anti-estrogenic pathway" (Fortunati. 1999) and does therefore exert anti-instead of pro-carcinogenic effects.

I guess there are more than just the following three lessons to learn from this study, but at the moment these appear to be the most important ones for me:

1. The beneficial effects habitual coffee intake has on type II diabetes risk are, contrary to the scientists hypothesis, not mediated by its effect on SHBG.
2. In overweight men caffeine has a very shortlived beneficial effect on testosterone and the testosterone to estrogen ratio. After 4 weeks the levels do yet return to baseline, so this cannot explain the long-term benefits of habitual caffeine consumption either (maybe you should cycle caffeine instead of testosterone booster < I am just kidding ;-).
3. In overweight women, there is a similar, yet negative effect on testosterone levels, which is likewise transient and lasts less than 8 weeks. 
4. The caffeine ads to the 'pro-testosterone' effects, but even decaffeinated coffee has some effects.
5. Stopping "cold turkey" is not a good idea, when you are "on caffeine"

Now, what is important here is that we are dealing with overweight individuals, in whom the endocrine millieu is usually off. In particular, men tend to have reduced, women tend to have increased androgen levels (think PCOS). The effects we see after short-term withdrawal and the subsequent consumption of a non-negligible amount of 5 cups of coffee everyday could actually have corrective effects on the endocrine milieu, of which both, men and women could benefit, if they would last for more than 4-6 weeks. The detrimental effects of stopping, on the other hand, could be due to the sudden absence of the benefits of caffeine.

Regardless of whether you stop or start drinking coffeine, the endocrine "disturbances" are relatively short-lived and only further testimony to the fact that our bodies will always try to find a new "steady state" in what they consider normal.

Bottom line: There are a myriad of good reasons to drink coffee, getting more manly or more feminine is yet not one of them. Disappointed? Well, on the other hand this means coffee is no endocrine disruptor - and at least in this overweight population it seems to have a marginally beneficial baseline effects (thus the detrimental effects of abstinence).

References:

• Beaven CM, Hopkins WG, Hansen KT, Wood MR, Cronin JB, Lowe TE. Dose effect of caffeine on testosterone and cortisol responses to resistance exercise. Int J Sport Nutr Exerc Metab. 2008 Apr;18(2):131-41. 
• Fortunati N, Becchis M, Catalano MG, Comba A, Ferrera P, Raineri M, Berta L, Frairia R. Sex hormone-binding globulin, its membrane receptor, and breast cancer: a new approach to the modulation of estradiol action in neoplastic cells. J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):473-9.
• Hryb DJ, Khan MS, Romas NA, Rosner W. The effect of extracts of the roots of the stinging nettle (Urtica dioica) on the interaction of SHBG with its receptor on human prostatic membranes. Planta Med. 1995 Feb;61(1):31-2.
• Nakhla AM, Romas NA, Rosner W. Estradiol activates the prostate androgen receptor and prostate-specific antigen secretion through the intermediacy of sex hormone-binding globulin. J Biol Chem. 1997 Mar 14;272(11):6838-41.
• Wedick NM, Mantzoros CS, Ding EL, Brennan AM, Rosner B, Rimm EB, Hu FB, van Dam RM. The effects of caffeinated and decaffeinated coffee on sex hormone-binding globulin and endogenous sex hormone levels: a randomized controlled trial. Nutr J. 2013 Oct 19;11(1):86.

Measuring Overtraining; Phosphatidic Acid to Potentiate the mTOR Effects of Leucine? Plus: Built-in Serm in Menopausal HRT Blocks Breast Cancer, Creatine Bumps Up Performance Not Body Weight, Estrogen Timing & Brain NDMA Toxicity

Weight-supported sports such as cycling precipitate overtraining

"20%", that's the SuppVersity figure of the week. It tailors directly to the first item in today's installment of On Short Notice and denotes the amount of professional athletes who exhibit symptoms of overtraining syndrome at any given time in their career.

"The prevalence varies by sport and is thought to be highest in endurance sports requiring high volume intense training, such as swimming, triathlon, road cycling, rowing and, to a lesser extent, distance running."  (MacKinnon. 2000)

What all those sports (except for distance running) have in common are long training hours on 6 days per week for several months without appreciable time off. Notably, the chances of overtraining also increase, when the equipment supports your body mass. With weight-bearing activities, such as distance running, on the other hand, the risk of musculoskeletal injury limits training volume and therefore reduces the chance of "running" (literally) into overtraining.

Overall, there is however no group of athletes that is immune to training too long, too hard and without appropriate recovery times. And yes, this goes for power sports, such as weight lifting and judo, as well (cf. Callister. 1990, Fry. 1994)!

Identifying overtraining by psychomotoric evaluation  

When you come to think of it, it does actually stand to reason: Static and dynamic tasks for finger, hand, and arm movements, as they are assessed during a  series of tests to assess motor performance are a way better yardstick to determine the stress (over-)load on the central nervous system (CNS), than simply looking at "how much ya bench". Why? The nasty, creepy and easy to overlook form of overtraining happens largely in your head and your nerves, it's not muscular. Your skeletal muscle can be fully rested, while your central nervous system is at the verge of collapsing.

What does the motor-skill test measure? (1) steadiness (one or both hands) - assesses hand unrest, tremor; (2) inserting long pins (one or both hands) - assesses rate of arm and hand movements, precision of arm-hand movements, manual and digital dexterity; (3) tapping (one or both hands) - assesses wrist-finger speed

Usually the latter goes hand in hand with other not exactly exercise related stress symptoms such as nervousness, and the inability to cope with the imposed stress and piling-up difficulties. Therefore Paul et al. required that all the one-hundred 18-25y athletes (M=65, F=35; university to international level) from various athletic backgrounds, i.e.

• hockey (14%), volleyball (14%), basketball (13%), handball (12%), football (6%), cricket (2%),
• cycling (13%),  running (11%), kabaddi (8%),  swimming  (5%),  gymnastics (1%), and sprinting (1%)

to fill out a "classic" Training Stress Scale (TSS) questionnaire as well. The TSS is a 19-item scale to check the symptoms of acute overtraining which includes a subset of questions designed to assess  the ability of bouncing back mentally after setbacks and mistakes (REB).

Figure 1: Motor performance (steadiness error duration; inserting long pins task duration; tap hits) in 100 athletes grouped into low (LS), medium (MSG), and high (HSG) groups according to their scores on the TSS test (calculated based on Paul. 2013)

As you can see in figure 1 the results of the motor performance test did not just correlate with the data from the stress test questionnaire, they also depict a very good picture of the state of the nervous system, with highly significant difference between the highly stressed and almost certainly overtrained athletes (green) and their lightly stressed peers (figure 1, blue; stress data was assessed by the aformentioned TSS test).

Professional athletes rarely end up  like Christian Bale in the Machinist but as I discussed at length in a previous post, overtraining was one of the two pillars of the crazy regimen the actor used to starve himself into a state that hardly allowed him to perform in front of the camera.

Aside from the high correlation and the confirmation of the hypothesis that psychomotoric tests could prove a valid tool to access the training status of athletes and ambitious gymrats, the investigation yielded the following main results:

• The athletes with lowest training stress symptoms showed the highest reboundability (resilience) from their mistakes. 
• Increased intensity of training stress symptoms indicates attention deficit leading to poor psychomotor performance.
• Along with physical training, psychological training has to be considered as one of the eminent aspects of overall development of an athlete.

In order to maximize athletic performance, it is therefore more or less obligatory to "carefully and timely diagnose for any signs and symptoms for physical and psychological distress" (Paul. 2013). Needless to say that the combination of the TSS and psychomotor performance test offers a way to do just that - to monitor, control and optimize the training routine.

Phosphatidic acid a novel 'mTOR potentiator' for superior gains?

I somehow forget this one in the last installment of On Short Notice, but before the first supplements are going to hit the market (two of the authors have already filed a patent back in 2011 that hasbeen  published in June 2013; see De Ferra. 2013), I thought I'd briefly discuss the results of a recently published study on the potential ergogenic and muscle building effects of phosphatidic acid (PA) by Hoffman et al. (Hoffman. 2013).

The study that was published online in the Journal of the International Society of Sports Nutrition evaluated the effects of an 8-week resistance training on 16 resistance-trained men who had been randomly assigned to consume either 750 mg of PA or a placebo.

Figure 2: Effect of 8 weeks of strength training + post-wporkout amino acid supplementation with and without  750mg phosphatidic acid  per day (left) and ratio of beneficial, trivial and negative effects of supplementation on the respective outcome parameters (Hoffman. 2013)

As the data in figure 2 goes to show you, the supplementation regimen had beneficial effects almost all of the (except for the pennation angle, btw. where greater the angles of pennation, means translates to a smaller amount of effective force transmitted to the tendon), however not a single statistical significant difference was observed. And while the scientists assessment that the overwhelmingly beneficial effect of PA supplementation on lean mass gains is "very likely beneficial", this does not change that the 750mg of PA did not add to allegedly highly beneficial effects of the workout regimen.

Figure 3: Training protocol and amino acid content (in g/100g) of the post-workout supplement (identical in both groups).

Since all particpants had taken part in identical 4-day per week, split routine resistance training programs for 8-weeks (70% of their 1-repetition maximum (1-RM) for all exercises;  90-s rest period was required between each set, for all exercises; for the exercises check out figure 3) and were advised to consume a standardized post-workout protein formula (containing 36-g amino acid and collagen protein blend) mixed in a 500 ml commercial sports drink within 30 minutes post-exercise, the supplemental confounding factors were pretty tightly controlled. If anything but the consumption of the PA supplement would have been responsible for the inter-group differences this would therefore have to be related to

• the non-supervised training sessions at the subjects respective local gyms (training logs regardless of whether they are evaluated by "certified personnel", or not, can obviously be faked), and
• the absence of a prescribed nutritional regimen (the participants kept 3-day food-logs and were advised to stay on their habitual diet; no significant differences in total intake ~3,200kcal/day; according to Hoffman et al. likewise not statistical significant, but wrt to the the changes in body composition maybe noteworthy, were the -17% lower carb and +18.2% higher protein intake in the active = PA arm of the study)

Both the missing supervision, as well as the absence of a fixed nutritional protocol would however pertain to both groups and are thus likely to average out. Plus, they actually make the study more realistic. After all, you are interested in what happens if the average strength trainee (in this case young men with a mean age of ~23years, at least 1 year of training experience and a BMI of 27.7kg/m²) and not to 10 identical clones, don't you?

"So this stuff is not useful, right?"

Figure 4: Exogenous phosphatidic acid is metabolized to lysophosphatidic acid (LPA) in the body and LPA has been shown to work synergistically w/ leucine to increase mTORC1 activity (in vitro data from Winter. 2010).

Despite the "likely" and "very likely beneficial" effects on lower body power and lean body mass, of which only the latter could maybe have reached statistical significance with a larger number of participants (with only 20 subjects, i.e. 10 per group differences need to be more pronounced to reach statistical significance). It should be quite obvious that PA is probably not the next creatine.

Maybe the increased mTORC1 expression Winter et al. have observed upon co-incubation of leucine with LPA are not pronounced enough (figure 4). Or simply not necessary with enough leucine and insulin in the blood stream. After all, the Winter study also showed that basically identical effects were observed when the cells were incubated with leucine + insulin, instead of LPA + insulin (data not shown in figure 4).

So even if oral PA acts just like in-vitro LPA synergistically with leucine to activate the mTOR pathway (Fang. 2001; Winter. 2010; figure 4), the real world benefits in the study at hand are probably about as significant as the hypothetical 500g increase in net protein retention I discussed in he protein timing news earlier this week. Whether this may change with higher and/or more frequent doses in future studies remains to be seen, though. It does at least not appear to be impossible...

Additional news

• 'Built-in SERM' could help making post-menopausal estrogen replacement breast cancer proof At least this is what the results of a recent rodent trial that was conducted by researchers from the Division of Endocrinology at the Department of Medicine of the University of Virginia Health System in Charlottesville would suggest. Even in the absence of a progestin, which does have some ameliorative effects on the pro-carcinogenic effects of estrogen, the addition of the tissue-specific selective estrogen receptor modulator bazedoxifene (BZA) to the allegedly questionable, yet still widely prescribed conjugated equine estrogen (CEE) blocked the CEE- and, in a second control study, even the more potent E₂-stimulated ductal and terminal end bud growth of mammary gland and the corresponding estrogen-responsive gene expression (Song. 2013). 

• 

  Just like any athlete, man or woman who is interested in increasing his / her athletic performance, German Olympic lifter Julia Rohde could benefit from taking regular creatine monohydrate without necessarily running the risk of having to compete in a higher weight class (img sportzentrum-flora.de)

  5g creatine monohydrate (CM) per day helps soccer players to improve their game - or, more precisely, the time they needed to complete a standardized sprint running and dribbling test. And while you will probably not be surprised that CM supplementation did not affect the accuracy of their shots, you may very well be surprised that it did neither induce greater weight gain or any other changes in body composition (Mohebbi. 2013).
  
  The latter may also be interesting for athletes competing in sports where increased muscle mass can become an issue. After all, the results Mohebbi et al. present in the latest issue of the Middle-East Journal of Scientific Research would suggest that unless your training is geared towards increased muscle gain (which is obviously shouldn't be if that would be an issue for you) regular creatine, i.e. not the sugar laden 'cell-volumizers', can help you increase your performance in the absence of the (again, only for certain people) disadvantageous weight gain.
• Whether estrogen will save your brain cells or actually exacerbate the damaging effect of NMDA exposure depends on timing I guess you will all have heard of the protective effects of estrogen against N-methyl-d-aspartate (NMDA) toxicity. Now, a group of researchers from the University of Catania and the University of Rome Sapienza,both obviously in Italy, found that only pretreatment with estrogen will provide these beneficial effects, while the co-incubation or subsequent administration of estrogen will only potentiate the NMDA-induced cell death (Spampinato. 2013)

Have a nice weekend, everyone! As far as the On Short Notice items go, that's it for today. If you want more, just check out the SuppVersity Facebook Wall. I must forewarn you, though, since I am pretty busy this weekend, I am not sure if there will be another installment of the Athlete's Triad Series, tomorrow. If that's not the case, you will however get a regular news item, so don't worry you won't get bored ;-)

References:

• Callister R, Callister RG, Fleck SJ, Dudley GA. Physiological and performance responses to overtraining in elite judo athletes. Med. Sci. Sports Exerc. 1990; 22: 816–24.
• Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J: Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 2001, 294:1942–1945.  
• De Ferra L, Heuer M, Hagerman S, Purpura S, Jäger R. Method for increasing muscle mass and strength. Filed November 23, 2011. US 2013/0141448 A1. Published on June 7, 2013.
• Fry AC, Kraemer WJ, van Borselen F et al. Performance decrements with high-intensity resistance exercise overtraining. Med. Sci. Sports Exerc. 1994; 26: 1165–73. 
• MacKinnon LT. Special feature for the Olympics: effects of exercise on the immune system: overtraining effects on immunity and performance in athletes. Immunol Cell Biol. 2000 Oct;78(5):502-9.
• Mohebbi H, Rahnama N, Moghadassi M, Ranjbar K. Effect of Creatine Supplementation on Sprint and Skill Performance in Young Soccer Players. Middle-East Journal of Scientific Research. 2013; 12 (3): 397-401.
• Paul M, Khenna N, Sandhu JS. Psychomotor analysis of athletes under overtraining stresss. Serb J Sports Sci. 2013;6(3): 95-10.
• Song Y, Santen RJ, Wang JP, Yue W. Effects of the Conjugated Equine Estrogen/ Bazedoxifene Tissue-Selective Estrogen Complex (TSEC) on Mammary Gland and Breast Cancer in Mice. Endocrinology. 2013 Oct 15.
• Spampinato SF, Merlo S, Molinaro G, Battaglia G, Bruno V, Nicoletti F, Sortino MA. Dual Effect of 17β-Estradiol on NMDA-Induced Neuronal Death: Involvement of Metabotropic Glutamate Receptor 1. Endocrinology. 2013 Oct 17.
• Winter JN, Fox TE, Kester M, Jefferson LS, Kimball SR: Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway. Am J Physiol Cell Physiol 2010, 299:C335–C344.

SuppVersity Science Round-Up Seconds: Topical Stevia Ointment and Oral Stevia Both Speed Up Wound Healing & Fight Bacteria. + Kinesio Taping, Exercise vs. Parkinson's and Non-Permanent Infertility Due to Low Dose Finasteride

The SuppVersity Science Round-Up live on SHR Thursdays 1PM EST!

As expected, Carl and I did not get to all of the potential topics in yesterday's installment of the SuppVersity Science Round Up on Super Human Radio (download the podcast here). The topics we covered were awesome (the protein study that was in the news, yesterday; nitrate supplementation; breast cancer and health benefits of minimalist multi- or rather tri-vitamins), but even the promised stevia based wound ointment did not make it into the 68min show (yeah, we went longer, once again). Therefore, it seems only logical to give you a brief summary of what you have or have not been missing in yesterday's installment of the thursdaily SuppVersity Science Round Up.

Alright, why don't we just start with the wound ointment and finish up with a brief mash-up of selected pieces from the 2nd line?

Stevia wound ointment improves tissue regeneration after incision

In a recent study that was conducted the St Johns College of Pharmacy in Bangalore, India, Kuntal Das investigated the effect of an easily compounded stevia containing wound ointment on the wound healing process of a pretty hefty excision wound that was 2.5 cm in width (circular area = 4.90 cm²) and 0.2 cm deep on the back of male Swiss Albino mice  and compared the results to a longstanding standard treatment (in the developing world still the goto ointment to be applied) with povidone-iodine, a stable chemical complex of polyvinylpyrrolidone and elemental iodine.

Stevia: Drink it, eat it, rub it, ... !?

How to prepare your own wound ointment: (1) Go and buy some decolorized 80%+ stevia extract and a parafin wax carrier wherever you want (2)  Mix the stevia into the white parafin base so that you get a 5/95 ratio of stevia to parafin.

Upon examining the wounds of the rats after 14 days of topical application of the self-made stevia ointments with a 2.5% and 5% w/w stevia content, Da found that the overall healing rate was dose dependently increased in the stevia group (Da. 2013):

• the rate of wound closure was significantly higher
  
• there was a decrease in the period of epithelialization 
  
• the skin breaking strength increased,
  
• the weight of the granulation tissue was decreased,
  
• the hydroxyproline content was elevated, and
  
• the wound surface microbial load decreased
  

In view of the anti-inflammatory effects of stevia and the recent news on similar effects being observed with a likewise anti-inflammatory curcumin ointment on burns (see "Curcumin to treat burns"), these improvements in wound healing and the formation of new unscarred tisse probably don't come as a surprise. With more and more germs becoming resistant to standard antibiotics, another item on the "benefit list", namely the anti-microbial effects of the topically applied stevia ointment, could however turn out to be of greater importance, than a speedier wound closure, anyway.

Figure 1: Effects of stevia ointment containing 2.5% or 5% stevia extract on excision wound surface microbial load (in CFU/ml; left); effect of orally administered stevia on parameters of wound healing (data expressed relative to untreated group; middle) and on on excision wound surface microbial load (in CFU/ml; right)

And if you are not into rubbing anything on your wound, I guess you will be happy to hear that similar, yet obviously less pronounced effects can be achieved if you simply eat or drink ~1.5-3g of 80% pure stevia extract per day - I know that's plenty, but this is the human equivalent dose of the 250-500mg/kg the rodents in the Da study received... what? No, I don't know if stevia suppositories will work as well, but maybe you could ask Mr. Da, if he was interested in doing another study ;-)

Selected additional "news quickies" that did not make it into yesterday's show

• 

  Suggested read: "Stretching before a workout can make you weak"

  Proprioceptive Neuromuscular Facilitation versus Kinesio Taping Application. In a recent crossover study with male healthy, physically active subjects, both regimen provided similar beneficial results in terms of the first-felt and maximum tolerant-felt range of motioncompared to control.
  
  Contrary to the correctly applied kineseo tape (just bandaging yourself all over with packaging band won't cut it, guys ;-), the proprioceptive neuromuscular facilitation protocol did yet not blunt the post exercise increase in hamstring muscle stiffness and the concomitant decrease in maximal knee flexion peak torque at 180 °/s that occured to similar extends in both the PNF and the no-stretch control condition (Chen. 2013).
• Treadmill running protects "Parkinson's mice" from neuronal loss. Listen up guys, even though you may not have been so concerned about the +117% and +236% increase in breast cancer risk in non-exercising and non-exercising women, who were also under psychological stress, Carl and I talked about on yesterday's show, you are by no means off the hook. After all, men may be (relatively) protected against breast cancer, but on the other hand more likely to develop Parkinson's. And as if that was not bad enough, the symptoms will also be more severe in men than in women (Haaxma. 2006).
  
  

  

  Just in case you forgot: Among tons of other health benefits, moderate daily caffeine intake in amounts similar to what you would get from 3 regular cups of coffee  (300-450mg) appears to exert protective effects against Parkinson's, as well (read more)

  Against that background, you are probably either relieved (if you are a physical culturist) or annoyed, when I am telling you that a recent rodent study clearly demonstrated how 30 min of aerobic exercise (as good as mice with existing MPTP/P induce "Parkinson's" can "exercise" on a treadmill) prevented further loss of nigrostriatal dopaminergic neurons, and ameliorated existing motor balance and coordination dysfunction (Sung. 2013).
  
  These results do by the way stand in line with recent findings from a human study by Abrantes et al. who found that "[c]ovarying for age and gender, higher levels of physical activity were associated with significantly less fatigue, as well as a trend for less apathy and depression and greater positive affect." (Abrantes. 2013) - regardless of the type of exercise the patient wanted / could still perform, by the way!
• Infertility due to finasteride usage: While it's real, it's rarely permanent As a recent case report that has been published ahead of print in the online edition of International Urology and Nephrology ealier this week shows, the "prolonged [8.5 years] use of low-dose [1 mg daily] finasteride for androgenetic alopecia" can induce DNA damage to sperm, which- in this particular case . rendered a 40-year old patient totally infertile (I don't want to think about what happened if the sperm was only "mildly damaged", though).
  
  With respect to the underlying mechanism, Ahmet Salvarci and Okan Istanbulluoglu, two researchers from the Rumi University in Meram, Konya  (Turkey) state:
  

  "It was reported in an in vitro study that dihydrotestosterone promoted the expression of claudin-11, the protein component in tight junctions between Sertoli cells. It has been shown that finasteride may cause a disruption of tight junctions and trigger a cascade of immunologic reactions, by causing germ cell atresia. Although the significance of dihydrotestosterone in spermatogenesis is not fully understood, the absence of this molecule may cause spermatogenic failure." (Salvaci. 2013)

  Now, the good news is, after the treatment was discontinued, the sperm recovered - slowly and from generation to generation, so to say, but it did- contrary to what dozens of horror stories on the Internet will make you believe,  eventually recover: 11 months after taking the last 1mg pill of the type II 5a-reductase inhibitor that blocks the conversion of testosterone to DHT (read more about 5-alpha reductase), his sperms DNA had recovered and his wife became pregnant. She gave birth to a healthy a baby boy and they lived happily... ah, wrong genre ;-)

So, that's it for today, but there are more news on Facebook and of course the official saturdaily installment of On Short Notice, tomorrow. So, stay tuned!

References:

• Abrantes AM, Friedman JH, Brown RA, Strong DR, Desaulniers J, Ing E, Saritelli J, Riebe D. Physical Activity and Neuropsychiatric Symptoms of Parkinson Disease. J Geriatr Psychiatry Neurol. 2013 Aug 20.
• Chen CH, Huang TS, Chai HM, Jan MH, Lin JJ. Two Stretching Treatments on Hamstring: Proprioceptive Neuromuscular Facilitation versus Kinesio Taping Application. J Sport Rehabil. 2013 Oct 11.
• Das K. Investigation of wound healing potential of aqueous crude extract and ointment of Stevia rebaudiana Bert. in mice. Asian Pacific Journal of Tropical Biomedicine. 2013: 1-6.
• Haaxma CA, Bloem BR, Borm GF, Oyen WJ, Leenders KL, Eshuis S, Booij J, Dluzen DE, Horstink MW. Gender differences in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2007 Aug;78(8):819-24.
• Salvarci A, Istanbulluoğlu O. Secondary infertility due to use of low-dose finasteride. Int Urol Nephrol. 2013 Oct 16.
• Sung YH, Kim SC, Hong HP, Park CY, Shin MS, Kim CJ, Seo JH, Kim DY, Kim DJ, Cho HJ. Treadmill exercise ameliorates dopaminergic neuronal loss through suppressing microglial activation in Parkinson's disease mice. Life Sci. 2013 Oct 12. pii: S0024-3205(12)00590-5.

Science Round-Up Seconds: DHA, Algae Oil, Fish Protein, Insulin Sensitivity, Fat Loss & Muscle Gain. Plus: Night Shifts & BPA = Pro-Carcinogenic From Breast to Prostate

It's somewhat ironic that Nurse's are one of the three high risk groups for breast cancer, because they work night shifts to help others. Who the other two groups are? Female military personnel and flight attendants on international flights.

If you did already listen to yesterday's installment of the Science Round-Up, you should actually be able to connect the dots between both, the first and second course of today's installment of the Science Round-Up Seconds, and the studies on the effects of DHA on fatty acid metabolism, as well as the fallacies of insufficient, interrupted, or irregular sleep Carl and I have been addressing, yesterday.

If all that does not ring a bell, I suspect you missed the show and have not had a chance to listen to the podcast (as usual the Science Round-Up starts in the 2nd hour of the show), yet. In this unfortunate case, I'd suggest you do at least start downloading the file while you take the first bite of today's two course menu ;-)

More things fishy from proteins with funky names to DHA and fish protein

Pollachius virens (Photo: Tino Strauss) is king, when it comes to the n:3/n:6 ratio, but with <1% of fat you will still be hard pressed to get tons of omega-3s from eating pollock... but is more really better, let alone necessary? Learn how to make the right fish choices here.

(Lane. 2013; Vikøren. 2013) -- Actually I wanted to title this one "Some Things Fishy", but then I remembered that there is already a SuppVersity post with this title, one I am still not able to make head or fin... ah, pardon tail of, by the way, because it clearly suggest that the consumption of oxidized fish oil is not a problem. Be that as it may, these are the SuppVersity Science Round Up Seconds, so the "more" does not refer to the said SuppVersity post on oxidized fish oil, but rather to the 70x* increase in the expression of a protein called Angiopoietin-like 4, which controls the availability of fatty acids for fuel I mentioned during the podcast (*the differential response for DHA was elucidated in a separate study on isolated rat hepatic cells, the general effect was however observed in a human trial, where all tested fatty acids, not just DHA, produced 11-12x ANGPTL-4 increases).

In view of the more of less undisputed benefits of having reasonable amounts of DHA (400mg) in your diet, it would obviously be nice if we could increase our intake of this relatively scarce omega-3 fatty acid in our diet, without having to resort  to fish and fish oil caps. A recently published overview of vegetarian dietary sources of omega-3 fatty acids by Katie Lane and her colleagues does however confirm what you've heard both Carl and me say on previous episodes of the SuppVersity Science Round Up, already.

The conversion of alpha linolic acid (ALA, the short-chain version of omega-3) from nuts (walnut) and seeds (flaxseed, echium) to DHA is literally zero. 

According to he researchers' review of the literature, only the ingestion of oils that were derived from micro-algae provide some, albeit preliminary evidence to support their usefulness as dietary source of DHA. The number of studies is yet relatively limited and "further research is necessary to evaluate optimal doses" (Lane. 2013) of respective supplements and/or food additives for "functional foods" (how I hate this word)

Micro-algae oils are not fish, though, and thus you would once more be missing out on the unique synergy only real foods have to offer: The fish proteins!

If you are not one of the many new visitors who have found their way to the SuppVersity only recently, the keyword "fish protein" should actually ring a bell... exactly! That's the stuff that has previously been shown to have astonishingly pronounced effects on glucose metabolism. Effect that have initially been observed in rodent studies and are not being replicated in human trials. Trials such as the one by Vikøren and his colleagues from the University of Bergen who report in their latest paper that was February issue of the British Journal of Nutrition that the provision of 3 g/d of a cabbed fish protein supplements for the first 4 weeks and 6 g/d for the last 4 weeks of a 2 months placebo controlled intervention study effectively and significantly

• 

  Table 1: Amino acid composition of fish, whey and casein protein (Hall. 2003; Vikøren. 2013)

  lowered the values of fasting glucose
• 2 h postprandial glucose and glucose-area under the curve,

• increased the important early insulin and 
• decreased the detrimental late insulin response to glucose ingestion 

• reduced the amount of  LDL-cholesterol (P< 0·05) and

• led to increases in lean (+0.8%) and decreases in fat mass  (-1.6%)

compared to the calorie-free placebo. Pretty impressive results, right? That's particularly true in view of the fact that neither the food intake nor the physical activity levels changed in the course of the 8-week intervention period.

What's that: Fish protein + fish oil? (Almost) whole fish, right!

Fish happens to be a way better source of taurine than the sperm of this Belgian Blue. There is in fact so little taurine bull sperm that it is "supplemented" with this amino acid in order to keep it fresh and stable and have it survive refrigeration. Apropos, you do remember that taurine can boost testosterone levels up to 250% - at least in rodents?

The obvious question therefore is: How does that work? The scientists don't provide a satisfactory explanation and to be honest, I have nothing more than a couple of half-assed hypotheses either. My best bet, and I am suggesting that despite the fact that a recent post of mine was entitled "Don't Judge a Protein By Its Amino Acid Content", would in fact be the amino acid content. If you take a look at table 1 it is obvious that the cod protein the scientists used in the study contained one amino acid you as a SuppVersity reader should by now be familiar with and neither whey, nor casein or any of the other standard proteins has to offer: Taurine!

Yet despite the fact that taurine has the potential to boost testosterone levels, increases insulin sensitivity and has in fact been shown to actively reduce body weight in a 2003 human study by Zhang et al. (Zhang. 2003), I am not sold on the idea that the relatively minor total quantity of taurine in the already low amount of fish protein (I mean 8g?) is the only reason for the non-negligible health benefits the scientists observed in their 10 male and 10 female participants (BMI 31-37kg/m²). Maybe it's another of those funky di-peptides you've read about in the context of the nutrient repartitioning effect of whey protein hydrolysate, only lately.

Regardless of what exactly it may be that facilitated the improvements in blood glucose management and the minor, but significant improvements in body composition, the health benefits you can derive from the consumption of cod protein make the notion of fish oil, let alone micro-algae oil supplementation appear even more retarded, when eating fish once or twice a week offers a way more natural and unquestionably more tasty solution to satisfy your DHA requirement.

Night shifts and breast, BPA and prostate cancer

There are two clockworks operating parallel in your body. The one in the brain has to be hacked by light exposure (learn more about "Sunlight a la Carte"), the one in your liver and other peripheral organs, on the other hand, can be (re-)set by specific feeding strategies, like Intermittent Fasting (learn more)

I simply assume that you have by now downloaded and listened to the podcast and are thus aware of what I said about the importance of rythmicity (if you did not really get the notion, I suggest you read up on the posts in the SuppVersity Circadian Rhythm Series to get a better grasp of the different clocks that are ticking in your body ;-) Exactly this kind of rhythmicity is continuously disturbed when you are either switching back and forth from day- to night-shifts or work the night-shift continuously and dare having a social life that's simply not compatible with sleeping all day and waking all night.

That the life of a nurse, for example takes it's toll on your health and precipitates not just the development of breast cancer (+36% after 30 years of rotating night shifts; Schernhammer. 2001), but colorectal cacers (+35% after 15 years of rotating night shifts; Schernhammer. 2003) and endometrial cancer (+47% after 20+ years and even +109% in obese women; Viswanathan. 2007), as well, has been debated ever since the early years of the 21st century.

With the recent publication of two meta-analyses the debate probably will not be over; and that despite the fact that even the less unsettling analysis by Kamdar et al. reports increases in breast cancer risk of +21% for women "with ever night-shift work exposure" (Kamdar. 2013).

"Subgroup analyses suggested that flight attendants with international or overnight work exposure and nurses working night-shifts long-term were at increased risk of breast cancer." (my emphases in Kamdar. 2013)

While the Kamdar study also included observational data, this 2nd meta-analysis, which was likewise published less than a week ago, included only case-control and cohort-studies yielding risk increases of +32% and +8%, respectively (Jia. 2013). Somethin else thatg may be worth mentioning is the fact that both, the studies the scientists ranked as "high quality" research, as well as the only existing study involving female military personnel observed even higher risk increases of +40%.

Despite methodological differences and slightly different outcomes of the two meta-analyses, both research groups do reach very similar conclusions stating that the evidence is still "weak", but does "support previous reports that night-shift work is associated with increased breast cancer risk" (Kamar. 2013) and that "large-scale epidemiological studies are needed" (Jia. 2013).

From breasts to prostates ;-)

Figure 1: Effects of 4-days of BPA injections at different dosages on systemic hormone levels (Castro. 2013)

I know the subheading sounds somewhat gross, but there are certain parallels. For one, there is the same need for large-scale epidemiological studies on the connection between BPA exposure and the development and malignancy of prostate cancer as it is the case with breast cancer and night shifts. On the other hand, BPS of which a recent study was now able to show that it messes with the aromatase and 5-alpha reductase activity in the prostate and can thus precipitate prostate cancer even in adulthood (Castro. 2013), is unquestionably relevant for the development of breast cancer, as well.

What's more, the reductions in 5α-R1 and 5α-R2 Castro et al. observed in their previously healthy, adult rodents after only 4-days of BPA injections at doses of 25, 50, 300, or 600 µg/kg per day and the concommitant increase in the expression of the third isoform of 5-α reductase (5α-R3) does not only precipitate cancerous growth, it's also a recently proposed as a biomarker of cancer malignancy. In conjunction with the quasi-reversal of hormones (see figure 1), the results of this study, which happens to be the first one to demonstrate such profound detrimental effects on mature mammals, should remind us of the fact gestation and early childhood are not the only time-points in our lives, we have to beware of endocrine disruptors.

---

That's it for the Seconds and in case you are missing the information about fruits and vegetables, I will serve those tomorrow as part of the as of in fact short, but way more numerous "Short News". In case you are still hungry for more, I suggest you make take a slight detour to the SuppVersity Facebook Wall before you you sally into the weekend. There are a couple of appetizers waiting for you there:

• 

  "Does the Usefulness of Vitamin E Supplementation Depend on Your Activity Level?" While the marathon runners in the facebook study took only 50IU, 400IU is what most supplements have to offer as a minimum. Is that too much, for you? Do athletes need more? What about the hormetic response to exercise - it it even hormetic? (learn more)

  EGCG is an "anti-folate" - You still don't have to worry, nature has made sure that those who value the synergy of whole foods, or in this case drinks, won't be harmed (read more)
• LOW(!) doses of vitamin C & E (125mg & 50IU) don't diminish the benefits of exercise - On the contrary, in marathon runners that's enough to blunt the neutrophil damage (read more)
• Smart Kids = Lean Adults  - General intelligence as assessed in childhood has a significant and direct effect on adult obesity risk (read more)
• Valine, vanadium and oxygenated water - All useless for athletes. That's at least what the latest installment of the "A–Z of nutritional supplements" says (read more)

When you are done with those, it's about to start news fasting, for a couple of hours until tomorrow's morning news (for you probably today's late evening news) will be published on Facebook. Have a great "Post-Valentine's Day", everyone - I just  hope your spouses were happy with their presents ;-)


References:

• Castro B, Sánchez P, Torres JM, Preda O, Del Moral RG, Ortega E. Bisphenol A Exposure during Adulthood Alters Expression of Aromatase and 5α-Reductase Isozymes in Rat Prostate. PLoS One. 2013;8(2):e55905.
• Hall WL, Millward DJ, Long SJ, Morgan LM. Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr. 2003 Feb;89(2):239-48.
• Jia Y, Lu Y, Wu K, Lin Q, Shen W, Zhu M, Huang S, Chen J. Does night work increase the risk of breast cancer? A systematic review and meta-analysis of epidemiological studies. Cancer Epidemiol. 2013 Feb 8.
• Kamdar BB, Tergas AI, Mateen FJ, Bhayani NH, Oh J. Night-shift work and risk of breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2013 Feb 12. 
• Lane K et al. Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: a review of the literature. Critical Reviews in Food and Science Nutrition. February 2013 [Epub ahead of print].
• Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA. Rotating night shifts and risk of breast cancer in women participating in the nurses' health study. J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8. 
• Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Fuchs CS, Colditz GA. Night-shift work and risk of colorectal cancer in the nurses' health study. J Natl Cancer Inst. 2003 Jun 4;95(11):825-8. 
• Vikøren LA, Nygård OK, Lied E, Rostrup E. Gudbrandsen OA. A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults. British Journal of Nutrition. 2013; 109:648-657.
• Viswanathan AN, Hankinson SE, Schernhammer ES. Night shift work and the risk of endometrial cancer. Cancer Res. 2007 Nov 1;67(21):10618-22.
• Zhang M, Bi LF, Fang JH, Su XL, Da GL, Kuwamori T, Kagamimori S. Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects. Amino Acids. 2004 Jun;26(3):267-71. Epub 2003 Dec 15.