Vitamin(S!) E, The Whole Picture: Delta Tocopherol a Rising Star in Cancer Protection

Those of you who have attentively followed my dissertation on fish oil (cf. SHR: ProfDrAndro talking on the Pros & Cons of Fish Oil) may remember that - as an aside - I mentioned that not alpha-tocopherol, which is what supplement companies add to their fish oils, but delta-tocopherol would be the anti-oxidant of choice to protect the highly oxidizable oil from going rancid.

Figure 1: Toco-8, one of the few
tocotrienol products on the market

A very recent report (Li. 2011) on findings of scientists from The State University of New Jersey is only one out of a whole line studies that imply that the real health value of "vitamin E" (we should better start writing "the vitamins E") does not lie in one, but in the combination of the tocopherols (alpha, gamma, delta) and the naturally ocuring tocotrienols, of which both the delta-tocopherol, as well as the group of tocotrienols have long been overlooked in the course of what one should probably call the "alpha-tocopherol"-hype.

According to Li et al., of the three tocopherols (alpha, gamma, delta @ a human equivalent dose of 800IU) the scientists fed to mice, which had previously been "infected" with "human lung cancer H1299 cells", the "δ-Tocopherol inhibited tumor growth most strongly" (delta > gamma > alpha). And with reference to the underlying mechanism of the observed superiority of delta-tocopherol to the two other isomers, the scientists argue:

The higher activity of δ-T in the inhibition of tumor growth corresponded well with its ability to inhibit the formation of 8-OHdG, γ-H2AX, and nitrotyrosine as well as to induce cell apoptosis.

With 8-OHdG being a marker for oxidative stress, γ-H2AX being a marker for cellular damage and nitrotyrosine being a reactive derived from nitrogen species and tyrosines in proteins, these findings suggest that delta-tocopherol protects against oxidative stress and cellular damage, and, at the same time, facilitates apoptosis of cancerous cell lines (on a side note: a characteristic feature of cancer is that the "normal" and healthy programmed cell death does not occur). Alpha-tocopherol, on the other hand, has "little or no influence" on these parameters.

If one also takes into consideration that the tocopherols appear to displace each other...

[...] dietary γ- or δ-tocopherol, however, decreased serum α-tocopherol levels, and dietary α-tocopherol decreased serum levels of γ-tocopherol.

...it is becoming more and more obvious that supplementation with isolated tocopherols, as it has been the case in many of the inconsistent studies on the effect of "vitamin E" on cancer, is not warranted.

So, if you decide to copy the study and supplement 800IU of vitamin E, make sure it comes from a source of "natural, mixed tocopherols" or even better tocopherols & tocotrienols, of which S. Wada in a very recent review (Wada. 2011) on the effects of vitamin E on cancer writes:

Vitamin E, especially tocotrienols, seems to be a potent agent for cancer prevention, however no large-scale clinical trial on the cancer prevention effect of tocotrienols has been conducted yet. Therefore it is expected that clinical trials overcoming the lower bioavailability of tocotrienols will be conducted, and it is urgently needed to assess the safety and the efficacy of the administration of the tocotrienols as a part of a cancer prevention regimen.

Ah, and don't forget: The SuppVersity is the place where you will read about these studies first ;-)

Algae Cake: Delicious & Healthy!? Wait Until You Learn that it is a Waste Product of Biofuel Production

Despite the Fukushima disaster and the possible contamination of seafood and algae from the pacific ocean, seaweed still has a very good reputation among the health & longevity "experts" (especially those who happen to sell respective supplements).

Figure 1: Algae cake (left) and differently processed algae (right);
pictures as they appear on homepage of Dr V Sivasubramanian

And though I do not want to argue that there are lots of studies that indicate beneficial effects of eating whole algae or supplementing with certain constituents, I must say that I was somewhat puzzled, when I read about the "terrific" idea, a group of Indian scientists (Singh. 2011) has recently come up with. They want to use algal cake (basically a waste product of the production of biofuel from algae) as ...

[...] extremely valuable, high protein by-product of our system that will be used for the production of nutritional food additives, vitamin supplements, animal/fish feed and other valuable consumer products.

Somehow that reminds me of the economically clever, yet from a health perspective questionable practice of feeding cows and other cattle with fishmeal, another "by-product"  which has traditionally been produced from the waste products of the fishery industry and has - among other health problems - been implicated as a contributing factor to the rise of BSE infection, everyone seems to have forgotten about, these days... But, hey, these are just my 2 cents. If anyone of you has the chance to taste one of these outstanding "cakes" let me know how it did you ;-)

TARFU: LaBrada Nutrition Financed Study Finds no Effect of Super Charge Xtreme N.O. on Training Induced Increases in Muscle Size. Minor Effects on 1RM Max.

As mentioned in previous blogposts, I highly credit all supplement companies which - instead of just putting out untenable claims about the "steroid-like" effects of their products - spend a few bucks of their immense marketing budgets on research on how fantastic their products actually are. In the case of LaBrada Nutrition's Super Charge Xtreme N.O. it does yet seem that it would have been wiser to do some research before formulating their new "NO booster".

Other than the guys over at LaBrada Nutrition probably have hoped or even expected, the study (JSCR. 2011) that was published in the March issue of the well-known Journal of Strength & Conditioning Research found no "significant improvements in LBM over the placebo drink" and only minor increases in bench press 1RM and squat power, which may well be attributed to CNS stimulation due to the hefty 450mg load of caffeine each serving of Super Charge Xtreme N.O. contains.

Other than that, the "15 physically active, resistance trained, college age (19.5 +/- 0.269 yr) males" in the placebo group attained the same changes in body weight, body [as measured via dual-energy X-ray absorptiometry (DEXA)] and maximal strength in the rest of the 8 different exercises of their 3-day/week exercise regimen:

A main effect for time was identified for each of the 1RM strength measures tested (p<0.05) except biceps curls (p = 0.34). [....] Significant main effects were found for lean body mass (F1/22 = 20.32, p<0.001), but there were no significant group x time interactions for changes in LBM (F1/22 = 0.142 p = 0.710).

But let's be honest. Did you still believe an NO booster will improve your gains? I, for my part, take them for the feeling of being pumped up. And although I have not yet had the chance to test this particular product, I am inclined to believe that it will provide similar results as the classics like NO Xplode & Co - that kind of cosmetic pump you either love or hate.

Beet Root Juice Supplementation Improves Exercise Performance. Nitrate Content of the Beets Decreases ATP Turnover in High Intensity Exercise.

Nitrates have long been decried as toxic and dangerous and I bet, before their latest appearance to the supplement market, none of you would even have remotely considered to consciously increase his/her dietary nitrate supply. Yet, recent scientific studies confirm that nitrate (in moderate doses) is not only safe, but also has, its effects on vasodilation aside, quantifiable effects on exercise performance.

A group of scientists from the UK tried to find out the underlying mechanisms of the ergodicity of supplemental nitrate (Baily. 2011). Following a six day supplementation period in the course of which seven males (aged 19-38 yr) consumed 500 mL per day of either nitrate-rich beetroot juice (~300mg nitrate content) or placebo (PL, with negligible nitrate content). What they observed is best described as a "tuning effect" that was observable both, in the course of high, as well as in the course of low intensity exercise training.

During low intensity exercise, the pulmonary VO2 amplitude and thus the oxygen need during this kind of aerobic exercise decreased by -7%. An even more profound effect of nitrate supplementation was observed during high intensity activity (knee extensor exercises) where the ATP turnover decreased by -25%. These results stand in line with an overall increase in exercise tolerance of +25% in the nitrate supplemented group over placebo.

Other than a some other researchers had speculated, Baily et al. did not find any indications of a changed phosphate vs. oxygen (P/O) ratio in the muscle. The changes in ATP turnover a 6-day loading phase with dietary nitrate from beet root juice triggers, must thus be considered the underlying mechanism of the ergogenic effect of nitrates, which, as you may have notices, appear in various forms (amino acid nitrates, creatine nitrates, etc.) in recently released supplements - not without reason, as it turns out.

Taking a Week Off? Sudden 7-Day Exercise Cessation Perceived as a Strain by Highly Trained Athletes. Overtraining is the Culprit!

Did you ever decide to take a week off and felt like hell? Did you feel how the gym, a place of which, only two days before, you thought you would be happy not to see for at least a month, suddenly seemed to draw you in as a giant magnet? Yes? Then you are either an exercise addict or just a highly trained athlete (probably you are both), of whom a recent study (Zeller. 2011) published in the Israel Medical Journal reports that

exercise deprivation is associated with change in non-articular tenderness threshold and reduction in quality of life scores. 

I already hear the exercise junkie within you jubilating: "24/7, 365 days a year! That's the way to go. That's my way." Before you do fall for this misunderstanding, you'd better thing about possible underlying reasons for the sudden tenderness and the decrease in perceived overall health (-4pts out of 100) the 26 asymptomatic healthy athletes who regularly exercise 6.75 ± 3.65 hours a week reported after the 7 days intervention.
In fact, the scientists conclude that it is not the resting that fatigued them, but rather the constant exercise that prevented them from feeling their ever-increasing level of fatigue (keyword: overtraining):

[...] healthy individuals who have hypoactive function of the biological stress response systems unknowingly exercise regularly to augment the function of these systems. 

Aside from falling victim to the mainstream believe in the "more helps more"-principle, this almost pathological behavior, i.e. to blunt exhaustion by exhausting oneself even more, is unquestionably the central mechanism behind the commonly observed tendency of athletes, who are already severly overtrained, to 'naturally' ramp up training volume and/or intensity in order to achieve the short term satisfaction the increased nervous system stimulus provides. In the long run, however, this will inevitably lead to performance declines, total exhaustion, susceptibility to infections and injuries, and so on.

Bottom line: Take a week or two off every now and then. If you crash badly, you know it was about time ;-)

Confusing Study Results: Saliva Testing "Adequate" For Free Testosterone, Yet Way Off For Cortisol!?

Many of us spend a fortune on "hormone optimization", but when it comes to actually testing our levels, most of us are pretty cheap: "200$ for labs? No way I rather buy another test booster for that money - won't hurt, I guess!" And even, if we finally decide to test our testosterone levels, we will usually choose the cheapest and most convenient testing method: saliva testing. But is this an adequate way of assessing one's hormonal status? Although these tests have been around forever, nobody appears to be sure how reliable they actually are. A recent study (Caenegem. 2011) from the University Hospital of Ghent, Belgium, attempts to provide answers.

The researchers tested two saliva collection methods, chewing on a cotton swab (Salivette, Sarstedt) and passive drooling on 30 healthy males with a median age of 27 years (range 19–65 years) and compared their findings against serum levels, which were measured on the same occasion. Here are their results:

For cortisol, we observed a mean positive bias of 65% for passive drooling versus Salivette. In addition, cortisol determined on passive drooling samples correlated much worse with calculated free cortisol than cortisol analyzed on the cotton samples (respectively r=0.34 versus r=0.70). However, for testosterone passive drooling correlated well with the calculated free fraction (r=0.66). A positive bias of 21% for testosterone collected by passive drooling versus Salivette was observed. In contrast to earlier reports, we found no artefactually high testosterone results with the cotton-based collection method.

Obviously, these results seem to indicate that saliva testing for testosterone is a good, while saliva testing for cortisol is a bad idea, BUT these results are in fact intrinsically flawed. By just calculating free serum values instead of using equilibrium dialysis to actually measure them, the scientists' control values and with them their assessment of the "appropriateness" and "inappropriateness" of salivary testosterone, respectively cortisol testing are questionable. 

From what I hear from practitioners like Dr Crisler, it is highly advisable to spend the extra cash to have measured (not calculated) serum testosterone levels as reliable baseline and 4x saliva cortisol profiles to see where your levels are at throughout a 24h period. Arguably, this is yet another case in which a questionable study design leads to results which refute common practice and aggravate a confusion around hormonal testing procedures which affects practitioners and patients, alike.

DHEA the Slimming Hormone? Study Finds: Dehydroepiandrosterone Directly Inhibits Cortisol Synthesis in Rodent Adipocytes

After initially being hailed as the fountain of youth, the pharma-financed medical sciences dropped DHEA, when investors realized that a naturally occurring hormone would not be patentable. This and some discouraging and/or inconclusive results from long-term studies had DHEA literally disappear from the research scene for quite some time. Therefore, I am positively surprised that on the forthcoming European Congress of Endocrinology 2011 researchers from the Kobe University in Japan are going to present a paper (Tagawa. 2011) that shows that there may in fact be more to the initial findings of DHEA induced weight loss than follow-up studies would have it.

Tagawa et al. investigated the possible mechanism behind the weight loss effects of DHEA and found that there is a direct inhibitory effect of DHEA on glucocorticoid (re-)synthesis in adipose tissue:

Using differentiated 3T3-L1 adipocytes, we demonstrated that DHEA inhibited 11β-HSD1 activity at a concentration of 1 μM within 10 min. Inhibition was also observed in a cell-free system comprised of microsomes prepared from rat adipose tissue and NADPH, a coenzyme of 11β-HSD1. A kinetic study revealed that DHEA acted as a non-competitive inhibitor of 11β-HSD1. Further, DHEA did not inhibit 11β-HSD type 2, which inactivates cortisol or corticosterone in tissues involved in water and electrolyte metabolism, in rat kidney microsomes at a concentration <25 μM. Moreover, no conversion from DHEA to other sex steroid hormones or their precursors was observed under the present experimental conditions.

These are three significant observations. Firstly, the presence of DHEA inhibits the synthesis of cortisol via 11Beta-HSD1. Secondly, it does not prevent exogenous cortisol to be converted to the "inactive" cortisone via 11Beta-HSD2 and thirdly, the dreaded conversion into estrogen, testosterone or DHT does not take place. All this would make the naturally occurring hormone DHEA a perfect selective 11β-HSD1 inhibitor, of which Stewart et al. from the University of Birmingham write (Stewart. 2011):

Selective 11β-HSD1 inhibitors lower blood glucose, improve insulin sensitivity and cause weight loss in animal models. Biomarkers have been validated to confirm target inhibition in primate and human studies. Recent clinical trials show reduction in HbA1c and blood pressure in obese patients with diabetes mellitus who have failed on metformin therapy. Potentially the therapy offers a ‘magic bullet’ for patients with Metabolic syndrome with reduced blood glucose accompanying improved insulin sensitivity, lower lipids and blood pressure and reversal of hepatic steatosis secondary to reduced autocrine generation of cortisol in liver, adipose tissue, pancreas and muscle. Liabilities include activation of the HPA axis secondary to increased cortisol clearance with hyperandrogenism, though the extent and significance of this is debated.

One thing, though, before you now go about eradicating cortisol to zero. Your body needs a healthy level of cortisol to function. It goes hand in hand with thyroid hormone, helps you manage stress, perform in the gym and is even necessary to "burn" body fat. Again, moderation is key and you certainly want to know where you stand before you start tweaking your cortisol levels into the wrong direction.

There Are Two Sides to Each Coin: Vitamin D Increases Insulin Sensitivity in Obese, Yet Decreases it in Lean Mice

I am probably repeating myself, but I cannot emphasize enough that a common fallacy of medical research is the focus on pathologies. A recent example with respect to the "omnipotency" (that's what the Internet news could make you believe) of vitamin D comes from researchers at George Town University (GU. Press Release).

The scientists were able to replicate the results of previous studies, where high dose vitamin D supplementation had "significantly reduced development of estrogen receptor-positive (ER+) breast cancer", but for estrogen receptor-negative (ER-) breast cancer they found either no effect (lean mice) or even an increased rate of cancerous growth in the group of obese mice.

What's yet even more interesting that a similar contradiction was evident with respect to vitamin D's widely perpetuated beneficial effects on insulin resistance. In the pathologic model of the obese mice, vitamin D @ 15-25k IU per day was in fact able to ameliorate insulin resistance, in the lean, naturally insulin sensitive mice, however, insulin sensitivity was reduced by supplemental vitamin D.

As I've discussed it in the context of the most recent fish oil study (and will probably repeat for other "super nutrients"), in 99.9% of the cases the effect of - especially high dose - supplementation with ostensibly harmless "vitamins" or "nutrients" vary enormously depending on the subjects current nutritional and health status. To derive one-size-fits-it-all recommendations from individual studies and to transfer results obtained from a pathological model without further scientific investigations to a healthy one is careless and may turn out to be very dangerous.

Victorious Veteran: Creatine Monohydrate Still First Class! Usefulness & Safety of “Innovative” Creatine Formulas Questionable.

If we discount a high protein intake as a regular constituent of a healthy diet, creatine is unquestionable the King of Natural Ergogenics. Its impact on athletics way beyond the Gold’s Gyms of the bodybuilding world is evident from its being cited as “effective and safe” in almost each and every “position stand” published in one of the journals of the various sports & nutritional societies all over the world in regular intervals. Thus, with the (nephro-)toxity myth being finally dispelled, creatine has become a stable in the supplement regimen of both recreational, as well as professional athletes.

Now, the financial revenue you can make from a non-patentable amino acid that is commonly found in fish and meat products is obviously limited. Thus, the steadily increasing number of players on the supplement market is continuously trying to “reinvent the wheel”, by putting forward a new, better-absorbed, more effect, side-effect free or whatever else the marketing guys had on their minds forms of N-(aminoiminomethyl)-N-methyl glycine (=chemical formula of creatine). These “superior” forms of creatine are then put forward as the must have for every seriously training athlete and/or creatine non-responders (these are people, where – due to various not fully understood mechanisms – creatine has no measurable effect on performance, (intracellular) water retention and body weight) and usually disappear from the market just about at the same time, the first batch has been sold and disappointed customers begin to vent their anger on the blogs and bulletin boards of the fitness world.

With reference to the purported superiority of novel forms of creatine R. Jäger, one of the leading researchers in the field writes in a recently published paper (Jaeger. 2011), the results of which have previously been presented at the 2010 Creatine in Health and Sports conference:

[…] the efficacy, safety, and regulatory status of most of the newer forms of creatine found in dietary supplements have not been well established. Additionally, there is little to no evidence supporting marketing claims that these newer forms of creatine are more stable, digested faster, and more effective in increasing muscle creatine levels and/or associated with fewer side effects than CM.

In their extensive review of the literature Jäger et al. dissect many of the commonly held views on the purported “instability” and “low absorbtion rate” of creatine monohydrate, evaluate the different creatine contents of various supplemental forms and their individual solubility, stability and bioavailability. And while some other forms are in fact more soluble…

Creatine monohydrate dissolves at 14 g/L at 20°C resulting in a neutral pH of 7. A saturated solution of tricreatine citrate in water has a pH of 3.2; whereas a saturated solution of creatine pyruvate even has a pH of 2.6 (pyruvic acid is a stronger acid than citric acid). The decrease in pH results in an increase in solubility: 29 g/L creatine citrate at 20°C, and 54 g/L creatine pyruvate at 20°C. Normalized by the relative amount of creatine per molecule (monohydrate 87.9%, citrate 66%, pyruvate 60%), creatine citrate (19.14 g/L) shows a 1.55-fold and creatine pyruvate (32.4 g/L) a 2.63-fold better solubility when compared with the monohydrate (12.3 g/L).

The acidity of your stomach is high enough, anyway, so that even if you just swallow the powder it will eventually dissolve, when it comes in contact with your gastric acid - for monohydrate [CM] Jaeger reports the absorption to be as high as 99%.

Furthermore, pre-solving of creatine in water is counter-indicated, because, as Jaeger et al. write, …

[…] solution precludes the manufacture of shelf-stable standard ingredient. If creatine is not consumed immediately after it has been dissolved in water, it should be stored at a low temperature to retard the degradation.

So you better throw away your liquid creatine - chances are its 99% degraded even before you bought it from your retailer.

The instability is even more of concern in the case of Creatine Ethyl Ester (CEE) which has been found to be “actually less stable than CM.” (Child & Tallon. 2007).

CEE is mostly converted into creatinine under physiological conditions encountered during transit through the various tissues, suggesting no ergogenic effect is to be expected from supplementation of CEE.

The latter, i.e. creatine ethyl esther, is also less bioavailable, 

Figure 1:Changes in total muscle creatine content in response to placebo (PLA), creatine monohydrate (CRT), and creatine ethyl ester(CEE) supplementation (Spillane et al. 2009, cf, fig. 1).

and studies (Spillane. 2009) suggest that its higher rate of degradation to creatinine may pose a possible health risk.

Also, while Jaeger et al. report some evidence for the beneficial effects of co-supplementation with glucose, protein or (low dose) D-pinitol, I personally doubt that either of them is necessary to take advantage of the repeatedly proven ergogenic effects you can get from the cheapest, most researches, safest and easiest to obtain form of creatine – creatine monohydrate.

On a side note: My friends @ironmagazine.com have found an interesting study on the effect of creatine + nitrate, which is currently hyped as “the next big thing”. Although, I suppose that the amount of the carcinogen N-nitrososarcosine, which is a byproduct of their reaction, is hardly high enough to trigger cancerous growth, the lack of direct scientific evidence that creatine nitrate has any beneficial effect over the individual use of nitrates (for pump) and creatine (for performance) at least makes me wonder if you could not eat a buckload of beet roots (high in nitrate) with your creatine monohydrate to achieve the same effect ;-)

Green Tea Inhibits Fat Gain, But Will It Also Hinder Muscle Gain? Decreased Protein Absorption in Rats Supplemented With Green Tea Extract

It has gotten relatively quiet around green tea within the past weeks. Everybody knows about its anti-oxidant effects, its modest efficacy as a weight loss supplement and the relaxing effect of taking a time-out from the stressors of daily life with a good cup of freshly brewed tea. Now, scientists from Poland (Bajerska. 2011) found another interesting, yet not so beneficial property of green tea extract.

The scientists fed laboratory rats on a high fat diet chow with either 0%, 1.1% or 2.2% of green tea extract [GTAE] added and found that only the chow containing 2.0% GTAE had significant effects on body weight gain (5.6% less than control) and visceral fat accumulation (-17.8% vs. control). Yet, they observed a

[...] considerably (P < .05), reduction in the digestion of protein (but not fat) was observed in both GTAE groups (1.1% GTAE: 82.6% ± 1.8%; 2.0% GTAE: 84.3% ± 0.8%) when compared to the control (93.3% ± 1.5%).

This novel finding appears to stand in line with previous studies, in which green tea supplementation decreased fat absorption in the intestine. Interestingly, this effect was absent / non-significant in the current study (cf. figure 1).

Figure 1: Daily food intake, FER, apparent digestion of protein and fat, energy value of feces, and visceral fat content of treatment and control groups (Bajerska. 2011)

These findings have yet to be put into perspective, in order to assess how significant these results are for you, as a potential consumer of green tea supplements. Do you have to increase your protein intake if you consume one or two caps of green tea extract or the occasional cup of freshly brewed tea? Probably not. The rats in the study consumed 11g/kg, respectively, 20g/kg body weight of the extract. For a 80kg human being this would be a daily GTAE consumption of roughly 260g. Personally, even a teaspoon of GTAE makes me nauseous within minutes, so I guess none of you will even come close to this (over-)dose of supplemental green tea.

It is also noteworthy that, in view of the dose-response relationship between the amount of extract the rats consumed and its effect on their body weight, these results do also indicate that the amounts of GTAE you usually find in so-called "fat burners" will hardly have any direct effect on your body weight or fat, no matter what the respective supplement companies are telling you.

Connelly, Andrich, Norton, Arnold, Lenore, Andro - BodyRX #17: Carbohydrate Intake For People Who Will NEVER Settle for Being "Normal"

BodyRX guest: Pete Ciccone, 
national-level NPC
competitive bodybuilder

For those who missed out on yesterday's episode of the new, totally revamped BodyRX Radio Show, episode #17 "Carbohydrate Intake For People Who Will NEVER Settle for Being 'Normal'" is now available for download.

 The Body RX Show - Episode #17

I will compile a write up of the most significant facts and include links to some research on the coming weekend. So stay tuned!

If you wanna be Super Human,
the SuppVersity is the place to read
and SHR and BodyRX the shows to listen to ;-)

More on Putting Carbs to Good Use: Scott Connelly's BodyRX Show - Tune in Live at 12:00pm PDT

Who listened to my interview on Super Human Radio, yesterday, may have heard my advice to tune in to today's BodyRX Show with Dr. Scott Connelly, Vince Andrich, Layne Norton, Patrick Arnold and (this is new) me, ProfDrAndro, being the brains behind a completely overhauled show concept, I promise you won't be disappointed.

BodyRx Radio Show #017

Tune in Live @ 12pm PDT

Here is a short glimpse onto what is waiting for you:

On our last BodyRx Radio show (#016) we learned that by reducing carb intake from levels at the top of the food pyramid (>60% of energy) to a modest 35-40% of energy, you can effectively “teach” your body to preferentially store the carbs you eat into muscle cells and NOT your fat cells [cf. Effect of Macronutrient Composition]. But, when does reducing carb intake negatively impact your performance in the gym, where the work to build muscle takes place? More importantly, does that number change if you alter your training program? We take this age old question head on with:

• A revealing interview with renowned researcher Dr. Kevin Tipton by our very own Dr. Scott Connelly.
  
• Next, Vince Andrich taps into the minds of two of the industries top physique competitors and personal trainer/coaches; Pete Ciccone and his wife Meriza Deguzman––listen for their practical advice that men and women can use right NOW!
  
• Lastly,  renowned chemist Patrick Arnold will take on a list of hard hitting questions that will give listeners an inside look at the popular diet and energy compound; geranium. We know you’ll agree this is a one-of-a-kind interview since it was Patrick Arnold himself who brought this compound to the market several years ago, and is now the darling of the supplement world.

The prominent line-up alone makes it worth listening - no doubts about that, folks!

ProfDrAndro @ Super Human Radio: Set to Be Obese? Of Set & Settle Points on Your Way to a Super Human Physique

Just in case you got nothing else to do: Tune in live and listen to some more (probably Carl) or less (probably me ;-) intelligent Supp-Talk on Carl Lenore's Super Human Radio!

Topic: Set & settle points and how contemporary science
may contribute & explain your personal weight loss success

Update: available for Download now

Listen live @ 9:00AM AM/12:00PM ET

Epidemiological Study Shows Correlation Between Anti-Oxidant Intake and C-Reactive Protein & Homocystein

After a sudden onset of discussions around the beneficial or even detrimental effects of vitamin supplements in general and antioxidants in particular in the mid to late 2000s, vitamins and, even more, other anti-oxidants have been put back on the map, lately.

A recent epidemiological study from the University of Connecticut (Floegel. 2011) provides further evidence for the hypothesis that, after all, consumption of adequate amounts of vitamins C and E, beta carotene, flavonoids and selenium would be beneficial to your overall health

Intakes of vitamins C and E and carotene were inversely associated with the probability of having serum CRP concentrations >3 mg/l in multivariate logistic regression models. Flavonoid and Se intakes were not associated with the odds of elevated serum CRP concentrations. The mean plasma Hcy concentration was 8·61 (95 % CI 8·48, 8·74) μmol/l. Intakes of vitamins C, E, carotenes and Se were inversely associated with the odds of plasma Hcy [Homocysteine] concentrations >13 μmol/l after adjusting for covariates

While all these results appear to be quite unambiguous, you still have to keep in mind that they support the interpretation "antioxidants are healthy" only, if we assume that the relation between high C-Reactive Protein [CRP], inflammation and the metabolic syndrome, as well as the relation between homocysteine and heart disease is more than just a correlative one; and, to my best knowledge, no study has yet been able to show that injection of homocysteine caused heart disease or an increase in CRP increases inflammation or causes tissue damage. In this context, for example, the hitherto hardly understood involvement of "positive inflammation", such as an exercise induced rise in IL-6 levels, come to mind. In this context, studies such as Ristow et al. (2009) that found the positive effects of exercise being blocked by antioxidant supplementation would warrant further research into what - irrespective of reductions in purported markers of inflammation and cardiac disease - the actual health outcome of higher antioxidant intakes are.


Note: Don't get me wrong. I do not want to argue against a diet rich in natural antioxidants. I just want YOU to be aware that the proven health benefits from eating healthy, antioxidant-rich foods cannot be extrapolated to high (or even mega-dose) vitamin & flavonoid supplements and that taking megadoses of isolated antioxidants such as alpha-tocopherol (especially in its synthetic form and without the complementary tocopherols and -trienols), which is the most commonly sold form of vitamin E, may in fact do more harm than good.

Effects of Macronutrient Composition on Metabolic Signaling: Higher Protein Diet Favors Glycogen Storage in Muscle Over Adipose Tissue

Those of you who have already listened to the latest, revamped (and improved) episode of Dr Scott Connelly's BodyRx Show will already have heard of Suzanne Devkota's and Donald K Layman's study (Devkota. 2011) on the effects of different meal compositions on the postprandial glucose disposal. For the rest of you who have missed the episode and those of you who like their info white-on-black, here are the main results...

For 10 days, Devkota and Layman fed 60 rats a diet containing either 60% of energy from carbohydrates, 12% protein, 28% fat (CHO) or 35% carbohydrate, 35% protein, 30% fat (PRO) and evaluated plasma levels of insulin, glucose and C-peptide, as well as muscle and adipose tissue Akt, p70S6K and Erk 1/2 (markers of glucose and protein metabolism and cellular growth, respectively).

The graphs in figure 1 illustrate their most significant finding quite nicely. Other than in the case of the protein-fed rats, blood glucose is preferentially stored in fat tissue in the 30-90 min time window upon the ingestion of a meal in the high carb (CHO) group

Figure 1: Muscle and adipose tissue Akt expression (marker of glucose metabolism) after "high" protein (PRO) and high carbohydrate (CHO) meal, respectively (Devkota. 2011

The authors summarize this effect of macronutrient partitioning on metabolic signaling that is supported by the rest of their data as follows:

Animals chronically consuming the CHO diet produced greater metabolic signaling in adipose tissue to handle excess glucose and blunted signaling in skeletal muscle consistent with interpretation of insulin resistance. Conversely, animals consuming the PRO diet produced greater metabolic signaling in skeletal muscle with little signaling in adipose.

To fuel your workouts, it thus seems not only unnecessary, but even detrimental, to consume high amounts of carbohydrates. A "lower"  [note: even the high protein diet that was matched to the USDA's acceptable macronutrient distribution ranges (AMDR) had a carbohydrate content of 35% and thus a 1:1 protein to carb ratio!] carbohydrate intake, on the other hand, appears to prime your body to store glycogen primarily in muscle tissue. On a "high" protein, "lower" carb diet, you thus get the performance benefit without the unwanted fat gain and isn't this what we all are looking for?

Protein's Effects on Gene Expression: Higher Protein Lower Carbohydrate Diet Spares Gylcogen, Lowers Insulin and Reduces Lipogenesis

High protein diets have become the "gold standard" within the fitness community. On the countless bodybuilding, fitness and weight loss related bulletin boards on the Internet, athletes, gymrats and even overweight house-wives report outstanding benefits of a higher than normal protein intake on weight gain and/or fat loss. French scientists (Stepien. 2011) have now taken a closer look at the mechanism behind these success stories and found a strong (epi)genetic component (for an introduction to epigenetics, I recommend listening to Dr Rouse's interview series on Carl Lenore's Super Human Radio).

 Figure 1: Effect of high protein diet on genes regulating lipogenesis [lipo = fat; genesis = production] in the liver (Stepien. 2011)

Stepien et al. fed 80 male winstar rats either a normal or a high protein (50% protein) diet for 1,3,6 or 14 days and evaluated the mRNA levels [indicators of how active these genes are] of genes "involved in carbohydrate and lipid metabolism", energy expenditure (EE) and substrate oxidation, as well as liver glycogen, plasma glucose and hormones. What they observed stands in line with the positive anecdotal evidence you will find if you google muscle gain or fat loss "success stories":

    In liver, HP feeding 1) decreased mRNA encoding glycolysis enzymes (GK, L-PK) and lipogenesis enzymes(ACC, FAS), 2) increased mRNA encoding gluconeogenesis enzymes (PEPCK), 3) first lowered, then restored mRNA encoding glycogen synthesis enzyme (GS), 4) did not change mRNA encoding b-oxidation enzymes (CPT1, ACOX1, bHAD).

So, interestingly, with the exception of the 1st day of the experiment (where the increase in protein intake resulted in a short-term increase in fat oxidation), fat oxidation was stable (cf. 4) The "fat burning" effect, which is often ascribed to high protein diets, thus is not existent - or let's say its not a direct one, but a result of the synergy of other genetic and metabolic adaptations and the calorie restriction all weight loss regimens have in common.

Figure 2: Postprandial macronutrient balance as assessed during a 4 h period after the intake of a calibrated meal consisting of 4 g of an adequate diet.  (Stepien. 2011)

Here is where the insulin lowering effect, the reduced hepatic glucose uptake and the reduction in lipogenesis (cf. fig. 1) come into play. Combined with an overall increase in postprandial energy expenditure (observed only under long term high protein feeding conditions, cf. fig 2, HP14) and a slight but significant increase in the percentage of fat (LOX, fig. 2) that is used to fuel these demands, these genetic and metabolic adaption (most prominently the lower insulin levels and the reduction in lipogenesis) are the most probable mechanisms to explain the reduced fat gains and increases in fat loss on high protein weight gain and weight loss diets, respectively.

Muscle Building Takes Time. Less in Newbies, Though: 9.6% More Muscle in 8 Weeks

"Patience is a virtue!" Many bodybuilders and fitness enthusiasts have to learn this the hard way - even on drugs, muscles won't grow (hypertrophy) within days and visible gains in lean muscle mass will take years or month. Although the results of a recent study (DeFreitas. 2011) done by scientists from the University of Oklahoma won't help to overcome the delay between training induced muscle stimulus and physiological hypertrophy response, the observations of DeFraitas et al. are nevertheless interesting.

By the means of weekly testing the scientists wanted to determine the "precise time course of skeletal muscle hypertrophy" in response to 8 weeks on a specifically designed high intensity resistance training program in 25 healthy, sedentary men. The measured outcomes were whole muscle cross-sectional area (CSA) of the dominant thigh (via computer tomography) and isometric maximum voluntary contractions (MVC). 

After only two training sessions (W1) [=week 1], the mean thigh muscle CSA increased by 5.0 cm² (3.46%; p < 0.05) from the pre-testing (P1) and continued to increase with each testing session. It is possible that muscular edema may have inXuenced the early CSA results. To adjust for this possibility, with edema assumedly at its highest at W1, the next significant increase from W1 was at W3. W4 was the Wrst signiWcant increase of MVC over P1. Therefore, signifcant skeletal muscle hypertrophy likely occurred around weeks 3–4.

While edema, unquestionably, are one possible reason for the sudden increase in "muscle mass" being a 'sedentary newbie' to strength training may well be another factor contributing to the immediacy of the muscle gains (do not expect to see similar results as an experienced athlete!). The scientists reliance on sedentary subjects compromises the significance of the whole study (in view of what athletes and gymrats may expect), thus the measured overall gains, impressive +13.9 cm² (9.60%) CSA, appear hardly transferable to a "reasonably" trained group of subjects, as well.

Figure 1: Development of muscle size (measured as CSA of thigh muscle) and force (measured as MCV) in 25 formerly sedentary subjects on an 8 week high intensity strength training program (DeFreitas. 2011)

Comment: Its really a pitty that out of monetary and organizational reasons all these studies are done on newbies, whom you could send work on a construction site for 8 weeks and see immense gains in strength and muscles, when they do not get hit by a block of concrete. So, do not feel discouraged if - in the course of the whole last year, you did not gain +13.9 cm² in your tigh muscle. You are probably just to athletic already ;-)

Chrysine: 5,7-dihydroxyflavone for Bigger Balls and Higher Serum Testosterone

Polyphenols in general and flavonoids in particular are every supplement producer's favorite. Its so easy to pick up some exotic plant from somewhere deep down in the jungle, extract an exotic flavonoid, give it a fancy chemical looking name and provide some in-vitro data on his anti-oxidant omnipotence or whatever. In most cases the compounds disappear from the market within weeks, yet chrysine which is extracted from the Common Passion Flower, has been around for years. A recent study (Ciftcy. 2011) by Ciftci et al. provides further evidence that its market persistence may not be without a reason.

Over the time course of the scientists fed a group of lab rats 50 mg/kg chrysin (human equivalent ~8mg/kg) or placebo for 60 days and found:

that chrysin significantly increased GSH, CAT, GSH-Px and CuZn-SOD levels, but did not change the formation of TBARS significantly. In addition, sperm motility, sperm concentration and serum testosterone levels significantly increased, whereas abnormal sperm rate significantly decreased with chrysin treatment.

In essence the improvement in antioxidant markers (vs. placebo) went hand in hand with a measurable increase in sperm health and serum testosterone.

Figure 1: Testosterone levels of rats after 60 day intervention with 50mg/kg chrysin. (Ciftcy. 2011)

 "Great", well, maybe not so... although this is an almost 50% increase in testosterone, we do not know how other important hormonal parameters such as SHBG (binds testosterone and thus renders it basically useless), estrogen or cortisol looked like. An estimation of the "muscle building effects", the producers of respective supplements are advertising, is thus futile. And, if you asked my opinion, even if SHBG did not budge and we have an appropriate increase in free testosterone, the latter is probably too little to induce noticeable changes in strength and/or body composition.

Low Dose Caffeine Ameliorates Catabolic Effects and Increases AMPK and PPAR Expression During Reduced Food Intake in Mice

Caffeine, "the mother of all stimulants", has lately developed a bad reputation. Stress, Cortisol, Adrenal Fatique, Insulin Resistance etc. are only the most recognized buzzwords occurring within the context of caffeine consumption. A very recent paper (Shermann. 2011) coming from scientists from the University of Jerusalem draws a wholly different picture.

Shermann et al. investigated the effect of caffeine consumption (3.5 mg/kg/day or 7 mg/kg/day) on circadian rhythms and expression of disease and metabolic markers in mice under two distinct dietary conditions over a period of sixteen weeks. When the rats were fed an ad libitum diet (meaning they could consume as much food as they wanted), ...

caffeine reduced the average daily mRNA levels of certain disease and inflammatory markers, such as liver alpha fetoprotein (Afp), C-reactive protein (Crp), jejunum alanine aminotransferase (Alt), growth arrest and DNA damage 45β (Gadd45β), Interleukin 1α (Il-1α), Il-1β mRNA and serum plasminogen activator inhibitor 1 (PAI-1).

For those of you who still want to shed some pounds of fat, it may yet be even more interesting to read that "caffeine supplementation led to decreased expression of catabolic factors under RF". With the RF = restricted feeding condition being comparable to what is known as "intermittent fasting" in the fitness community, this finding is highly significant.

Figure 1: Metabolic markers PPAR-Gamma (above) and PPAR-Alpha (below) in mice fed an ad libitum (AL) or a restricted diet (RF) (Shermann. 2011)

This is particularly valid given the fact that there was a highly significant increase in PPAR-Gamma, PPAR-Alpha (cf. figure 1) and AMPK (not shown) activities in the group receiving "high dose" (7mg/kg; for humans this would equal a pretty low dose of about 0.6mg/kg) caffeine. Both, peroxisome proliferator activated receptor (PPAR), as well as AMPK are regarded as master metabolic regulators that have been implicated in the physiology of fat loss. A moderate caffeine consumption, i.e. about one cup of coffee, in the course of an intermittent fast, may thus well spare muscle protein and burn body fat, at the same time.

Omega 3 Attenuates Exercise Induced Rise in Inflammatory Markers, BUT is This Necessarily a Good Thing?

I want to take the results of a recent study (Bakhtyar. 2011) published in the Clinical Journal of Sport Medicine as an opportunity to readdress the question of whether or not the Omega 3 induced suppression of inflammation must be considered a good or a bad thing, both in view of athletic performance, as well from a health and longevity perspective.

Those of you, who listened to my interview on Carl Lenore's Super Human Radio show, will know that my understanding of "inflammation" is somewhat different from the mass market "explanation" of "a fire that causes damage". To be precise inflammation, or what scientists generally measure, is the release of signals (inflammatory markers) that tell immune cells to do their jobs. So, saying that inflammation is the root of all disease would be like saying that someone who calls the firefighters is to blame for the fire - but I am digressing from the topic at hand...

After administering 1.5g/day of an omega 3 supplement (experimental group) to every third of 45 previously untrained volunteers, Bakhtyar et al. found the subjects' "inflammatory" response to eccentric exercise to be modified:

The experimental group showed less elevation in TNF-α and PGE₂ immediately, 24, and 48 hours after exercise, when compared with the other groups. Significantly less elevation was shown in the concentration of IL-6, CK, and Mb for the experimental group at 24 and 48 hours after exercise. The experimental group also demonstrated a significant trend toward reduction in the plasma concentration of LDH immediately, 24, and 48 hours after the exercise program.

Now, what does this tell us about the training effect and health outcomes of the exercise regimen?

• With inflammation being a not yet fully understood prerequisite for muscular repair and hypertrophy, it would warrant further investigations like muscle biopsies and consistent training regimens with continuously monitored strength and muscle gains to conclude that omega 3 supplementation is beneficial in terms of physical performance.
• In view of the conclusions Pedersen draws in a recent review (Pedersen. 2011) of the role of exercise induced myokines, i.e. inflammatory markers released by muscles (myo- = muscle-), in chronic disease, blunting of muscular IL-6 release, which has been linked to muscular AMPK activation, increased glucose uptake and fat oxidation, omega 3 supplementation is probably counter-indicated in a health oriented exercise regimen, anyway.

I hope more scientists such as Pedersen will begin to question the current "anti-inflammatory" paradigm, so that major players in the medial landscape will be forced to take on their findings and stop portraying long chain polyunsaturated fatty acids in general and fish oil in particular as the savior of the fat and diabetic. Instead they should encourage people to finally get their asses off their sofas to induce exactly that amount of healthy, exercise-induced inflammation omega 3 supplementation appeared to suppress in the aforementioned study.