Fructose Impairs Fatty Acid Oxidation: Replacing 26g of Starch and Lactose in low GI Meal by Fructose Decreases Postprandial and Exercise Fatty Acid Oxidation by -21%

Image 1: With just bacon and eggs for breakfast you would not run the "risk" of reducing fatty acid oxidation.

A carby meal, i.e. a meal with a high amount of carbohydrates, right before workout triggers a shift in substrate utilization, i.e. the type of energy resource, your body will use to fuel the subsequent workout, from fats to carbohydrates, right!? But does it make difference whether you eat a Snickers bar or drink a can of Coca Cola, if both contained the same amount of carbs? Or, in other words, does the source and/or the glycemic index of your pre-workout meal have an impact on the respiratory quotient (RQ), which is the quotient of the amount of exhaled CO2 and inhaled oxygen, with higher RQs (towards 1.0) indicating that you are predominantly running on carbs, and low RQs (towards 0.7) indicating that you derive a greater part (not all!) of your energy from fatty acids.

Orange juice with breakfast? Better not...

The question, whether GI and carbohydrate type of a meal would have a significant impact on the postprandial glucose, lactate and free fatty acids levels, as well as the insulin response and the subsequent carbohydrate and fatty acid oxidation in the course of a low intensity 1h walk, has been bothering Feng-Hua Sun and his (or her?) colleagues from the Department of Sports Science and Physical Education at the Chinese University of Hong Kong, too. In a counter-balanced crossover design (>=7 days between trials; identical, recorded diet in the 3 days before each trial), all 10 healthy male subjects reported fasted (10-12h) at the laboratory, where they consumed one out of three meals with identical macronutrient composition, yet varying carbohydrate sources and glycemic indexes (cf. figure 1).

Figure 1: Macronutrient (in g) and ingredient composition of
the three test meals (according to Sun. 2011)

As you can see, the meals have identical caloric values and macronutrient compositions. Unfortunately, the differences between the ingredients go beyond their plain sugar vs. starch vs. fructose content. After all, spaghettis are not rice and milk is not ham ... this is a design flaw, of which I think that it impairs the significance of the results, but hey! At least the Chines have grasped the idea that calorie is not a calorie...

After all participants had finished eating their "delicious" breakfast, they remained seated for another 120min, in the course of which they had to drink 2ml of water per kg of body weight every 30 minutes "to ensure adequate hydration and balance the water content of the meals".

After these sedentary 2 hours, the subjects performed a standardized 5 min warm-up at 40%  of their individual VO2 and then completed 60 min of brisk walking at 50% of their VO2max.

Figure 2: Differential postprandial (2 hours) glucose (left) and insulin (right) response to the three test meals
(data adapted from Sun. 2011)

As you can see in figure 2, there were significant difference in the postprandial (120 min before exercise) glucose and insulin response to the different meals. Yet, while the difference between the low and high GI meals was something you should have expected, judged by the GI, the fructose enriched LGF meal should not have produced greater glucose (+63% area under the curve, cf. figure 2, left, small graph) and insulin (+62% area under the curve, cf. figure 2 right, small graph) responses than the low GI, no fructose meal, which, in fact, had a slightly lower glycemic index.

Figure 3: Postprandial (2 hours) lactate concentration in the 10 subjects after ingestion of the three test meals
(data adapted from Sun. 2011)

What is yet even more striking is the profound increase in lactate concentration during the prostprandial (not the exercise phase) in the subjects who consumed the fructose-containing meal (cf. figure 3). With +211% (lactate AUC) the postprandial lactate concentration in the LGF group is more than 3x higher than in the LG group! A clearcut sign for an increase in hepatic glycolysis and probably part of the reason that we are seeing increased carbohydrate and decreased fatty acid oxidation rates in the course of the subsequent walking exercise (cf. figure 4).

Figure 4: Postprandial, during exercise and total substrate utilization (in g) subsequent to the ingestion of the three different test meals (data adapted from Sun. 2011)

Postprandially, the increase in carbohydrate oxidation is even more pronounced in the LGF group than in the HG (sugar) group. That being said, the total reductions in fatty acid oxidation are -21% for the low GI fructose (LGI) and -23% for the high GI sugar (HG) group and thusly, within their respective statistical margins, identical!

With respect to the underlying reasons of this disadvantageous shifts in substrate utilization, Sun et al. speculate, that the mechanism

[...] behind this may be the reduced hyperglycemia and hyperinsulinaemia during the postprandial period following LGI meal consumption. [...] In addition, it is well known that insulin can suppress the lipolysis. This suppression appears to be long lasting, even when insulin concentration has returned to basal levels.

The last part, here, is of particular interest, because, obviously, after a few minutes of walking and with the increased need for carbohydrates the insulin levels of all subjects (regardless of the composition of their prior meals) dropped to levels ~2-3mU/L. Now the insulin response in the LGF group was still smaller than the one of the high GI (HG) group, so that the scientists assume that the ability of the fructose to bypass first rate-limiting enzymes of glycolosis in the liver, which renders it readily available for oxidation, must explain why the ratio of carbohydrate to fat oxidation was still similarly skewed in both, the low GI, plus fructose, and the high GI groups.

Image 2: I wonder if nutritionists will ever understand that there is difference between fructose powder (left) and an apple (right)

Although these results stand in line with the detrimental effects of fructose sweetened foods, I would still like to see two methodologically flawless studies with a) meal 1 not using different foods (I mentioned that in the 4th paragraph of this post already) and b) fructose from whole fruit and not in the form of the powdered poison Sun et al. just dissolved in water and added to their meals... and you know, in case these studies will be done - sometime in the distant future, when mainstream nutritionists will finally understand that not only is a calorie not a calorie, but that powdered fructose is also not an apple, you will read about that on the SuppVersity, first!

Licorice More Estrogenic Than Estradiol: Some of the Flavonoids in Glycyrrhiza Glabra Roots Turn Out to Be Superinductors of the Estrogen-α & -β Receptors

Image 1: In view of the fact that most confectionary licorice contains no more than ~3% of the roots of the licorice plant, I would rather bother about the tricks the ~74g of carbohydrates (on a 100g base) of this treat may play on your insulin levels than about any potential negative effects the consumption of a few or even a whole bunch of these licorice wheels may have on your testosterone levels or overall manliness ;-)

You probably have heard about licorice, the root of Glycyrrhiza glabra, a legume with a slightly sweet taste and one of the ingredient of the eponymous candy being a potent adrenal "revitalizer" that is used and advocated my many naturopathic doctors. If you frequent any of the major health and fitness boards on the Internet, you will yet also be familiar with some of its unwanted side-effects, first and foremost its scientifically validated anti-androgenic (specifically testosterone reducing) effects (Zamansoltani. 2009). While Zamansoltani et al. yet still speculated, whether the reduction in serum testosterone they observed as a result of administration of 150-300mg/kg of licorice extract (HED ~ 40-80mg/kg; 3.2-6.4g for a 80kg human) to male rats still speculated, whether these reduction were the result of "[i]ncreas[es] in T metabolism, down-regulation of androgen receptors or activation of oestrogen [sic!] receptors", a recent study that was published in the Annals of Bioanalytical Chemistry shows that the latter, i.e. the (profound!) activation of both types of estrogen receptors probably was the underlying cause of the emasculation of the licorice treated bucks (Simons. 2011).

Estrogen receptor superinductors were not invented by Dr. Spock

In a pretty meticulous analysis, Rudy Simons et al. found that several fractions of an ethyl acetate extract from licorice root displayed estrogenic activities at either the estrogen-alpha or estrogen-beta receptor that were more pronounced than the ones of the reference "drug", estradiol (E2).

Figure 1: Relative estrogenic activity (in % of estradiol = E2) of 51 fractions that were isolated from an ethyl acetate extract from licorice root (data adapted from Simons. 2011).

If you take a closer look at the 51 fractions the scientists identified by liquid chromatography-massspectrometry and analyzed for their activity by the means of yeast estrogen bioassays, you will recognize that not just one or two, but a whole host of these "fractions", which themselves were complex mixtures of similar compounds, exhibit partly profound estrogenic activity. In that it is particularly noteworthy that the superinduction (activity >E2=100%) was not caused by a post-translational stabilization of the firefly luciferase reporter enzyme, which would have disqualified these results as shortcomings of the yeast essay Simons et al. had used - a effect which has been previously described for genistein, one of the phytoestrogens in soy and soy products.

Figure 2: Relative content and estrogenic activity of individual fractions F1-F5, F6-F21 and F22-F51 from the ethyl acetate extract from licorice root used in the study (calculated based on Simons. 2011).

Of all the fractions, the scientists isolated from the licorice extract, which was supplied by Frutarom US, fraction 41 (F41) with an estrogen-alpha receptor activity of 159.9% at the low (3µg/ml) and 186.9% at the high (10µg/ml) concentrations was by far the 'worst offender'. In view of the fact that we do not know how much of these flavonoids actually make it into the bloodstream, the 103.1, 97.9, 95.5, 74.6, 68.7, 57.2 and 57.3% estrogen-beta activity of fractions F24-F30 at a much lower concentration of 0.3µg/ml is probably more of a concern and most likely the underlying cause of the anti-androgenic effects of licorice, which have also been established in a human study on seven 22-24 year old healthy male subjects by Decio Armanini et al. in 1999 (Armanini. 1999):

Figure 3: Changes in testosterone, androstenedione and 17-hydroxy-progesterone levels (ng/dl) in 7 healthy men upon oral adminstration of 7g of a commercial licorice preparation (data based on Armanini. 1999)

As you can see in figure 3, the 7 g of a commercial preparation of licorice (containing 0.5 g of glycyrrhizic acid) the men in the Amanino study received in the form of tablets (Saila, Bologna, Italy) on a daily basis had an immediate and pretty profound anti-androgenic effect (-44% total testosterone within 2 days!) resulting from the negative feedback of the phytoestrogenic components from Glycyrrhiza glabra. The levels of androstenedione and 17-hydroxy-progesterone on the other hand did not change.

Image 2: Licorice could help with menopause symptoms such as hot flashes, but it has potential corticosteroid-like side effects you should keep an eye on.

Update: Evelyn from CarbSane asked in the comment section whether licorice would not make a good addition to any natural menopause treatment. In fact, she is right that the very estrogenicity of the licorice extracts that is detrimental to men could be of great use for women going through menopause. A cursory search of the databases (how else could it be in view of the fact that you cannot patent licorice) does yet reveal that no one appears to be willing to invest serious money into studies on the effects of licorice / licorice extracts in menopausal women. Nevertheless, there is evidence for estrogen-like bone-building effects (Somjen. 2004) and a -2.4% reduction in the dreaded hot flashes over placebo (Nahidi. 2011).

Moreover, licorice appears to act as an SSRI (selective serotonine reuptake inhibitor) and may thus also help with moodswings and neurotransmitter-imbalances (Ofir. 2003), which can also cause sugar cravings and thusly induce weight gain. If you add to that the growth-inhibitory action the glabridins in licorice exhibit on breast-cancer cells (Tamir. 2000), it may be well worth to try to alleviate menopause symptoms with licorice. In that, it is yet important to know that the glycyrrhetinic acid in licorice has mineralocorticoid-like side effect (i.e. it works like cortisol), which can become problematic especially if licorice is taken as part of one of the typical pharmacological protocols conventional doctors tend to prescribe to their patients (e.g. Inada. 2007). My advice would thus be to carefully monitor your reaction, Ladies ;-)

Against the background of the results of both the initially mentioned rodent study by Zamansoltani et al. (Zamansoltani. 2009), as well as the certainly more relevant data from the 1999 study by Armanini et al. (Armanini. 1999) the 'test-tube' findings by Simons et al. gain a degree of practical significance many of the likewise bio-essay based studies, the manufacturers of purported (!) testosterone boosters like to cite to underline the scientific validity of their products, are lacking... you may want to keep that in mind before you try to counter the unwanted side-effects of a licorice-based "adrenal optimizer" by popping a few servings of the latest and greatest "scientifically proven testosterone booster" ;-)

Intermittent Thoughts on Intermittent Fasting - Programing Success: Building Muscle Begins With Losing Body Fat.

Image 1: Arnold does the "double bicep" + vacuums. If you want to look like a bodybuilder, muscle alone is not enough.

First, I want to thank Jahed, Pablo, RF, Angimal, Garrett and Rudolf for their patience. After all, it has been two weeks now since you have submitted your (meta-)goals, which were all more related to building muscle and increasing performance, then to losing body fat, which was the topic the last installment of the Intermittent Thoughts dealt with. Yet although, at first sight, both topics have little (to nothing) to do with each other, there are are at least three important factors by which a reduction in body fat is very well related to increased muscularity and skeletal muscle hypertrophy. Let's get back to the "Peter Griffin" type of chubby person from the last installment, for a few seconds. Imagine "Peter" has packed on, say 10lbs of lean muscle and now stands in front of you, does the "double bicep" and vacuums, just like Arnold does in image 1... what? Why are you laughing?

Do you want muscles? Or do you want to look muscular?

Now, obviously the first intersection of bodyfat and muscularity (in a broader sense) relates to the question whether or not your body fat level is low enough for any increases in skeletal muscle mass to be visible. I mean +10lbs on the ripped frame of a 202lbs (now 212lbs) bodybuilder look absolutely freekish. On our Peter Griffin, a gain of 10lbs of lean muscle tissue will probably go completely unrecognized - this also puts "chubby" beginners at risk of neglecting the strength training component of their exercise regimen, because, from a mere "cosmetic" stand point, each gram of body fat they drop will make a significant difference in terms of the way they look. Building muscle beneath the thick layers of adipose tissue, on the other hand, initially appears to have little value... but remember: looks are deceptive, and I hope that my elaborations in the last installment made it quite clear "building a bigger metabolic engine" and not starving the latter away on a low-calorie diet, is the cornerstone of maintainable reductions in body fat levels.

Figure 1: Where are you on the fat/muscle mass (FFMI = weight/height[in m]²) continuum? *indicates age-group 20-29 in the NHANES dataset (data based on data from Hattori. 1999; Picket. 2005; CDC, NHANES data from 2010)

Interestingly enough, being lean, or, I should say, the metabolic and endocrine consequences of being lean actually have way more profound implications on "building muscle", than the mere advantage of the immediate visibility of the newly acquired lean body tissue. On "the boards" (meaning bulletin boards like bodybuilding.com, anabolicminds, etc.) it is a recurrent topic whether you should "bulk" (people there interpret that mainly as "eat to gain" and often as "overeat to gain") or "cut" (meaning lose fat) first. And while the answer obviously depends on where you are starting from, it stands out of question that the average American male (aged 27-62) who gets fatter and fatter every year and currently has a body fat percentage of 24.9% (Rohrmann. 2011) would be ill-advised to even think about the word "bulking".

Image 2: Just to put the 24.9% body fat of the average American male into perspective. The average bodyfat percentage of a sekitori sumo wrestler is 28.6%
(Hattori. 1999)!

Please note, that the "no bulk with high body fat percentage" rule does also apply to the female physical culturists out there. The reason that I am mainly addressing the male faction of my readership here, is that women are not so stupid to think, they would have to down 2-3 portions of "weight gainers" (these products are exactly what they are called, they will make you gain weight, not muscle) and 4-5 protein shakes in addition to a hypo-caloric (junkfood-)diet in order to build a muscular physique, anyways. Things would be different, though if the physique of a sekitori sumo wrestler (one of the higher ranked sumos, cf. image 2), is what you are aspiring. In that case you can start "bulking" with weight gainers and all the other "high class" products the industry has to offer... I mean the average sekitori sumo has 109kg of lean muscle tissue hidden somwhere beyond the 45.4kg of fat he is carrying around the dohyo.

If you want to "program success" and your "motivational elevator pitch" from part one of this part of the Intermittent Thoughts Series contains sentences like "look like a cover model." (Garrett; November 14, 2011 3:05 AM) or "[building] a stronger body, bodyfat below 8%" (RF, November 7, 2011 12:22 PM) or my favorite one which obviously nobody was dared to say, yet 90% of the Men's Health readers probably have on their minds "build muscle just to look good at the beach / impress the ladies", it is imperative that you lose your love handles first! Not to (just) to be able to see the gains you are making, but to set yourself up for optimal lean muscle gains (in essence, this is also related to the assumption Jahed Momand's assumption made in his "motivational elevator pitch" that leaning out prior to building his maximal clean and jerk and snatch to compete at 85kg probably is the smartest way to go, after all a low body fat percentage is obligatory if you want to be competitive in the lower weight classes).

The endocrine advantage of low(er) body fat percentages

The first and often overlooked advantage of a decent degree of leanness (cf. "active American", figure 1) is a hormonal one. According to the findings of the latest (published) NHANES data (National Health and Nutrition Examination Survey III; Rohrmann. 2011) there is a direct correlation between body-fatness as measured by BMI, waist circumference and body fat levels, on the one hand, and total and free testosterone and estrogen levels and their binding globulin SHBG:

Total and free testosterone and sex hormone binding globulin concentrations decreased, whereas total and free estradiol increased with increasing BMI, waist circumference, and percent body fat (all p trend < 0.05). 

Further statistical analysis of the data reveals that a body fat increase of one-quartile (e.g. from the lower 1/4 of the study population to the next fatter quartile) goes hand in hand with a decreases in sex hormones into the next lower quartile (e.g. from the highest into the next lower quartile). A sample calculation for a 50 year old white non-smoker revealed that for each 5.2cm increase in body waist circumference or +2.7% increase in body fat, the free testosterone level decreased by 2%. With an increase of "only" +3.7cm or +1.8% in waist circumference or body-fatness, respectively you can however bump up your estrogen levels by 2%.

Figure 2: Relative free testosterone and free estradiol levels in men from the NHANES study; data expressed relative to serum levels of "lean" men with <84.9cm ~ 33.4" waist circumference; values above the bars are the differences between relative testosterone vs. estradiol levels compared to "lean" men (calculated based on Rohrmann. 2011)

In view of the differential response of androgenic and estrogenic free (i.e. "active") hormones to changes in body-fatness (cf. figure 2), it is no wonder that we see a characteristic and in terms of lean muscle gains highly unfavorable pattern in the "fatter" quartiles of the study population, with maximal  free estradiol levels (1.08pg/ml; +30% vs. min) and minimal free testosterone levels (0.097ng/ml; -13% vs. max) in the "fattest" quartile of the study population (I deliberately selected waist circumference over "body fat levels" which were measured by bio-impedence, as my body fat marker of choice). Even if you as a SuppVersity reader should by now be aware that testosterone alone does not "build muscle", its highly facilitative effect on exercise induced increases in lean body tissue is significantly blunted by the fat-induced reduction in free testosterone and the (by the way fat promoting) increase in free estradiol in "chubby" men.

The endocrine factor: By leaning out first you set the hormonal scene (a higher testosterone to estrogen ratio) for optimal lean muscle gains.

The metabolic advantage of lower body fat levels

While testosterone and estrogen levels obviously figure large in the orchestrate that determines whether the nutrients you ingest (remember no one of you eats "calories") end up being stored as body fat, used as "fuel" or building block for lean muscle tissue, insulin, the "most anabolic agent in the world" (a quote from steroids.com; obviously a very questionable statement), may play an even greater role, when it comes to building muscle, not fat. Those of you have have listened to Dr. Layne Norton's and Dr. Connelly's dissertations on the largely misunderstood role of insulin in relation to the protein synthetic response to exercise, as well as its highly undesirable effects on fat storage during the last episodes of BodyRX Radio, will be aware that the often touted idea that "insulin is the most anabolic agent in the world" applies, above all else, to adipose tissue.

Image 3: "Insulin the most anabolic agent in the world"!? Correct, if we are talking about fat,  not muscle tissue ;-)

While "broscience" and the producers of sugary "weight gainers" and "post-workout recovery formulas" still maintain the myth of the "muscle building insulin spike" the (post-workout) ingestion of large amounts of fast-acting carbohydrates would provide, a recent study from Stuart Phillips lab at McMasters University into the purported benefits of the "insulin spike" produced by the co-ingesting 50g of carbohydrates with your 25g of whey protein post-workout found neither an increase in muscle protein synthesis, nor decreases in muscle protein breakdown, which are often cited as another benefit of increased insulin levels (Staples. 2011). More specifically, the additional +1,250% (!) increase in insulin (over +400% with whey alone) did not have any additional effect on protein synthesis, or, in other words: With insulin some (here 5x above fasted baseline) appears to be good, more, on the other hand is not only not better, it is in fact worse.

That being said, the improvements in insulin sensitivity which go hand in hand with reductions in body fat levels (increases in leptin sensitivity, reductions in inflammation, etc.) will decrease your basal, as well as your postprandial insulin levels, because your body will simply need less of the storage hormone to get the job done. This, in turn, will allow you to fuel your workouts with appropriate (not exorbitant) amounts of carbohydrates without running the risk of storing additional body fat. This is particularly true, in view of the fact that the "type of insulin sensitivity" you acquire when you selectively lose body fat (not muscle) favors the storage of blood sugar as muscle glycogen over its conversion to triglycerides and subsequent storage in adipose tissue (note that the latter happens both in obese and insulin resistant, as well as in "reduced obese" individuals, who have lost a lot of body mass, not fat, on prolonged calorie restricted diets).

The metabolic factor: By reducing your body fat levels first (leaning out vs. just losing weight) you decrease the risk that (superfluous) carbohydrates (and other nutrients) get stored as body fat.

The anti-livelong-obesity advantage of lower body fat levels

Image 4: There are two ways to get fat, adipose tissue hypertrophy and adipose tissue hyperplasia. While you obviously want to avoid both, only the latter is potentially irreversible (Otto. 2005).

The third and maybe most far-reaching  advantage of lowering your body fat level before bulking up is actually related to the leeway you have in terms of the unavoidable fat gain that is part of every "bulk" no matter how "clean" it may be (see also red box below). It should be obvious that just as the myonuclei in your skeletal muscle have a limited capacity to "grow" (also to hypertrophy, i.e. to simply increase their size /we will discuss the three pathways of muscle growth in one of the upcoming installments in more detail), your fat cells can only store a finite amount of lipids before they begin to "burst from the seams" (some scientists even believe that this is part of what triggers the detrimental inflammatory cascade in obese individuals). When that is about to happen, the only way your body can protect itself from suffocating in glucose and triglycerides that can neither be burned as fuel nor stored in the bristling adipocytes is to generate new fat cells (adipocyte hyperplasia).

My definition of a clean bulk: You may now be shocked to hear that even a "clean bulk" will necessarily also increase the amount of body fat you are carrying. That, and this is a very important point, does yet not mean that your body fat % must necessarily increase. A "clean bulk" by (my) definition is a bulk where you add more muscle than fat tissue to your frame. Now, even if you you were an absolute zero in math, you should recognize that this implies that your body fat percentage would actually drop, although your overall body fat levels may increase. Keep that in mind, whenever you are trying to gain muscle. Your goal should never be to cut fat (reduce overall fat mass) and build muscle (increase lean muscle tissue) at the same time - if you try that you program stagnancy, not progress!
Now, the unfortunate truth is that it is pretty easy to "empty" those cells again (you can do this in weeks), yet uncertain on which time-scales (if at all) and by which means (other than surgery) you can get rid of newly acquired adipocytes ever again.

An infant usually has about 5 to 6 billion fat cells, the number of which naturally increases during early childhood and puberty, so that the average healthy adult ends up with 25 to 30 billion fat cells. If those 30 billion adipocytes are already filled up when you start bulking, chances are that your body feels compelled to increase its storage capacity, so that - in the worse case - you end up with the roughly 75 billion fat cells, the typical overweight adult is carrying around on his "chubby" frame. If you still insist that you are not "big" enough and continue to eat whatever you can grab, the number of fat cells can increase up to 250, even 300 billion... it stands to reason that even when you emptied all of those, you would still be "fat".

The anti-obesity factor: By leaning out first, you reduce the risk of a (potentially irreversible) increase in adipocyte number that may set you up for lifelong weight problems.

An intermittent conclusion on the first step of programming skeletal muscle hypertophy

Image 5: After a handful of unsuccesful bulking efforts, SuppVersity Student Duong Nguyen eventually made it right - he leaned out first. If you are interested in his subsequent bulk, check out his blog!

As you may notice, I (once again) went off on a tangent. I hope you don't mind that you have not yet learned about effective ways measure your progress, about how to improve your gains by setting realistic, but challenging goals and about the often-overlooked impact the mind-muscle will (not could!) have on the real world outcomes of your efforts in the gym, in this installment of the Intermittent Thoughts.

But hey! For (hopefully) a minority of you the "time to bulk" may not have come anyways ;-) So, if you have not achieved a degree of leanness comparable to that of the "average active American" (cf. figure 1), I suggest you re-read last week's installment on setting yourself up for body-fat loss and thusly take appropriate measures to increase the effectiveness of your first or next "bulk" and decrease the propensity of doing permanent "aesthetic" or even metabolic damage.

As for the rest of you, I would hope that you could at least gain a few new insights into the challenges your not so lean friends are facing when they are trying to gain muscle without adding another inch to their waistlines.

Update on Antioxidants & Exercise - Neither Vitamin C Nor E Have ANY Effect on the Response to Intense Exercise.

Image 1: If you add some reactive oxygen species to this mitochondrium, this will trigger beneficial, (mito-)hormetic adaptations, that could be blunted by too many antioxidants.

As a diligent reader of the SuppVersity, you have probably been following my posts on antioxidants and their potentially negative effect on the adaptive (hormetic) response to the exercise induced formation of reactive oxygen specimen. Although, I still believe that the theory may have its merit - especially in metabolically deranged people, where the exercise induced ROS formation would initially have to overcome the low-grade chronic "background" stress - it appears that for healthy people, and "moderately trained young men" on an intense exercise protocol, in particular, the ingestion of reasonable amounts (<1g of vitamin C and <400IU of vitamin E) does not pose a problem. At least this is what the results of two relatively recent studies by scientists from Washington School of Medicine (Higashida. 2011) and researchers from universities in Denmark and France (Yfanti. 2011) would suggest.

The hormetic benefits of inflammation

According to the mitohormesis hypothesis, the beneficial effects of exercise on health, in general, and glucose metabolism, in particular, are at least partly mediated by an increase in reactive oxygen species, which triggers downstream "hormetic" adaptation processes which result in increased oxidative capacity and insulin sensitivity, as well as a reduction in total inflammation (cf. previous posts on the work of S. Schmeisser and M. Ristow from the Department of Human Nutrition at the University of Leipzig. If this theory held true, or let's be more specific, if this theory which is largely based on observations in metabollically derranged, i.e. obese and/or type II diabetic subjects, was applicable to healthy people and athletes, as well, this could mean that the multi-vitamin, the vitamin C pills, the alpha-tocopherol (vitamin E) and all the other little helpers you have been taking religiously to increase your exercise performance would actually have hampered, not promoted your muscle gains, fat loss and whatever else you may have had in mind, when you hit the gym, the road, the field, the court or the green ;-)

Figure 1: Neither the high-dose supplementation protocol in rodents (HED: Human Equivalent Dose for 80kg), nor the moderate dose protocol in humans did block any of the measured beneficial adaptations to exercise in the studies by Higashida (2011) and Yfanti. (2011), respectively.

Let me say this right away: As long as you have not been following the recommendations of dubious nutritional gurus and self-proclaimed fitness "experts" to take 10g+ of vitamin C and vitamin E supplements in the 3000IU+ range, the little vitamin pills and powders are probably not the reason that your biceps is not growing and your belly is just as fat as it was, when you began training.

Figure 2: Serum vitamin C and vitamin E levels (µmol/L) in 21 subjects before, at the beginning and after 12 weeks of 5x a week strenuous cycling exercise with and without supplemental vitamin C & E (adapted from Yfanti. 2011)

As you can see in figure 2, supplementation with 500mg of vitamin C and 400 IU of vitamin E (more on the protocols used in the studies in figure 1) before and during 12 weeks of strenuous bicycle exercise training with a frequency of 5 sessions per week (HIIT, HIT and stead state, cf. figure 6) did increase the concentration of antioxidants in the blood of the 21 healthy, physically active subjects (age 18-40years) of the Yfanti study, who had not participated in physical exercise more than twice a week before the experiment. Despite higher vitamin C and E plasma levels, and contrary to the research hypothesis of the scientists, who had expected that the anti-oxidant supplementation would blunt the adaptive response to the exercise protocol,

[...] the present study showed that combined supplementation with vitamins C and E before and during 12 weeks of supervised, strenuous bicycle exercise training of a frequency of 5 days/week had no effect on maximal oxygen consumption, maximal power output, workload at lactate threshold, glycogen content, and CS and β-HAD activity in muscle.

In other words, supplementing with "reasonable" amounts of vitamin C and vitamin E had absolutely NO EFFECT (!) on the exercise induced metabolic adaptations or performance increases - that does yet also imply that taking anti-oxidants is of little benefit as long as the minimal dietary requirements are met... and if you still insist to poor money down the literally rat hole, you may be interested to hear that (assuming that the results from Higashida's rat study translate to humans), even 10g of vitamin C and 3000IU of vitamin E a day probably would not really make a difference - as long as you train heavy enough.

Figure 4: Exercise induced changes in GLUT-4 expression (arbitrary units) and 2DG transport (µmol/ml/20min) in rats subjected to 8 weeks of high dose antioxidant supplementation and 6days/week swimming exercise in the last 3 weeks (data adapted fro Higashida. 2011)

Of particular interest in this context is the effect of "mega-dosing" anti-oxidants on the exercise induced increase in insulin sensitivity, which has been reported to be impaired in previous studies (Ristow. 2009). As the data in figure 3 shows, the increase in glucose transporter (GLUT4) expression is slightly greater in the non-supplemented rats, BUT neither this difference nor the difference in measured 2-Deoxy-D-glucose (2DG) transport reach statistical significance.

Figure 5: Exercise induced changes in MDA, SOD and PGC-1α in rats subjected to 8 weeks of high dose antioxidant supplementation and 6days/week swimming exercise in the last 3 weeks (data adapted fro Higashida. 2011)

Moreover, Higashida et al. found no statistically significant differences in the increases of malondialdehyde (MDA), superoxide dismutase (SOD1 & SOD2) or PGC-1α, a marker for the mitochondrial fatty acid oxidation, between the rats in the two groups (cf. figure 5).

Now, I a confused and don't know what to believe

So what does all that tell us? Well, we can now be relatively certain that supplementing with vitamin C and vitamin E is a waste of time and money for most of us. What we still cannot say for sure, though is why the Ristow study from 2009, which even made it to mainstream media news, found detrimental effects of supplementing with 1g of vitamin C and 400IU of vitamin E on the adaptive response to 4 weeks of 5days/week 20min steady state aerobic training + 45 minute circuit training + 20 min warm up + cool down (Ristow. 2009), while the Yfanti study, with 500mg of vitamin C and 400IU of vitamin E did not find any effects of supplementation...

Figure 6: Exercise protocol that was used in the Yfanti study.

...the only reasonable explanation I have is that the protocol in the Ristow study may not have been intense enough. Unfortunately there is no detailed information on what the subjects did in the course of the "circuit training", but if that was your usual sissy type walk from one machine to the next, chances are that the level of ROS that was induced by this "exercise" protocol was so low that it was completely blocked by the supplemental anti-oxidants. The "cycling protocol" in the Yfanti study, on the other hand, is pretty intense. If you look at the schedule in figure 6 you will concede that this is almost the way athletes (and maybe you) train.

All that being said, it appears that all is coming back to what I have been writing (and also saying on SHR) several times before: Controlled oxidation is likely to be beneficial. It's like the fire in the oven that keeps you warm - the one you carefully take care of, in order to prevent your whole house to catch fire... if you are a marathon runner, the latter can happen pretty quickly and you will need (tons of ;-) antioxidants and even that will probably not suffice. If you are the housewife on the treadmill, who walks at 5km/h for 20min two times a week, on the other hand, even a few milligrams of vitamin C and a few units of vitamin E will blunt the little oxidative "damage" that you do and your "efforts" to increase your insulin sensitivity or whatever your intentions may be will be sabotaged by your vitamin supplements.

Alarmingly High Levels of Lead in Calcium Supplements: Pb Content per Serving Up to 18x Over "Acceptable Levels".

Image 1: You better pick the right source of calcium: healthy milk / dairy vs. lead poisoned pills from your local pharmacy or supermarket - you still have the choice.

This, I can assure you, is a "SuppVersity News", i.e. something you will not read on the major news portals, simply because there is too much money at stake in the 3billion $ market for calcium supplements (figure according to January 2008 edition of "Heartwire") - money a huge part of which is spent by Novartis & Co to advertise their products to consumers from all age groups, regardless of the individuals' dietary calcium intake; and that despite accumulating evidence for an association of supplemental calcium intake and heart disease (for one of the latest reviews cf. Bolland. 2011)! A very recent study published in the Journal of Biological Trace Element Research (Rehman. 2011) does yet cast another, even darker shadow onto the "healthy" white chalk tabs...

What? "Pb" is not the symbol for Calcium in the Periodic Table?

Lead, that stuff nuclear physicists value, because it effectively absorbs radioactive radiation, is one of the most toxic "heavy metals" we are exposed to. And this is by no way a recent discovery. Even in ancient times, people knew about the toxic effect vessels made of this metal had on the water they contained. Back in 1990 E.K. Silberberg summarized the contemporary knowledge about the dangers of environmental lead exposure in a paper for the Environmental Defense Fund as follows (Silberberg. 1990):

[...] epidemiological studies have suggested that central nervous system (CNS) effects in children are observed at the lowest increments of lead exposure [...] Similarly, clinical studies indicate that early exposure to lead produces functionally irreversible damage to the CNS; experimental research demonstrates that this irreversibility may involve failure to remove lead from brain, permanent effects on synaptogenesis; and chelant-induced redistribution of lead from the periphery to the CNS. [...] New data on release of bone stores of lead during physiological conditions of demineralization indicate that mobilization of bone lead adds to in utero exposure of the fetus. Furthermore, postmenopausal demineralization of bone can increase blood lead levels in women by 25%; this raises concern about the potential effects of lead in an aging population and the difficulties in comprehensive exposure assessment.

As you may have guessed, time has not affected the dangers or the irreversibility of lead toxicity, so that you would assume that the results of an investigation into the lead content of 27 "commonly used" commercially available calcium supplements should be alarming enough to receive at least some public recognition. After all, it would suffice to read the abstract to be alarmed by the fact that of the calcium supplements Sohaila Rehman and her colleagues from the Pakistan Institute of Nuclear Science Technology analyzed only one out of ten "met the criteria of acceptable Pb levels (1.5µg/daily dose) in supplements / consumer products set by the United States" (Rehman. 2011).

Figure 1: Lead levels in µg in daily dose of respective calcium supplement; solid red line = acceptable Pb level for calcium supplements, dashed red line = tolerable total daily Pb intake for children <7y, dotted red line = tolerable daily Pb intake for women in childbearing age (data adapted from Rehman. 2011).

"One out of ten", well that does not sound so bad, does it? I guess you will change your mind, when you take a closer look at figure 1 - the red line at the bottom of the graph is the "acceptable Pb level" and as you can see it is met by exactly 1 out of 13 calcium chelate products (CAC 1000 by Novartis), and none of the 3 calcium chelates the researchers tested for their lead content.

Figure 2: Lead levels in µg in daily dose of respective calcium supplement; solid red line = acceptable Pb level for calcium supplements, dashed red line = tolerable total daily Pb intake for children <7y (data adapted from Rehman. 2011).

And while the lead levels of the calcium + vitamin C and calcium + vitamin D levels in figure 2 look somewhat better, there are still several outliers with Cal-C Plus from Himont Pharma, for example, providing more than 2x the tolerable daily lead intake for a child under the age 7 y (and remember these are only the official FDA figures - and you know what that means ;-) on a per serving base.

Note: The results of the study at hand may well explain a) the different outcomes of (controlled) trials and epidemiological studies on the effects of calcium supplements on cardiovascular health and b) the beneficial effects of milk and dairy intake on heart health (Soedamah-Mutuh. 2011). After all, a very recent study that was published in the Journal of Neurotoxicology and Teratology in October 2011, shows that there is a "potential for autonomic dysregulation" that manifests in "significantly greater vascular resistance and reduced stroke volume and cardiac output" in 9-11 year old children even "at levels of Pb typical for many US children" (the exact levels were 1.01µg/dL, cf. Gump. 2011).

And as if all that was not enough, the US Food and Drug Administration (FDA) and the glorious Center for Disease Control and Prevention (CDC) would have been aware of the potential of serious chronic lead intoxication from calcium supplements, if they spent more time reading scientific journals than counting the cashflow from the BigPharma companies that finance their bureaucracy. After all, Bourgoin et al. conducted a very similar study back in the 1990s, the results of which the scientists summarize in their abstract as follows (Bourgoin. 1993):

Daily lead ingestion rates revealed that about 25% of the products exceeded the US Food and Drug Administration's "provisional" total tolerable daily intake of lead for children aged 6 years and under.

In the Rehmann study it were 16 out of 27 tested calcium supplements (59%) which exceeded this limit. So  maybe the "feds" just did not act, because 1 out of 4 is not bad enough? Well, if you look at the individual results in figure 3 (usually I redo graphs, but in this case the original looks just too damn impressive), it is immediately obvious that the averages the scientist report in their abstract, do not reflect the actual potential of lead toxicity from the 70 supplemental sources Bourgoin et al. tested.

Figure 3: Results of a 1993 large-scale analysis of the lead content of 70! commercially available calcium supplements and milk (my emphasis), the safe exception (from Bourgoin. 1993)

Obviously, some of the bone based and a whole host of the "natural sources" ("natural source of calcium carbonate" according to label claim; note that coral calcium would fall into this category, as well!) are about as toxic as the worst offenders in the Rehman study. What I find do yet find particularly interesting, is that the lead content in one serving of commercial milk, which would provide the same amount of (even more bioavailable) calcium as the supplements in the study did, would provide no more than 0.71µg/day and is thusly the one and only "natural source" of dietary calcium that does not set you up for lead toxicity!

"Pah, lead!? What doesn't  kill you just makes you stronger"

Image 2: So, calcium supplement with lead are a safe source of dietary calcium, but raw milk is not? (img CounterThink)

In view of the "longstanding" history of ignorance on behalf of the governmental agencies, it sounds almost sarcastic, when Bourgoin et al. conclude their article by citing the Center for Disease Control's (CDC) statement on lead poisoning, which according to these reputable protectors of the health of the American society *cough* is "one of the most common and preventable pediatric health problems today". Notwithstanding this early insight (this is from a 1991 document from the CDC) the officials obviously have neither taken Bourgoin et al.'s advice to control calcium supplements "more rigidly" in order to "prevent unnecessary exposure in all segments of the population, particularly young children" (Bourgoin. 1993), nor have they followed the recommendation of a more recent study by Kim et al., which  estimates the mean lead intake from calcium supplements to about 5µg/day and recommends that "measures to prevent potentials of Pb toxicity from overtaking some Ca supplements should be considered" (Kim. 2010).

And while the CDC and the FDA could incidentally have missed those papers. They should actually be aware of Proposition 65, which is the common name for California's Safe Drinking Water and Toxic Enforcement Act of 1986 (Dietary Supplement Standard 173, Metal Contaminant Acceptance Levels. NSF International. August 19, 2003). In this paper, of which W.W. Kilgore writes in retrospective that (Kilgore. 1990)

[i]t creates a list of chemicals (including a number of agricultural chemicals) known to cause cancer or reproductive toxicity; [i]t limits discharges of listed chemicals to drinking water sources; [i]t requires prior warning before exposure to listed chemicals by anyone in the course of doing business; [i]t creates a list of chemicals requiring testing for carcinogenicity or reproductive toxicity; and [i]t requires the Governor to consult with qualified experts (a 12-member "Scientific Advisory Panel" was appointed) as necessary to carry out his duties.

the proposed Acceptable Intake Level (AIL) for inorganic lead (as extrapolated from animal studies) is 0.5µg/day and thusly 1/3 of the current Californian standards and 1/50 of the FDA allowance of 25µg/day! But hey, who cares? As long as the American citizens are protected from the dangers of raw milk, everything is all right, isn't it?

Adelfo Cerame - Road to The Wheelchair Nationals '12: Ambitious Short-Term Goals Pave the Way to Success.

Image 1: This guy likes to suffer - no, not
what you are thinking now ;-)

I don't know about you, but I cannot stand how people constantly complain about how bad things are, how hard they are working (mostly these are the laziest people I know), how little they are paid, how desperate the economy was,... you know the whole litany, don't you? Then, Adelfo Cerame's weekly blogpost is exactly the diversion you probably need today. I mean don't get me wrong. Adelfo is only human, so he likes to complain, as well. But believe it or not, this guy complains about not suffering enough!? So just to make sure you get this right. Adelfo Cerame Jr. aspiring future pro-wheelchair bodybuilder suffers, because he does not suffer enough... does not make sense? Well, I guess, I'll better have him explain his "problem", then ;-)


Goalsetting 101: Short-term goals keep you on track

You think you could use some advice on your own training, diet and supplementation regimen and want it from someone who obviously knows what it takes to build muscle and lose fat? You can reach out to Adelfo via Facebook.

When you want to achieve something in life, setting specific and testable goals is always the necessary first step. Mostly, you won't have any difficulties naming your long-term goals - in my case, for example the it is to win the 2012 Wheelchair Nationals. It is, however, also necessary to pick short-term goals in order not to lose yourself on your journey from A to B. After all, long-term goals are exactly what their name implies.... they are LONG. More often than not, you will feel that you have been working towards them for ages, which can become so discouraging that you end up in despair, negate all the small steps you have already taken and surrender to what you believe would be the "fate of the loser" that you are. Some people, on the other hand, react completely different. They become complacent, keep telling themselves how good they already look, how much they already achieved and how well everything worked out... obviously a completely different mistake, yet with similarly unrewarding outcome. To prevent these types of roadblocks, I have made a habit of setting up an exact time-line of short-term goals to accomplish. By doing this, I keep myself motivated, and on my toes (or in my case, on my wheels) to get to the one "distant" long-term goal of which you can lose sight so easily.

I am in week 7 of my contest prep, now. And, psychologically, this has been one of my easiest contest preparations, so far... this does not mean that it could eventually become tough further down the road, but based on my previous experience, I can usually tell if it's going be a rough cut pretty early on in my prep. When the hunger pangs, temptations and cravings are starting early, you know your in for a long cut. But so far nothing! No cravings, no temptations, and rarely any hunger pangs or none at all on most days of the week. I rarely even get excited or anxious on my designated re-feed / cheat days. I don’t feel sleepy, or tired, and my strength and energy is still up at the gym, and I haven’t been using any type of pre-workout, N.O. or creatine supplements, yet.

This is intriguingly easy - too easy!?

Ironically, the ease and smoothness with which things are rolling is what begins to scare me. Being used to the psychological stress, battles and mind games that I use to play with myself during dieting, I am constantly battling the thought that this ease is not what I am supposed to feel when I am dieting or preparing for a bodybuilding show… “If you’re not suffering, then you’re not doing it right!” But I’m not suffering. And yet I seem to be right on track or maybe even ahead of my schedule.

I mean, I do "suffer" the usual pain and fatigue you get while training heavy and intense, but if you remember the statement from Arnold about "da pump", Dr. Andro quoted a few blogposts ago, you will know that this kind of "pain" is what every serious bodybuilder is looking for. What I refer to as "suffering" is what the mental drain the incredible fatigue, the constant huger, the battle against cravings and hunger pangs... the kind of "suffering", when you you are dead tired from dieting so hard that you cannot even perform your daily routines... yet, thinking about it, even calling that "suffering" makes me feel somewhat ashamed. There are millions of people starving - these people have real issues, and people like you and me are complaining about something we are voluntarily doing to ourselves!? But anyway, let's get back to the topic at hand...

Image 2: Cream of Roast Beef, post-workout meal of the week.

Recipe of the Week: Cream of Roast Beef
(Post workout meal)

Ingredients:

• 7 oz roast beef (bottom round roast)
• 6 oz yam
• 5 baby carrots
• ½ c cottage cheese, topped w/ ½ c chopped apples, sprinkled w/ground cinnamon
• 2 tbs. low-fat sour cream
• 1 tbs. A1 steak sauce

Macros: 62g protein / 57g carbs / 20g fat

Quick tip: Personally, I eat more carbs around my workouts, but base all my meals on protein and fat on my off-days. So, if this was a rest day meal, I would take out the yam and replace the apples with a lighter fruit (lower in calories & carbs) like blueberries.

Raising the bar to outdo yourself: "Show ready" by week 12!

Since I’ve been cruising through my prep these past 7 weeks, I’ve decided to give myself a challenge or a short-term goal to prevent me from getting distracted and complacent, but to also keep me motivated (well I never really lost motivation, so I guess it's to add to my motivation) and give more light and focus to the real goal at hand, which is winning an overall title in March. The goal I picked is to be as close to "show ready" as possible by the 12-week mark, which should be Christmas day. Basically I’d like to be in the same type of condition Duong was in when he ended his 12 weeks (if you have not done that already, check out his amazing transformation in the SuppVersity Student Spotlight). Since it’s my first run at IF, I've been really gauging my progress with Duong's - from his macros, the type of foods he ate, to the schedule of his fast & feeding hours. I'm using Duong's progress as a checkpoint or marker, which means that if I am not in the same outstanding (or even better - sorry Duong ;-) physical condition as Duong was, when he hit his 12 weeks, then I need to pick up the pace and make some adjustments.

That being said, Duong gave himself "only" 12 weeks. I, on the other hand, deliberately started early and thusly do not have to cut my calories just as fast as he did ... it is nevertheless imperative that I do not develop the aforementioned complacency and eventually end up even worse than I would have when a relatively drastic, but short cut does not work out.

A log holds you accountable for your progress

My current plan is to maintain a daily caloric intake of 1.800 kcal/day until the end of November. This is in fact -100 kcal lower than the original plan. A plan, my instinct told me would not get me to where I decided I want to be by Christmas. Accordingly, I will drop my daily allowance to 1600 kcal/day in the first week of December '11. I am logging all my food and keeping track of all my calories and macros to a “T”, to be able to analyze which dietary tweaks worked, which didn't an which further alterations to my regimen will be most helpful.

Figure 1: Here’s an example of a program I made on my Macbook where I log my foods.

For the first month I was inconsistent with logging my foods. It was just easier for me to keep track in my head, but ever since giving myself this short-term goal, I made logging my foods just as much a priority as I do my training. Logging your foods and keeping track of your calories and macros also holds you accountable. You know every bite that you put in your mouth, so there’s no lying to yourself when you realize that you’re not making any progress, all the evidence is written down. When you look back and re-evaluate, you’ll know if you stuck to your diet or not... and what's more, logging my foods and keeping track of my numbers, soothes the feeling of "not suffering enough", it reassures me that I am doing everything to the literally "T" - no second guessing myself, no guilty conscious, and no elevated cortisol levels due to constant worries ;-)

It’s always a good idea to keep logs, especially if you’re just starting to learn about nutrition and dieting. Other than holding you accountable, food-logging helps you with learning about serving sizes, and how to count calories and macronutrients. And let me tell you, only when I began logging what I ate, I realized how little I actually knew about what I ate. Looking back four years, I have to admit that I did not even really know what a "protein" is, back in the days when I started.

Knowing your body and its limits is the key to success

On the non-dietary side of things, I noticed that I was getting a little burned out with the EDT in the course of the last week. My strength did not increase as much as it did the previous weeks, and I really felt fatigued the last training session of the week. So I took a break from EDT training this week and changed my workouts to a 5x5 routine, where I do 5 sets of 5 reps. I still lift heavy though. Depending on what muscles I train, I’ll do 7 exercises, and each exercise is 5x5. So for example on chest days, I’ll do 5 chest exercises and 2 triceps exercises, each exercise is 5x5, heavy. It felt pretty awkward going back to a regular split routine. I have gotten so used to the fast paced high-intensity EDT workouts that I wasn’t as hyped or amped during my workouts this week. Although I lifted heavy and intense (probably about the same if not more weight), I was not as mentally focused as I have been when I did the EDT cycles. I figure the best solution to this problem would be to alternate between a "regular" 5x5 split training and escalating density training regimen on a weekly basis. After all, the one week back on the "old" training split already paid off: my strength increased a lot! I guess after a few weeks without "classic" 5x5 training, my muscles were pretty shocked by what my brain tells me is an old hat ;-)

"In my opinion, classic cardio is way overrated and is for suckers!"

Image 3: Low-intensity cardio free! The only high intensity cardio I did during my prep in 09’ was hitting the heavy bag every other day for 30 minutes for the last 4 remaining weeks of my prep. I let my diet take care of the rest and suggest you do the same!

The comparatively low metabolic demand of 5x5 training also gave me the chance to pick up some 20-minute high intensity cardio during my rest days. I’m not a big fan of cardio, and I rarely do it, but when I do, I always enjoy doing high intensity cardio like hitting the heavy bag, doing sprints with my wheelchair or doing the burn machine (it’s a 10 pound hand cycle). I like to “get at it” for as hard as I can for 20 minutes, then I’m done. Don’t waste your time jogging on a treadmill for hours. That’ll get you nowhere fast (not even slow ;-)! Lift Heavy weights and do some sprints. That’s more productive and you burn more body fat than running on a treadmill for hour (assuming that you have your diet in check) .

You should never depend on cardio to transform your physique.

So whatever short- and long-term goals you may be setting in the course of the one week you will have to get along without another blogpost of mine, don't forget: "TRAIN SMARTER, NOT HARDER!"

Milk Thistle in PCT - Tamoxifen (Nolvadex) Still a Liver Killer, Despite Hepatoprotective Effect of Silymarin or Ziziphus

Image 1: Silybum marianum, a medical plant that has been used to treat liver disease for >2,000 years and is a staple in many "post cycle therapy" supplements you can current purchase at your favorite supplement store.

Whether or not you are into "performance enhancing drugs" does not really matter. If you have browsed through the range of one of the myriad of on-line supplement vendors, you will have seen them: the "liver protectors", "supplements for liver health", or simply "post-cycle recovery" supplements. The most common ingredient, you will see on the labels of supplements listed in these or similar categories, is silymarin, a flavonoid complex consisting of silybin (the most active component), silydanianin and silychristin, which is either extracted or simply contained in a crude extract of the seeds of Silybum marianum, a flowering plant of the daisy family, the manufacturers put into their capsules. While scientists still debate whether and for which type of liver disease(s) the use of the obviously non-patentable (you know that this means that no big pharma company will be willing to acknowledge that it works ;-) flavonoid would be an appropriate treatment option (Loguercio. 2011), generations of bodybuilders may actually have saved their live(rs) from the toxic effect of a highly "underrated" liver-killer, the "bros" know as "Tamox" - the Selective Estrogen Receptor Modulator (SERM), Tamoxifen, which is the active ingredient in the "anti-breast-cancer drugs" Nolvadex, Istubal, and Valodex.

In a mouse model (using 60 male Balb/c mice), scientists from Malaysia and the Middle-East conducted a 4-week study on the toxicity of orally administered tamoxifen (20mg/kg; HED ~1.2mg/kg) and the potential protective effect of milk thistle or jujube (Ziziphus, a tree from the buckthorn family, and the 'silymarin of the middle' east; Shahat. 2011) extracts at 300mg/kg (HED ~24mg/kg; ~2g for an 80kg human). To this ends, the animals were randomly assigned to one out of four 6 groups (Al-Jassabi. 2011):

1. control - no tamoxifen, no silymarin extract, no ziziphus
2. silymarin control (SC) - no tamoxifen, 300mg/kg silymarin extract, no ziziphus
3. ziziphus control (ZC) - no tamoxifen, no silymarin extract, 300mg/kg ziziphus
4. tamoxifen control (TC) - 20mg/kg tamoxifen, no silymarin extract, no ziziphus
5. tamoxifen silymarin (TS) - 20mg/kg tamoxifen, 300mg/kg silymarin extract, no ziziphus
6. tamoxifen ziziphus (TZ) - 20mg/kg tamoxifen, no silymarin extract, 300mg/kg ziziphus

Now, if you look at the actual effects the admittedly high dose of tamoxifen that was administered to the animals (note: while a 100kg bodybuilder would have to take 160mg to achive the same exposure I have seen obviously idiotic recommendations on various boards which suggest starting off your PCT with doses in the 80mg+ range!), I suppose that those of you who have (for whatever reasons) already used Nolvadex & Co. will probably be shocked.

Figure 1: Changes in transaminase enzymes, lipid peroxidation and anti-oxidant enzymes in male mice after 4 weeks treatment with 20mg/kg tamoxifen per day (data calculated based on Al-Jassabi. 2011).

7-12x elevations in transaminase levels (ALT, GPT, GOT), >70% reductions in antioxidant enzymes (SOD, CAT, GSHpx), on average, and the incredible 68x elevation in lipid peroxidation after "only" four weeks of treatment should make every steroid user reconsider, whether a tamoxifen-based post-cycle protocol does not do more harm than good. After all, one of the most common causes of gynecomastia is liver cirrhosis (Swerdloff. 2011), and you will probably agree that taking a drug to "protect" yourself from the estrogen rebound after (or even in the course of a cycle) which has gynecomastia as a possible side-effect of a side-effect does not really make sense.

Moreover, scientific data on the efficiacy of tamoxifen in the treatment of male hypogonadism (which is basically what steroid users will experience at the end of a "cycle") is pretty scarce, if not non-existent and from a "scientific point of view" clomifene citrate (clomid) would appear to be the SERM of choice, here (cf. Katz. 2011).

I hope that you notice the stupidity of the typical bro-scientific approach to taking B to counter the side-effects A, C to counter the side-effect B, D to counter the side-effects of C... and so on and so forth..., because, after all, even if C or D were silymarin or ziziphus, the use of these potent liver-protectants would still leave you with profoundly elevated transaminase levels and reduced anti-oxidant capacity (cf. figure 2):

Figure 2: Changes in transaminase enzymes, lipid peroxidation and anti-oxidant enzymes in male mice after 4 weeks treatment with 20mg/kg tamoxifen + 300mg/kg silymarin or ziziphus per day (data calculated based on Al-Jassabi. 2011).

And what's more the lipid peroxidation would be significantly ameliorated by the use of 2g of silymarin (HED) per day, but still 13x over normal. If that is what you want, go ahead and terminate a harsh cycle with a harsher PCT, if not - select another method to get your HPTA (hypothalamic-pituitary-thyroid-axes) back in shape and use the milk thistle to counter potentially hepatoxic effects of the cycle itself.

Ah, and I don't know if you have even remotely considered that: Not taking steroids would make any PCT and potential on- or off-cycle liver toxicity obsolete. The use of milk thistle extracts could yet nevertheless make sense! After all, the staff at ScienceDaily posted a short news-item on the anti-lung-cancer effects of silymarin, just this morning - so if your "drug of choice" is nicotine (not AAS), don't forget to take your milk thistle ;-)

Building a Bigger Engine: Resistance After Endurance Training Increases Mitochondrial Biogenesis & Protein Synthesis and Ramps Up Fat Metabolism

Image 1: There is nothing wrong with some "classic cardio" training, especially if you spike it up to build your mitochondrial engine

In a recent review of the literature, J.M. Wilson from the University of Tampa analyzed the results of 27 studies to determine whether and to which extend concomitant endurance training does / could have detrimental effects on the outcomes of resistance training (Wilson. 2011). And I suspect that it will not surprise you that Wilson found negative correlations "between frequency (-.26 to -.35) and duration (-.29 to -.75) of endurance training [and] hypertrophy, strength, and power." What is yet also noteworthy is a similarly significant (p<0.05) correlation with lower body fat levels and maximal heart rates on part on those strength athletes who did some sort of endurance exercises. Now, a more recent study which is soon going to be published in Journal of Applied Physiology sheds some more light on the complex interplay of endurance and resistance training and the potential benefits of combining both to build a "bigger mitochondrial engine" (Sahlin. 2011).

Interestingly, the Swedish scientists started out with a diametrically opposed hypothesis. Sahlin et al. expected that the signaling of mitochondrial biogenesis, of which it is common knowledge that it is promoted by "classic" low(er) intensity endurance exercise, would be impaired by resistance exercise. To validate their hypothesis, the scientists had a group of ten healthy subjects (7 males and 3 females; age, 26 ± 1.2 (mean ± SE) yr; height, 177 ± 2.9 cm; weight, 72 ± 3.5 kg) perform either 60min of endurance exercise (65% of VO2Max on a cycle ergometer) alone (E), or in combination (R+E) with a subsequent bout of 6 sets of leg presses at workloads corresponding to 70, 75, 80, 80, 75 and 70 % of the individual 1RM with 3 min rest between each set (cf. figure 1)

Figure 1: Graphical overview of the study outline (based on Sahlin. 2011).

Muscle biopsies were taken before and after the exercise protocol, to which the subjects had been randomly assigned and which was repeated 2 weeks (4 weeks in the female participants to avoid any influence of the menstrual cycle) later with subjects from the E group performing E + R and vice versa. The results, I'll say so much, were by no means what the researchers had expected.

Figure 2: Changes in lactate and muscle glycogen content in response to endurance (E) and combined endurance and resistance (E+R) training (calculated based on Sahlin. 2011).

While there were the expected differences in lactate levels, and glycogen content of the biopsied legs (cf. figure 2), the increase in the phosphorylation of mTOR and its upstream regulator Akt (you should know these promoters of protein synthesis from the posts in the Intermittent Thoughts series and my dissertations on other studies, by now ;-) was not only exclusive to the endurance + resistance training group (E+R), it was probably also much more pronounced than one might expect with 6 sets of leg presses and lead to an almost dramatic increase in p56Sk1 phosphorylation (do I have to mention that this happened "although" the subjects trained >12h fasted and remained fasted for the whole study period?) - a relatively reliable marker for protein synthesis (cf. figure 3).

Figure 3: Changes of key enzymes envolved in the phosphorylation of key enzymes in the protein synthetic cascade in response to endurance (E) and combined endurance and resistance (E+R) training (calculated based on Sahlin. 2011).

Morover, and totally contrary to what the scientists had expected, the expression of the key enzyme for mitochondrial biogenesis and increased fatty acid oxidation, PDK4 was significantly elevated, not suppressed, in response to the additional leg training (cf.  figure 4).

Figure 4: PDK4 phosphorylation (arbitrary units) in response to endurance (E) and combined endurance and resistance (E+R) training (calculated based on Sahlin. 2011).

The research hypothesis that a (relatively short, but intense) bout of resistance training subsequent to a mitogenic "classic" cardio regimen would blunt the beneficial effects of the latter on mitochondrial biogenesis is thusly more than falsified. As it turns out, the 6% increase in total work-load due to the addition of the 6 sets of leg presses makes a huge and desirable (!) difference (way beyond what an over-simplified workload = output equation would explain) in terms of "building a bigger engine" - an engine that will keep you lean on a bulk and help you lean out while your dieting.

If you are no powerlifter, it is thus probably no mistake to keep some "classic cardiovascular" exercise in your regimen, especially if you spice it up with a subsequent short bout resistance exercise - another option, and I am repeating myself here, would obviously be a high intensity cardio session (cf. HIIT). That being said, change has time and again proven to be the key to continuous improvements in exercise performance, muscular growth and strength, to incorporate both spiced up "classic cardio" and HIIT in your routine could not only improve your results (in view of the protein synthetic response, you could even "grow" on such an E+R day), it will also prevent you from getting bored with performing the same routine day in and day out and if you asked me, that is an even more fundamental key to success than a X% increase in the phosphorylation of whatever key enzyme ;-)