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marylin monroe
Showing posts with label IGF1. Show all posts
Showing posts with label IGF1. Show all posts

Intermittent Thoughts on Building Muscle: The Skeletal Muscle Hypertrophy 101 - Part 2: Getting Big Means Growing Beyond Temporary Physiological Limits.

Image 1: This is another type of "dysfunctional muscle"; distinct from the one we are talking about, here
Although I assume that you all have read the last installment of the Intermittent Thoughts, I took FatFree's comment that he (or she?) was missing the "too comlicated check box" from the old design to the heart (I do so with every comment, btw, so keep them coming) and kick off today's installment of "The Thoughts" with a brief and even more "dumbed down" summary of what we have learned about the (possibly) ascertained and, even if human skeletal muscle hyperplasia existed, dominant factors in the trinity of skeletal muscle growth: Protein synthestic increases in myonuclear domain sizes and the satellite cell driven incorporation of new myonuclei.

Getting big goes beyond ballooning up

You probably will remember the balloon-metaphor, I introduced in the red infobox toward the end of the last installment. Let's briefly get back to that and use it to reavaluate the results from the Quaisar study (Qaisar. 2011, see also "What is Hypertrophy"). Rizwan Qaisar and his colleagues from the Uppsala University in Sweden had analyzed the differential effect of insulin-like growth factor 1 (IGF1) over- and myostatin-underexpression on muscular size and function (the latter is important, since we know that a complete lack of the "muscle growth blocker" myostatin leads to huge, but disfunctional / weak muscles). 
Figure 1: Domain sizes of EDL and soleus muscle fibers in wild-type control, myostatin negative and IGF1 overexpressing mice (data based on Qaisar. 2011)
Now to really understand the meaning of what may be the main message of the study, it is imperative to understand the basic architecture of muscle fibers. If you think about a complete muscle fiber as a bundle of ballons that is wrapped into a strechable net, then each balloon would represent one myonuclear domain. The owe their name to the fact that they actually are the "domains" which surrounding a single myonucleus (lat. plural "myonuclei") within a given skeletal myocyte, which - contrary to other cells in your body - has the ability to hold multiple nuclei. Now, the most obvious determinant of the myonuclear domain size is the ratio of protein in- to protein efflux. And it is this connection on which researchers base their belief that by simply measuring the protein synthetic response to exercise and/or supplementation would suffice to predict long-term increases in muscle size (and subsequently strength / performance).

Growth is limited and myostatin is not just a pain in the ass of anyone who wants to "get big"

Image 2: Sketch of a mammalian skeletal muscle fiber - myonucleus (turqouis), mitochondria (blue),  sarcoplasmic rectilium (buff), tubules (orange), myofibrils (pinkish)  - Artist: Lesley Skeates. Originally from Gray's Anatomy 29th ed. Elsevier. 2008
If you take another look at the data from the Qaisar study (cf. figure 1), you will notice that uncontrolled growth in "one dimension", i.e. exclusive increases in domain size, generates larger muscles, but at the same time renders them dysfunctional, a process of which Qaisar and his colleagues believe that it is caused by a decrease in the number of strongly attached cross-bridges, which are the primary source of the small specific force in muscle fibers with very large MNDs. This hypothesis is by the way supported by a lowered myosin (contractive motor-protein) content per muscle volume in the myostatin negative mice.

In order to really understand why this is the case, it may help if you take a look at the (awesome) sketch of a mammalian skeletal muscle fiber on the right (image 2). The myonuclei are colored in turquois-green, they are connected to the mitochondrion (blue) and the sarcoplasmic rectilium (buff), which is traversed by transverse tubules (orange, and not easy to distinguish). The major part of the muscle fiber is yet made up by myofibrils, which are protein chains containing actin, myosin, and titin...

Ah... wtf. Before someone wants to click the "too complicated"-button again, let's just say the myofibrils are the ones who do the actual work. Now, with the increased domain size (obviously the domain is the "zone" comprising all the aforementioned components that a single nucleus is "responsible" for) and the consequent decrease in myosin content (per volume), as well as the reduced number / density of cross-bridges, i.e. links between the myofibrils to coordinate their action, the muscle loses its functionality. Just like a labor brigade with 5 smaller, smart guys who listen precicely to what their foreman says and work hand in hand can get the job done more efficiently than 5 big, but dump guys, who do not even listen to what their foreman tells them, this type of one-dimensional growth, i.e. an exclusive increase in domain sizes, goes at the expense of muscle function.

From satellite cells to broadcasting towers and back again

Image 3: Myonuclei have a domain, similar to the broadcasting area of a transmitter mast.
So, the myonuclear domain, has nothing to do with some sort of "fenced off" area that is protected by a cell membrane. In physics, we would probably talk about a field, a field of influence, just like an electromagnetic field, with the exception that the signalling from the nucleus does not work via EM radiation, but via gene-signalling... mTOR & Co says hello ;-) Satellite cell recruitment and the "installation" of new myonuclei would thusly be equal to the installation of new broadcasting towers, which make the existing system more effective and allow for further expansion. If you are a mobile communications veteran, who knows the "good" (or rather bad) old days of poor reception you'll know what I mean.
In this context it may be interesting that a very recent study by Antonios Matsakas et al. was able to show that the voluntary wheel running or swimming was able to restore the function of the "over-blown" muscle of myostatin-null (MSTN-) mice (Matsakas. 2011). Another clear cut evidence that exercise induces structural changes which go well beyond the accrual of protein that is not adequately controlled in the MSTN- mice.

Do you take my point now? Ok, then let's get on...

The expression of myostatin, which prevents the myonuclear domains from further expansion is thusly a means by which your body maintains muscular function. Contrary to my friend Adelfo, your body has no interest in looking like Phil Heath... the only reason it has to grow is to be able to survive and survival requires functional strength, not size. There is yet some leeway as far as increase in domain sizes are concerned and it is this leeway that explains the "exorbitant" gains you have been making when you first hit the gym. The lazy bastard (sorry ;-) you have been before, your myonuclear domains were probably far beyond their "functional" limit and, consequent to the acute protein synthetic response to your 1001 biceps curls, "ballooned up" until, just as Darryn S. Willoughby observed it in his 2004 study (Willoughby. 2004), the contemporary increase in skeletal muscle myostatin content brought the expansion of the "bloated" myonuclear domains to an "abrupt halt" (at least that was probably your perception).
Figure 2: Relative myofibrillar protein content and myostatin mRNA expression in the thigh muscles of 11 previously untrained subjects in response to a 12-week (3x per week) resistance training regimen with 3 sets of leg presses and knee extensions à 6-8 reps @85-95% of the 1RM (data calculated based on Willoughby. 2004)
As the relative amount of myofibrillar protein content and myostatin mRNA expression in skeletal muscle from the previously 22 untrained male subjects of the Willoughby study shows (cf. figure 2), the myofibrillar protein accretion is accompanied by profound increases in the expression of muscular myostatin. Or, put simply, the bodies of the subjects, whose thigh volume increase by roughly 16% in the course of the 12-week study period, were sensing that without structural changes, this type of muscle growth would eventually lead to huge, yet dysfunctional muscle fibers - something that obviously would not promote survival and is thusly not part of our genetic program.

Structural changes facilitate new growth

On the other hand, the constant overload to which (I hope) you are exposing yourself in the gym signals your body that without increasing strength (again, your body does not care about size), it will not last much longer is the "adverse environment" of the gym. So, the only way to "survive" is to rebuild / restructure the muscles, a process of which we have seen in the last installment of this series that it goes hand in hand with decreases in the number of purported hypertrophy prone "ultra-fast" twitch type IIb muscle fibers (or rather the content of respective myosin heavy chains within your muscles). Whether the resulting phenotype is that of a bodybuilder, characterized by increases in both the number and size of slow-twitch type I and fast-twitch (intermediate) type II-x fibers, or that of a powerlifter, characterized mainly by increases in the number and size of (intermediate) type II-x fibers, depends on the training stimulus, alone:
    Image 4: Our bodies respond to different training routines by distinct changes in the muscular structure.
  • Wanna get strong like a German Olympic gold medalist Matthias Steiner? Then goto the gym, 10x a day and do a 1-rep max plus minimal auxiliary work like people the Bulgarian O-lifters are supposed to do. 
  • Wanna get big like Arnold? Then follow his example and break into your local gym on Sunday (Arnold's was not open 24/7 back in the day, but that did not stop him from training) and pump out rep after rep, after rep to make sure your body understands that you want to maximize both type-I as well as type-II fiber size.
This does not mean that you cannot get big and strong, it does yet mean that a competitive bodybuilder will - per pound of lean body mass - always be weaker than a powerlifter.

"I need YOU!" ... to pick my brain and steer this series in the right direction

The sixty-four-thousand-dollar question now is: What is the "best" way to let your body know what you (not even your brain, but rather your mind) wants? And even at the risk that I am losing my "guru status" now, I want to be honest with you: I don't know the answer... at least not yet ;-) I thusly depend on your help, on people like Steven Acerra, who is constantly picking my brain with interesting questions and studies on facebook, Mike T Nelson, who lately jumped in on an interesting discussion on training stimuli, "Fat Free", Aaron, Matt, Erik Istre, Lerner (whose comments I have been missing lately) and all the rest of you who chime in with questions, suggestions or the simple assessment that the "good Dr. Andro" is once again making things only more complicated ;-)

And as a food for thought, I give you a sneak peak at what should come next in this series: It is the intricate relation of protein and endocrine signaling by which your muscles and no central governor or transient elevations in isolated systemic testosterone, growth hormone or insulin levels regulate the concomitant increases in muscle protein synthesis and satellite cell recruitement and changes in the myosin heavy chain composition. So, assuming that this installment of the Intermittent Thoughts did not raise further questions as far as the basics are concerned, the next installment will revolve around the role of IGF1 and its local (=intra-muscular) cousins MGF and IGF-IEa, which appear to play a key role in the the coordination of the restructuring process that will keep your muscles functional, even when you are approaching a Olympia stage ready bodybuilding physique.

Intermittent Thoughts on Building Muscle: The Skeletal Muscle Hypertrophy 101 - Part 1: What is Hypertrophy?

Image 1: Governator, Arnold Schwarzenegger, as a teen and in his early twenties. What - puberty aside - were the underlying mechanisms of the obvious increase in sleeve-size? I mean on a strictly myocellular level, of course ;-)
Those of you, who have been following the Intermittent Thoughts series over the last weeks will probably already have realized that I finally dropped the "Intermittent Fasting" from the title... this is something I have been thinking about for quite some time now. After all, the series has evolved way beyond its initial focus on a specific dietary protocol and has become more of an educational "how do you find your way to success"-series. With the format, intermittent thoughts, being still the same, the upcoming posts in this series, which will certainly touch on the topic of intermittent fasting, again, will be titled "Intermittent Thoughts on..." whatever the topic of the week may be... and for this week's installment the latter is going to be "Building Muscle: The Skeletal Muscle Hypertrophy 101".

I can already foresee that this is only the first in yet another series of posts. An introduction into the myocellular mechanisms that turn a normal teen like into a symbol of physical culture, or, to put it simply:  

What actually is skeletal muscle hypertrophy? 

Before I even try to answer this question let me remind you of something you have learned about "growth" in one of the previous installments of this series. In "Building Muscle Starts With Losing Weight" you have learned that one of the greatest fallacies of "classical" bulking, as in "eating everything that cannot escape your ravenous hunger for mass", is adipocyte hyperplasia. You may also remember that this increase in the number of fat cells occurs, when your existing fat stores are ready to burst and your body is in need of new storage capacities. Analogously, you would expect your muscle fibers to "hypertrophy" (from mechanical overload and constant nutrient abundance) until they are "ready to burst" and then divide and form new muscle fibers. (Un?)fortunately, myocytes are not adipocytes and thusly things are working somewhat different, here.
Figure 1: Overview over the three (?) pathways by which your skeletal muscles "grow".
If you take a look at the graphical overview I have come up with in figure 1, you will see that there are two, maybe three distinct pathways which contribute to what the average trainee subsumes under "hypertrophy".
  1. Pathway A - hypertrophy via satellite cell recruitment and increases in the number of myonuclei per muscle fiber,
  2. Pathway B - hypertrophy via increases in myonuclear domain size within an existing muscle fiber, and
  3. Pathway C - hyperplasia, which would be the increase in muscle size by cell division and thusly an increase in the number of muscle fibers
The existence of different fiber types, or to be precise, the co-existence of different fiber types (fast twitch, slow twitch and various sub-types) at varying ratios within a single muscle group complicate things even further. Instead of giving you the usual theoretical lowdown on type I and type II fibers and how the former are supposedly used for endurance and the latter for strength training, I want to discuss the matter from a more practical perspective and first pose the question: What is that we actually want? 

I mean, you do not want "hypertrophy", but you want to get big and buffed, right?

Assuming that this is the case we should initially define "big and buffed" on a myofibrillar level by taking a look at how the muscles of the forerunners of physical culture actually look like - and I promise, what you will be learning today will, once again(!), go against conventional wisdom. Or would you have expected that bodybuilding is a sport that is characterized by a loss in highly glycolytic type IIb fibers and increases in both the intermediate type IIa, as well as the "endurance type" slow-twitch muscles? No? Well, then you should have a look at the data in figure 2:
Figure 2: Fiber composition of bodybuilders, recreational lifters, endurance rowers and sedentary control; determined via myosin heavy chain (MHC) isoform content of the triceps brachii muscle (data adapted from Jurimäe. 1997)
The results of the 1997 muscle biopsies by Jurimäe et al.  (cf. figure 2) clearly show that "getting big and jacked" is by no means about maximizing the "hypertrophy-prone type II fibers", as you may have read it numerous times on one of the thousand bulletin boards, or the numerous blogs of self-proclaimed fitness experts (Jurimäe. 1997). A bodybuilder is rather a person who has maximized the expression of myosin heavy chain I and IIa. Specifically with reference to the latter, the authors write:
It is interesting to note that Kraemer et al. (1995) have reported a lack of change in the area of fibres consisting predominantly of MHC type IIb proteins (i.e. FTb fibres) as a consequence of a 12-week resistance training programme. This suggests that a shift from MHC type IIb proteins to type IIa MHC isoforms may be a necessary prerequisite for FT fibre hypertrophy to occur. Consistent with this was the significant negative correlation (r = -0.67) between the percentage of MHC type IIb isoforms and arm circumference. Similarly, the smaller arm girth of the C group may have been partially due to the greater content of MHC type IIb isoforms in this group.
Or put simply,  the "strong" type IIb fibers have a very limited (if any) propensity for hypertrophy. So that, in order to maximize growth, it is necessary to trigger a shift towards the more "intermediate" type IIa fibers. If you take into consideration, how almost all bodybuilders got, where they are now, i.e. by a volume training approach, this is actually something you should have been able to infer simply from what has been and is still working for 99% of the trainees.
Figure 3: Intercorrelations between myosin heavy chain (MHC) isoforms and isoinertial (1-RM max), isometric (extension) and isokinetic (extension peak torque) strength indices (data adapted from Jurimäe. 1997)
Moreover, the data in figure 3 shows that this does not necessarily mean that they have to sacrifice their strength, as the percentage of type IIa fibers does not only correlate with increased muscle size, but also with increased isoinertial (1-RM max, r=0.66), isometric (workload, r=0.51) and isokinetic (peak torque, 0.61). strength. Getting big and buffed and getting strong thusly both require a profound shift in the "God given" fiber composition, but why?
Skeletal muscle hyperplasia - yes or  no? While there are a handful of studies which speak of hyperplastic responses to stretch or other form artificial overload, many (if not all) of them have been done on avian myofibers (Kelly. 1996), which, due to their special make-up, make it a) very difficult to distinguish between increasing overlap due to the longitudinal growth of intrafascicularly terminating skeletal muscle fibers and "real" hyperplasia and b) may not even translate to human beings. That's the reason, why I will disregard the issue of hyperplasia in the following discussion.
A very recent study by an international group of scientists from Sweden and the USA, may provide some insights, into why these fiber-transformations are necessary if you want to grow tree-trunk legs and sleeve-bursting arms. In this study, which was published on November 28, 2011, in the FASEB Journal (Qaisar. 2011), Rizwan Qaisar and his colleagues provide a detailed analysis of the the muscle fiber composition of mice who are either myostatin-negative or over-express the muscle building growth hormone IGF1 (we are talking about intra-muscular IGF1, here! More on that in future installments of the series).
Figure 4: Cross sectional area (CSA), number of mynuclei and myonuclear domain size of myostatin negative mice and mice overexpressing IGF1 relative to wild-type control (data calculated based on Qaisar. 2011)
As you would expect, both the myostatin-negative, as well as the IGF1 mice were more muscular than their wild-type cousins. There were, as you can see in figure 4, yet significant differences in fiber sizes (CSA), the number of myonuclei per fiber, and the domain sizes of the individual myonuclei in the exclusively fast-twitch extensor digitorum longus (EDL) and the predominantly slow-twitch soleus muscle.
Image 2: The balloon metaphor of skeletal muscle hypertrophy.
Note: If you picture a muscle fiber as a number of balloons which are held together by an elastic net, then the myonuclei would be within the individual balloons, which, in turn, would represent the myonuclear domains. You could thusly increase the muscle size, i.e. stretch the net, by either inflating the balloons, i.e. increasing the domain size, or simply adding more balloons to the net. The latter would then be equivalent to the recruitement of new myonuclei from the satellite cell pool in the sarcoplasma of the muscle fibers.
If you take a closer look at the data you will notice that in the IGF1 mice the predominantly fast-twitch EDL muscle growths mainly by increases in myonuclei number, a feature that is absent in the predominantly slow-twitch soleus fibers. The profound increases in myonuclear domain size that occur in the myostatin-negative mice, on the other hand, result in profound reductions in muscle function.
Figure 5: Specific force, stiffness and myosin content (secondary axes) of EDL and soleus muscle in wild-type control, myostatin negative and IGF1 overexpressing mice (data based on Qaisar. 2011)
Both specific force, as well as as muscle stiffness, are profoundly reduced in the EDL muscle of the myostatin negative mice (cf. figure 5), because they have surpassed the maximally sustainable domain size and have thusly become dysfunctional.
Figure 6: Domain sizes of EDL and soleus muscle fibers in wild-type control, myostatin negative and IGF1 overexpressing mice (data based on Qaisar. 2011)
This becomes even more obvious if we take a look at the domain sizes in isolation (cf. figure 6). It is the "uncontrolled" growth that is partly a result of a lack of satellite cell recruitment and consequent increases in myonuclei number, which cripples most of the animals with mutations in the myostatin gene.

Muscle hypertrophy = increases in myonuclear number & domain size

Healthy muscle growth, that is the intermittent take-away of this installment of the Intermittent Thoughts on building muscle, is thusly a direct result of "hypertrophy", as it is commonly associated with increased protein synthesis (and decreased or constant protein breakdown) and the subsequent expansions of individual myonuclear domains and the recruitement of satellite cells, which will then form new myonuclei.

As you may have noticed from the increasing amount of typos, of which I have probably overlooked 50% (sorry for that), my Sunday time-budget is already exhausted, so that I will have to postpone the discussion of what triggers these processes to the next installment. I do yet hope that the stuff you learned today provides enough food for thought to get you through the week ;-)

When Rodents Squat, Scientists Gain Insights into How Muscles Grow. IGF-1 Response to Exercise Does Matter - Locally, not Systemically, of Course!

You want to build big wheels? Look no further get yourself the "Squat T-Bar" with integrated 15mA electrical 'motivator' (Aguiar. 2012)
"A rodent study investigating strength workouts?" Yeah, I know it does not sound like that would be in any ways news-worthy, but if you take a look at the image on the right, you will immediately realize: This study is different! Instead of using a treadmill or simply stitching down (or rather up) one of the hindlimbs of the rodents to induce a chronic overload on the other one (don't laugh, many rodent studies have done just that), the study at hand (Aguiar. 2012), which is going to be published in the next issue of the International Journal of Sports Medicine, used a not innovative, but unfortunately largely forgotten (or overlooked?) torturing device that has been developed by Japanese researchers roughly 20 years a ago (Tamaki. 2012).

The rodent torture... ah pardon squat rack ;-)

After being fitted with a canvas jacket in a way that would enable the researchers to limit the twisting and flexion of their torsos (no, that was not a weight lifting belt ;-), the 32 male Wistar rats (80 days old, 250–300 g) were suspended in a standard position on their hind limbs and "encouraged" to exercise by "electrical stimulation [...] that was applied to the rat’s tail through a surface electrode"  (Aguiar. 2012).

Using their neat little toy, the eight researchers from the University Estadual Paulista, in Botucatu, Brazil, were able to submit the rats to a relatively realistic progressive resistance training regimen for either 8 or 12 weeks. Three times per week each rodent had to do 4 sets  of squats for 10-12 repetitions at 65-75% of its individual 1-RM (maximal weight the rodent could handle). During the study period, Aguiar et al. adjusted the weights twice a week to ensure the same training intensity throughout the experiment (something I would highly recommend to anyone of you, as well; try to pack on 1.25lbs - 2.5lbs at least every other week).
Figure 1: Body weight, muscle weight (plantaris, only) and food intake relative to body weight of the control (C8, C12) and trained (T8, T12) rats before and after the 8-week (C8, T8) and 12-week (C12, T12) intervention (data adapted from Aguiar. 2012)
As you can see in figure 1, this minimalist approach to leg training lead to an increase in both body weight and muscle weight that may initially look as if it was strongly linear. You do yet have to be careful about statements like that, because (a) the rodents did gain weight irrespective of whether they were training or not (80 day old rats are still growing!), so comparing the four bars next to each other and saying "yep, linear!" is not feasible, because this would mean linear as in not training for eight weeks < training for 8 weeks < not training for 12 weeks < training for 12 weeks, which is obviously nonsensical. That being said, there is simply (b) insufficient data to say anything about the linearity -- after all, we do have only three data points per group.
"All groups started the experiment with similar body weight. There was a significant increase (p < 0.05) in the body weight of the 4 groups in the resistance training program (C8: 35.5 %; T8: 27.7 %; C12: 46.9 %; and T12: 40.1 %) and final body weights were not significantly (p > 0.05) different between groups. Furthermore, no significant (p > 0.05) differences in the weekly food intakes were observed between the groups."(Aguiar. 2012)
What does yet stick out, is that the obviously age-dependent weight gain in the control groups C8 and C12 did not increase the weight of the plantaris muscle to a weight anywhere near to the muscle weight, the rats in the trained groups achieved.

Muscle gains and strength gains went hand in hand

In the rats who were subject to the three-times-per-week exercise regimen, on the other hand, those increases in muscle size went hand in hand with highly significant improvements in 1-RM squat power; While all groups had begun the training protocol with similar absolute 1-RMs of ~450g (that's about 130% body weight, pre) ...
"[...] training for 8 and 12 weeks promoted a significant (p < 0.05) increase in the RM/BW ratio in the T8 (pre- vs. post-training: 35.7 % increase, p < 0.05) and T12 (pre- vs. post-training: 57.1 % increase, p < 0.05) groups, while no statistical (p > 0.05) difference was observed in their respective control groups." (Aguiar. 2012)
Consequently, the ratio of 1-RM to body weight was 36.1 % and 57.7 % higher in the groups who had been training fot the last 8 or 12 weeks than in the lazy controls and the time-effect yielded another +22% increase in strength in those rodents who trained for 12 and not just 8 weeks.
Figure 2: Strength gains (left) and increases in cross sectional area, as well as intramuscular IGF1, myogenin and myoD expression (data adapted from Aguiar. 2012)
Now you may have heard all that before, what really makes this study stand out, however, is the observation of statistically highly significant correlations of intra-muscular IGF1, myogenin and myoD  mRNA expression, which speaks in favor of my previous hypothesis (read up on that in the Intermittent Thoughts on Building Muscle) that muscle growth is triggered, driven and maintained almost exclusively at a local level.

What are myogenin and myoD? Both are myogenic regulation factors with myogenin actually being part of the myoD family of transcription factors that will make stem cells develop into myocytes (myo D is highest in recently activated satellite cells).
So, when you are looking for "hormonal" (or other pro-anabolic) ghosts (Phillips. 2012), it is imperative to look for them right where the spook, or, in this case, the muscle building magic happens. If you do just that (see figure 2) and correlate the intra-muscular mRNA expression of IGF-1, myogenin and myoD, you will find the "ghostly" explanation for strength and size gains, as well as the confounding structural changes in the architecture of the muscle, with corresponding correlations between the increases in muscle cross-sectional area (CSA) of r = 0.85 (p = 0.0001), r = 0.87 (p = 0.0001) and r = 0.88 (p = 0.0001) for myoD, myogenin and IGF-1, respectively.

Fiber type changes take their time and occur only within the type II spectrum

A neat side-finding, which is actually no news, though, pertains to the fiber-type conversions that took place in response to the exercise regimen. Firstly, the scientists confirmed the notion that these changes occur exclusively within a certain fiber type. In other words, while Aguiar et al. observed conversions from the metabollically more flexible type IIX/D to the highly glycolytic (power) IIA type, no conversions of the highly oxidative type I to type II fibers were observed. And though the results would generally suggest that fiber IIX/D-to-IIA type conversion, as they 
"[...] also appear to occur during endurance training in humans, so that it would [be] reasonable to think that any exercise stimulus (e. g., endurance or strength) that is sufficient in duration and/or intensity can potentially induce conversions within the fast fiber population from type IIX/D to type IIA" (Aguiar. 2012),
the time-frame in the course of which these changes took place -- namely 12 weeks -- would confirm that the common fear of strength and endurance athletes could provoke negative structral adaptations from doing a "cardio" or "strength" workout from time actually is actually unwarranted. Neither will the former turn a powerlifter into a weakling, nor will the latter make a marathon runner "bulky". Both powerlifter and marathoner are on the contrary going to benefit from the conditioning effect and increase in strength, respectively -- not to mention the important effects on overall health both and not as mainstream stupidity will tell you only the powerlifter can derive from, figuratively speaking, "killing some game in the other's territory"

Bottom line: More food for intermittent thoughts on building muscle ;-)

Figure 3: Correlations between acute GH (A), free testosterone (B), IGF-1 (C)  and cortisol (D) responses (area under the curve—AUC) and gains in type II fibre CSA (Burd. 2012).
Eventually, this study is an excellent example of a way to design a rodent study in a way that will render its results actually meaningful. And what's more, in this particularly case these results are not just meaningful, but can also help us to make some sense of a couple of things we have not fully understood / appreciated, as of yet.

What I am particularly thinking about here, is the contrast between the in-vitro effects of IGF-1 and the (more or less absent) real-world effects of the IGF-1 response to exercise (=systemic increase), as it was observed by West and Phillips in a 2012 study. In their well-powered longitudinal study, neither the acute increase in systemic testosterone, nor the exercise induced increases in systemic IGF-1 showed significant correlations with the gains in type II CSA in a cohort (n = 56) of young men in response to 12 weeks of resistance training (West. 2012; see figure 3).

Another interesting finding of the West study was that, contrary to the circulating testosterone and IGF-1 levels, GH and cortisol did show direct correlations with increased muscle cross sectional areas in type II fibers.

And while the former correlation may be explained by the influence of growth hormone (GH) on the local expression of IGF-1 (Hameed . 2004), there is another open question left: How does cortisol actually figure in here? I mean, the chronic elevation / exogenous adminstration of cortisol, has been show to do the exact opposite, i.e. it decreases the local IGF-1 mRNA expression (Inder. 2010).

Figure 4: Graphical summary of what you should have learned Intermittent Thoughts on Building Muscle ... you didn't 'cause you are new to the SuppVersity or simply forgot about it? No problem read the preliminary summary and browse the individual chapters here!
What was missing in the Inder study, however, was the exercise component: Working out does not just exert protective effects against the negative side effects of the provision of exogenous "cortisol" (in this case Dexamethason), as they were observed in the afore referenced study by Inder et al., exercise will also lead to profound increases in local IGF-1 mRNA expression (e.g. +60% in Bamann. 2001), despite the fact that it will also increase the release of the falsely vilified anti-inflammatory glucocorticoid, cortisol... acute vs. chronic, local vs. system, peak values and amplitudes vs. plateaus and AUC values - you got to keep all these contrastive, yet complementary pairs in mind, when you are thinking about the endocrine and intracrine (within the cell) mediators of skeletal muscle hypertrophy.... what? Sounds familiar? Well, you must have been following the Intermittent Thoughts on Building Muscle, then ;-)

References:
  • Aguiar AF, Vechetti-Júnior IJ, Alves de Souza RW, Castan EP, Milanezi-Aguiar RC, Padovani CR, Carvalho RF, Silva MD. Myogenin, MyoD and IGF-I Regulate Muscle Mass but not Fiber-type Conversion during Resistance Training in Rats. Int J Sports Med. 2012 Oct 11.
  • Bamman MM, Shipp JR, Jiang J, Gower BA, Hunter GR, Goodman A, McLafferty CL Jr, Urban RJ. Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. Am J Physiol Endocrinol Metab. 2001.
  • Ding H, Gao XL, Hirschberg R, Vadgama JV, Kopple JD. Impaired actions of insulin-like growth factor 1 on protein Synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect. J Clin Invest. 1996 Feb 15;97(4):1064-75. 
  • Inder WJ, Jang C, Obeyesekere VR, Alford FP. Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1--implications for steroid-induced myopathy. Clin Endocrinol (Oxf). 2010 Jul;73(1):126-32.
  • Phillips SM. Strength and hypertrophy with resistance training: chasing a hormonal ghost. Eur J Appl Physiol. 2012 May;112(5):1981-3-
  • Sculthorpe N, Solomon AM, Sinanan AC, Bouloux PM, Grace F, Lewis MP. Androgens affect myogenesis in vitro and increase local IGF-1 expression. Med Sci Sports Exerc. 2012 Apr;44(4):610-5.
  • Tamaki T, Uchiyama S, Nakano S. A weight-lifting exercise model for inducing hypertrophy in the hindlimb muscles of rats. Med Sci Sports Exerc. 1992 Aug;24(8):881-6.
  • West DW, Phillips SM. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. Eur J Appl Physiol. 2012 Jul;112(7):2693-702. 

Differences in Growth Hormone, Insulin and IGF-1 Response in Trained and Untrained Resistance Trainees - Further Evidence That GH Builds Neither Muscle Nor Strength

Image 1: Rookie (top) or veteran (bottom, Jack Lalanne), their hormonal response to push-ups is different, but does not explain the different outcomes of strength training.
If you are a regular, here at the SuppVersity, you will have hear me lament the fact that in many of the mainstream studies on the effects of exercise on body composition, endocrine parameters and so on, the study participants are either sickly, obese or both... admittedly, whenever measures of muscle hypertrophy are involved, the subjects are usually healthy rookies, which is by  no means better, as you all know from your first weeks in the gym that, despite doing everything wrong, your strength and size gains were tremendous. Now, the obvious question is, are the endocrine adaptations / responses distinct, as well? According to the results of a recent study by Rasani Ranjbar et al. they are (Hasani-Ranjbar. 2011) - surprisingly, though, on paper, the endocrine milieu of the veterans appears more conducive to strength and size gains than that of the rookies... but let's take a look at the actual results, before we even start discussing their implications.

The Iranian scientists recruited 15 previously strength trained and 19 untrained male (how else could it be in this lovely country?) students at the Tarbiat Moallem University, divided them in an experimental (trained) and a control group and took blood samples at 10am (pre-test) after the students, who had arrived at the lab at 7am, had been served identical breakfasts (at 7:30-8:00am). Subsequently, the training groups (E1 = previous strength training experience; E2 = rookies) performed a resistance training protocol at 70-80% of their maximum strength in the 10-12rep range (i.e. a classical "hypertrophy training"), consisting of 4 sets of chest presses, stretch wires [I have no clue what kind of Iranian specialty that is], leg extensions and leg curls to failure with rest times of 2 minutes in between sets and 4 minutes between exercises.
Figure 1: Training induced changes in growth hormone (GH) compared to untrained control (Hasani-Ranjbar. 2011).

Blood was drawn at four timepoints: pre-test (T1), immediately after cessation of the exercise session and before lunch was served (T2), five hours post training (T3) and seven hours post training (T3). The samples were analyzed for growth hormone (GH), insulin, insulin-like-growth-factor 1 (IGF1), IGF1 binding protein 1 and 3 (IGFBP1 & IGFBP2). I have plotted the relevant data (i.e. data where you see meaningful changes) in figures 1 & 2.
Figure 2: Training induced changes in insulin and IGF1 compared to untrained control (Hasani-Ranjbar. 2011).
Now, what do we make of these results? Obviously the immediate GH response to resistance training is more profound in the veteran group, it is yet more sustained in the rookies, whose insulin levels interestingly skyrocket in the late post exercise period, yet in the absence of any significant increases in IGF1 levels (the same was true for the binding proteins) over the untrained control group.
Figure 1: Absolute IGF1 levels (in ng/ml) in trained and untrained rookies and veterans (Hasani-Ranjbar. 2011).
I don't know which data the Iranian scientists analyzed, but despite the fact that there is as they state a steady decline in IGF1 this probably isn't a result of the strength training regimen (as the Iranians would have it) but simply related to the lack of food intake in the 5-7h post lunch, which was ingested right after the post blood draw, i.e. exactly 5 hours before the 5h post blood was drawn....

Be that as it may, the more relevant result is that there may be differences in the endocrine response to exercise, but those are exactly contrary to what we would have to see, if the highly marketable GH increase, you are supposed to spike with all sorts of supplements had any effect on your gains in the gym. After all, you bet that if any of the two groups had had measurable strength or size increases at a subsequent training session / body composition measurement, it would have been the rookie group. That being said, this study further supports the position of the Phillips group from McMaster University (cf. Arms Don't Grow Faster with Prior Leg Training), who maintain that the exercise induced GH increase has absolutely no effect on strength or size gains... in other words, spending money on respective supps or focusing on training techniques that have been shown to increase GH (and have not been shown to be productive in terms of size and strength gains) is not advisable.

Cardio, Fat and IGF-1: Study Investigates Modulatory Effect of Endurance Exercise and High Fat Meals on IGF1 Binding Protein Levels in Obese Human Subjects

Image 2: 3D structural model of the IGF1 protein (rendered by Emw)
It's probably less than 24h ago, that you read about growth hormone (GH) here, at the SuppVersity. Its increase during fasts was one of the points, I addressed in yesterday's installment of the Intermittent Thoughts on Intermittent Fasting series. In fact it has been known for quite some time now, that fasting does increase the release of the 191-amino acid, single-chain polypeptide from the anterior pituitary gland, which in turn facilitates the (mostly) desirable switch to non protein-catabolic metabolic state, where fat becomes the major energy substrate. GH's growth promoting magic, on the other hand is believed to be largely mediated by the growth hormone induced production and release of insulin like growth factor 1 (IGF-1) in the liver, as well as directly at the level of target tissues. Apart from the sheer amount of IGF that is produced, its binding to respective carrier proteins, so called insulin like growth factor binding proteins, or IGFBPs, is yet another major determinant of the half-life and more importantly the mode of interaction of the IGF peptides with their target receptors at the cell surfaces.

From previous studies into the effects of exercise on IGF-1 levels activity, we already know that trained endurance athletes exhibit higher levels of IGFBP-1 (insulin like growth factor binding protein 1) than their sedentary counterparts (Manetta. 2003). Other studies have shown that after acute (vs. chronic) bouts of aerobic exercise the levels of IGFBP-1 return to baseline within 12-24h (Nindl. 2009; Berg. 2008; Koistinen. 1996) In that, the IGF-binding effect of exercise appears to be restricted to endurance type of exercises, as a more recent study by Nindl et al.found no increase in IGFBP-1 levels in young lean women after 8 weeks of strength training (Nindl. 2010).
Image 2: Ronny Coleman's belly is recurrent topic on various bulletin boards. This image was part of a discussion on the muscular development forum. Is it s imply fat or the results of the false(?) belief in "the muscle building magic" of IGF-1? (photo by Dan Ray for MuscularDevelopment.com)
The results from the Nindl study are also important in view of the interpretation of "increased" or "reduced" endogenous (i.e. produced by the body) IGF-1 levels in terms of their purported anabolic effect on muscle tissue, as Nindl. et al. point out...
[...] increased lean mass, aerobic fitness, and upper and lower body strength resulting from an 8-wk exercise training programs can occur without concomitant increases in either circulating bioactive or immunoreactive IGF-I, as well as associated IGFBPs. In terms of reflecting positive anabolic neuromuscular outcomes, these data do not support a role for endocrine-derived IGF-I. (Nindl. 2010)
All horror stories about GH-guts aside, you may want to keep that in mind before you condemn all aerobic exercise as being anti-anabolic and pay a shitload of money for supplements that "have been shown in clinical trials" (why are you laughing? ;-) to increase IGF-1 levels.
From epidemiological studies (Heald. 2003; 2005), we also "know" (you are probably familiar with my antipathy against epidemiology) that high fat diets are associated with lower levels of IGFBP-1. It has also been implicated as more or less reliable predictor of cardiometabolic diseases in longitudinal studies (Heald. 2001). Reason enough for Prior et al. to probe the combined effect, or I should say, the interference of 6 months of potentially IGFBP-1 lowering aerobic exercise ("3 weekly sessions of 20 minutes at 50% of heart rate reserve and gradually increased to 3 weekly sessions of 40 minutes at 70% of heart rate reserve"), on the one hand, and IGFBP-1 suppressing high fat meals (84% was derived from fat, 13.7% from carbohydrates, and 2.7% from protein), on the other hand, in a group of 10 overweight (bodymass index = 28.7 ± 0.9 kg/m²), older (61± 2 years) men and women.
Figure 1: Effect of 6 month of aerobic exercise on serum free glucose, free insulin, HOMA-IR and IGFBP-1 levels in obese subjects (data calculated based on Prior. 2011).
As the data in figure 1 goes to show, the exercise regimen had profound beneficial effects on insulin sensitivity - evidenced by the increase in serum free insulin levels and HOMA-IR (considered a "reliable" long-term marker of insulin resistance). As previous research had suggested, these changes were accompanied by a major increase in IGFBP-1 (and thus presumably a decrease in IGF-1 receptor activity). The increase in IGFBP-1 was however (almost completely, cf. figure 2) 4h after the study participants consumed a single high fat meal.
Figure 2: Effect of high fat meal (84% fat, 13.7% carbohydrates, and 2.7% protein) on IGFBP-1 levels (data calculated based on Prior. 2011)
This negative effect of high fat feeding on IGFBP-1, as can be seen in figure 2, was almost identical before and after the 6-month exercise intervention, which led the scientists to conclude that despite the fact that ...
[...] aerobic exercise training has a potentially beneficial effect to increase fasting plasma IGFBP-1 concentrations in previously sedentary middle-aged to older adults  [..., a]erobic exercise training did not attenuate the adverse effect of a high-fat meal on plasma IGFBP-1 concentrations
Image 3: Germany's former foreign minister Joschka Fischer is a famous "victim" of the "low-fat-marathon-style-endurance-training" fat loss myth with built in YoYo-effect - I guess you will have your own celebrities with similar impressive "transformations" ;-)
and (you probably expected this) use this as a welcome opportunity for repeating the good (I should rather say "bad") old mantra of the benefits of chronic endurance exercise and low fat dieting.... I mean, come on. Look at our (Germany's) former foreign minister, Joschka Fischer (cf. image 3) - don't we all know that low-fat cereals and marathon running are no solution.

It would be nice to see some scientists going beyond this illusive paradigm, in order to gain insights into the underlying mechanisms or, even more fundamentally, to answer the question whether high(er) levels of free IGF-1 are causative or just corollary to cardiovascular disease, cancer and all the other maladies IGF-1 is currently held responsible for and which role all the healthy low-fat grains we are supposed to eat play in the etiology of these diseases... in case that is going to happen within my life-time, you can be dead-certain (pun intended) that the SuppVersity is the place, where you will read about it first.

Ask Dr. Andro: Are Colostrum and Milk Products in General Healthy Muscle Builders, a Waste of Money or Toxic Waste?

Image 1: Colostrum and other milk products
Milky muscle builders or murky allergens?
(image from SportRevue 6/2010)
Question from Peter Art (via Facebook): Do you still have a plan to release a write up about colostrum or it may be delayed? I am just asking.

Answer Dr. Andro: In fact it got delayed, the delay got delayed again and now there is so much delay that I felt like further delaying the write-up would border pathological procrastination... Instead of citing the three existing studies on colostrum, however, I decided to do a more comprehensive "Ask Dr. Andro" segment on the powers and perils of the milky mammalian life-elixir that has been used and later abused (I am referring to the modern way of food processing here) by generations of human beings and is still considered as an "evolutionary inappropriate" foodstuff by some.

"Muscle building magic happens, when you put the right stack together", says Carl Lenore in a spot for IronMagLabs prohormones - Well, guess what milk may be the original "stack"

Image 2: If you are interested in the way
the US government treats non-compliant
raw dairy producing listen to Carl Lenore's
rant against the "Rawsome Raid"
It is not by accident that milk (and colostrum) have always had the reputation of being powerful muscle and strength builders. Few modern bodybuilders would go without their whey protein and at least among the non-carbophobic body builders there are still a few who swear by the consumption of gallons of the "white gold" - at least in the off-season. In fact, nature invented the milky liquid not as "a", but as "the" source of essential amino acids and more. And, as we will see, part of this "more" is what either fascinates or scares people about milk.

Depending on which expert you are asking you will either be told about the life-threatening dangers or the almost magical benefits of the biologically active proteins, peptides, lipids and sugars in milk and related dairy products. In that, it stands out of question that these peptides display antimicrobial, opioid, mineral-binding , antihypertensive, antithrombotic, and immunomodulating properties. 
Physiological Effect / ClassificationCompound(s)
Opioid agonists (decrease gastric mobility, increase electrolyte and amino acid uptake) α- ,β-caseins, α-lactalbumin, β-lactoglobulin, serum albumin
ACE inhibitors (increase blood flow to intestinal epithelium)α- ,β-caseins
Mineral binding (increase absorption) α- ,β-caseins
Immunomodulators (increase immune response and phagocytic activity)α- ,β-caseins, gG, IgA, lactoferrin, glycolipids, oligosaccharides, prolactin, cytokines
Antimicrobial αs1 and s2-casein, lactoferrin, oligosaccharides, prolactin
Antithromboticκ-casein
Probiotic κ-casein, lactoferrin, oligosaccharides
Opioid antagonistκ-casein, lactoferrin
Organ development and function IGF-1, TGF-α, EGF, TGF-β
Increase calcium metabolism and uptakeParathromone - P
Table 1: Milk as a "functional food". Physiological effects and their respective triggers.
(adapted from Schanbacher. 1998; Meisel. 1998 and Clare. 2000)

The overview in Table 1 makes it quite clear, milk derived peptides are hardly inferior to pharmacological agents. Whey proteins and peptides derived from the enzymatic proteolysis of casein and whey, for example, modulate a variety of processes such as lymphocyte activation and proliferation, cytokine secretion, antibody production, phagocytic activity, and granulocyte and natural killer (NK) cell activity (Gauthier. 2006).
Illustration 1: Bioactive components in milk and their respective beneficial effects on health markers.
(adapted from Corhonen. 2009; in Park, ed. 2009, ISBN 978-0-8138-1982-2)
Whether we want to exploit or rather avoid these effects (cf. illustration 1) is yet still a matter of constant debate and the increasing financial interests of the "functional food" industry is beginning to compromise the objectivity, or, to be fair, I should say the "balance" of scientific research.
Did you know that a 2007 forecast estimated the sales in functional foods for the US to 3,478 million US$? I suppose now you will begin to understand why companies are willing to spend millions of dollars into respective research and nobody really cares about potential negative side effects of what I would like to call "functional food gone disfunctional"... its a pity!

The Immunoglobulin / Allergy Side of the Coin

In view of the current scare of gluten-, soy and whatever anti-bodies to food your body is able to produce, it must be said that mammalian immunoglobolins (IGs) are essential to the humoral part of the immune defense of the neonate. Milk, and colostrum in particular, one could say, are specifically "designed" by nature to provide the newborn with antibodies until its own immune system learns to handle the constant assault on its own.
Figure 1: Bioactive substances in colostrum and milk - note the particular differences in immunoglobolin, lactoferrin, serumalbumin and growthfactors (data adapted from Corhonen. 2009; in Park, ed. 2009, ISBN 978-0-8138-1982-2)
From the perspective of the opponents of milk / colostrum consumption, a keyword in this context is "immune maturity". "Why?", they will be asking the proponents of milk consumtion (or even deliberate enrichment of dairy products with immunoglobulins), "Why would a grown up mammal want to consume foreign anti-bodies, if he/she is well able to produce all the necessary immunoglobulins on his/her own?"

Image 3: It is a reasonable, yet not
scientifically studied question, if
milk per se, or rather the industrialized
variety you buy at the grocery store
is the cause of all sorts of autoimmune
reactions (image from CCRecycling)
If you just have a look at the sheer amount of studies PubMed returns for the keywords "milk AND immunoglobulins AND allergy" (1639 hits!) the answer appears to be a clear "No reasonable mammal would want that!" (This does yet raise the question if humans can be regarded as "reasonable mammals"... well, you decide ;-) Already at the ninth position, right after a comprehensive review on the "Epidemiology of food allergies" there is a study reporting beneficial effects of fermented milk products grass allergies (Wassenberg. 2011) and a random klick on review #5, "Food allergy therapy: is cure within reach?" by Nowak-Wegrzyn and Muraro (2011) is surprisingly not about curing milk allergies, but about curing allergies with milk products.

These random examples are not meant to negate the well-established prevalence of autoimmune reactions (often in its immediate form, which most of us associate with the term "allergy) to milk products. According to Cattan et al. (2011) 2%-3% of young children display are affected by cow's milk allergy. I do yet wand to submit that even this unfortunate statistic does not answer the question whether it is the "living nutrient" milk or rather its dead, highly contaminated industrial incarnation that affects the children.
Figure 2: Concentration of immunoglobulins in bovine and human milk and colostrum; mind the logarithmic scale!
(data adapted from Stelwagen. 2009 according to Butler. 1973)
Although the immonoglobulin-composition of bovine milk is obviously different from the one of human milk (cf. data in figure 2), the increasing number of studies which show beneficial immunological effects related to the consumption of colostrum or respective concentrates, as well as epidemiological and controlled studies on the consumption of "real", i.e. raw milk from pastured cows, seem to suggest that individual genetic factors aside, the "contamination" of commercial milk products could well be one of the underlying factors of its allergy-triggering effects in certain populations. After all, milk is meant to nourish an infant, so that it becomes a carbon-copy of its parent, which, as it survived evolutionary selection pressure and successfully reproduced, should be healthy and not unviable and drugged to the eyeballs as the average dairy cow, today.

Is there any "Raw Truth" to the Stories About Unpasteurized Milk?

The remarks on the industrialized dairy production at the end of the previous paragraph bring up the question whether milk from the opposite site of the spectrum, i.e. raw milk from happy pasteur-fed cows, would really be a better or even generally healthy alternative to the white potage in your fridge. A first clue that this may in fact be the case can be found in a 2006 paper (with no declared conflict of interests) by the British scientists Michael R. Perkin and David P. Strachnan on the inverse association between farming lifestyle and childhood allergy (Perkin. 2006), in which they state that
current unpasteurized milk consumption was associated with significantly less current eczema symptoms (adjusted OR, 0.59; 95% CI, 0.40-0.87; P 5 .008) and a greater reduction in atopy (adjusted OR, 0.24; 95% CI, 0.10-0.53; P 5 .001) [... and] was associated with a 59% reduction in total IgE levels and higher production of whole blood stimulated IFN-g (P = .02)
The most interesting finding, however, was that "the effect was seen in all children, independent of farming status".
Figure 3: Percentage of pathogen infected samples of different foodstuffs; missing bars indicate no sample available
(data adapted from a presentation by Baars. 2010)
Now, you may say that all this sounds fine, but everyone knows that raw milk contains pathogens that are a potential thread to your life... well, the actual data on the issue of microbial risks and foodborne illnesses by pathogens like campylobacter, salmonella, staph. aureus, EHEC, etc. in raw milk, presented by Prof. Dr. Ton Baars from Department of Biodynamic Agriculture at the University of Kassel (Germany) at the 2nd Annual International Raw Milk Symposium in Madison (WI) on April 2010 speaks a very different language. Obviously, people who are afraid of raw milk would never even remotely consider eating raw chicken (the worst offender on the list), but some of them may have been to one of the hip sushi restaurants, lately, and would thus have had a 7.4x higher chance of infecting themselves with listeria, an infection of which 20 to 30 percent of the clinical infections result in death, than raw milk drinkers... But hey, I am losing track, here. The raw vs. pasteurized, conventional vs. grass-fed and medically treated vs. medication-free debate would be a topic for an individual installment of the "Ask Dr. Andro Series" and thus I will try to get back to the question at hand.

Colostrum, Milk and the Athlete

Image 4: Over years, milk has
been marketed by athletes in
Germany (image (c) CMA)
German soccer star Miroslav Klose (image 4) says "Milch ist meine Stärke!" (loosely translated "Milk is the reason for my success!") in an advertisement of the German CMA which mentions the usual suspects, calcium, lactose and protein, as the cornerstones of what a world-class striker needs. And in fact, an "expert" discussion on the benefits of whey vs. casein as part of the ideal post-workout supplement in an old thread of the Mind and Muscle Forum yielded a result with a nutrient composition that looked surprisingly familiar: some fast digesting whey + some casein for a sustained protein supply, a few carbs, some minerals and vitamins = the ideal post-workout supplement, or put more simply, MILK! And in fact, science seems to confirm what the brainy trainees on a bulletin-board have thought out.

As an avid reader of the science news on the SuppVersity you will probably be familiar with the fact that, time and again, plain chocolate milk, with its mixture of fast and slow digesting carbs and proteins, has either stuck with or even outperformed expensive post-workout formulas (cf. table 2)
Author(s)Result(s)
Ferguson-Stegall. 2011b"CM [chocolate milk] postexercise improves aerobic power and body composition more effectively than CHO [carbohydrate] alone"
Ferguson-Stegall. 2011a"CM supplementation can improve subsequent exercise performance and provide a greater intracellular signaling stimulus for PRO synthesis compared to CHO and placebo"
Gilson. 2010 "CM provided similar muscle recovery responses to an isocaloric CHO beverage during four-days of ITD [increased training duration]. Future studies should investigate if the attenuated CK [creatine kinase = marker of muscle damage] levels observed with CM have functional significance during more demanding periods of training"
Pritchett. 2009"These findings indicate no difference between CHOC and this commercial beverage as potential recovery aids for cyclists between intense workouts."
Thomas. 2009"Participants cycled 51% and 43% longer after ingesting CM (32 +/- 11 min) than after ingesting [commercially available] CR [carbohydrate drink] (21 +/- 8 min) or FR [fluid replacement drink] (23 +/- 8 min)"
Carp. 2006 "[...] chocolate milk is an effective recovery aid between two exhausting exercise bouts"
Table 2: A selection of recent studies on the ergogenic effects of (chocolate-)milk

On the other hand, most of these beneficial effects on regeneration, protein synthesis etc. could be attributed to the nutrient content of (chocolate) milk alone. A question that would be of much greater interest to the majority of athletes and fitness enthusiasts would though be, whether or not they could benefit from the various growth factors scientists have found in milk and dairy products since the initial discovery of growth-promoting or -inhibitory peptides in colostrum in the 1980s.

Colostrum: A Miracelous, White "Growth Factors" Elexir!?

Now, as the data in figure 1 indicates, colostrum is by far the best source of these growth-regulators, as I would like to call them. BTC (beta cellulin), EGF (epidermal growth factor), FGF1 and FGF2 (fibroblast growth factor), IGF-I and IGF-II (insulin-like growth factor), TGF-β1 and TGF-β2 (trans- forming growth factor) and PDGF (platelet  - derived growth factor) - for all of them applies that their concentration, both in human, as well as in bovine colostrum is highest during the first hours after childbirth / calving (cf. figures 3 and 4).
Figure 4: Reduction in immunoglobulins in colostrum after two and three days relative to immunoglobulin content of colostrum on day one post-partum (data calculated based on Kelly. 2003)
The question we would have to answer to understand whether and to which extend athletes could benefit from the presence of this 53 to 425 amino residue polypeptides in colostrum (and in much lower concentrations in milk) is threefold:
  1. Which of these growth factors could improve athletic performance?
  2. Is the dose of the respective growth factors in milk / colostrum sufficient to illicit physiological effects? And most importantly...
  3. Can these oral growth factors nature intended as a supplement for the newborn calf do their magic in adult human beings, as well?
The latter question obviously implies that the large majority of athletes won't be able to obtain human colostrum and would thus have to rely on the bovine variety, which is readily available at local farms and, as a powdered supplement, at various bulk supplement vendors on the Internet.
Figure 4: Reduction in cytokines in colostrum after two and three days relative to cytokine content of colostrum on day one post-partum (data calculated based on Kelly. 2003)

With regard to the powdered supplements, but also in view of the potential benefits of "regular", i.e. pasteurized milk, it should be noted that the growth factors present in milk seem to withstand pasteurization and even ultrahigh temperature (UHT) heat treatment of milk relatively well (Gauthier. 2006). While EGF and BTC, as stimulators of epidermal, epithelial and embryonic cells, are relatively uninteresting for healthy athletes, their ability to promote wound healing and bone resorption could be particularly interesting for injured athletes. The same is true for the two forms of TGF-β, both of which stimulate the proliferation of connective tissue cells.

The two forms of IGF, on the other hand, stimulate the proliferation (cell growth) of various tissues, and regulate metabolic functions such as glucose uptake and the synthesis of glycogen. It stands to reason that their highly marketable presence in colostrum is the main reason for athletes and fitness enthusiasts to invest a non-negligible share of their hard-earned money into respective supplements. The question yet remains, are they wasting their money?

Will the Growth Factors Be Absorbed, At All?

It has been established by animal studies that EGF, TGF and also both IGF isoforms "provoke various local effects on the gastrointestinal tract and can be absorbed intact or partially from intestine into blood circulation" (Korhonen. 2009; in Park, ed. 2009, ISBN 978-0-8138-1982-2). As you may have read in my dissertations related to the IGF1-spray, rodent studies show that naturally occuring proteins (e.g. casein) and protease inhibitors in milk protect these peptides against gastric and intestinal breakdown. The number of human studies on the subject is yet not very extensive, to say the least. The most comprehensive research has probably been done by Antti Mero and his group at the Department of Biology of Physical Activity at the University of Jyväskylä in Jyväskylä, Finland. Their results show that in the absence of performance increases in vertical jump performance, 8 days of supplementation with a commercially available colostrum product (Bionervie) dose-dependently increased serum IGF-1 levels (Mero. 1997).
Figure 5: Changes in IGF serum concentration [in nmol/L] between pre- and posttraining in 9 male sprinters and jumpers; note: a follow up study showed that the increase in IGF was not a result of immediate oral absorption, but a downstream effect of colostrum supplementation (data adapted from Mero. 1997)
These observations are not only noteworthy because they suggest that IGF1 from bovine colostrum survives gastrointestinal passage and would (read the rest of this post!) be readily absorbed into the blood stream by the gut lining in human beings, but also because the effects of 25ml and 125ml also compensated the training induced decrease in IGF1 measured in the placebo group (cf. figure 3).
Image 5: Creatine Monohydrate increases
IGF1 by 24% over placebo (Burke. 2008).
Did you know that plain creatine monohydrate, taken at a dose of 0.25 g/kg lean-tissue mass for 7 days (loading phase) and 0.06 g/kg lean-tissue mass for 49 days (maintenance phase) increased intramuscular IGF1 levels in 12 men and women, who did nothing but 30 minutes of very light aerobic activity per day, by a whopping +24% over placebo? Regardless of whether or not you believe that colostrum works. Creatine certainly does! And I stand to what I said before: Creatine monohydrate is still the king of all dietary supplements.
Within the scientific community the results of Mero's study were highly disputed, claims were made that the increase in IGF concentrations was "spurious, caused by inaccurate measuring techniques" etc. In an experimentally more sophisticated (gel electrophoresis techniques) follow up study, Moreno et al. were however able to replicate the results from the previous study with another colostrum product (Dynamic). Much to the scientists surprise, however, the measured increase in serum insulin like growth factor was not a result of direct oral absorption of the growth factors from the colostrum, but the result of an increased endogenous IGF production that was triggered by the intake of the supplement (Mero. 2002):
Absorption data show that ingested 123I-rhIGF-I [that is the previously radiolabelled IGF1 in the colostrum] is fragmented in circulation and that no radioactive IGF-I is eluted at the positions of free, or the IGF, binding proteins, giving no support to the absorption of IGF-I from bovine colostrum.
Yet even if colostrum does not do its magic by delivering IGF and other growth factors into the bloodstream, it appears to "work" and thus the question that remains to be answered is whether plain milk, or rather a whey protein supplement, which currently is the gold-standard for the majority of athletes and fitness enthusiasts, would not be as effective as the more expensive colostrum supplements.
Illustration 2: According to Buckley. 2003 there may be a 500% difference in price, the effect on serum IGF1 and exercise performance of 60g colostrum and 60g whey per day, are yet 100% identical.
The answer to this question comes from a 2003 study by Buckley et al. who compared the effect of 60g of bovine colostrum to the effects of the same amount of a standard whey protein supplement and found similar performance increases in both groups and no effect on IGF levels in any of the 51 men (Buckley. 2003). Moreover, Burke and Deakin remark in their review of the literature in Chapter 16 of the third edition of Clinical Sports Nutrition that studies using trained subjects were less likely to show any effect of colostrum supplementation at all (Burke. 2006).
Author(s)Result(s)
Shing. 2006"[10g/day] bovine CPC [colostrum concentrate] supplementation elicited improvements in TT40 [40 km time trial] performance during an HIT period and maintained ventilatory threshold following five consecutive days of HIT"
Buckley. 2003 same increase in peak power for 60g colostrum as with whey protein; no increase in IGF1
Brinkworth. 2004a"[cross sectional area of biceps increased more in trainees supplemented with 60g bovine colostrum than in whey control, but that was] due principally to a greater increase in skin and subcutaneous fat (SSF) CSA"
Buckley. 2003 same increase in peak power for 60g colostrum as with whey protein; no increase in IGF1
Buckley. 2002b"[...] latively few scientifically controlled studies have been conducted. The limited evidence that is currently available suggests that BC supplementation can increase lean body mass and improve exercise performance and recovery for a number of athletic activities, but an understanding of the mechanism by which this supplement exerts these effects remains elusive"
Buckley. 2002a"[...] supplementation with intact powder did not increase plasma IGF-I concentrations or improve performance during an initial bout of incremental running to exhaustion in our sample. However, performance during a second bout of exercise may be improved by as much as 5.2% in the average subject after 8 weeks of supplementation, possibly due to an enhancement of recovery"
Coombes. 2002"Oral bovine colostrum supplementation at 20 g or 60 g/d provided a small but significant improvement in time trial performance in cyclists after a 2-h ride at 65% VO2max." [improvements were 20g colostrum+40g whey  60g+ colostrum 60g+ whey]
Antonio. 2001"[...]supplementation with bovine colostrum (20 g/d) in combination with exercise training for 8 wk may increase bone-free lean body mass [+1.5 kg, while whey-placebo group increased overall BM by +2 kg] in active men and women."
Mero. 1997"appears that a bovine colostrum supplement (Bioenervi) may increase serum IGF-I concentration in athletes during strength and speed training" (cf. discussion in the text)
Table 2: A selection of studies on the ergogenic effects of colostrum

Personally, I would trace these subject-specific differences back to an already optimized nutrient supply, where the addition of the beneficial amino acids, minerals and vitamins from colostrum (or milk) does not make much of a difference. Otherwise, I would allign myself with the following statements Burke and Deakin make in view of the expedience of colostrum supplementation
[t]he only consistent findings from the present studies of colostrum supplementation are that there are no apparent benefits to the outcomes of resistance training (Antonio et al. 2001; Buckley et al. 2003; Brinkworth et  al. 2004), and that when benefits are detected, they are apparent only after more than 4 weeks of treatment (Buckley et al. 2002, 2003).

[...] The lack of a plausible hypothesis to explain how colostrum might enhance the response to exercise is also an important absence.

[...] Whether all colostrum supplements are of equal quality or efficacy is also a concern.
In view of the exorbitant costs of a colostrum supplements (cf. illustration 2) and the absence of any reliable quality standards (you never know if "your" colostrum has even remotely the same nutrient / growth factor composition as the one used in one of the studies) I thus strongly advise against spending the roughly 270$ a month supply of bulk colostrum powder (of questionable quality) would cost you, if you wanted to mimic the 60g/day dose that was used in the majority of studies with beneficial outcome.

Figure 6: 1st-day Colostrum is a particularly
rich source of antibody against all
sorts of pathogens (adapted from
Stephan. 1990 and Rump. 1992)
Colostrum, Pathogens and Infections

I've broached the issue of possible infections from (raw) milk in a previous paragraph, already. As it turned out, chicken, meat and most notably fish, one of the only foods even the "hip", health-conscious Men's Health or Shape readers are scarfing down raw, are the major offenders, when it comes to pathogen infections. Now, what's even more interesting is that to protect the growing calf from harm, colostrum comes with a whole host of antibodies against all your favorite pathogens:
  • Helicobacter plyori
  • E. coli (remember the recent death-toll in Europe?)
  • Rotavirus
  • Salmonella 
  • Staphylococcus
  • Candida albicans
  • and many more
And these are only the best-known of the antibodies that have hitherto been identified in 1st-day colostrum (cf. titer=antibody count values in figure 1).

In view of the sheer amount of highly bioactive compounds in colostrum, it is no wonder that the "early milk" has also been implicated as a viable treatment for several gut pathologies. Its ability to eradicate gut parasites such as candida or helicobacter plyori aside, its effect on intestinal permeability may be of greatest value for athletes, who experience significant (sometimes more than 2.5x, which is similar to what is seen upon the administration of particularly nasty NSAIDs such as indomethacin) increases in gut permeability as a consequence of streneous exercise.
Image 6: Could Glutamine be
the cheap colostrum?
Did you know that the cheap supplement l-glutamine has also been shown to protect athletes from exercise induced increases in gut permeability and the consequent influx of toxins and pathogens into their blood stream? No? Well I guess than you have missed the Amino Acids for Super Humans Series, a joint project of the SuppVersity and Carl Lenore's Super Human Radio and a "must read / listen", if you are interested in the ergogenic of these nitrogen containing molecules which are much more than just building blocks of protein and muscle.

Click here to read all about l-glutamine
A very recent study by Marchbank et al. shows that the administration of 20g/day of colostrum in the 14 days prior to a standardized exercise test blunted 80% of the detrimental effects on intestinal permeability and thus protected the subjects from the influx of luminal toxins in the post-exercise period (Marchbank. 2011).

Staving off the Common Cold (and Other Ailments) with Supplemental Colostrum!?

Compared to the information on its effect on gut health, the scientific data on the immune-strengthening effects many people associate with, or even expect from the consumption of colostrum is less unequivocal. While long term studies (10 and 12 weeks of 25g/day supplemental colostrum) showed improved immunity and reductions in upper-respiratory tract infections in distance runners (Crooks. 2006) and swimmers (Crooks. 2010), respectively, a 2011 study by Carol et al. showed no improvement in the immune reaction to a 90-minute glycogen-depletion trial over skim-milk, when the subjects had consumed a similar colostrum supplement as it was used in the Crooks studies in the ten days prior to the experiment (Carol. 2011).
Image 7: Long distance endurance athletes
such as swimmers and marathon runners
probably benefitmost from colostrum.
Regarding the results of the 2006 Crooks study, it is important to note that a 2010 study by Peters et al. (Peters. 2010) found that their markers of immune status, i.e. the number and composition of immunoglobulins, did not correlate with incidences of upper-respiratory tract infections in marathon runners. It is thus questionable how significant the increases in salivary immunoglobulins they observed in their 35 distance runners actually is, as far as its real-world outcomes are concerned.
Whether the differences we see in the results of these studies are related to milking time (remember the immunoglobulin content is highest in day 1 colostrum) and thus the product quality, the type of exercise (repeated long-distance endurance exercises such as running and swimming are notorious for wreaking havoc on your immune system) or simply the duration of supplementation is hard to say. If you nailed me down to a single answer, I would say chronic stress, as in long-distance running, requires chronic supplementation of a stress-reducing supplement. Thusly, I would blend the last two of my suggested explanations into a single more comprehensive one.... Nevertheless, even if you are a marathon runner or Ironman competitor you should ponder, whether these inconclusive results really warrant an investment of more than 112$ for a month supply of colostrum (this is what it would cost you if you used the 25g/dose that worked for the swimmers in Crooks. 2010).

Hormones and Other 'Fun' Compounds in Milk and Colostrum

Figure 7: Androgen and estrogen content in
milk from French supermarkets collected in 2006
and 2007 (data adapted from Courant. 2008)
Last but not least, and as we will see probably less related to athletic performance than to unwanted side-effects, is the often cited endless list of
  • gonadal hormones (estrogens, progesterone, androgens), 
  • adrenal (glucocorticoids), pituitary (prolactin, growth hormone), and hypothalamic hormones (gonadotropin - releasing hormone, luteinizing - hormone – releasing hormone, thyrotropin - releasing hormone), and 
  • peptides and hormone-like substances like somatostatin, bombesin, calcitonin, insulin, melatonin, and parathyroid hormon, and
  • pesticides and other toxins, beta-agonists, non-steriodal-antiinflammatory drugs, etc.
  • melamine (the stuff the Chinese add as a protein substitute that then kills their babies)
that have been found in colostrum or milk of bovine origin.

I've already broached the issue of peptides, will leave aside the toxins, pesticides and co, simply because these are exogenous contaminants you may or may not find in your milk products (not to mention that this blogpost is already epic enough ;-) and conclude this epic "Ask Dr. Andro" segment with a brief discussion of the potential dangers or benefits of naturally occuring hormones in milk. 

By now, the presence of all sorts of hormones in "white gold" actually should not surprise you anymore. I've already mentioned in one of the previous paragraphs that the milk of a mammal is just as much a mirror of its metabolic and endocrine status, as is its blood. This obviously entails that if you inject your cows with growth hormone (as it is obviously still allowed in the US) or other hormones to increase milk production or whatever other wicked intention you may be harboring, you will obviously find "traces" of these exogenous hormones in the milk and, even more so the, colostrum of your cow.

Figure 8: Naturally occuring androgen and
estrogen content in different forms of colostrum
(data adapted from Farke. 2011)
Other factors that will influence the type and amount of hormones you will find in your milk, i.e. the milk you buy at your grocery store, farmers market or friendly dairy farmer, are related to
  • what the animals were fed
  • which medications the animals received
  • when, i.e. in which hormonal phase (note: the melatonin content even varies with the time of the day), the cows are milked
  • what "happened" to the milk on its way from the cow / farmer into your fridge
These are, quite obviously, too many factors for me to consider, but if you look at the little publicized data, there is, you will find that some information that applies to pretty much all (uncontaminated) milk and colostrum products, regardless of whether you bought them from your local farmer or the grocery store (cf. figures 8 and 9):
  1. colostrum (skimmed) contains roughly 19x more androgens and 213x more estrogens than whole milk
  2. for milk and colostrum the full fat variety tends to have generally higher levels of both androgens and estrogens - for colostrum, for example the fat fraction contains 10x androgens and 10x more estrogens than the skimmed variety, which is also used as a base for most powdered colostrum supplements
  3. in the case of milk, the ratio of androgens to estrogens (AE-ratio) drops by -34% during the skimming process; in fact, skimmed milk contains more estradiol (per liter) than whole milk.
Now to put these general observations as well as the data in figures 7 and 8 into a "health perspective" we got to have a look at the respective "acceptable daily intake" (ADI) established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and the maximum secure daily intake established by the FDA:
  • 17beta-testosterone - 2µg/kg (ADI), 320ng/kg (FDA)*
  • 17beta-estradiol - 50 ng/kg, 65ng/kg (FDA)

    * Isn't it strange how the FDA allows roughly 160x the amount of testosterone to be present in foodstuff than the WHO considers an "acceptable daily intake"? How come steroids are illegal in the US, then ;-)?
Now how much of our milk products would an 80kg human or his/her 1 year old toddler have to consume in order to surpass these levels?
Figure 9: Number of 0.3l cups of milk or colostrum an 80kg adult human being or a 1 year old 10kg toddler would be "allowed" to consume according to the JECFA acceptable daily intake (ADI) and the maximum secure intake as established by the FDA (FDA); data has been calculated on the basis of figures 8 and 9, i.e. based on naturally occuring levels of the respective hormones
As my calculations in figure 9 clearly show, the general public is not really in danger of hormonal "intoxication" by colostrum, let alone milk consumption - at least as long as the dairy does not come from cows who have been treated with hormones. Even if we assume that all the hormones would pass right through the endothelial layer of your intestines and into your blood stream it would still take 4 full 0.3l cups of the fat fraction of colostrum for a toddler to surpass at least the WHO's very rigid acceptable daily intake recommendation for testosterone.
Image 7: If you want the anabolic effect
from milk or colostrum you better buy
yourself this 45,000$ milk truck!
Just a short note on possible performance enhancements. Let's say the average bobybuilder does not even start to see significant results below a weekly dose of 500mg of testosterone. Now (we are again assuming that he would in fact assimilate all the hormonal content of milk and colostrum), this would mean that the poor guy would have the choice between 388 milk trucks with whole milk, 18 milk trucks full of skimmed milk or just two 5000 gallon trucks that are filled to the seams with the fat fraction from 1st day colostrum per day(!) to get his weekly dose of anabolics - Cheers!

An Overdue Preliminary Conclusion

Image 8: Even colostrum won't
make you unbreakable... it is
yet about as unlikely that it
will kill you, as some anti-dairy
activists would have it.
Will milk and/or colostrum kill you? No. Will milk and/or colostrum make you look like Jay Cutler and unbreakable like Bruce Willis aka David Dunn in the Y2K thriller Unbreakable within days? Certainly not. 

Well, I guess these are the two polar extremes of the preliminary conclusion to this "Ask Dr. Andro" segment and, as it is so often the case, the truth lies somewhere in between. I cannot tell you your exact position on the death to ultimate health continuum as far as your personal reaction to dairy consumption is concerned, I can only tell you that even if your genetic polymorphisms allow you to consume dairy, the chance that replacing your whey protein by a 6x more expensive colostrum powder will make a beneficial difference in how you look, feel and perform are minimal. I am not so sure however, if you would not see some, if only psychological (placebo) benefits if you mixed that whey into some real, i.e. whole, liquid and not powdered, 1st day colostrum you bought the very same day from your local farmer ;o)

That being said, I could certainly go on forever on milk, organic milk, milk from happy and milk from pasteur fed cows, the effects of soy on the milk you consume, raw milk, 1st day and 4th day colostrum, and so on and so forth, but I suppose that Peter, who posed the original question (just in case you forgot due to the informational overkill of this not even half-done write-up), and the rest of you have enough to think about for the coming week. Ah... and in case you can't get enough of milk (I mean metaphorically) just pose another, hopefully more concrete "Ask Dr. Andro" question in the comment area or on the SuppVersity's facebook page  ;-)