Intermittent Thoughts on Building Muscle: IGF-1 and its Splice Variants MGF, IGF-IEa & Co - Master Regulators or a Bunch of Cogs in the Wheel of Muscle Hypertrophy?

Image 1: With regard to IGF-1 and its splice-variants like MGF, there is probably 10x-100x more bro- than pro-scientific data out there - this does not help us, though, since you never know which of the bro-reports is bogus and which is not.

In view of the fact that we have not covered much ground with the last installment (we did build a pretty solid foundation, though ;-), I will try my very best to steer a middle course between presenting impressive amounts of facts and explaining the complex and in part not even completely elucidated physiological underpinnings of skeletal muscle hypertrophy, or, as the bros would say, getting big and buffed! A pros pros Bro, you will unquestionably have read on one of the myriads of bodybuilding-related bulletin boards how the injection of X amounts of IGF-1 right into the muscle made BigGuns, or whatever the poster's pseudonym may have been, grow "3 inches in 2 weeks"... ok, his profile picture looks impressive, but is that credible? Does IGF-1 really have such profound effects on muscle growth? And about what type of growth are we talking here? The myostatin-negative "ballooning up" of the muscle, which leaves you with overblown myogenic domains and dysfunctional muscles?

IGF-1: Insulin, growth hormone, or what?

To be able to answer these and related question we will first have to understand what exactly this "insulin-like growth factor 1" actually is. From a (bio-)chemical perspective it is nothing but a bond of 70 amino acids which are entangled into a specific peptide structure that is characteristic for somatomedin C, as IGF-1 is also called. Both the "growth" in IGF-1, as well as the "somato" in its old-fashioned appellation already suggest that what we are dealing with, here, is a "growth hormone related" polypeptide. And in fact, the synthesis of IFG-1, which, in the case of the systemically available fraction, takes place primarily in the liver, and is triggered by systemic growth hormone (somatotropin) levels.

Figure 1: Changes in systemic IGF-1 levels after 5-weeks on either a "normal" (=55:15:30 carbs:protein:fats) or a low carb "high protein" (=20:30:50) diet in 8 men with untreated type II diabetes (data adapted from Nuttal. 2006)

The "insulin" in its name, however, is pretty misleading... or I should say people mislead themselves, by not reading  the name correctly: It's not "insulin-growth factor", but "insulin-like growth factor" and the "like" refers to the structure of the molecule and does not imply that it is released in response to insulin spikes, as you may have read it on one of the aforementioned bulletin boards. If you do take a look at the growth hormone and IGF-1 levels of eight male subjects in a 2006 study on the metabolic of 5-weeks on what the scientists call a "high protein, low carbohydrate diet" (Nuttall. 2006), you will see that an increase in protein and fat from 15% to 30% and 30% to 50%, respectively elicited an 34% increase in serum IGF-1 levels over the treatment period, a finding that is corroborated by the recently published results of Matthew B. Cooke and his colleages from the Department of Health, Human Recreation and Performance at Baylor University.

Figure 2: Serum IGF-1 levels in response to whey vs. maltodextrin supplementation and subsequent lower body resistance training (data adapted from Cooke. 2011)

In their randomized double-blinded cross-over study, Cooke et al. had a group of 10 recreationally active men (2-3 non-resistance training exercise sessions per week) perform a lower body exercise program (leg presses and knee extensions, 4 sets, 8-10 reps at 80% of the individual 1RM) with either 10g of maltodextrose or 10g of whey 30 minutes before the exercise bout (Cooke. 2011). The results of the study (equal IGF-1 response regardless of whey or carbohydrate supplementation) imply that even in the short term, in healthy subjects and in conjunction with exercise the ingestion of carbohydrates is not superior to the provision of fast acting protein sources as a means to either increase or maintain systemic IGF-1 levels.

On a side note: The insulin-mediated induction of Akt, which subsequently triggers the phosphorylation of the mammalian target of rapamycin (mTOR) and thusly does its bit to elevate protein synthesis, has no direct relation to IGF-1, which - I cannot emphasize that enough - has a structure resemblance to insulin, nothing more, nothing less. And what's more, the insulin response in the aforementioned study by Cooke et al. was identical in the whey vs. maltodextrin arm of the study.

Systemic vs. local IGF-1 expression: A crucial distinction

If you have been following the daily research updates here at the SuppVersity over the last months, you may now be wondering why I am even caring about those growth hormones (after all you should, after reading the first paragraph, realize that IGF-1 is something like the active incarnation of somatotropin), when Stuart Phillips lab has quite conclusively shown that even the exercise induced elevation of testosterone does not correlate with subsequent increases in muscle protein synthesis. Certainly a good question, but nevertheless not difficult to answer:

1. The previous installments of the Hypertrophy 101 (Part 1, Part 2) should have made it quite clear that protein synthesis alone is not sufficient to grow. Without intra-muscular restructuring / reorganization and the recruitement of new myonuclei from satellite cells, you would sooner or later grow beyond the maximally allowed myonuclear domain sizes (assuming that by whatever means you block the healthy upregulation of mystatin that will prevent that) and end up as an over-muscled but completely dysfunctional wrack.
2. In a very recently published study, the results of which I have actually been holding back, because I thought I would get to them much earlier in this series, the very same Stuart Phillips whose studies are "responsible" (in fact it is the way they are discussed by the lay-press and abused by the supp-companies that is actually "responsible") for the current over-emphasis on acute increases in the protein synthetic response to exercise and/or supplements, reports that there actually was a statistically significant correlation between exercise induced growth hormone release and increases in mean type I fiber (p<0.06) and type II (p<0.04) cross-sectional area (CSA) in 56 healthy previously non-resistance trained healthy young men in response to a 12-week, 5-day per week resistance training regimen (West & Phillips. 2011).
3. While we have hitherto been talking about systemic IGF-1, it has become evident in the course of the last decade that the hepatic IGF-1 output, which is the main determinant of circulating IGF-1 levels, has little to no impact on the IGF-1 induced increases in skeletal muscle mass and remodeling of muscle tissue that has been previously studies in Petri dishes. In fact, recent research suggests that, just like the liver produces IGF-1 for "the whole body", muscles produce their own IGF-1, or I should say, their own IGFs-1, whenever they are challenged to grow and/or repair (Velloso. 2010), and that the decline of muscle mass with age is at least in parts attributable to a defect / reduction in the expression of local IGF-1 splice variants (for an explanation of what this is, see red box below).

If we now count 2. and 3. together the result is not 5. but rather that it is the growth hormone mediated, exercised-induced local expression of IGF-1 splice variants, which drives the repair and restructuring process that allows for continuous (healthy) muscle growth.

Did you know that the intra-muscular (=autocrine, meaning directly in the tissue where it is supposed to work) "construction process" of the mature 70 amino acid polypeptide IGF-1 gives rise to three different splice variants of insulin-like growth factor (note: the structure of IGF-1 gene does theoretically allow for 6 variants)? And though we are just beginning to understand the physiological roles of IGF-IEa, IGF-IEb and IGF-IEc, also known as MGF (mechano-growth factor), their distinctly timed expression in response to physical overload appears to constitute one of the major driving forces of myocellular hypertophy.

In order to fully understand the role "the" insulin-like growth factor 1 plays in the physiology of muscle growth, it is thusly important to realize that the common perception of IGF-1 as a systemic hormone is, at best, incomplete - I would even venture to say that it is totally flawed.

MGF?! Yeah, I have heard of that one!

Figure 3: Stained myocyte migration (top) and infiltration (bottom) essays for IGF-1 and MGF; more stains = greater effect (taken from Mills. 2007).

Of the three primary splice variants that are expressed in skeletal muscle, IGF-IEc, or MGF (Mechano-Growth Factor) has probably received the greatest attention - so much attention that even the aforementioned bros, will probably have grasped the notion that this is somewhat of a local isoform of IGF-1 which is expressed in response to exercise induced muscle damage and could potentially be the magic bullet to grow beyond what we have hitherto believed to be possible... and, guess what, in essence this appears to be correct.

In one of the earlier studies on the cellular effect of MGF, Yang et al. were able to show that MGF stops the IGF-1 mediated cell differentiation process (in practice this means that it stops the satellite cells from differentiating = specializing and becoming muscle cells) and increases their proliferation. Or put more simply: While in vitro exposition to IGF would suffice to build muscle, as long as there are enough progenitor cells (satellite cells) available, MGF is necessary to replenishes the satellite cell pool of which you have learned in the previous installments that it is necessary to a) repair damaged muscle tissue and b) increase the number of myonuclei in order to grow beyond the physiological growth limit that arises due to the muscle-type-specific upper limit to the myonuclear domain size (cf. previous installments).

Figure 4: Cell proliferation data in response to MGF treatment after blocking the IGF-I receptor.

As the data in figure 4 goes to show the effects of the complete polypeptide IGF-1 and its splice variant MGF appear to be mediated, at least partly via distinct receptors. And while recent research suggest that MGF also exerts similar effects on tendon (Olesen. 2006), brain (Dluzniewska. 2005) and nervous tissue (Aperghis. 2004), our primary concern here, is its pivotal role in muscle repair, which involves the activation of satellite cells, their proliferation (Yang. 2002) and migration (Mills. 2007).

A series of studies by Hammad et al., which was originally intended to investigate the effects of age on the expression of the different IGF splice variants, goes to show that the "muscle (re-)building effects" of MGF are not restricted to the test tube. In their 2002 study (Hamed. 2002), the researchers were able to show profound increases in the MGF expression in the quadriceps muscles of 8 healthy young men (age 29.5 ± 1.5 years, body mass 81.1 ± 2.4 kg, height 179.3 ± 1.8 cm) 2.5h after a single muscle-damaging leg-extension exercise (10 sets of 6 repetitions at 80% 1-RM, 2 min rest between sets):

Figure 5: MGF (ng mRNA / 10^8 µg RNA) and IGF-IEa ng mRNA / 10^5 µg RNA) expresion in quadriceps muscle of young subjects before and 2.5h after 10 sets of 6 repetitions at 80% 1-RM on a leg-extension machine with 2min rest between sets (data adapted from Hamed. 2002)

If you take a closer look at the data in figure, you will probably notice that there was one subject with an extreme MGF response, the scientists explain by a particularly high type-IIx fiber content of the quadriceps of this individual. If you remember the mouse studies and the analysis of the muscle composition of bodybuilders from the previous installments, you will be aware that the shift from type IIb to type IIx muscle fibers is one of the main characteristics of "getting real big". The extreme MGF response (>10x higher than the mean MGF expression across the other subjects) in this subject thusly suggests the increased growth capacity of type IIx muscle fibers is in part due to their ability to release MGF in response to strenuous exercise and thusly multiply / replenish their satellite cell pool to prepare for future growth.

Figure 6: MGF (ng mRNA / 10^8 µg RNA) and IGF-IEa ng mRNA / 10^5 µg RNA) expresion in quadriceps muscle of young subjects after eccentric HIIT exercise on cycle ergometer (data adapted from Hamed. 2008)

Interestingly, a 2008 follow up study (this time involving nine healthy young men aged 20–27 years, cf. Hamed. 2008) with a completely different training protocol that consisted of

60min of opposing the rotation of the pedals down to 60 r.p.m. Subjects performed the following program of six working intervals: six working intervals: 0–6min at 50%, 6–12min at 75%, 12–20min at 100%, 20–25min at 130%, 25–40min at 100% and 40–60min at 75% of the load  eliciting concentric VO2max

illicited surprisingly similar results (cf. figure 6). And in both cases, it appears to be the MGF splice variant not the IGF-IEa variety that drives the short term (hours to days) response to strenuous exercise.

HIIT and resistance training a dynamic duo for MGF expression

Assuming that you are following each and every post here at the SuppVersity (you know you should be ;-), this should remind you of a previous blogpost of mine (cf. "HIT Your Satellite Cells to Increase Your Gains!"), in which I explained that one of the many advantages of high intensity training (not even interval) over classic "cardio" training is that it can increase satellite cell proliferation. Now, with this installment of the Intermittent Thoughts you finally understand, why this is the case.

Image 2: This is not the kind of muscle damage you should be aiming for in the gym.

Now, while protein synthesis and increases in domain size are partly mediated via nutrition, the intra-muscular expression of the IGF-IE splice variants appears (at least based on the current research) to depend solely on exercise, or I should say the wear and tear that goes hand in hand with heavy exercise. In that it seems to be less important, whether you are "pumping away" or "cycling like maniac", as long as its "hard" - to put that into perspective, in the 2008 study by Hamed et al. the subjects underwent ~3600 eccentric muscle contractions in only 1 h, their creatine kinase (CK) levels (marker of muscle damage) increased by +183% and all subjects reported profound muscle soreness.

This controlled amount of muscle damage ties in nicely with the topic of next week's installment which will center around the the intricate relation of the inflammatory response to exercise, the expression of the well-known and less known inflammatory cytokines, TNF-alpha, IL-6 and IL-15 (sorry, Trevor, I have already gone overtime, so your question will have to wait till next week ;-) and the muscle (re-)building effects of IGF-1 and its intra-muscular children.

Add Two Pounds of Lean Mass in Three Weeks W/ HIIT. HIIT Sprint Training Builds Muscle & Anaerobic Power While Reducing the Exercise Induced GH Response by 64%

HIIT - A GH diminishing mass builder?

I know it sounds contradictory, at first. If you take into considerations that previous studies show that the post-exercise increase in growth (and other) hormones does not correlate with the beneficial adaptational effects of exercise, it's actually no longer that surprising that researchers from the Department of Exercise Physiology at the Winston-Salem State University found that "[o]ne week of HIT significantly decreased GH release, with a simultaneous significant increase in anaerobic power and lean body mass of the lower extremities." (Ritsche. 2014)

In their latest paper which appeared in the December edition of the Journal of Exercise Physiology Kevin Ritsche, Jason Smith, Paul Mellick, and Laurie Wideman report the results of a recent experiment in the course of which 19 recreationally active male subjects (24.9 ± 3.9 yrs) completed a one-week high intensity interval training.

You can learn more about HIIT at the SuppVersity

Never Train To Burn Calories!

Tabata = 14.2kcal /min ≠ Fat Loss

30s Intervals + 2:1 Work/Rec.

Making HIIT a Hit Part I/II

Making HIIT a Hit Part II/II

HIIT Ain't For Everyone

The training protocol used in the study was based on similar high-intensity protocols published by Burgomaster et al. (2005) and Gibala et al. (2006) and began 24 hrs after the completion of a pre-test that was designed to measure the baseline fitness, body fat and lean body mass (by DEXA), as well as the acute GH response to high intensity exercise in the 19 young subjects.

The training protocol consisted of 4 to 6 repetitions of 30-sec maximal sprints and was performed three times per week for 3 weeks. One day of rest intervened each training session.

"The first 3 training sessions consisted of four 30-sec repetitions at 7.5% body mass with 4 min of active recovery at 50 W between each repetition. Training sessions 4 to 6 (wk 2) consisted of 5 repetitions, and sessions 7 to 9 (wk 3) consisted of six 30-sec maximal repetitions. During each repetition, each subject was encouraged verbally to provide maximal effort" (Ritsche. 2014).

At the end of each week, 48 hrs after the third training session for the week, subjects completed the acute sprint test protocol outlined previously (including blood draws).

Figure 1: Changes in body composition in response to the 3-week hiit-training protocol. the percentages above the bars indicate the relative difference between pre- and post-value. The light bars tell you that the corresponding changes were not statistically significant (Ritsche. 2014).

At least 48 hrs after the final blood profile, a post-training DXA scan was completed as outlined previously.

Figure 2: (a) Peak power; (b) peak power-corrected for subjects’ body mass; and (c) fatigue index during each 30-sec maximal cycle ergometer acute sprint (as) before and after 3 wks of hit; and (d) total combined workload of every sprint during each training week (Ritsche. 2014)

As you can see in Figure 1, the DXA-scans revealed significant increases in total and leg lean mass, albeit only non-significant reductions in body fat - changes which went hand in hand with a profound increase in exercise performance (see Figure 2) and a significant reduction of the initially observed post-exercise growth hormone spikes (see Figure 3).

Figure 3: Peak growth hormone concentrations after the workouts during the pre-test and after 1, 2 & 3 weeks of training; %-ages indicate difference to pre-value (Ritsche. 2014).

Bottom line: If you take into consideration that there is a close association between the post-workout growth hormone release and the relative exercise intensity - i.e. relative to one's individual fitness level and the corresponding demands of the exercise - the amelioration of the growth hormone response could be a consequence of the adaptation process that occurred in the course of the three week intervention.

It is thus not necessarily a bad thing and does therefore not stand in contrast to the adaptational response Ritsche et al. describe in their latest paper. If you take another look at Figure 3 and compare the GH response to the adaptations in Figure 2, it rather indicates that the subjects got used to the exercise | Comment on Facebook!

References:

• Burgomaster, Kirsten A., et al. "Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans." Journal of applied physiology 98.6 (2005): 1985-1990.
• Gibala, Martin J., et al. "Short-term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance." The Journal of physiology 575.3 (2006): 901-911.
• Ritsche, Kevin, et al. "Acute Exercise-Induced Growth Hormone is Attenuated in Response to Short-Term, High-Intensity Exercise Training." Journal of Exercise Physiology (2014).

Arginine Blunts Growth Hormone Response to Resistance Training: Will the -41% Reduction in Post-Workout Growth Hormone Release Hamper Your Strength & Size Gains?

Arginine-based pre-workout products are more popular with guys than with girls. Could this be the reason that only women complain about unlovedly rapid muscle gains? ;-)

No, this is not a typo! The verb in the headline of today's SuppVersity article really is "to blunt", as in "to neutralize partially" (OED Online 2013). I have to admit that I was also surprised, when I spotted the study over in the "ahead of print" section of the International Journal of Sports Nutrition and Exercise Metabolism. Unless Forbes, Harber and Bell, of whom you will learn later that they've already conducted another 'arginine study', messed up, the results of their most recent experiment do yet leave little doubt: Arginine, an amino acid that is used to test the function of the GH-releasing somatotropic cells within the lateral wings of the anterior pituitary, does - when it is administered at a dosage of 0.075 g·kg-1 body mass right before an acute bout of resistance exercise (3 sets of 8 exercises, 10 repetitions at ~75% 1RM) attenuate the post-workout growth hormone surge in strength trained individuals (Forbes. Nov 2013).

You want more details? Here you go...

With ~5-6g of arginine being taken before a workout that consists of 3 sets of 8 classic strength training exercises that are performed for 10 repetitions and at an intensity ~75% of the personal 1RM of the 14 strength trained men [age: 25±4 y; body mass: 81.4±9.0 kg; height: 179.4±6.9 cm; and training experience: 6.3±3.4 y], the researchers from the Faculty of Physical Education & Recreation at the University of Alberta in Edmonton, Alberta, Canada designed an experimental setup which comes "shockingly" close to what the average and extraordinaire gymrat is doing, when he or she is hitting the grind.

Figure 1: Level of arginine, GHRH and IGF-1 at T = 0, 15, 30, 60 min of rest-recovery + integrated area under the curve for growth hormone (iAUC GH); all values expressed relative to placebo control (Forbes. Nov 2013)

Against that background the question whether you and the rest of the millions of hobby athletes who spend hundreds of bucks on pre-workout products every year have been hampering their own progress is, as hilarious as it may sound, not a totally unwarranted one. I mean, we can hardly ignore the statistically highly significant -41% reduction in total growth hormone secretion in the one hour "anabolic window" after the workout, Forbes and his colleagues measured - can we?

What do we make of these results?

Most of you will probably remember the often referenced results of West & Phillips, whose 12-week resistance training intervention in the course of which the researchers from the Exercise Metabolism Research Group at the Department of Kinesiology of the McMaster University in Hamilton, Ontario,  made the following observations (West. 2012):

• 

  Suggested Read: "Anabolic Workouts Revisited!" | more

  No correlations between GH, testosterone or IGF-1 and the lean mass gains of their 56 recreationally active young men, who were not actively participating in any weightlifting
  activities <8 months before the study.
• Significant correlations between GH and the increase in type I (slow twitch, oxidative) muscle fibers, but no correlation between testosterone, IGF-1 and cortisol.
• Significant correlations between GH, as well as cortisol and the increase in type II (fast twitch, gylcolytic) muscle fibers, but no correlation between testosterone and IGF-1.

Unlike Forbes, Harber and Bell in the study at hand, West and Phillips measured the hormone levels for up to 2h after the workout. It is thus possible, but in view of the progression of the GH levels in the Forbes study relatively unlikely, that we'd see a rapid increase in the 2nd hour of the rest period and thus an increase in the total amount of GH that's released in response to the combination protocol (arginine + exercise).

Is the decrease the result of a previous GH "overload"?

With respect to the possible involvement of an auto-negative feedback, which is another, previously suggested explanation for this phenomenon, of which I had to realize during my research for this article that it has been covered in the literature before (Kanalay. 2008), Forbes et al. remark that their data would basically exclude the possibility that "the GH suppression was not due to a GH or IGF-1 induced autonegative feedback loop." (Forbes. Nov 2013)

It may not be the perfect muscle builder and maybe not even something you want to take in the vicinity of a workout, but there is still promising data on the metabolic effects of arginine esp. for (pre-)diabetics | more

In other words, Forbes et al. exclude the possibility that the subjects experienced a rapid increase in growth hormone as we would see it in response to the intravenous injection of arginine (10x increase with 20g/m² surface area of the 12 normal men in a 1996 study by Rahim et al.) that would then have shut down the GH production just as the exogenous administration of steroids would shut down your natural testosterone production.

If we focus on the available data, the conclusion of the researchers from the University of Alberta is certainly right. If we do take into account that we are talking about post workout supplementation and remind outselves that "the somatotrope is also known to have a refractory period" (Kanaley. 2008), it should be obvious that post-workout measurements, alone, cannot exclude the possibility that the GH spike that's responsible for the auto-negative feedback occurred during, not after the workout.

In other words: Instead of focusing exclusively on the post-workout GH levels, Forbes, Harber and Bell would actually have had to measure the pre & intra-workout GH response, as well. The GH spike that would cause the auto-negative feedback could after all have been caused by a sudden drop in blood glucose in response to the insulin sensitizing effects of arginine and the 'glucose hungry' strength training session.

Auto-negative feedback is still possible, but isn't there something else?

An alternative explanation for the lowered growth hormone response may come from a closer reading of the 'prequel' to this study. In January, Forbes et al. published a paper with the same supplement, but a different exercise protocol. Instead of hitting the weights, their 15 aerobically trained male subjects cycled for 60 min at 80% of their personal VO2_max - again, immediately after ingesting 5-6g of l-arginine (0.075g/kg body weight).

Is there anything arginine is good for, if it's not a muscle builder and it's effects on nitric oxide are overblown? There is a previous SuppVersity article that would suggest so: "Arginine a BAT Building WAT Killer & Repartitioning Agent?" | more

Contrary to the strength training routine, the (relatively) high intensity cycling had identical effects on the hormonal, metabolic and cardio-respiratory markers of the subjects, the two things that differed, though, were

• the rate of fatty acid oxidation at the onset of the workout, which was reduced in the l-arginine group, and
• the levels of the sugar alcohol glycerol at the 45-min time point, which were slightly, but significantly increased

These observations stand in line with the effects McConell et al.  observed in a 2006 study in response to the infusion of l-arginine.

The arginine infusion increased the glucose uptake and blunted the increase in nonesterified fatty acid and glycerol concentrations during 120min of cycling at 72% of the VO2max which were followed immediately by a 15-min "all-out" cycling performance bout (McConell. 2013). Whether it also changed the GH response is however something I can't tell you, because reseachers from the The University of Melbourne did not measure the effect the arginine infusion had on the growth hormone levels of their study participants. I would yet guess that it will have been similar to the one on the cycling study Forbes did. This, in turn, would suggest that the effect depends on (a) duration and energy expenditure, or (b) the substrate utilization during the workout (lifting weights = glycolytic; cycling = rather oxidative). In the end both of these are related to the reliance on fat, not glucose / glycogen to fuel the energetic demands of your workout and as you all know the acute provision of  glucose is the prerogative of glucocorticoids (i.e. cortisol), not GH.

There may be another reason arginine does not make you "big": It's one out of three amino acids that have an especially pronounced satiety effect | learn about the others!

I can't exactly tell you why, but I can tell you that... I openly admit that I was surprised by the results of the study at hand. I  surprised that I missed this (side) effect of arginine, before, but I am not worried that the arginine supplements you may be or may have been taking are / were  hampering your training success.

 If that was the case one of the many "real-world" arginine supplementation studies, where the study outcome wasn't some funky hormonal marker of which we still don't know whether / to which extent it actually affects skeletal muscle hypertrophy, would have shown a trend for decreasing performance, lean mass and strength gains with arginine supplementation - this, I can assure you was not the case.

In fact, those of you who remember one of my posts on the 'arginine powered' VPX preworkout products (learn more), will remember that the scientists observed, if anything, opposing, i.e. beneficial effects from complex preworkout products as most of you will be using. A somewhat different picture emerges for the 'arginine only studies' where "only" three out of five acute supplementation and four out of eight chronic supplementation studies showed measurable, but in many cases negligible performance gains (Alvares. 2011). And the null-effect the authors of the other papers observed is no reason to be concerned, either.

References:

• Álvares TS, Meirelles CM, Bhambhani YN, Paschoalin VM, Gomes PS. L-Arginine as a potential ergogenic aid in healthy subjects. Sports Med. 2011 Mar 1;41(3):233-48.
• "blunt, v.". OED Online. September 2013. Oxford University Press. http://www.oed.com/view/Entry/20664?rskey=iZQVcA&result=3&isAdvanced=false (accessed November 19, 2013).
• Forbes SC, Harber V, Bell GJ. The acute effects of L-arginine on hormonal and metabolic responses during submaximal exercise in trained cyclists. Int J Sport Nutr Exerc Metab. 2013 Aug;23(4):369-77. Epub 2013 Jan 8.
• Forbes SC, Harber V, Bell GJ. Oral L-Arginine Prior To Resistance Exercise Blunts Growth Hormone in Strength Trained Males. Int J Sport Nutr Exerc Metab. 2013 Nov 13. [Epub ahead of print]
• Kanaley JA. Growth hormone, arginine and exercise. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):50-4. Review.
• McConell GK, Huynh NN, Lee-Young RS, Canny BJ, Wadley GD. L-Arginine infusion increases glucose clearance during prolonged exercise in humans. Am J Physiol Endocrinol Metab. 2006
• Rahim A, Toogood AA, Shalet SM. The assessment of growth hormone status in normal young adult males using a variety of provocative agents. Clin Endocrinol (Oxf). 1996 Nov;45(5):557-62.
• 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.

Sleep to Grow, Train to Sleep: How Strength and Endurance Training Effect Your Sleep Patterns & Exercise Performance and May Help or Hinder Fat Loss & Muscle Gains

Image 1: As a toddler you already knew - "Sleep is the most anabolic agent there is"; Sleep - Train - Eat, repeat! Remember that ;-)

If you like Dave Palumbo's Heavy Muscle Radio, you will probably have heard an advertisement that (a few other questionable statements aside) contains a real gem of wisdom: "Sleep is the most anabolic agent there is!" But how come? Well, if you remember the comments I made on the way your muscles grow by both, increasing mononuclear domain sizes (protein synthesis) and the accumulation of new myonuclei, you will probably also remember that, next to estrogen, nitric oxide and a handful of other factors, growth hormone, in general, and the IGF-1 (and MGF-1) that is locally released in response to its secretion, are the primary drivers of satellite cell driven muscle hypertrophy (and possibly hyperplasia)... now, guess when your body produces the lion share of growth hormone (and downstream IGF-1?) in a given day?

You got it, in those cosy (hopefully) ~8 hours you are snorkeling away in between your sheets (Cauter. 1998) - it is in these hours, that your GH levels spike at 600% of their daytime average and your cortisol levels plummet into the abyss. As studies show, this is yet not the only thing on which you are missing out if you do not get your share of quality sleep day in, day out: Even short-term (let alone chronic) sleep deprivation has been shown to significantly increase rates of perceived exertion in athletes and - and this may be even more detrimental - decrease insulin sensitivity and glucose tolerance (VanHelder. 1989). So that after nights and nights of low-quality or insufficient sleep, your secret weapon against tiredness, your pre-workout high-carb-get-me-going shake will no longer get you going in the gym, but rather out of the gym and right to your doctor to ask him for a script for some Metformin to get your blood sugar levels back to normal.

Assuming that I now got your full attention, I want to share the results of two very recent studies with you. One on the differential effect of strength and endurance training in the morning (10am) on sleep quality and duration in 15 healthy trained men (Roveda. 2011) and a second one on the beneficial effects even a single session of resistance training (at 60%RM) has on the sleep pattern of 22 65-85 year old men (Viana. 2011).

Always remember: Sleep is the most anabolic agent there is

One thing upfront: A reasonable amount of physical activity will - regardless of your age and fitness level - make it easier to fall asleep, lengthen the time you spent in bed actually sleeping and not tossing and turning, and contribute to an overall improvement in sleep quality.

Figure 1: Relative changes (compared to baseline) in assumed and actual sleep on day 1 and day 2 after a 10am strength (bench press 4x80RM + 10 min warm up)or endurance training (10min warm-up, 30min 80%VO2max, 10min cool-down) session in 15 healthy young men (data calculated based on Roveda. 2011).

As figure 1 goes to show there was a distinct effect of both strength and endurance training on the time spend in bed (assumed sleep) and the actual sleep time on the first day after the physical activity. In that, it is particularly noteworthy that the actual sleep time increased by +8% and +12.5% and thusly ~2% more than the time the subjects spent in bed. This increase in sleep quality is something we also see in the older subjects of the Viana study, whose REM latency, i.e. the time it took them to enter into the valuable rapid eye movement phase of their sleep, decreased by a whopping -48%, on days on which they had performed their 3 sets of 12 reps (60%RM) of chest presses, leg presses, vertical tractions, leg curls, biceps curls, abdominal crunches, arm extension, and lower back exercises.

Figure 2: Relative changes in sleep efficiency and sleep latency on day 1 and day 2 after a 10am strength or endurance training session in 15 healthy young men (data calculated based on Roveda. 2011).

Now, while we see a "rebound" effect (a decrease in sleep time) in the 2nd night after the morning exercise in the young subjects (comparative data were not collected in the Viana study), the increase in sleep efficiacy, i.e. the amount of time the young men spent in bed vs. the amount of time they actually sleep persisted (cf. figure 2)! And the sleep latency, i.e. the time it took the subjects to fall asleep was still significantly reduced on day 2 after the respective physical activities.

Although there probably is no doubt that physical activity may benefit sleep quality and sleep quality in turn may benefit not only the performance during the former, but also its effects on your metabolic health and body composition (cf. image 1), it is still a matter of constant debate how much, is too much - after all, both forms of overtraining, the sympathetic form, which puts you into a chronic fight and flight mode and will wreak havoc on both your sleep quality and its duration (usually associated with higher intensity training than the bench pressing session 10min warm-up + 4x80%RM the Rovenda subjects performed) and the parasympathetic form, which is what people usually refer as "burnout syndrome" and will have you sleep hours after hours waking totally unrefreshed, produce quite distinct, yet of many athletes carelessly overlooked sleeping patterns, which - and here lies the culprit, still appear to be one of the best, yet by far not "objective" measures of whether you are "hitting your sweet spot" or are just digging a deep black hole by keep pushing and pushing, when your batteries have long run out of energy (Urhausen. 2002)... but this, my friends is a topic for another blog post ;-)

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.

Trimethylglycine aka Betaine Sets the Anabolic Stage for Increased Muscle Growth: Higher IGF-1 & Lower Cortisol - Statistically Significant, but Physiologically (Ir-)Relevant?

Figure 1: Betaine content (in mg/100g) in some common food items (data based on Craig. 2004). Makes me wonder if Popeye ate wheat germ as well or whether he was celiac and stuck to spinach to get his daily dose of pro-anabolic betaine?

Trimethylglycine (TMG) the sciency name for a molecule most of you probably know by the name "betaine" is actually no longer a new-comer to the supplement scene (please note that this is not betaine HCL(!), the stuff you will find in digestive aids). I have already written about its purported ergogenic effects several times and there are actually quite a handful of proprietary blends with mostly undisclosed, but judged based on the total serving size and amount of ingredients in them, hilariously underdosed amounts of the zwitterionic compound and a methyl derivative of glycine in it on the market.

Friends and followers of the SuppVersity will also be aware that betaine is also found naturally in a variety of food sources such as sugar beets, wheat bran, spinach, shrimp, and many others (see figure 1) and that it can be synthesized from choline in your body, when dietary intake exceeds your current metabolic demands (Ueland 2011).

What you probably don't know, however, is...

... that the latest study from the Human Performance Laboratory at the Department of Kinesiology,
of the University of Connecticut, shows that "betaine (vs. placebo) supplementation enhanced
both the anabolic endocrine profile and the corresponding anabolic signaling environment, suggesting increased protein synthesis" (Apicella. 2012).

Figure 2: Effects of a standardized full-body workout (see text for details) on growth hormone (µmol/L), IGF-1 (nmol/L) and cortisol (µmol/L) levels in 12 recreationally trained young men after 2 weeks supplementation with betaine (2x 1.5g/day) or placebo (data based on Apicella. 2012)

And if we temporarily lose sight of the fact that the devil is in the detail, the data in figure 2 certainly looks as if you should run to the next best store with fishing equipment and get yourself a huge pot of trimethylglycine, of which the shop assistant will probably tell you that "This is a good choice Sir! The carps love the sweet taste!" But I am digressing, so let's get back to what's really sweet, namely ...

• stable growth hormone levels (vs. -17% in the placebo group)
• an 18% increase in IGF-1 (vs. a -10% decrease in the placebo group), and
• a -5% reduction in cortisol (vs. a 6% increase in the placebo group)

- they all sound pretty sweet, as well. Especially in conjunction with the stable p-AKT levels the scientists observed, when they analyzed the tissue samples. Unfortunately (but earnestly), Apicella et al.'s conclusion, still contains one word, too many people who read the abstract, are probably going to ignore:

"Betaine (vs. placebo) supplementation enhanced both the anabolic endocrine profile and the corresponding anabolic signaling environment, suggesting increased protein synthesis." (Apicella. 2012; my emphases)

Which one is it? A tip: It is none of the words I emphasized in bold. After all, that would make it way too easy for you... ha? Yeah! I see you've done your homework. Suggest(-ing) is in fact the most important word in this and the conclusions of many objectively written scientific papers.

So, the study "suggests increased protein synthesis"...

... and this means it does not even prove that the protein synthetic response in the immediate vicinity of the workout was increased in response to the to the two weeks of BID (=twice daily) supplementation with 1.25 g of betaine. In other words, all we know is that the funky gene essays for p-AKT and serum tests for growth hormone, IGF-1 and cortisol "suggest" that it could be the case, if we assume that marginally higher IGF-1 levels, stable growth hormone levels and lower cortisol levels (rememeber we are not talking about increasing any of them into the supraphysiological range, here) would

1. result in increased protein synthesis and ultimately
2. greater lean mass accrual,

because, if we are honest, no one is interested in a number you can measure, when you infuse a marked amino acid into the circulation and check how much of it goes into the muscle, but doesn't come out of it, afterwards.

Something to remember: What I find remarkable - and this is by no means something you will see only in this study, neither is it "fraud" or whatever, is how by simply adding a break into the Y-axes of the graph and thus omitting the lower 80% of the bar Apicella et al. give the impression that the effects on IGF-1 were more than twice as large than they actually are... remember that, because you will encounter that in many studies, and reproductions of graphs from scientific papers, especially if they are used to market certain products.

What we want is to get bigger, stronger and all that faster, and whether the 12 recreationally trained men (age 19.7±1.2 years; lean body mass 65.2±8.8 kg; fat mass 15.6±8.5 kg; body fat percentage 18.7±7.0 %; BMI 28.2±4.0) would have gained even a single inch of muscle more on whatever body part, if they had performed a real workout instead of the funky "AES" (=acute exercise session) that consisted of

• 10x maximal vertical jumps without pause, 
• 1x 10-s isometric squat, 
• 1x 10-s isometric bench press on a smith machine, and
• 1x 10 min of repeated box lifting (RBL)

is more or less guesswork. In view of the previously discussed results from the researchers at the McMasters University in Ontario (see "Anabolic Workouts Revisited"; a brief reminder. the systemic hormonal response to an acute exercise bout is irrelevant, if anything higher cortisol levels correlate with greater increases in lean muscle mass) and the "statistically significant", but physiologically probably irrelevant increases and decreases in IGF-1 and cortisol at least highly questionably (please take a look at the additional information in the red box to the right, as well).

... but there are still way too many "ifs" in here!

The sheer number of "suggests", "is touted", "is likely", "also possible", "as we presume", etc. is honest and speaks in favor of the quality of the study, but against the reliability of the statement that followeed the initially cited "suggests" in the conclusion. Moreover, the researchers freely admit that...

"[...] the mechanisms by which betaine may have affected the hormones measured in this study are still unclear and require further research" (Apicella. 2012)

so that even the fact that betaine is an organic osmolyte and could thus help stabilize skeletal muscle protein, promote / maintain optimal hydration and protect against

• hypertonic stress (Alfier. 2006), 
• urea-induced inactivation of muscle myosin ATPases (Ortiz-Costa. 2002), and 
• structural changes in myosin due to urea accumulation (Ortiz-Costa. 2002)

does lend credibility to the hypothesis that betaine could help you build muscle, but it does not prove it. In conjunction with the results of previous trials, like...

Betaine does not increase nitric oxide While I have no idea why everyone is so keen about those nitrate supplements, one thing is for sure: Betaine has no effects on serum nitrate or nitrite levels. The vasolidation effect of beet roots / beet root juice is simply a result of the nitrate that's in there along with the betaine (+ the sugar and the insulin spike, which will also trigger an increased NO-response).

At least this is what a study by Bloomer et al. which consisted of three independent experiments using 1.25 and 5.00g B, acutely, 2.5g per day for 14 days, chronically, and a combination of chronic (6g for 7 days) + acute (6g acutely before the test) betaine supplementation (Bloomer. 2011).

• Hoffman. 2009 - 2.5/day for 14 days; jump squat, squat, bench press; "Two-weeks of betaine supplementation in active, college males appeared to improve muscle endurance of the squat exercise, and increase the quality of repetitions performed." 
• Lee. 2010 - 2x 1.25g/day for 14 days; bench squat and jump tests; "[Betaine] supplementation increased power, force and maintenance of these measures in selected performance measures, and these were more apparent in the smaller upper-body muscle groups."
• Hoffman. 2011 -  2.5g/day for 15 days; 5 training + testing sessions; "15 days of betaine supplementation did not increase peak CON or ECC force outputs during an isokinetic chest press but did appear to reduce subjective measures of fatigue to the exercise protocol"
• Trepanoswki. 2011 - 2.5g/day for 14 days; resistance training; "moderate increase in total repetitions and volume load in the bench press exercise, without favorably impacting other performance measures."
• del Favero. 2012 - 2g/day for 10 days; muscle strength and power, muscle PCr content, and body composition, three "familiarization sessions" preparing the participants only to perform the tests; "we showed that betaine supplementation combined or not with creatine supplementation does not affect strength and power performance in untrained subjects."
• Pryor. 2012 - 2.5g/day for 7 days; cycling performance; "betaine ingestion significantly increased average peak power (3.4%; p = 0.026), maximum peak power max (3.8%; p = 0.007), average mean power (3.3%; p = 0.034), and maximum mean power (3.5%; p = 0.011) in recreationally active males and females"

... there is still room for long-term improvements in muscle gains as a consequence of the general ergogenic effects of betaine (every rep more counts!), but it appears unlikely that the "anabolic" hormonal milieu observed in the study at hand are the fundamental cause of the latter.

Reminder: If you want to try it, you got to get yourself "trimethylglycine" (TMG) not "betaine HCL" and you better don't buy it in capped form if you don't have lots of money to burn. I just checked with the next best bulk supplier - they got 1kg for $33.50. Even if you double dose, i.e. take 2x 2.5g per day (most studies mixed it with Gatorade) this will last you for 200days(!), which is probably the time it will take until you can actually see and not just measure any potential, possible, suggested, etc. anabolic effects ;-)

References:

• Alfieri RR, Bonelli MA, Cavazzoni A et al (2006) Creatine as a compatible osmolyte in muscle cells exposed to hypertonic stress. J Physiol 576:391–401.
• Bloomer RJ, Farney TM, Trepanowski JF, McCarthy CG, Canale RE. Effect of betaine supplementation on plasma nitrate/nitrite in exercise-trained men. J Int Soc Sports Nutr. 2011 Mar 18;8:5.
• Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004; 80: 539–549.
• del Favero S, Roschel H, Artioli G, Ugrinowitsch C, Tricoli V, Costa A, Barroso R, Negrelli AL, Otaduy MC, da Costa Leite C, Lancha-Junior AH, Gualano B. Creatine but not betaine supplementation increases muscle phosphorylcreatine content and strength performance. Amino Acids. 2012 Jun;42(6):2299-305.
• Hoffman JR, Ratamess NA, Kang J, Rashti SL, Faigenbaum AD. Effect of betaine supplementation on power performance and fatigue. J Int Soc Sports Nutr. 2009 Feb 27;6:7.
• Hoffman JR, Ratamess NA, Kang J, Gonzalez AM, Beller NA, Craig SA. Effect of 15 days of betaine ingestion on concentric and eccentric force outputs during isokinetic exercise. J Strength Cond Res. 2011 Aug;25(8):2235-41.
• Lee EC, Maresh CM, Kraemer WJ, Yamamoto LM, Hatfield DL, Bailey BL, Armstrong LE, Volek JS, McDermott BP, Craig SA. Ergogenic effects of betaine supplementation on strength and power performance. J Int Soc Sports Nutr. 2010 Jul 19;7:27. 
• Ortiz-Costa S, Sorenson MM, Sola-Penna M (2002) Counteracting effects of urea and methylamines in function and structure of skeletal muscle myosin. Arch Biochem Biophys 408:272–278
• Pryor JL, Craig SA, Swensen T. Effect of betaine supplementation on cycling sprint performance. J Int Soc Sports Nutr. 2012 Apr 3;9(1):12.
• Trepanowski JF, Farney TM, McCarthy CG, Schilling BK, Craig SA, Bloomer RJ. The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation and associated biochemical parameters in resistance trained men. J Strength Cond Res. 2011 Dec;25(12):3461-71.
• Ueland PM. Choline and betaine in health and disease. J Inherit Metab Dis. 2011;34:3–15.

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.