Morphological Hypertrophic Muscle Adaptations (aka, Mechanisms Behind “I Wanna Get Hyoooge!!”)

Pop your head into just about any gym in America, and observe the male population (especially the younger ones) train. While the training methods are interesting in themselves, the common battle cry of the young Arnold wannabes is usually the same “I Wanna Get Hyoooge.” In an effort to explore the mechanisms behind the scenes in the body to help out these “bros” it is time to board the magical muscle mystery tour. Tour stops include a drive by of the nervous system, muscle fiber types, and how muscles adapt to exercise to get bigger and badder (as in a Michael Jackson “bad” is now good way).

Before we dive in head first into this, we need to do a short little anatomy tour. They say a picture is worth a thousand words, so check out figure below.

This time around I will spare you all the details on the exact names of each, but notice how a single fiber at the end goes into another group of fibers and then THAT group goes into another group until we are all the way up to the muscle itself. Muscle fibers can be broadly defined as type2 fast twitch or type 1 slow twitch (8). Fast twitch (type 2) fibers can produce more force, but they don’t last as long (26). Think of an NFL lineman. He can produce a ton of force to knock you into next week, but it is unlikely he will be chasing your around the block or very far at all. Type 2 (slow twitch) muscle fibers are like the slower cousin to the type 2, think energizer bunny. They can’t produce as much force, but they keep going and going and going and going………..

Remember that the nervous system is the head cheese, numero uno, el presidente, the commander in charge that controls all muscle movements. The nervous system also controls which fibers are type 1 or 2! Buller et al. (9) in 1960, carefully did the ole “switcheroo” on cats and switched nerves and a type 2 muscle fiber with a new type 1 NERVE now took on the properties of a type 1 muscle fiber! Think of this as “what the commander says goes.”
Another key point is that “living systems are build up through use and atrophy (get smaller) with disuse.” So when you are in the gym blasting away, you are actually making your muscle SMALLER! Yikes! The good part is that your body responds by BUILDING up those damaged fibers during the recovery period (33). So next time you do a similar exercise, the body has “new and improved” muscle tissue to better handle the damage. Pretty sweet!

Muscle Growth Time
Skeletal muscle is a very dynamic tissue capable of adapting to the stress placed on it. The process of exercise-induced adaptation in skeletal muscle involves a multitude of signaling mechanisms all the way down to the genetic level, ultimately putting together strings of amino acids to form new proteins in the form of more muscle tissue (10). Whooo ha, and the gym “bros” rejoice!

As mentioned, muscle growth is commonly referred to as “hypertrophy” (34) or more accurately as an increase in muscle fiber SIZE. How does this happen? While a complete answer to that question is beyond this short article, what do you think are some key processes? “TESTOSTERONE!” Good guess and there is a fair amount of data to support this (16, 17, 29, 30), there is also data (although less) to show that in castrated (denutted—youch!!!) animals (yeah I know it was not done in humans but do you want to volunteer for those studies?) are still able to increase muscle size despite having testosterone levels at very low levels (22, 24). “NUTRITION!” Yes, there is no denying that nutrition especially extra calories and protein are needed for muscle hypertrophy (11, 13, 19) but even in caloric restriction muscles can still get bigger (12). “INSULIN!” While insulin is the most anabolic (building) hormone in the body, it is not required either (7). (Side note, I am using the term “anabolic” in the physiologic sense where it is taking small things and making bigger things with them. This can be proteins into new muscle or fatty acids into new fat storage around your waist. And yes, too much insulin can make you a fat bastard). So the muscle building process is a complicated one.

How Do These Genes Look
Further down the hole, we have a whole slew of molecular signaling guys, some newly discovered like Mighty that can dramatically influence muscle growth. Mighty is a downstream metabolite of myostatin. Most have probably heard of myostatin now or seen the huge picture of the Belgium Bull.

Belgian Blue Bulls (say that fast three times in a row) have a mutation in the myostatin gene that produces a truncated, ineffective form of the protein (20), so in English there is almost no myostatin hanging around. The absence of myostatin allows unchecked muscle growth and interferes with fat deposition; the result is a lean, “double-muscled” bull. Yikes! Remember that LESS myostatin = MORE muscle.

The new kid on the block now is Mighty. Mighty is expressed in a variety of different tissues but appears to be specifically regulated by myostatin in skeletal muscle. Overexpression of Mighty in certain cells (ok, C2C12 cells if you really want to know) results in enhanced and accelerated differentiation and hypertrophy of myotubes (this is good for muscle growth, trust me) and leads to increased and earlier expression of MyoD and insulin like growth factor II (IGF-II) (both are good for muscle growth) (23).

Enough Biochem Yacking already
So I spared you from a detailed talk on Interleukin-4 (IL-4) and interleukin-13 (IL-13) that are involved in getting hyoooge (27), so be thankful! Watch out—Geek alert! Serrano et al. (28) recently showed a role for IL-6 in hypertrophic muscle growth and provide mechanistic evidence for the contribution of satellite cells to this process, in our fury friends the mouse.

So back to our irregularly scheduled program. So far we know 1) nutrition is key-calories and protein are needed to build muscle 2) we need a stimulus—weight training works well here (31) 3) certain hormonal and biochemical changes need to take place—from hormonal changes down to even the molecular level.
Shut Up Already and Tell Me HOW to Get Hyoooooooooge!
During short term studies of less than 10 weeks, it was shown that type 2 fibers hypertrophy (get bigger) much faster from training than their slow cousins the Energizer bunny type 1 fibers (1). MacDougall et al.(21) however investigated a longer time period of 5–6 months of heavy resistance training (weight lifting) in seven males and demonstrated a significant cross sectional increase in type 2 AND type 1 fibers; so long term it appears that BOTH fiber types can increase in size. Take home message, use a wide variety of reps.

Damage Plan
The goal of some dedicated Arnold wannabes is to destroy tissue! No pain no gain! Go hard or go home! Is there any research to support this method if we can get hyoooooooooge? There is actually some evidence to support this notion. Goldspink about 30 years ago proposed that if you literally tear the muscle fiber in half (these would be very small tears of course), that this may promote splitting of the muscle fibers once the body goes to work repairing those fibers; thus resulting in more fibers over time. More fibers= more siz
e. The fancy word associated with increasing muscle fiber NUMBER is hyperplasia. The downside is that this phenomena is highly debatable with virtually the studies being conducted on animals (primarily cats and birds), so how it applies to humans is not currently known (2-6, 15, 18, 32).

We know that eccentric (lowering a heavy weight) can scramble the muscle fibers (induce lots of damage) and it appears that fiber disruption induced by habitual weightlifting exercise is essentially repaired after 5 days of inactivity in trained men (14) and oxidative stress indices changed significantly with most peaking at 48 hours (25).

What does any of this mean?
Although data is somewhat limited on the “destroy tissue” approach in relation to hypertrophy there is enough to support the idea for muscle hypertrophy, but keep in mind that your recovery time may be longer with this approach. Your muscles get bigger OUTSIDE the gym when they are repairing!

Conclusion
Thus ends our very brief ride on the magically, muscle mystery tour! I hoped you have enjoyed the tour and kept your hands inside the bus at all times. We got to spend some time in the land of the nervous system, fiber types, stimulus for adaptation (aka weight training), and the adaptation process itself. The take away is that muscle hypertrophy is a complicated process and our best bet in the quest for huge-dom is 1) excellent nutrition with a surplus of calories and proteins and 2) consistent weight training with adequate time for recovery; especially if eccentric movements are used to induce muscle damage.
Time to get to the gym!

Mike T. Nelson has a BA in Natural Science, a MS in Mechanical Engineering (Biomechanics) and is currently a PhD student in Kinesiology (Exercise Physiology) at the University of Minnesota. His research interests are on the effects of energy drinks on metabolic health and the nervous system.

References
1. The effect of weight-lifting exercise related to muscle fiber composition and muscle cross-sectional area in humans. Eur J Appl Physiol. . 1979; 40(2):95.
2. Antonio J, WJ Gonyea. Muscle fiber splitting in stretch-enlarged avian muscle. Med Sci Sports Exerc. . 1994; 26(8):973-7.
3. Antonio J, WJ Gonyea. Progressive stretch overload of skeletal muscle results in hypertrophy before hyperplasia. J Appl Physiol. . 1993; 75(3):1263-71.
4. Antonio J, WJ Gonyea. Role of muscle fiber hypertrophy and hyperplasia in intermittently stretched avian muscle. J Appl Physiol. . 1993; 74(4):1893-8.
5. Antonio J, WJ Gonyea. Role of muscle fiber hypertrophy and hyperplasia in intermittently stretched avian muscle. J Appl Physiol. . 1993; 74(4):1893-8.
6. Antonio J, WJ Gonyea. Skeletal muscle fiber hyperplasia. Med Sci Sports Exerc. . 1993; 25(12):1333-45.
7. Bolster DR, LS Jefferson, SR Kimball. Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signalling. Proc Nutr Soc. . 2004; 63(2):351-6.
8. Brooks GH, TD Fahey, Baldwin, Kenneth David Sutherland. Exercise physiology: human bioenergetics and its applications. Boston : McGraw-Hill, c2005.; 2005. p. 22.
9. BULLER AJ, JC ECCLES, RM ECCLES. Interactions between motoneurones and muscles in respect of the characteristic speeds of their responses. J Physiol. . 1960; 150:417-39.
10. Coffey VG, JA Hawley. The molecular bases of training adaptation. Sports Med. . 2007; 37(9):737-63.
11. Cribb PJ, AD Williams, CG Stathis, MF Carey, A Hayes. Effects of whey isolate, creatine, and resistance training on muscle hypertrophy. Med Sci Sports Exerc. . 2007; 39(2):298-307.
12. Donnelly JE, T Sharp, J Houmard, et al. Muscle hypertrophy with large-scale weight loss and resistance training. Am J Clin Nutr. . 1993; 58(4):561-5.
13. Dreyer HC, MJ Drummond, B Pennings, et al. Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab. . 2008; 294(2):E392-400.
14. Gibala MJ, SA Interisano, MA Tarnopolsky, et al. Myofibrillar disruption following acute concentric and eccentric resistance exercise in strength-trained men. Can J Physiol Pharmacol. . 2000; 78(8):656-61.
15. Giddings CJ, WJ Gonyea. Morphological observations supporting muscle fiber hyperplasia following weight-lifting exercise in cats. Anat Rec. . 1992; 233(2):178-95.
16. Herbst KL, S Bhasin. Testosterone action on skeletal muscle. Curr Opin Clin Nutr Metab Care. . 2004; 7(3):271-7.
17. Kadi F. Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement. Br J Pharmacol. . 2008; 154(3):522-8.
18. Kelley G. Mechanical overload and skeletal muscle fiber hyperplasia: a meta-analysis. J Appl Physiol. . 1996; 81(4):1584-8.
19. Kerksick CM, B Leutholtz. Nutrient administration and resistance training. J Int Soc Sports Nutr. . 2005; 2:50-67.
20. Li ZB, HD Kollias, KR Wagner. Myostatin directly regulates skeletal muscle fibrosis. J Biol Chem. . 2008; 283(28):19371-8.
21. MacDougall JD, GC Elder, DG Sale, JR Moroz, JR Sutton. Effects of strength training and immobilization on human muscle fibres. Eur J Appl Physiol Occup Physiol. . 1980; 43(1):25-34.
22. Mackova EV, P Hnik. Some hormonal factors (hypophysectomy, castration and testosterone administration) modifying the course of “compensatory” muscle hypertrophy in the rat. Physiol Bohemoslov. . 1976; 25(4):325-32.
23. Marshall A, MS Salerno, M Thomas, et al. Mighty is a novel promyogenic factor in skeletal myogenesis. Exp Cell Res. . 2008; 314(5):1013-29.
24. Max SR, NE Rance. No effect of sex steroids on compensatory muscle hypertrophy. J Appl Physiol. . 1984; 56(6):1589-93.
25. Paschalis V, MG Nikolaidis, IG Fatouros, et al. Uniform and prolonged changes in blood oxidative stress after muscle-damaging exercise. In Vivo. . 2007; 21(5):877-83.
26. Powers SK, ET Howley. Exercise Physiology : Theory and Application to Fitness and Performance. McGraw-Hill Humanities/Social Sciences/Languages; 2006. p. 624.
27. Prokopchuk O, Y Liu, L Wang, K Wirth, D Schmidtbleicher, JM Steinacker. Skeletal muscle IL-4, IL-4Ralpha, IL-13 and IL-13Ralpha1 expression and response to strength training. Exerc Immunol Rev. . 2007; 13:67-75.
28. Serrano AL, B Baeza-Raja, E Perdiguero, M Jardi, P Munoz-Canoves. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. . 2008; 7(1):33-44.
29. Singh R, JN Artaza, WE Taylor, NF Gonzalez-Cadavid, S Bhasin. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. . 2003; 144(11):5081-8.
30. Sinha-Hikim I, SM Roth, MI Lee, S Bhasin. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab. . 2003; 285(1):E197-205.
31. Spiering BA, WJ Kraemer, JM Anderson, et al. Resistance exercise biology : manipulation of resistance exercise programme variables determines the responses of cellular and molecular signalling pathways. Sports Med. . 2008; 38(7):527-40.
32. Taylor NA, JG Wilkinson. Exercise-induced skeletal muscle growth. Hypertrophy or hyperplasia? Sports Med. . 1986; 3(3):190-200.
33. Wernig A. Regeneration capacity of skeletal muscle. Ther Umsch. . 2003; 60(7):383-9.
34. Wilmore JH, DL Costill. Physiology of Sport and Exercise, Fourth Edition. Human Kinetics Publishers; 2007. p. 574.

Updates
To all those that celebrate Halloween–Happy Halloween!

Fitcast Interview
Kevin Larabee gave me an opportunity to yack about Z Health and other training items over at the Fitcast and answer some questions. Special thanks to Kevin and check out the interview HERE. Be sure to listen to the podcast version of the Fitcast each week too at the same link or look for it on iTunes. Kevin does a great job and I listen in every week.

Staley Updates
Staley Seminar updates will start next week. I had to push them out a bit since I need to finish up my IRB questions for my upcoming research study.

New Article Up
Brand new original article is up in another blog entry for this date on muscle growth

Z Health Seminar Friday to Sunday with Dragon Door
If you happen to read this and are in town for the seminar, I will be there helping out on Sat and Sun; so please say hi! It will be a great time.

Rock on
Mike N

More information once again that exercise may help your brain function better! I know it is a fury critter study, but there are not many that are going to sign up for brain damage as part of a study (unless they already have brain damage).

Be sure to check the other blog entries such as
Be smart exercise your heart:exercise and cognition
and
Movement and brain deterioration-new study

The abstract:
Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain

Andrew S. Naylor*,†,‡, Cecilia Bull*,‡, Marie K. L. Nilsson§, Changlian Zhu*, Thomas Björk-Eriksson¶,?, Peter S. Eriksson*, Klas Blomgren*,**,††, and H. Georg Kuhn*,

Cranial radiation therapy is commonly used in the treatment of childhood cancers. It is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors.

Is only fear stopping you?

Staley Seminar Wrap Up

The Staley Seminar in AZ this past weekend was AWESOME! I will have a full update starting next week and I learned tons of new stuff. It was great to see old friends like Dr. Lonnie Lowery and Dave Barr–I got off the shuttle to the hotel and ran into them walking out the door for dinner on Friday night, so perfect timing. The Tilted Kilt in Scottdale is a great place for dinner! It was so good we went back there twice in one night (longer story).

It was great to meet new people also such as Cassandra Forsythe-New Last Name (I owe you some studies and follow up yet, great to meet ya in person), Rob “Fortress” Fortney who has the most hilarious stories ever and is a huge metal music fan, Anthony Almada, all the presenters on both days, Nick Nillson (nice to chat business and thanks for the rides around), Phil Stevens (last time I saw Phil was Test Fest in DC), Matt and Vick from CT (nice to chat and thanks for the coffee Vick), and everyone else there I met and special thanks to Charles and friends of course for putting it all together and Velocity sports for the use of their venue. Great times!

Exercise in a Pill?
Below is a great short article just published the other day in the New England Journal of Medicine about exercise in a pill. Great stuff.

NEJM Vol 359:1842-1844 October 23, 2008 Number 17

The Exercise Pill — Too Good to Be True?

Laurie J. Goodyear, Ph.D.

PubMed Citation Regular physical exercise has undisputed health benefits in the prevention — and in some cases, the treatment — of many diseases. The problem is that for the great majority of Americans, probably as much as 70% of the population, there is an inability or unwillingness to meet the minimum physical activity guidelines established by the American College of Sports Medicine. The idea of taking a pill to gain the benefits of exercise is extremely attractive for the millions of “couch potatoes.” A recent study by Narkar et al.1 suggests that a couple of molecules could mimic some effects of exercise training. Skeletal muscle is an extraordinary tissue that is critical not only in locomotion but also in controlling an organism’s metabolic homeostasis. Skeletal muscles are composed of different types of elongated, multinucleated cells called myofibers. Type I myofibers have a slow-twitch speed of contraction, are exceedingly oxidative, and have a reddish appearance. Type II myofibers have a faster-twitch speed of contraction, can have both oxidative and glycolytic metabolic properties, and are fairly white in appearance. Skeletal muscle is highly adaptable, or plastic, in that exercise training effects a change in metabolic and contractile properties of the myofibers. For aerobic exercise training, such as running and swimming, myofibers take on a slow-twitch phenotype, with an increase in the levels of oxidative enzymes, glycogen, and glucose transporter 4 (GLUT4), the protein that transports glucose into the muscle. These changes are accompanied by an increase in insulin sensitivity of the muscle and an overall improvement in glucose homeostasis in the body. When a rodent or human becomes inactive, a number of myofibers may convert to the fast-twitch phenotype, making them less able to perform sustained aerobic work and contributing to an insulin-resistant state.

See the rest of the article by clicking HERE

I had some questions recently if there are any compounds around that may help to increase testosterone “naturally” and if there are any data to support it.

In short, there are few but the 2 most popular appear to be 6-OXO and Novedex (product name). Both are in a class called aromatase inhibitors and they work to prevent the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization.

Clinically, there are drugs that do this and they are used as a potential treatment for breast cancer since breast tissue is stimulated by estrogens, thus decreasing their production is a way of suppressing recurrence of the breast tumor tissue.

So as we just learned in this short and FREE organic chemistry lesson, aromatase is responsible for the conversion of testosterone to estrogen. Blocking aromatase causes the body to decrease its levels of estrogen (primarily estradiol for those uber geeks out there), this results in increase of LH and finally testosterone. And the people rejoice!

This is all find and dandy, but are there any over the counter (currently) supplements that can do this? Here are 2 studies on two of them (below)

Another class of compounds that are supposed to have similar effects are methoxyisoflavone, ecdysterone, and sulfo-polysaccharide supplementation. There is a study and my notes on those at the end also.

On to the science!

Effects of eight weeks of an alleged aromatase inhibiting nutritional supplement 6-OXO (androst-4-ene-3,6,17-trione) on serum hormone profiles and clinical safety markers in resistance-trained, eugonadal males.

Rohle D, Wilborn C, Taylor L, Mulligan C, Kreider R, Willoughby D. Department of Health, Human Performance, and Recreation, Baylor University, Box 97313, Waco, TX 76798, USA. darryn_willoughby@baylor.edu.

ABSTRACT: The purpose of this study was to determine the effects of 6-OXO, a purported nutritional aromatase inhibitor, in a dose dependent manner on body composition, serum hormone levels, and clinical safety markers in resistance trained males. Sixteen males were supplemented with either 300 mg or 600 mg of 6-OXO in a double-blind manner for eight weeks. Blood and urine samples were obtained at weeks 0, 1, 3, 8, and 11 (after a 3-week washout period). Blood samples were analyzed for total testosterone (TT), free testosterone (FT), dihydrotestosterone (DHT), estradiol, estriol, estrone, SHBG, leutinizing hormone (LH), follicle stimulating hormone (FSH), growth hormone (GH), cortisol, FT/estradiol (T/E).

Blood and urine were also analyzed for clinical chemistry markers. Data were analyzed with two-way MANOVA. For all of the serum hormones, there were no significant differences between groups (p > 0.05). Compared to baseline, free testosterone underwent overall increases of 90% for 300 mg 6-OXO and 84% for 600 mg, respectively (p

Conclusion: Body composition did not change with supplementation (p > 0.05) and clinical safety markers were not adversely affected with ingestion of either supplement dose (p > 0.05). While neither of the 6-OXO dosages appears to have any negative effects on clinical chemistry markers, supplementation at a daily dosage of 300 mg and 600 mg for eight weeks did not completely inhibit aromatase activity, yet significantly increased free testosterone, dihydrotestosterone, and free testosterone /estradiol.

My notes:
So this small study shows that this supplement does cause some increase in testosterone and its anabolic friends although I hate it when only percentages from BASELINE are reported since it can be completely misleading.

BUT there were no body composition changes. Hmmmm. If it was increasing muscle and/or decreasing fat there would have been some body composition change. It did appear to be safe in those doses for a short length of time.

Eight weeks of aromatase inhibition using the nutritional supplement Novedex XT: effects in young, eugonadal men.

Willoughby DS, Wilborn C, Taylor L, Campbell W.

Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX 76798-7313, USA.

This study examined the effects of an aromatase-inhibiting nutritional supplement on serum steroid hormones, body composition, and clinical safety markers. Sixteen eugonadal young men ingested either Novedex XT or a placebo daily for 8 wk, followed by a 3-wk washout period. Body composition was assessed and blood and urine samples obtained at weeks 0, 4, 8, and 11.

Data were analyzed by 2-way repeated-measures ANOVA. Novedex XT resulted in average increases of 283%, 625%, 566%, and 438% for total testosterone (P=0.001), free testosterone (P=0.001), dihydrotestosterone (P=0.001), and the testosterone:estrogen ratio (P=0.001), respectively, whereas fat mass decreased 3.5% (P=0.026) during supplementation. No significant differences were observed in blood and urinary clinical safety markers or for any of the other serum hormones (P>0.05).

Conclusion: This study indicates that Novedex XT significantly increases serum androgen levels and decreases fat mass.

My Notes:
See my thoughts above about percentages. Although this one did show some body comp changes which is good. Hormones are completely non linear and while more (in general) is good of our anabolic friends, this does have a limit where the optimal amount should be is up for debate. Remember, the body has all sorts of feedback systems in place for good reason and what goes up must come down at some point.

I do like that this study was a double blind, placebo controlled flavor. Body fat was done by DEXA (gold standard), although it was statistically significant–it was still very small. I pulled the full study and it is only about 1-2 lbs total change (effect size of 0.6 for the stats geeks out there). The variation also on the changes in hormones was huge, although there did appear to be a statistical/significant change, we are still stuck that lean body mass did NOT change.

Interestingly enough, while marketed to change estrogen levels (which should therefore change testosterone levels), it was shown to NO decrease on estrogen and a non significant INCREASE in E1, E2 and E3.

So, some hormones may change but it did NOT appear to alter body composition in this study. The study was funded by Gaspari Nutrition and I do applaud them for doing a randomized, double blind study. This is WELL beyond what most supplement companies do.

Effects of methoxyisoflavone, ecdystero
ne, and sulfo-polysaccharide supplementation on training adaptations in resistance-trained males.

Wilborn CD, Taylor LW, Campbell BI, Kerksick C, Rasmussen CJ, Greenwood M, Kreider RB. Human Performance Lab, University of Mary Hardin Baylor, Belton, TX.

PURPOSE : Methoxyisoflavone (M), 20-hydroxyecdysone (E), and sulfo-polysaccharide (CSP3) have been marketed to athletes as dietary supplements that can increase strength and muscle mass during resistance-training. However, little is known about their potential ergogenic value. The purpose of this study was to determine whether these supplements affect training adaptations and/or markers of muscle anabolism/catabolism in resistance-trained athletes.

METHODS : Forty-five resistance-trained males (20.5 +/- 3 yrs; 179 +/- 7 cm, 84 +/- 16 kg, 17.3 +/- 9% body fat) were matched according to FFM and randomly assigned to ingest in a double blind manner supplements containing either a placebo (P); 800 mg/day of M; 200 mg of E; or, 1,000 mg/day of CSP3 for 8-weeks during training. At 0, 4, and 8-weeks, subjects donated fasting blood samples and completed comprehensive muscular strength, muscular endurance, anaerobic capacity, and body composition analysis. Data were analyzed by repeated measures ANOVA.

RESULTS : No significant differences (p > 0.05) were observed in training adaptations among groups in the variables FFM, percent body fat, bench press 1 RM, leg press 1 RM or sprint peak power. Anabolic/catabolic analysis revealed no significant differences among groups in active testosterone (AT), free testosterone (FT), cortisol, the AT to cortisol ratio, urea nitrogen, creatinine, the blood urea nitrogen to creatinine ratio. In addition, no significant differences were seen from pre to post supplementation and/or training in AT, FT, or cortisol.

CONCLUSION : Results indicate that Methoxyisoflavone, 20-hydroxyecdysone, and sulfo-polysaccharide supplementation do not affect body composition or training adaptations nor do they influence the anabolic/catabolic hormone status or general markers of catabolism in resistance-trained males.

My notes:
Don’t even bother wasting ANY of your money on these. Historically this class of supplements has a horrible track record. The only thing they are good for is dropping some weight from your wallet. If anyone has any peer reviewed research that otherwise, please post it in the comments.

Some fascinating brand new studies in the land of neuroscience recently. Check out the 3 studies and write ups below from our friends at PhysOrg.com

Any thoughts?
Mike N

Scientists restore movement to paralyzed limbs through artificial brain-muscle connections

Researchers in a study funded by the National Institutes of Health have demonstrated for the first time that a direct artificial connection from the brain to muscles can restore voluntary movement in monkeys whose arms have been temporarily anesthetized. The results may have promising implications for the quarter of a million Americans affected by spinal cord injuries and thousands of others with paralyzing neurological diseases, although clinical applications are years away.

“This study demonstrates a novel approach to restoring movement through neuroprosthetic devices, one that would link a person’s brain to the activation of individual muscles in a paralyzed limb to produce natural control and movements,” said Joseph Pancrazio, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS).

The research was conducted by Eberhard E. Fetz, Ph.D., professor of physiology and biophysics at the University of Washington in Seattle and an NINDS Javits awardee; Chet T. Moritz, Ph.D., a post-doctoral fellow funded by NINDS; and Steve I. Perlmutter, Ph.D., research associate professor. The results appear in the online Oct. 15 issue of Nature. The study was performed at the Washington National Primate Research Center, which is funded by NIH’s National Center for Research Resources.

In the study, the researchers trained monkeys to control the activity of single nerve cells in the motor cortex, an area of the brain that controls voluntary movements. Neuronal activity was detected using a type of brain-computer interface. In this case, electrodes implanted in the motor cortex were connected via external circuitry to a computer. The neural activity led to movements of a cursor, as monkeys played a target practice game.

After each monkey mastered control of the cursor, the researchers temporarily paralyzed the monkey’s wrist muscles using a local anesthetic to block nerve conduction. Next, the researchers converted the activity in the monkey’s brain to electrical stimulation delivered to the paralyzed wrist muscles. The monkeys continued to play the target practice game—only now cursor movements were driven by actual wrist movements—demonstrating that they had regained the ability to control the otherwise paralyzed wrist.

The group’s approach is one of several lines of current neuroprosthetic research. Some investigators are using brain-computer interfaces to record signals from multiple neurons and convert those signals to control a robotic limb. Other researchers have delivered artificial stimulation directly to paralyzed arm muscles in order to drive arm movement—a technique called functional electrical stimulation (FES). The Fetz study is the first to combine a brain-computer interface with real-time control of FES.

“A robotic arm would be better for someone whose physical arm has been lost or if the muscles have atrophied, but if you have an arm whose muscles can be stimulated, a person can learn to reactivate them with this technology,” says Dr. Fetz.

Until now, brain-computer interfaces were designed to decode the activity of neurons known to be associated with movement of specific body parts. Here, the researchers discovered that any motor cortex cell, regardless of whether it had been previously associated with wrist movement, was capable of stimulating muscle activity. This finding greatly expands the potential number of neurons that could control signals for brain-computer interfaces and also illustrates the flexibility of the motor cortex.

“The cells don’t have to have a preordained role in the movement. We can create a direct link between the cell and the motor output that the user can learn to control and optimize over time,” says Dr. Fetz.

Dr. Fetz and his colleagues found that the monkeys’ control over neuronal activity—and the resulting control over stimulation of their wrist muscles—improved significantly with practice. Practice time was limited by the duration of the nerve block. Comparing the monkeys’ performance during an initial two-minute practice and a two-minute peak performance period, the scientists found the monkeys successfully hit the target three times more frequently and with less error during the peak performance. In the future, greater control could be gained by using implanted circuits to create long-lasting artificial connections, allowing more time for learning and optimizing control, Dr. Fetz says.

The researchers also found that the monkeys could achieve independent control of both the wrist flexor and extensor muscles.

“An important next step will be to increase the number of direct connections between cortical cells and muscles to control coordinated activation of muscles,” says Dr. Fetz.

If researchers are able to establish a connection between the motor cortex and sites in the spinal cord below the injury, people with spinal injuries may be able to achieve coordinated movements.

Clinical applications are still probably at least a decade away, according to Dr. Fetz. Better methods for recording cortical neurons and for controlling multiple muscles must be developed, along with implantable circuitry that could be used reliably and safely, he says.

Source: National Institute of Neurological Disorders and Stroke

Mike says
If you liked this article, check out this one Army Funds “Synthetic Telepathy” Research from Wired Magazine

Experiments support alternative theory of information processing in the cortex

Neurons in the sound-processing part of the brain’s cortex are experts at timing. With remarkable precision, they fire electrochemical pulses or “spikes” in sync with the cues they receive from other neurons, even when these cues are separated by very small time intervals.

A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL), studying this phenomenon in rats, has demonstrated that “spike timing” in cortical neurons can influence behavior even at minuscule time intervals, more precise than previously imagined. Experiments focusing on the auditory cortex revealed that animals in the midst of decision-making have the ability to distinguish incoming signals separated by as little as three milliseconds.

Probing the relation of neuronal firing rates and behavior

The finding, published ahead of print October 12 in the online edition of Nature Neuroscience, adds to the current understanding of how neuronal activity in the brain’s cortex modulates behavior. According to the standard model of cortical activity, behavior is thought to be determined by the rate of spiking — the number of spikes occurring within a given interval. The CSHL team, led by Professor Anthony Zador, Ph.D., wanted to determine whether spike timing had any impact on decision-making and measure the shortest decision-driving interval between spikes.

Zador’s group designed an experiment in which rats wer
e trained to behaviorally distinguish between two sounds. When placed in a cage with two water outlets, the rats were trained to turn either to the left or to the right waterspout depending on the sound. The sounds were then replaced by electrical impulses delivered directly to two spatially separated groups of neurons in the auditory cortex. The animals were then re-trained so that simultaneous stimulation of both groups of neurons spurred the animal toward the left waterspout, whereas sequential stimulation of the neuron bundles led the animal to the right waterspout. The rats consistently homed to the right waterspout until the timing between the two sequential stimuli narrowed to below 3 milliseconds. “This suggests that the cortex is capable of ‘reading out’ very precise nuances in spike timing to drive behavior,” says Zador.

Deciphering the “Neural Code”

The group’s discovery helps make the case for an alternate theory of how the brain processes information. Neuroscientists have made vast leaps in understanding how neurons communicate with each other in the brain. But they are still in the dark about what the neuron-to-neuron message actually consists of and how it’s processed. Known as the “neural code,” this blueprint for the brain’s information-processing language has proved to be much more elusive than language that is encoded in our genome, which was deciphered decades ago.

The prevailing theory behind the neural code is based on the observation that neurons spike faster when they are transmitting information. This supports a “rate” code model, which stipulates that information is contained within the spiking rate of the neuron. But the CSHL team’s new data suggest that the neural code might actually be a “timing” code, where information is encoded within the precise pattern of spiking – something that can be deduced by examining how the spikes are distributed over time.

Zador explains the difference between the two possibilities by likening the brain to an office and neurons to the people working in the office. “If lots of people are talking within each department in a company, you might get a good idea of what’s going on in the company by just measuring how loudly people are talking within a given department, which is what the classical ‘rate’ model predicts,” he says.

But as Zador also observes, conversation is not just about loudness; it’s also about the identity of the speakers, their speech patterns, etc. “Our results demonstrate directly that there is more to this ‘office’ than just how loudly people are talking, and motivate us to try to figure out what that extra dimension is,” he says. He and his CSHL team will continue to probe for the answers as their work on this and related mysteries about neural communication continues.

Citation: “Millisecond-scale differences in neural activity in auditory cortex can drive decisions” appeared October 12, 2008 as an advance online publication in Nature Neuroscience. The complete citation is: Yang Yang, Michael R DeWeese, Gonzalo Otazu, Anthony M Zador. The paper is available online at http://www.nature.com/neuro/journal/vaop/ncurrent/scriptbs/nn.2211.html

Source: Cold Spring Harbor Laboratory

Emotion and scent create lasting memories — even in a sleeping brain

When French memoirist Marcel Proust dipped a pastry into his tea, the distinctive scent it produced suddenly opened the flood gates of his memory.

In a series of experiments with sleeping mice, researchers at the Duke University Medical Center have shown that the part of the brain that processes scents is indeed a key part of forming long-term memories, especially involving other individuals.

“We can all relate to the experience of walking into a room and smelling something that sparks a vivid, emotional memory about a family member from years or even decades ago,” says Stephen Shea, Ph.D., the lead author of the study published in The Journal of Neuroscience. “This research sought to understand that phenomenon on a cellular level.”

The researchers examined how strong memories are formed by creating new memories in the minds of mice while under sedation and monitoring their response to a memory-inducing stimulus afterwards, when they were awake.

“Our work is unique because it allows us to examine the cellular make-up of a memory, evaluate how the neurons change when a memory is formed and learn how that memory affects behavior,” Shea adds.

The researchers created memories by stimulating the release of noradrenaline, a chemical present in the body during strong emotional events ranging from excitement to fear.

Previous studies have established a link between noradrenaline and the formation of enduring memories, especially during intense social events such as mating and childbirth. In mice and humans, the presence of noradrenaline also creates changes in the odor processing center of the brain, called the olfactory bulb.

“When an animal forms a strong memory about another, it is reliant on odor cues and noradrenaline. Both need to be present at the same time in order for the memory to be formed,” Shea says. “Long-term memories created under these conditions often result in a permanent change in behavior.”

The Duke team administered anesthesia to a mouse and stimulated the release of noradrenaline with an electrode while wafting the scent of either food or the urine of another mouse under the nose.

“We wanted to see if these two elements – noradrenaline and odor – present at the same time were the key ingredients needed in the recipe for creation of memory – this is a concept that had not been directly tested before this study,” Shea says. “In essence, we recreated the chemical reaction that would occur when the mouse experiences a social event, such as giving birth,” Shea says.

Researchers knew they could observe brain activity in more detail when the mouse was under anesthesia. If awake, the mouse would be forming memories from the surrounding environment. “When the animal is asleep, you can watch neurons in the brain rewire to store a memory and once awake see what the mouse learned even though it was asleep when the memory was created.”

What they saw was an approximate 40 percent reduction in neuron activation after triggering the noradrenaline release – suggesting that a memory of the odor had been formed.

A day later, after the mouse was awake, the team observed changes in behavior in response to the scents, showing that they remembered the smells from when they were asleep.

“This work may have implications for furthering our understanding of how long-lasting memories are formed that are important to social bonding,” says Richard Mooney, Ph.D., co-author and associate professor of neurobiology.

Source: Duke University

New Exercise Study, Cool Quote and in AZ this Weekend!

Very interesting study below from Dr. Kraemer and friends. Once again, it shows that animal studies tend to not match human studies, but those little critters are so much easier to study than humans!

While this study shows that testosterone did NOT change, this only applies to the specific exercise they used and was an acute study, so it did NOT look at any changes in protein synthesis (building muscle). We know from many other studies that lifting weights helps build muscle and strength, but the exact mechanism is pretty complicated.

Effect of Resistance Exercise on Muscle Steroidogenesis.

Vingren JL, Kraemer WJ, Hatfield DL, Anderson JM, Volek JS, Ratamess NA, Thomas GA, Ho JY, Fragala MS, Maresh CM.

J Appl Physiol. 2008 Oct 2. [Epub ahead of print]

University of Connecticut. Circulating testosterone is elevated acutely following resistance exercise (RE) and is an important anabolic hormone for muscle adaptations to resistance training. The purpose of this study was to examine the acute effect of heavy RE on intracrine muscle testosterone production in young resistance trained men and women. 15 young highly resistance trained men (n=8; 21+/-1 years, 175.3+/-6.7 cm, 90.8+/-11.6 kg) and women (n=7; 24+/-5 years, 164.6+/-6.7 cm, 76.4+/-15.6 kg) completed 6 sets of 10 repetitions of Smith’s machine squats with 80% of their 1-repetition maximum. Before RE, and 10 min and 70 min after RE, muscle biopsies were obtained from the vastus lateralis.

Before RE, after 3 and 6 sets of squats, and 5, 15, 30 and 70 min into recovery from RE blood samples were obtained using venipuncture from an anticubital vein. Muscle samples were analyzed for testosterone, 17beta-hydroxysteroid dehydrogenase (HSD) type 3, and 3beta-HSD type 1-2 content. Blood samples were analyzed for the glucose and lactate concentrations. No changes were found for muscle testosterone, 3beta-HSD1-2, and 17beta-HSD3 concentrations. However, a change in protein migration in the Bis-Tris gel was observed for 17beta-HSD3 post-exercise; this change in migration indicated ~2.8 kd increase in molecular weight.

Conclusion: These findings indicate that species differences in muscle testosterone production may exist between rats and humans.

In humans, muscle testosterone concentrations do not appear to be affected by Resistance Exercise. This study expands on the current knowledge obtained from animal studies by examining resting and post-exercise concentrations of muscle testosterone and steroidogenic enzymes in humans.

Cool Quote
“Only in the absence of certainty can we have open-mindedness, mental flexibility and willingness to contemplate alternative ideas.”

—Robert Burton from “The Certainty Bias”

Charles Staley’s Training Summit
I am off to Charles Staley’s Training Summit this weekend. It will be a short trip as I fly out Friday evening and then back on Monday. I am excited about seeing some people that I have not seen in a long time. I will be crashing in a room with Dave Barr, so that will be a trip! Be sure to check out his products the Anabolic Index books HERE (I get no money for any sales of his books and I do recommend them as I have both).

Charles Staley’s Training Summit
Sunday, October 18 &19th, 2008
Scottsdale, AZ

If you are going to be there, please come up and say hi to me! I still need to find a place to crash on Sunday night, but I am sure something will work out.

The agenda (which may change at our discretion) is as follows:

Day 1 Oct 18th

8:00 AM Charles Staley
10:30 AM Phil Stevens
11:45 AM Lunch
1:00 PM Cassandra Forsythe
2:15 PM Robert Fortney
3:30 PM David Barr
4:45 PM Christopher Drummond
6:00 PM Optional Dinner

Day 2 Oct 19th

7:00 AM Dr. Lonnie Lowery
8:15 AM Tim Larkin
9:30 AM Luiz Da Silva
10:45 AM Lunch
12:00 PM Joe Micela
1:15 PM Anthony Almada
2:15 PM Joe Marsit
3:30 PM Q and A Roundtable

It will be a blast and I am looking forward to it. I will provide updates most likely once I return, so stay tuned!