Heretics in the High Country: Muscle Growth (Hypertrophy) Research from Dr. Lonnie Lowery

Dr Lonnie Lowery and Me
One of the great things I love about my job is that I get to talk to really smart people. One of those uber bright guys is Dr. Lonnie Lowery. Not only is Lonnie a PhD and an RD, he has spent a lot of time under the bar in the gym too.
Below is a great article on some brand new research on how to get bigger muscles (muscle hypertrophy), effects of cortisol, fat burning drugs, and set new personal records in the gym.
Be sure to check out the bio below and Dr. Lowery and friends on Iron Radio. It is an awesome podcast that you will love.
Take it away Dr. Lowery
Heretics in the High Country: Muscle Growth (Hypertrophy) Research from Dr. Lonnie Lowery
Not all scientific conferences are of interest to strength athletes. Sometimes I find myself wading through oceans of obscure biochemistry or data with unsure applicability. Sometimes the topic matter veers too far into food and nutrition, or some clinical treatment, with no immediately apparent implications for those who are laser-focused on bigger guns or a broad back. But when I go to ski country in Barrie, Ontario in late January each year, I expect cutting edge science and an element of controversy that is sure to intrigue most bodybuilders. This year I saw some early data that seemed absolutely heretical; if the physiology and nutrition labs up there weren’t absolutely world class, I wouldn’t even have sat through some of the lectures. Some of the data and audience discussion flatly flew in the face of what many of us have long-accepted.
As a preview, here are some of the topics:
· Cortisol: friend or foe to body fat?
· New insight into satellite cells and muscle size
· The optimal number of sets beyond which one is wasting time
· The pros and cons of clenbuterol
· Why women are tougher than men
· Stacking stimulant drugs for maximal performance and alertness
· The importance of insulin compared to leucine in muscle gain
· The single best training intensity for muscle hypertrophy
If you’re interested, read on for a brief synopsis of some of the outside-of-the-box thinking I saw and what it might mean to scientific training recommendations in coming years. Of course, not every little study warrants an immediate change in your training or eating regime; nonetheless, I‘ll make some speculative or clarifying comments after each section as food for thought. Whether or not a particular study is revolutionary or game changing, having new knowledge is always good in my opinion.
Cortisol: friend or foe to body fat?

Dr Lowery and the Mighty Fortress
Glucocorticoids, as stress hormones, have long been known to increase lipolysis (fat breakdown and mobilization) and yet cause fat deposition on the torso. This study helped explain this seeming contradiction. It revealed how basal concentrations of corticosterone (think “rat cortisol”) enhance certain lipolytic enzymes in adipose tissue (which sounds good for leanness) but high concentrations induce fat cell hyperplasia (multiplication) over time. If the same holds for humans – and it probably does (consider the appearance of Cushing‘s Syndrome patients) – I personally don’t want high levels of stress causing new fat cells to slowly start appearing across my torso. Further, these researchers suggested that a high-fat diet (they weren’t specific about which type of fat) doubled corticosterone in rats. To me, this offers some insight into why stressed-out, fast food-swilling Americans (and Canadians) are sporting giant bellies and uni-pecs.
What this could mean to you: We now have even more understanding of why cortisol in excess (which is elevated by emotional stress, coffee, potentially diets high in total fat, and overtraining) is not the friend of the physique athlete. Keep in mind that the data above are from rats, not humans, but that this is indeed a valid model that offers solid information which is probably relevant to humans. It looks as though cortisol – although necessary at modest concentrations – could lead to more detriment than simply degrading muscle tissue or temporarily storing fat in certain anatomical regions; it could literally multiply one’s number of fat cells making future dieting attempts harder.
New insight into satellite cells and muscle size

Dr Lowery teaching a Staley’s Seminar 2008
Exercise,especially eccentric lifting (“negatives”) not only causes muscle soreness but is also great at activating satellite cells. Among other things, these are cells that lie among the mature muscle fibers and “wake up” to donate their nuclei to help maintain a larger muscle fiber. They can also fuse together themselves into a new entity. This research group was showing a new lab technique that can quickly count how many muscle building satellite cells get activated in response to a new anabolic stimulus. In a matter of hours this automation will offer valid results, eliminating the weeks and weeks of forcing a hapless grad student to physically count stained muscle samples under a microscope.
What this could mean to you: New training techniques can now be tested for this aspect of hypertrophy (increasing muscle cell number or muscle cell “permanent size” in a sense) at a realistic pace. This could mean less speculation and more rapid progress in the science of muscle gains. Cool.
The optimal number of sets beyond which one is wasting time

Dr Lowery looking very professosorial
A graduate student from Stu Phillips’ noteworthy lab shared insider data that three sets appears to maximize the protein synthetic response in a muscle. Earlier work from a partner lab showed that six sets were no better than three and these grad students were taking it a step further: looking at three sets versus one. Using a 70% of one-rep max (moderately heavy weight) protocol, combined with 20g whey protein immediately post-exercise, their data was such that significant elevations in fractional synthetic rate (read “anabolism”) was possible at 5 hours post-exercise from either three sets or one set, but that only the three set protocol still had anabolism kicking at 29 hours post-exercise. Note that although they’re looking at just synthesis here and not breakdown, it is muscle protein synthesis that’s largely responsible for net gains post-workout.
What this could mean to you: If you are the kind of person who performs many many sets for each muscle group in the gym, it might be worth planning certain mesocycles to purposefully cut back on the total number of sets you do, perhaps down to just three per muscle group. This is strictly from a protein synthetic (muscle size) perspective. This is not to say that extra sets might not be good for overall leanness of other benefits. Also note that they used one particular, common intensity level (70% of max) and other intensity levels may alter the picture to some extent. I think this study does make one wonder how much time he or she might be wasting in the gym if strict bodybuilding (size gains) are the immediate goal.
The pros and cons of clenbuterol
Yes, there was actually a study on the usually taboo bodybuilding drug clenbuterol – in rodents. The inhumanly large doses often given in animal studies were again present here: 30mg per liter of drinking water. The study revealed a decrease in mitochondrial (aerobic) function, including less fat oxidation (“burning”). There was also a rise in glycolysis (carb breakdown) capability. It was all suggestive of a switch toward a faster muscle fiber type. What struck me during this session was a comment from the audience (to paraphrase): “So, this stuff is bad. If it is given clinically to patients, we need to warn them of the aerobic declines and risk of fatigue.” After witnessing hard data on increased muscle mass and a significant drop in body fat, the main conclusion from this attendee was “so this stuff is bad”? Maybe I’m biased toward bodybuilding but I for one saw a few pros among the cons.
What this could mean to you: If you are someone who has used clenbuterol or are considering it, this study suggests that you may shift toward a faster, more carb-focused muscle fiber type, possibly meaning less aerobic (endurance) capacity. Of course, this is an arena where self-administering bodybuilders and even Hollywood celebrities probably know more on a practical level than do the cautious scientists: At tolerable microgram (not milligram) doses, body fat can indeed decrease dramatically (for gross calorie expenditure reasons) and strength can climb significantly. (Sheer muscle mass is not altered very much at human-tolerated doses.) In any case, I sure hope researchers start giving clenbuterol a closer look in humans before any stigma creates a bandwagon of negativity that‘ll keep its possibilities in the dark forever.
Why women are tougher than men
Many readers know that women exhibit less post-exercise muscle damage than men. Estrogen is a big part of this. These researchers went further, showing data that exercised women also exhibit less fatigue during recovery days than men do – at least when it comes to “lighter intensity“ (lower frequency) testing. The study had an almost comical title: “The effects of sex on human skeletal muscle fatigability” and used repeated bouts of electrically-stimulated isometric knee extension exercise as the initial stressor. They concluded: “These results suggest that females are more fatigue resistant than males and are able to recover force at an accelerated rate following an acute bout of intermittent isometric exercise.” Wow.
What this could mean to you: If you’re a woman, this talk provided evidence that not only do you resist muscle damage better than guys but in some respects, you outperform them. I’ve often wondered why we don’t see a sport designed around less intense but more punishing, ongoing demands. It looks like women would dominate such an event.
Stacking stimulant drugs for maximal performance and alertness
An ironically calm student was sharing a proposal to stack caffeine (in an extra strength military gum) with a drug called modafinil to max-out alertness and performance among emergency workers and/or military personnel. Earlier work from his mentor suggested 22% increased time to exhaustion with modafinil and other data suggest around 5-30% improvements on cognitive tests of memory, reaction time, etc. after sleep deprivation. We all know caffeine has similarly energizing effects. The researchers weren’t very concerned that a dose of caffeine typically peaks at 60 min. (entry into blood is fast, starting in about 5-15 min.) while modafinil doesn’t peak until 120 minutes; both drugs have lingering improvements for a few hours.
What this could mean to you: Although at the proposal stage, this talk offered information on the pharmacokinetics (onset of action, blood levels over time) of these stimulant drugs and how they might “stack“ (additive effects). I may live under a rock, but I haven’t heard much about modafinil before. It’s cognitive and physical performance benefits are intriguing. Stay tuned for future results.
The importance of insulin compared to leucine in muscle gain
Many of us know that insulin and the amino acid leucine both stimulate the protein synthetic “mTOR pathway” in skeletal muscle. This group wants to see just how crucial the insulin aspect really is. They compared the anabolic effects of leucine in mice with and without pancreases (surgical removal in half of the animals). What happened? The normal pancreas-sporting (and thus insulin-capable) animals responded as expected to leucine, with a full anabolic response. The muscles of the insulin-lacking critters were not uniform in their ability to respond to leucine, however. It looks like different muscle groups (probably due to slow- versus fast-twitch fiber differences) react differently to leucine when insulin isn‘t around. Some can respond (at least on some level) and others cannot. Particular aspects of the mTOR pathway responded well in slow twitch muscle fibers but not in fast twitch fibers. Of course, fast twitch (and moderately fast-twitch) fibers are what strength athletes typically value for size and strength, so this suggests insulin remains an important part of the picture for us.
What this could mean to you: If you’re an endurance athlete or just interested in maintaining slow-twitch muscle fibers, leucine in a fasted state seems like an effective strategy for you. Of course it’s very preliminary (i.e. new research) but it will be interesting to see if endurance guys or those trying to hold on to endurance muscle fibers can get away with leucine-only meals at otherwise unfed times of the day. (I realize some dieting bodybuilders already try this.) If you‘re all about fast twitch muscle fibers, however, it currently looks as though regular meals throughout the day maintain insulin levels that help leucine induce fast-twitch-specific growth. A final caveat: even in a fasted state you have basal (“single digit”) concentrations of insulin and not essentially zero insulin as in the pancreas-free animals; it’s an experimental model trying to tease apart mechanisms. I for one am very interested in how important leucine is versus insulin. Perhaps one day we’ll see a consensus that humans can get away with leucine-only meals during periods of fasting.
The single best training intensity for muscle hypertrophy
This presentation from Nick Burd in Stu Phillips’ impressive lab at McMaster University was almost blasphemous. Here’s the title: “Low intensity-high volume resistance exercise promotes greater anabolic signaling and myofibrillar protein synthesis versus traditional and work-matched resistance exercise paradigms”. Come again? I’m going to get bigger with light weights? It appears so, based solely on protein synthesis data. These guys compared heavy, 90% of one-rep max lifting (subjects failed at five reps) with a work-matched set at just 30% of one-rep max (subjects were stopped at 14 reps) and finally a set to failure with 30% of one-rep max (subjects failed at 23 reps). Although protein synthesis was up at four hours-post exercise in all groups, muscle protein synthesis was still elevated at 24-hours only in the 30% to failure group. Longer periods of lingering heightened protein synthesis sound good to me.
What this could mean to you: You may benefit from (at least considering) periods of the year in which you cycle-in light, 30% of max lifting exclusively to max-out muscle size. This may be doubly true if you’re an intensity hound like me and haven’t done a set over 8 reps in ages. I was so intrigued by the protein synthesis data and with subsequent talks with Nick on www.IronRadio.org, I’m trying a “two week light (30%) / two week heavy (85-90%)” type of periodization. (A recent and timely snowboarding accident sort of forced me away from heavy lifts for a couple weeks anyway.)
I’m still trying to get my head around barbell curls with an empty Olympic bar and benching with 95-135. I’ve got to admit, this one is tough to swallow but a combined effort from universities like McMaster and Nottingham has me suspending my disbelief until their planned training study is completed. It’s then that we’ll know with more certainty whether the very light, roughly 23-rep per set protocol will be as effective or even more effective than the heavy training for mass gains.
Dr. Lonnie Lowery is a former regionally-competitive bodybuilder, exercise physiologist and nutrition professor who travels to scientific conferences often, looking for new data and new ideas that may progress the field of bodybuilding and sports nutrition. He can be reached and listened-to by way of www.IronRadio.org.
Thanks again Dr. Lowery!
Comments? Do you want to see more research and Dr Lowery again? If so, drop some comment love and let us know!
rock on
Mike T Nelson
Sign up to my RSS feed and any time I update a post, you will know about it instantly!

You can also help out by hitting this 
