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Science-type stuff related to diet, training and comp prep

Tatyana

Elite Mentor
Bodybuilder Nutrition Roundtable
By Josh Beaty

The following interview was conducted by Josh Beaty with Layne Norton, Jamie Hale, Alan Aragon and Will Brink. Sit back and enjoy a very informative discussion.

J Beaty: The big focus in hypertrophy research lately has the mtor pathway. What impact does this research have on bodybuilders?

L Norton: The mTOR pathway is a major cellular anabolic pathway that is responsible for much of the anabolic response to nutrient stimulus. In adult subjects, amino acids (specifically leucine) are responsible for triggering mTOR activation. mTOR essentially acts as a 'leucine gage.'

If leucine levels increase, mTOR becomes active & activates other components of the protein synthetic pathway because it high leucine levels indicate a fed state and ample amino acids are present for protein synthesis to occur.

If leucine levels drop, mTOR becomes less active as it senses that there are not enough amino acids & energy to continue protein synthesis. mTOR is also sensitive to total energy intake and if total energy drops too low, then mTOR becomes less activated.

This research indicates what many bodybuilders have known for sometime: if you're goal is to build muscle mass, make sure you provide a diet with ample calories and ample amino acids.

W Brink: I'm not going to have a great response to this question as it's really not my area of focus or expertise. As far as I know, there is no practical application of the mTOR pathway to athletes at this time. That is to say, I don't know of any particular change an athlete can make to their approach that will profoundly alter this pathway to give any advantages. It may also simply be that the approach we know is optimal for strength and or LBM - loading, volume, tempos, etc - are already the best we can do as far influencing mTOR is concerned. Like so many areas of research that may have applications to wasting diseases and such, such as myostatin, it's more of an intellectual exercise versus having any real practical application to athletes at this time, non pharmacologically speaking at least.

There is no doubt that the intensive research going on that examines the signaling events that are activated by aerobics or resistance training will explain how muscle adaptations take place, and pharmaceutical interventions are a focus of many researchers, but I am unaware of any direct application an athlete can incorporate in their training or diet that will be an improvement on what we already know. The other guests on this roundtable may be more up to date on the literature and have a better answer! I'm a bit jaded at this point in that I don't get particularly excited or interested in the latest holy grail of signaling molecules until some real practical application shows itself.

J Hale: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a key role in anabolism. MTOR stimulates cell growth by phosphorylating p70 ribosomal S6 kinase (S6K) and eukaryote initiation factor 4E-binding protein 1 (4EBP1).

mTor is stimulated by resistance training, insulin and Leucine (bcaa). When mentioning mtor pathway it is probably necessary to mention there are also other kinases that inhibit anabolism when activated. In particularly I am referring to the Ampk/ Akt mtor switch.

Basically when Ampk is elevated protein synthesis is inhibited. Ampk (5 Amp-activated protein kinase) is a heterotimeric serine/ threonine kinase. Ampk is often referred to as a cellular fuel gauge. Ampk is activated by endurance exercise, elevated levels of cellular AMP, hypoxia, glucose deprivation and ischemia. When Ampk is elevated cellular fuel regenaration is top priority, while pathways the consume energy are inhibited (ex: protein synthesis).

This applies to athletes as we know various conditions stimulate these pathways. By optimizing stimulation of anabolic pathways and minimizing catabolic pathways (intensity and duration of) we obviously optimize performance and physique benefits. Does t his really tell us any more than we already knew (proper resistance, protein intake and sufficient cals maximize growth)?

For myself and other practical scientists I feel like this info is very helpful with enhancing our knowledge of what's going on at a cellular level. It also helps with program design and recognizing at a molecular level factors that affect anabolic and catabolic pathways. As far as the typical bodybuilder or trainee is concerned knowledge of mtor pathway may or may not be beneficial. Depends on bodybuilder and how serious he is about furthering his knowledge concerning physique and performance.

A little off the subject alcohol intoxication has also been shown inhibit mtor pathway. Studies involving mtor pathway also are important in treating muscle wasting disease.

A Aragon: First off, I'd like to thank Jamie for inviting me to this roundtable. It's definitely an honor to be among a carefully chosen few. If I come off too long-winded in this, it's because I made Jamie wait for months for me to participate, so I figured I might as well show some gratitude and babble for aeons

Ah, the good ol' phosphatidylinositol 3-kinase-mammalian target rapamycin signaling pathway. There, that should take care of any lack of technical jargon I contribute to this roundtable right off the bat. mTOR research is not likely to have a significant impact on the furthering of what bodybuilders can physically achieve, but it certainly is giving us some understanding of how these achievements occur. Let's face it, the majority of the biggest, most ripped guys on the planet haven't even heard of mTOR.

The first thing most folks think about in relation to mTOR and bodybuilding is leucine, and rightly so, since leucine phosphorylates/activates the downstream metabolites of mTOR.

But alas, there’s a caveat. A lot of folks who place an excessive focus on leucine will indiscriminately dose the hell up on it. They’ll tank down isolated leucine, BCAA, and/or whey, thinking they’ve found the ticket to net anabolism. There’s also this false implication that whey, being higher in leucine than casein, is superior. Not true, at least according to the current body of research, which indicates that casein, or at the very least, a blend of casein & whey, is superior to whey alone for affecting a number of parameters bodybuilders care about.

What people seem to constantly forget is that net gains in muscle are the result of not just protein synthesis, but the inhibition of protein breakdown.

Casein’s antiproteolytic effect is more profound than whey or leucine’s protein-synthetic effect. Hence its lead spot in the current body of research. The name of the game seems to revolve back to the old cliché of mixing things up, and achieving a variety of sources of protein from whey to casein, to flesh, to the range of sea & land flesh, to Asian women. Just kidding, I wanted to make sure everyone was awake. In sum, mTOR activation is just a piece of the puzzle. Thus, the beloved leucine is a mere cog in the complex engine of variables that cause net gains in muscle.

J Beaty: What are your thoughts on the reemergence of the macronutrient food combining theory where carbs shouldn't be mixed with protein/fat meals and fat shouldn't be mixed with protein/carb meals?

L Norton: This is a rather simplistic way of looking at nutrition and focuses mainly on insulin rather than looking at the whole picture. While it probably isn't a good idea to have a really high carb meal with a really high fat meal, there's nothing wrong with having moderate amounts of both.

W Brink: like many theories, it comes around every few years or decades and gets people all worked up over their food. Problem is, it's no more true today then it was when the book Fit for Life by Harvey and Marilyn Diamond came out. The theory had no scientific support then and it has none now. Humans have been combining fats, carbs, and proteins quite successfully for eons and as omnivores, are perfectly capable of digesting mixed meals.

J Hale: You are probably referring to the theory that assumes insulin and blood levels of fat should never be raised at the same time. This theory assumes that insulin is the key contributor to obesity. There are a few things wrong with this line of thought.

One of the key problems is not recognizing something called Acylation Stimulating Protein. Acylation stimulating protein (ASP) is a hormone produced by adipocytes and is of importance for the storage of energy as fat. The consumption of dietary fat alone can increase fat storage. Dietary fat affects fat cell metabolism with NO INCREASE in insulin.

Some studies have indicated dietary fat loading found a decrease in HSL (hormone sensitive lipase) and an activation of fat storage despite no increase in insulin. The key reason was activation of acylation stimulating protein (ASP) which is activated by the presence of chylomicrons (basically packaged triglycerides that are found in the bloodstream after the meal). ASP increases glucose uptake into the fat cell, increases insulin release from the pancreas and has been described as 'the most potent stimulator of triglyceride storage' in the fat cells by numerous scientists.

Another problem with this line of thought is some proteins causes substantial elevations in insulin. Minimal levels of insulin affect fat cell metabolism. Basal levels can decrease lipolysis by 50%. Another consideration is most bbers are eating every 2-3 hrs so nutrients are still absorbing from previous meals; therefore previous meals interact with the blood levels of nutrients of the present meal.

A study conducted by Golay and colleagues compared a diet with equal macronutrient content and substrate percentages; that differed only in how the substrates were consumed (mixed diet vs. food combining). The results were no difference in weight loss. Here are the exact results reported by the researchers.


“Results: There was no significant difference in the amount of weight loss in response to dissociated (6.2 +/- 0.6 kg) or balanced (7.5 +/- 0.4 kg) diets.

Furthermore, significant decreases in total body fat and waist-to-hip circumference ratio were seen in both groups, and the magnitude of the changes did not vary as a function of the diet composition. Fasting plasma glucose, insulin, total cholesterol and triacylglycerol concentrations decreased significantly and similarly in patients receiving both diets.

Both systolic and diastolic blood pressure values decreased significantly in patients eating balanced diets. The results of this study show that both diets achieved similar weight loss. Total fat weight loss was higher in balanced diets, although differences did not reach statistical significance. Total lean body mass was identically spared in both groups.

CONCLUSION: In summary at identical energy intake and similar substrate composition, the dissociated (or 'food combining') diet did not bring any additional loss in weight and body fat”. Actually looks like a slight increase in fat loss with mixed diet (balanced diet).

We have tons of anecdotal evidence that denies the need for food combining. We have evolved on a mixed diet. With all of that said food combining may be beneficial regarding calorie control. Once you eliminate an entire macronutrient from a meal this can go a long way in decreasing total caloric intake. If this is what you need to do to control energy intake feel free to do so.

A Aragon: I think that the “P+C & P+F = okay but avoid C+F” principle is idiotic when applied across the board without any contingencies or attention to individual situations. For example, if someone is low-carbing for whatever reason you choose (pathological carbophobia included), they might be done with their carb intake by early afternoon, and their meal construction for the rest of the day is gonna be primarily P+F by sheer default. In the latter scenario, I can see the principle being legit.

However, when issued blanketly, it’s usually based upon the wacky idea that you don’t want fat floating around systemically when your insulin levels are high, because this will magically shift your net adipose balance in the positive. That’s false for a number of reasons.

First of all, the insulin response generated by CHO + fat generally depends upon the degree of the fat’s saturation. Unsaturated fats tend to either lower insulin response of the coingested carbs, or not affect insulin response at all.

Coingested sat fat, on the other hand, tends to raise insulin response, and can do so in a synergistic fashion. But then the question becomes, so what? Others have mentioned the more direct role ASP has in TG synthesis, and indeed, insulin is more of a multi-tasking anabolic/anticatabolic agent in comparison to ASP, which seems to exist solely to pump up the adipocytes. And of course the kicker is that ASP can do its TG-synthesizing magic in the sheer absence of insulin.

And then there’s energy balance… In a negative energy balance, insulinogenesis is wonderful thing, as long as the training stimulus & nutrition is there to work in concert with it to preserve LBM.

In the condition of a positive energy balance, trainees in general are gonna have a lot more carbs to throw around, so this makes the whole separation thing even more dicey. Which meals should be carb-free or fat-free in order to pull of this magic separation tactic, and why? The logical answers to this question simply don’t exist.

If you were to actually adhere to the mechanics of separation, you’d actually be hard-pressed to maintain a stable insulin profile – which is ironic, since the control of insulin is what “separatists” are aiming for. Regardless of all the previous points, the fundamental shortsight is that digestion/absorption of meals overlap each other when meal frequency is as high as it should be. Therefore, attempting strict separation of the macros = kidding yourself. Not to mention, most foods in nature are a combo of all the macros to begin with.

J Beaty: Some "experts" claim coffee should be avoided because of the insulin response that ensues, in lieu of the recent studies that have come out on coffee and blood glucose what is your stance on this?

L Norton: While acute caffeine ingestion may impair glucose tolerance, studies suggest that long term caffeine ingestion actually lowers the risk of developing type II diabetes(1). In my opinion there is probably not enough information at this point to say definitively one way or the other, but I believe caffeine is fine in moderation, much like many other compounds, if you don't abuse it there is little to worry about.

W Brink: As far as I am concerned, there is no sunshine without coffee! Kidding aside, it's essential to separate an effect seen in the lab and the larger picture. Insulin is an essential hormone in the pathogenesis of various afflictions. It's also a hormone we can't live with out, and there is not a direct insulin spike = terrible things happen equation, no matter how hard people attempt to paint insulin as the mother of bad guy hormones. Do we see a correlation between coffee and obesity?

No. In fact, a study I was just reading found decreased rates of type 2 diabetes in men who drank coffee. If coffee had a negative effect on whole body glucose metabolism, that is it elevated insulin for long periods of time, or decreased insulin sensitivity to a great degree, or what have you, we would not see this reduced risk of type 2 and coffee consumption.

If anything, it appears to have positive effects on glucose metabolism. There are several studies that suggest coffee reduces the rates of metabolic syndrome, which is yet more proof that it's far too over simplistic to paint coffee as a negative due to one outcome, in this case affects on insulin.


There have also been a bunch of other potential benefits to coffee drinking, so as usual, it's about balance and common sense. A few cups of coffee per day are fine, 10 cups a day, probably not such a good idea. It's also possible that coffee may be contra indicated for some populations, but perfectly fine for the majority of people.

J Hale: I am assuming you are referring to caffeinated coffee. Caffeine increases the release of catecholamines (adrenaline, nor-adrenaline, dopamine). Adrenaline hormones increase FFA mobilization from fat cells. Dopamine increases feelings of pleasure and well being. Increased FFA blood levels due to high concentrations of adrenaline hormones induce insulin resistance. The effect is generally short term. The severity varies among individuals. We have to ask ourselves is insulin resistance a bad thing? Not always just depends.

Fat cell insulin resistance means insulin can’t inhibit fat breakdown or promote nutrient storage in fat cell. Muscle cell resistance means the muscle cell can’t uptake glucose therefore it use an alternative source of fuel FFAs. The glucose is utilized by the brain and nervous system and other tissues that need it. During times of dieting and low carbs insulin resistance is not necessarily a bad thing. When eating excess calories it generally is a bad thing.

With that being said athletes have used coffee for years as a performance enhancer. Endurance athletes often ingest coffee because of its benefits on fat metabolism. Some studies suggest coffee may actually reduce chance of developing type 2 diabetes. Coffee contains other substances which have also shown health benefits. I recommend coffee if your body can handle it. Some people get the shakes and just can’t seem to handle the CNS boost. There is also a big difference between drinking 2 cups of coffee and 10. Moderation is probably the key to enhancing performance and preventing any negative health consequences.

A Aragon: I’m a coffee lover, so I’ll defend it with all my might, research be damned!! But seriously, all you can do in this instance is take a hard look at the data. The anti-coffee camp says that coffee consumption contributes to insulin resistance. This is a classic case of focusing on acute effects while disregarding what really matters – the chronic effects, along with a few critical details.

This is also a case of context-confusion. Most of the work leading to this conclusion is based on obese folks using isolated alkaloidal caffeine, not coffee. So, to begin with, that pretty much takes most athletes out of the picture, who use caffeine for ergogenic purposes. They use it to increase exercise capacity, which inherently improves insulin metabolism, so pretty much the issue ends right there.

But we’re unrepentant nerds here, so we can still look at the data. Caffeine acutely raises insulin response when applied to oral glucose tolerance tests. Okay, great.. Cocoa raises insulin response when coingested with other foods, but long-term cocoa use also appears to improve insulin sensitivity.


Rewind back to coffee. Coffee’s acute insulinogenic nature doesn’t have any negative impact when studies are carried out long-term. For example, Several epidemiologic studies found that ingestion of caffeinated (and decaffeinated) coffee may actually reduce the risk of diabetes compared with those who never drank coffee. In addition, coffee was recently seen to have a beneficial effect on endothelial function, which implies cardiovascular benefit. For those not impressed by the uncontrolled nature of epidemiology & prospective studies, I challenge anyone to compile the controlled studies on caffeine and dish out the conclusion that moderate coffee consumption has negative effects on health markers.

In addition, there are non-caffeine compounds in coffee currently under investigation such as chlorigenic acid, trigonelline, quinides, antioxidants, and others that have the ability to enhance insulin sensitivity. Moral of the story: a) Athletes (and regular folks) can use caffeine and/or coffee to their distinct advantage for performance & bodycomp improvement; b) Regardless of population in question, coffee can actually improve insulin sensitivity over the long term, likely due to its various beneficial non-caffeine phytonutrients. Check out this recent review, it covers way more than I’d ever care to:

Coffee, diabetes, and weight control -- Greenberg et al. 84 (4): 682 -- American Journal of Clinical Nutrition

Beaty: What are the most ignorant dietary theories and philosophies out there that are still incorporated by the bb population?


L Norton: 1. Don't eat carbohydrates after 'X' o'clock. People believe that since they are closer to sleeping they should curtail carbohydrate intake, this is simply ludicrous. Carbohydrates at night don't make you fat; too many total calories make you fat. Additionally, if you train at night you NEED those carbohydrates to properly recover.

2. The notion that high rep ranges stimulate slow twitch fibers & low reps stimulate fast twitch fibers. The fact of the matter is that while high reps do
stimulate slow twitch fibers, SO DO LOW REPS with heavy weights.

You see your fiber types are recruited in order of need: slow twitch first, then intermediate, then fast. So as you can see, if you are lifting heavy loads for low reps you have already maximally stimulated your slow twitch fibers.

3 The notion that a specific rep ranges yields the best results. Some people believe you should only lift high reps because the pump is so important while others believe that you should only do low reps with heavy weights because training this way maximally activates all fiber types. The reality is ALL rep ranges have benefits and they should ALL be utilized to achieve optimal results.

W Brink: I actually think things in this area have improved greatly. The advent of the Internet has probably helped a great deal there. It seems that almost everyone at this point understands and appreciates the basics, which is you need adequate protein, fat, and carbs to gain lean body mass. For example, the ultra high carb low fat diets popular back in the day have all but disappeared. Most people know they need some fat in their diet, know they need some EFA's, and know the basics between low GI and high GI carbs, and so on. That's not to say there is not confusion and questions about all of the above, but as a general rule, I think most people have at least a basic understanding better then they did say 10 years ago. The area of real ignorance that seems to persist no matter how hard people like me attempt to counter it is in the area of supplementation. Supplements seem an endless source of confusion and scams.

J Hale: A couple that come to mind immediately are the assumption bbers trying to get lean should not eat fruit and bbers over-reliance on supplements.

The fear of fruit comes from studies suggesting 50gms or more of fructose per day can upregulate de novo lipogenesis (fat synthesis in liver), increase blood triglycerides, and induce insulin resistance. Keep in mind fruit generally contains 6-7 gms of fructose.

That means it would take a bunch of fruit to get 50gms of fructose. The high consumption of fructose seen in most studies is generally due to the consumption of high levels of high fructose corn syrup (processing where varying portions of are converted to fructose). Another consideration is fructose causes minimal insulin secretion. Even if fructose consumption was high enough to elevate fat synthesis lack of insulin would probably result in increased fat oxidation. Assuming calorie deficit it probably all evens itself out at the end of the day. Eat fruit it's nutritious and generally low in calories.

Bodybuilders have forgotten the meaning of supplementation. It means supplement the training and nutrition regimen. Be sure your training and nutrition are efficient before spending hundreds of dollars on supplements. Some supplements are beneficial and more convenient than fixing food all the time. They (very few) have a role in physique and performance enhancement when used in the appropriate manner.

A Aragon: The bodybuilding population as a whole is carbophobic. And I’m talking about carbs in all forms. Don’t get me wrong, in the event that calories must be reduced, or reduced to a heightened degree such as pre-contest, its plain stupid to incur a protein deficiency.

But in general, bodybuilders are just plain afraid of carbs. Hell, only a small percentage of bodybuilders are up on the science of the matter, so the rest are victims of the asinine mass media just like every other layperson. Would it alarm you to know that the majority of “serious” recreational and competitive bodybuilders are literally afraid to have carbs in their final meal? Imagine that, they’re mortally afraid of muscle loss while simultaneously being afraid of a key tactic that can enhance lean mass preservation. True story.

On those same lines, you have the carbophobes who have a mortal fear of insulin, yet megadose highly insulinogenic BCAA during training. What a lot of folks don’t realize is that amino acids can elicit insulin responses comparable to pure glucose. On those same lines, you have folks who are stuck on acute substrate utilization during training. I was talking to a friend of mine Alwyn Cosgrove the other day (Braveheart is still a cool movie even though Mel lost it), and the following realization dawned on me as a matter of what we discussed:

Caring about how much fat is burned during cardio makes as much sense as caring about how much muscle is built during weight training.

I recently had a rather public debate, and by all counts absolutely destroyed my opponent’s argument that fasted cardio was across the board better for fat loss than fed cardio. He was focused on acute effect (during & shortly after exercise), not long-term effect, or anything close to the research blatantly refuting his stance. More reading on the subject of “fat burning” cardio can be found here:

Articles - AlanAragon.com

This brings me to another rant.. Folks with any intention to use being published in peer-reviewed journals as some sort of credibility crutch have another thing coming. People of sound mind don’t give half a rat’s ass where someone’s been published.

We don’t care what degrees you have, we don’t care how many hours you’ve spent in a classroom listening to the drone of professors who have never driven near the gym. I can tell within 5 sentences whether someone is worth listening to or not. Paper credentials are fine and dandy, but they mean nothing compared to the ability to reason, comprehend, and synthesize ideas and information. In the realm of bodybuilding, academic degrees also must take yield to experience using these abilities firsthand either on yourself and/or in working with clients – that’s the most relevant “lab”, as far as I’m concerned.

This brings me to the duality of scientific research. We as “thinking” bodybuilders rely on research to mold our beliefs, support our stance on controversial issues, and ultimately, dictate our protocols. Science indeed is infinitely more reliable than random opinions of buff dudes with hyooge byceptz & rippt abz. But unfortunately, even science is puppeteered by money and politics. For example, whoever pays for the study is gonna get the results they want.

That’s brutal but true. The best we can do in any given debate is see whether controlled research over time is able to produce counter-results from the opposition (which hasn’t yet occurred in the case of the anti-milk camp, HAH!), or whether relatively non-vested replication and further validation ensues. It goes without saying that all research must be scrutinized for strengths and weaknesses.

Which brings me to another rant… I can’t stand it when anyone picks a stance and makes a bulletproof commitment to it, turning a blind eye to any opposing data, regardless of its legitimacy. A lot of guys in this industry seriously handicap themselves by assuming a singular position that they feel defines them. This is something we’re all guilty of from time to time, and it definitely impedes the growth of wisdom.

There’s more, perhaps we could cover them in another segment.

J Beaty: Who are the brightest minds in the world of nutrition?

L Norton: I'm bias since he is my graduate adviser, but Dr. Donald Layman really has a tight grasp of most facets of nutrition. He understands the biochemical details but never loses sight of the big picture and always is asking the question "how does this (insert topic) relate to the real world & how can we apply it effectively?" Dr. Peter Garlick's work on protein metabolism is outstanding as is Dr. Leonard Jefferson's. I comment on these individuals as they are some of the best in the field of protein synthesis/metabolism which is the field I specialize in. I'm sure there are many other great minds that I have left out, but I don't feel qualified to comment on experts in other areas of nutrition.

W Brink: Too many to list. Also, no matter how many people I list, someone will be left out and take it personally.

J Hale: I like numerous people in the field including Lyle McDonald, my fellow panelists for this roundtable, MJ Rennie, Kevin Tipton, and Dan Moore to name a few.

A Aragon: As far as authors go, my earliest influences were Michael Colgan and Dan Duchaine. I don’t know anyone in his right mind who lived during Dan’s rise in print media who wouldn’t name him on their list either at or near the very top. More recently, Lyle McDonald has impressed me in terms of both his books and his ongoing science & logic-based contributions to the fitness community at large. That’s the thing. A lot of guys attempt to be scientific, but they miss the boat on being logically consistent. That list isn’t very voluminous, but I’m open to suggestions. I just happen to spend way too much time on medline, and I’m sure much of the current crop of worthwhile book authors has escaped my radar.

As far as research scientists go, it would give me a headache to rattle off even a fraction of the ones whose work I’ve admired & benefited from. Peter Lemon, Kevin Tipton, David Costill, Mark Tarnopolsky, Susan Holt, Robert Demling, Xavier Pi-Sunyer, Robert Wolfe, William Kraemer, Edward Melanson, and Mark Febbraio really stand out. I’m sure that on any given moment I can think of others I missed who’ve really made an impact on my personal methods and perspectives.

Bobo of anabolicminds.com isn’t a book author or researcher in the formal sense, but he’s a bodybuilder who influenced how I view the current dogma. Almost any intelligent person who you have a lengthy heated debate with inevitably imparts some sort of wisdom upon you, and Bobo stands out in that arena.

Oh yeah Jamie, go ahead and add yourself to the list .. Readers, let me tell you that Jamie is one of the most obsessively voracious students of this game that I’ve ever met. The guy’s idea of a good time is exchanging & discussing full text articles via email.

I’m sure there are others I missed.

J Beaty: Generally speaking, what bodyfat percentage do you allow your bodybuilders to reach before beginning a lean out phase?

L Norton: It all depends upon their body fat set point. If a person is heavier by nature, then they probably need to carry a tad more body fat in order to put on muscle mass, whereas an ectomorph can probably stay at a lower body fat & put on muscle mass.

Typically I aim for a percentage range. If a person is typically around 15% I try to keep them within 13-16%, while if a person is typically 6%, I'll try to keep them within a range of 5-8%. If they fall below the range, I suggest increasing calories; if they start to go above that I temporarily restrict calories. As a rule however, no one should ever allow themselves over 20% body fat.

The more body fat one puts on, the more they will desensitize themselves to insulin, making it harder to build lean tissue. Additionally, at higher body fat levels, the body may not merely just increase fat cell size, it may start making new fat cells and once your body makes new fat cells, they are yours to keep you can't get rid of them. The long term effect of this would be an elevation of a person's body fat set point.

W Brink: For men, approx 12-14% is as high as I would let a man go. For women, around 16-18%. Both are not written in stone however. People carry their weight differently. I recall Lee Haney saying his rule of thumb was as long as he could see a hint of his abs, he was OK for an off season fat percent, but if he could not see his abs, it was time to drop some fat. I do think for people to really optimize increases in LBM and or strength, its counter productive to attempt to stay in single digit bodyfat levels year round.

J Hale: Hard to place a specific number on that value as athletes widely vary. I have seen athletes get up to 18% and have no problem getting lean when it was time. I have seen others who really seem to have problems if they get over 12-13% bodyfat. In the past I recommended that bbers didn’t get over 13%. Based on my experience I now play that by ear as it completely depends on the individual.

A Aragon: This question carries the implication that all bodybuilders must undergo separate phases. This really only applies to my clients in formal competition, where specific phases are unavoidable. For non-competitors, and even competitors to a modified degree, I prefer the “culking” approach.

This is a tongue-in-cheek term I coined which basically fuses the whole cutting & bulking cycle in to one slow, steady, refinement of the physique in terms of both size AND leanness.

This is entirely possible to achieve, but the timeline is generally a period of years rather than months. In the purest sense, culking is a perpetual process that’s linear for the most part. The typical cycle scenario is spending half the year looking like a bloated mess, and the other half looking decent to drawn. At fleeting points for only a few weeks (or days) at a time, they look great. That doesn’t sit too well with me.

Back to the question, which I’ll apply strictly to competitors. I’ll speak from the perspective of calipers since that’s my preferred instrument. Given that, I’m a huge proponent of the slow approach to competition prep. I don’t like to see much more than 1% BF drop per month, and even less than that is warranted (closer to 0.5% a month) as mid single digits approach. It stands to reason that for a 3-6 month dieting phase (depends on the individual),

I don’t recommend that guys go more than appx 3-4% above their competition level, which again varies with the individual. With calipers, some guys look good enough to hit the stage in the 3’s, younger folks with tighter/less collapsible skin often look good enough in the 4-5’s. Keep in mind that ultimately, the mirror beats the calipers.

J Beaty: In terms of nutrition, what are the biggest psychological barriers you feel bb face?

L Norton: Trying to get results too fast, either trying to lean out to quickly or trying to add muscle mass too quickly. When a person tries to lose body fat too fast, they end up sacrificing muscle mass, but when a person tries to add muscle mass too fast they end up putting on way too much muscle mass. The name of the game is patience. Bodybuilding is not a sprint, it is a marathon.

W Brink: Nutrition is such an emotionally loaded topic people often make decisions on what they eat based psychological considerations, like what their mom forced the to eat, or what their religion tells them they should eat, etc.

Classic barriers I see are people that can't accept one needs to eat some fat to lose fat and be healthy or that they need to eat additional calories if they want to add muscle and the fact that some bodyfat increases will occur. Bodybuilders are no different then regular people in that respect. In fact, they are often more neurotic then the general population which can be both an advantage and a detriment to their progress depending on how that neurosis manifests itself.

It's been my experience that half the time you are deprogramming people to get them passed all the hang ups, neurosis, and misinformation, they carry around.

J Hale: For competitive bbers one of their biggest obstacles to overcome is their fear of becoming too small. When pre-contesting dieting happens some bbers see significant decreases in bodyweight and measurements (depending of body comp pre pre-contest diet). This actually affects many in a negative way especially when people starts asking what’s happening are you sick. In fact, I have had numerous athletes start a pre-contest diet and stop the diet about half way through because they can’t handle the drastic drop in weight and measurements.

Some trainees could actually do great in competitive bodybuilding if it wasn’t for the fear of becoming too small. Another common psychological barrier for bbers is the assumption they need to look like a pro to compete. There is a big difference between amateur and pro bodybuilding.

A Aragon: Bodybuilders in general are psychologically traumatized individuals. But this is true with most great athletes regardless of sport. On a subconscious level, they’re trying to overcompensate in order to rectify some sort of trauma or perceived inadequacy.

So, they face the primary demon of giving a damn about what everybody else thinks, and trying to compete with everyone but themselves. They let their environment dictate their standards, when they should be setting & competing with their own standards. Improving yourself from one day, week, month, or year to the next is really what it’s all about.

J Beaty: What are the biggest mistakes you've seen bb's face both in pre-comp and mass building phases?

L Norton: Pre-comp mistakes are numerous but include: massive carb ups, massive water depletion, massive sodium depletion coinciding with potassium loading. Probably the biggest mistake is UNDERESTIMATING how much weight one will have to lose to be in contest condition.

Mass building mistakes: Trying to put on mass too fast and end up putting on body fat would be the most common one. Another mistake is trying drastic diets such diets super high in any macronutrient or super low in another. Moderation is the name of the game... there are no shortcuts to a great physique.

W Brink: Pre contest, Attempting too many last minute tweaks in hopes it will help them peak only to have it blow up in their face. Most body builders think they don't look and feel terrible the last few weeks up to a show, they are doing something wrong.

Carb depletes and loading, sodium loading, and all manner of last minute alterations that more often then not, leave the person looking worse not better. It either back fires in their face and does not work at all or they miss their peak and look great a few days after the show.

I recall talking to Dorian Yates who maintained he didn't bother with any of those extreme last minute changes and just stayed a steady predictable course pre contest. If you look great a few weeks out, then just keep doing what you are doing. I do tell people a small carb load a 3-4 days out is often a good idea as a proper pre contest diet is mildly glycogen depleting anyway
and so topping off the tanks seems to help fill people out without water retention, but no drastic loading or depleting is needed if you have done your homework the months before. 9 out of 10 times.

Off season, seems one of two extremes: bodybuilders who want to stay lean and eat nothing but rice and chicken, then cant figure out why they don't grow, and bodybuilders who use the off season to get sloppy fat and eat what ever they want.

J Hale: It is really hard for me to give an answer that does not require an entire article. To keep it brief doing way too much activity while dieting and losing bodily proteins. In the off season developing horrible eating habits that are hard to over come; once its time to start the pre-contest diet.

A Aragon: Precontest mistakes basically fall into 2 categories that beget each other: 1) Underestimating prep time; 2) Pulling drastic last-minute moves to try to fix mistake number one.

I’ve found that many guys actually do their first show as a motivator to get out of fatville. That’s fine and dandy, but if you’re a guy clocking in at 20% BF, and you think you won’t be stressed out about your lower abdominal pudge in 12 weeks, then go for it. We’ve all seen dudes get onstage chubby by contest standards, but just having a blast and enjoying their current peak shape.

Guys often think of the first set of Body For Life 12 week before & after shots and don’t realize that the guys who got shredded for that were more than likely what I call “rebound rippers”. They’ve been in great shape before, so their body had the pre-existing infrastructure and “memory”. For them it was simply a matter of bouncing back after a period of extreme slack. If you’ve never been there, it’s quite the road to get there.

The drastic last-minute moves I’m talking about mainly deal with desperate random water & sodium moves, as well as exponential hikes in exercise coupled with precipitous drops in caloric intake. Not to mention doubling & tripling the reps, thereby forcing useless endurance adaptations at the expense of preserving size.

As far as off-season mistakes go, that’s pretty easy, getting too fat. Also, guys need to take more extended rest periods. 1 full week (even up to 2) of zero formal training appx every 3-4 months. These objectives may seem contradictory, but they’re actually not when executed properly. Regular extended rest can actually accelerate progress more than the absence of it.

J Beaty: How do you manipulate water consumption pre-comp?

L Norton: I don't. It should stay high the whole time. Unless a person is on androgens that cause massive extracellular water retention there is NO NEED to cut water! Natural competitors just DO NOT hold that much extracellular water. If you cut water, not only does your body fight you by releasing hormones that cause you to retain more water, you also flatten yourself out and make any carb loading you do ineffective.

Muscle tissue is 70% water, and cutting it out will deplete subcutaneous water, but it will also deplete water from inside the muscle cell causing the competitor to look flat, stringy, with no vascularity. At my last show where I won my NGA pro card, people were looking at me like I was crazy while I was downing water backstage. They asked "aren't you worried about retaining water?" I just smiled & said "not a bit." Then they couldn't believe how full & dry I was when I took my clothes off & started pumping up. The competitors I prepare for shows also typically have the same comments, they can't believe how dry they stay while drinking so much water and they can't believe how much more vascular they are.

W Brink: To be honest with you, I don't work with precontest bodybuilders much any more. The use of lasix and other diuretics was not something I was comfortable with, and decided the smart thing to do was to step away from that line of work. Non pharmacologically speaking, as far as simple water consumption, limiting water a few days before often helps dry people up, but I am not a fan of seeing people go to essentially zero water intake for days before a show. It's damn unhealthy and does not seem to yield the results people want. Now, people who really know how to manipulate water via diuretics and other drugs and tricks can do some amazing things. I recall seeing one very well known pro about 3 weeks out from a big show. He looked terrible and I thought there was no way in hell he would peak for the show. He employed a well-known pre contest guru known for being particularly adept at the use of diuretics, and the transformation was amazing. He won the show.

J Hale: Three days from the show I advise bbers to increase water intake above previous levels. Two days from the show the water depletion process begins. Example: they drank 2 gallons of water the previous day, two days before the show they drink 1 gallon. One day from show water consumption drops further to approximately ½ gallon (distilled water). The day of the show I recommend consuming 12-16oz distilled water up to the pre-judging. After pre-judging sipping water as needed. At the same time I am manipulating sodium, Vit C, Carbs, and potassium in the quest to achieve that dry as a bone appearance. Being dry is very important for competitive bbers.

A Aragon: I hold very strongly to the philosophy that the best possible manipulation of water is to not need to manipulate water at all. Fact is, it’s easy to actually be 4 weeks out at the 4 day mark, but blame it on water, when it’s actually good ole subcutaneous fat. That’s the first principle: dial in your BF at least 2 weeks in advance. That’s how Dorian did it (among other means of course), but he would go shopping on the day of the Olympia while other guys stayed in their hotel rooms and prayed in desperation.

That said, if last minute tweaks need to be done, the effect vary drastically from one individual to the next, so it’s important to do a dry run far out from a show if you plan on tweaking. Kevin Levrone made it popular to overdo water intake beginning a couple days out from the show, all the way through to the stage. Well, actually he’d get a alcohol buzz right before going on. He figured that if he was coming in bigger and harder than the water-starved competition, why monkey with the strategy. But it does make sense (the increased water, not necessarily the buzz) from a physiological standpoint, and I’ve been heavily influenced by that approach, and have used it with reasonable success with clients when the need arose.

Then you have other guys who swear by the cut-it-low 2-3 days out method, which actually activates your body’s water-retentive defenses, and puts most natural guys at a greater risk for coming in skinny AND softer than they would have been. I think it’s ludicrous to believe that you can manipulate exactly whether water will escape the subcutaneous layer versus the intramuscular space. People confuse the aforementioned respective terms with extracellular & intracellular space. If you can keep water & sodium relatively constant throughout prep, that’s ideal. In my experience, water and sodium increases/decreases should generally be in tandem with each other, and not too different from habitual amounts. Gotta see how the individual responds, bottom line.

J Beaty: Describe the perfect bb...in one word.

L Norton: Impossible lol

W Brink: Flex Wheeler. I guess that's two words..

J Hale: An individual with good bodybuilding genetics (naturally muscular, basically mesomorporhic bodytype, small joints, nice shoulder to waist ratio-tapered look, high p-ratio) great discipline, incorporates scientific findings into his training, thinks with and open mind, and can handle criticism.

A Aragon: Sane.

~~~~~~~~~~~~~~~~~~~~~

Panelist Profiles:

Layne Norton, IFPA & NGA Pro www.physiquescience.com
1. Battram DS, Arthur R, Weekes A, Graham TE. J Nutr. 2006 May;136(5):1276-80. The glucose intolerance induced by caffeinated coffee ingestion is less pronounced than that due to alkaloid caffeine in men.

Will Brink, Author and industry consultant, Will Brink @ www.BrinkZone.com

Jamie Hale is a Sports Conditioning Coach, author, gym owner, fitness and nutrition consultant. He has contributed to numerous exercise and sports publications (nationally and internationally). He has authored four books and is currently working on his fifth. Jamie is a member of the World Marital Arts Hall of Fame in recognition of his conditioning work with Martial Artists. He is considered by most in the industry as a specialist in agility and sledgehammer training. He is also known for his ability to get bodybuilders lean and dry as a bone for competition. To learn more about Jamie visit his website at www.maxcondition.com and www.CoachHale.com.

Alan Aragon has over 13 years of success in the fitness field. He earned his Bachelor and Master of Science in Nutrition with top honors. Alan is a continuing education provider for the Commission on Dietetic Registration, National Academy of Sports Medicine, American Council on Exercise, and National Strength & Conditioning Association. Visit his site at www.AlanAragon.com.


January Research Review:
http://user210805.websitewizard.com/files/unprotected/AARR-Jan-2008.pdf
 
BUMP

I know it is a long read, but print it out and read it later if you don't have the time to read it online.

I felt like a dinosaur m'self upon initially scanning the article, though, I will admit. :worried:
 
BIKINIMOM said:
BUMP

I know it is a long read, but print it out and read it later if you don't have the time to read it online.

I felt like a dinosaur m'self upon initially scanning the article, though, I will admit. :worried:

Theories do change.

I am really interested in training for different muscle fiber types, and although Layne does say he doesn't think it makes a difference, I think it has with a lot of hardgainers.

I am a complete geek though, I love things like cell cycle control, apoptosis, biochemical pathways.

I am going to see if I can find a pic of the mTOR pathway that triggers muscle synthesis.

It's always easier when you have a diagram or picture. :)
 
The part that REALLY made me go :worried: was the notion that eating complex carbs later in the day or that cutting carbs getting closer to contest time made no difference when dropping bf%.

Could this be true?

Is it REALLY *all about* calories in/calories out?
 
BIKINIMOM said:
The part that REALLY made me go :worried: was the notion that eating complex carbs later in the day or that cutting carbs getting closer to contest time made no difference when dropping bf%.

Could this be true?

Is it REALLY *all about* calories in/calories out?

Before I had read anything much on BBing or any internet forum, I didn't realise it was impossible to drop to sub 10% bodyfat without any fat burning supps, natural diuretics or eating 200 g/carbs per day.

But I did.

I even ate rice cakes late at night.

I train late at night, so I also eat carbs after training late at night.

I haven't been doing much cardio, but my bodyfat is dropping slowly but my weight is going up.

Insulin is anabolic. Especially when the fat to muscle ratio is around 17% and less for women.
 
I thought this was great, I have always been fascinated by cell cycle control and how muscle cells get bigger or hypertrophy.

It really still is an unknown.

The Mystery of Skeletal Muscle Hypertrophy
Richard Joshua Hernandez, B.S. and Len Kravitz, Ph.D.

Introduction
Through exercise, the muscular work done against a progressively challenging overload leads to increases in muscle mass and cross-sectional area, referred to as hypertrophy. But why does a muscle cell grow and how does it grow? Although an intense topic of research, scientists still do not fully understand the complete (and very complex) picture of how muscle adapts to gradually overloading stimuli. In this article, a brief but relevant review of the literature is presented to better understand the multifaceted phenomenon of skeletal muscle hypertrophy.

What is Muscular Hypertrophy?
Muscular hypertrophy is an increase in muscle mass and cross-sectional area (1). The increase in dimension is due to an increase in the size (not length) of individual muscle fibers. Both cardiac (heart) and skeletal muscle adapt to regular, increasing work loads that exceed the preexisting capacity of the muscle fiber. With cardiac muscle, the heart becomes more effective at squeezing blood out of its chambers, whereas skeletal muscle becomes more efficient at transmitting forces through tendonous attachments to bones (1).
Skeletal muscle has two basic functions: to contract to cause body movement and to provide stability for body posture. Each skeletal muscle must be able to contract with different levels of tension to perform these functions. Progressive overload is a means of applying varying and intermittent levels of stress to skeletal muscle, making it adapt by generating comparable amounts of tension. The muscle is able to adapt by increasing the size and amount of contractile proteins, which comprise the myofibrils within each muscle fiber, leading to an increase in the size of the individual muscle fibers and their consequent force production (1).

The Physiology of Skeletal Muscle Hypertrophy
The physiology of skeletal muscle hypertrophy will explore the role and interaction of satellite cells, immune system reactions, and growth factor proteins (See Figure 1. for Summary).

Satellite Cells
Satellite cells function to facilitate growth, maintenance and repair of damaged skeletal (not cardiac) muscle tissue (2). These cells are termed satellite cells because they are located on the outer surface of the muscle fiber, in between the sarcolemma and basal lamina (uppermost layer of the basement membrane) of the muscle fiber. Satellite cells have one nucleus, with constitutes most of the cell volume.
Usually these cells are dormant, but they become activated when the muscle fiber receives any form of trauma, damage or injury, such as from resistance training overload. The satellite cells then proliferate or multiply, and the daughter cells are drawn to the damaged muscle site. They then fuse to the existing muscle fiber, donating their nuclei to the fiber, which helps to regenerate the muscle fiber. It is important to emphasize the point that this process is not creating more skeletal muscle fibers (in humans), but increasing the size and number of contractile proteins (actin and myosin) within the muscle fiber (see Table 1. for a summary of changes that occur to muscle fibers as they hypertrophy). This satellite cell activation and proliferation period lasts up to 48 hours after the trauma or shock from the resistance training session stimulus (2).

The amount of satellite cells present within in a muscle depends on the type of muscle. Type I or slow-twitch oxidative fibers, tend to have a five to six times greater satellite cell content than Type II (fast-twitch fibers), due to an increased blood and capillary supply (2). This may be due to the fact that Type 1 muscle fibers are used with greatest frequency, and thus, more satellite cells may be required for ongoing minor injuries to muscle.

Immunology
As described earlier, resistance exercise causes trauma to skeletal muscle. The immune system responds with a complex sequence of immune reactions leading to inflammation (3). The purpose of the inflammation response is to contain the damage, repair the damage, and clean up the injured area of waste products.
The immune system causes a sequence of events in response to the injury of the skeletal muscle. Macrophages, which are involved in phagocytosis (a process by which certain cells engulf and destroy microorganisms and cellular debris) of the damaged cells, move to the injury site and secrete cytokines, growth factors and other substances. Cytokines are proteins which serve as the directors of the immune system. They are responsible for cell-to-cell communication. Cytokines stimulate the arrival of lymphocytes, neutrophils, monocytes, and other healer cells to the injury site to repair the injured tissue (4).

The three important cytokines relevant to exercise are Interleukin-1 (IL-1), Interleukin-6 (IL-6), and tumor necrosis factor (TNF). These cytokines produce most of the inflammatory response, which is the reason they are called the “inflammatory or proinflammatory cytokines” (5). They are responsible for protein breakdown, removal of damaged muscle cells, and an increased production of prostaglandins (hormone-like substances that help to control the inflammation).

Growth Factors
Growth factors are highly specific proteins, which include hormones and cytokines, that are very involved in muscle hypertrophy (6). Growth factors stimulate the division and differentiation (acquisition of one or more characteristics different from the original cell) of a particular type of cell. In regard with skeletal muscle hypertrophy, growth factors of particular interest include insulin-like growth factor (IGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). These growth factors work in conjunction with each other to cause skeletal muscle hypertrophy.

Insulin-Like Growth Factor
IGF is a hormone that is secreted by skeletal muscle. It regulates insulin metabolism and stimulates protein synthesis. There are two forms, IGF-I, which causes proliferation and differentiation of satellite cells, and IGF-II, which is responsible for proliferation of satellite cells. In response to progressive overload resistance exercise, IGF-I levels are substantially elevated, resulting in skeletal muscle hypertrophy (7).

Fibroblast Growth Factor
FGF is stored in skeletal muscle. FGF has nine forms, five of which cause proliferation and differentiation of satellite cells, leading to skeletal muscle hypertrophy. The amount of FGF released by the skeletal muscle is proportional to the degree of muscle trauma or injury (8).

Hepatocyte Growth Factor
HGF is a cytokine with various different cellular functions. Specific to skeletal muscle hypertrophy, HGF activates satellite cells and may be responsible for causing satellite cells to migrate to the injured area (2).
Hormones in Skeletal Muscle Hypertrophy
Hormones are chemicals which organs secrete to initiate or regulate the activity of an organ or group of cells in another part of the body. It should be noted that hormone function is decidedly affected by nutritional status, foodstuff intake and lifestyle factors such as stress, sleep, and general health. The following hormones are of special interest in skeletal muscle hypertrophy.

Growth Hormone
Growth hormone (GH) is a peptide hormone that stimulates IGF in skeletal muscle, promoting satellite cell activation, proliferation and differentiation (9). However, the observed hypertrophic effects from the additional administration of GH, investigated in GH-treated groups doing resistance exercise, may be less credited with contractile protein increase and more attributable to fluid retention and accumulation of connective tissue (9).

Cortisol
Cortisol is a steroid hormone (hormones which have a steroid nucleus that can pass through a cell membrane without a receptor) which is produced in the adrenal cortex of the kidney. It is a stress hormone, which stimulates gluconeogenesis, which is the formation of glucose from sources other than glucose, such as amino acids and free fatty acids. Cortisol also inhibits the use of glucose by most body cells. This can initiate protein catabolism (break down), thus freeing amino acids to be used to make different proteins, which may be necessary and critical in times of stress.
In terms of hypertrophy, an increase in cortisol is related to an increased rate of protein catabolism. Therefore, cortisol breaks down muscle proteins, inhibiting skeletal muscle hypertrophy (10).

Testosterone
Testosterone is an androgen, or a male sex hormone. The primary physiological role of androgens are to promote the growth and development of male organs and characteristics. Testosterone affects the nervous system, skeletal muscle, bone marrow, skin, hair and the sex organs.
With skeletal muscle, testosterone, which is produced in significantly greater amounts in males, has an anabolic (muscle building) effect. This contributes to the gender differences observed in body weight and composition between men and women. Testosterone increases protein synthesis, which induces hypertrophy (11).

Fiber Types and Skeletal Muscle Hypertrophy
The force generated by a muscle is dependent on its size and the muscle fiber type composition. Skeletal muscle fibers are classified into two major categories; slow-twitch (Type 1) and fast-twitch fibers (Type II). The difference between the two fibers can be distinguished by metabolism, contractile velocity, neuromuscular differences, glycogen stores, capillary density of the muscle, and the actual response to hypertrophy (12).

Type I Fibers
Type I fibers, also known as slow twitch oxidative muscle fibers, are primaritly responsible for maintenance of body posture and skeletal support. The soleus is an example of a predominantly slow-twitch muscle fiber. An increase in capillary density is related to Type I fibers because they are more involved in endurance activities. These fibers are able to generate tension for longer periods of time. Type I fibers require less excitation to cause a contraction, but also generate less force. They utilize fats and carbohydrates better because of the increased reliance on oxidative metabolism (the body’s complex energy system that transforms energy from the breakdown of fuels with the assistance of oxygen) (12).
Type I fibers have been shown to hypertrophy considerably due to progressive overload (13,15). It is interesting to note that there is an increase in Type I fiber area not only with resistance exercise, but also to some degree with aerobic exercise (14).

Type II Fibers
Type II fibers can be found in muscles which require greater amounts of force production for shorter periods of time, such as the gastrocnemius and vastus lateralis. Type II fibers can be further classified as Type IIa and Type IIb muscle fibers.

Type IIa Fibers
Type IIa fibers, also known as fast twitch oxidative glycolytic fibers (FOG), are hybrids between Type I and IIb fibers. Type IIa fibers carry characteristics of both Type I and IIb fibers. They rely on both anaerobic (reactions which produce energy that do not require oxygen), and oxidative metabolism to support contraction (12).
With resistance training as well as endurance training, Type IIb fibers convert into Type IIa fibers, causing an increase in the percentage of Type IIa fibers within a muscle (13). Type IIa fibers also have an increase in cross sectional area resulting in hypertrophy with resistance exercise (13). With disuse and atrophy, the Type IIa fibers convert back to Type IIb fibers.

Type IIb Fibers
Type IIb fibers are fast-twitch glycolytic fibers (FG). These fibers rely solely on anaerobic metabolism for energy for contraction, which is the reason they have high amounts of glycolytic enzymes. These fibers generate the greatest amount of force due to an increase in the size of the nerve body, axon and muscle fiber, a higher conduction velocity of alpha motor nerves, and a higher amount of excitement necessary to start an action potential (12). Although this fiber type is able to generate the greatest amount of force, it is also maintains tension for a shortesst period of time (of all the muscle fiber types).
Type IIb fibers convert into Type IIa fibers with resistance exercise. It is believed that resistance training causes an increase in the oxidative capacity of the strength-trained muscle. Because Type IIa fibers have a greater oxidative capacity than Type IIb fibers, the change is a positive adaptation to the demands of exercise (13).

Conclusion
Muscular hypertrophy is a multidimensional process, with numerous factors involved. It involves a complex interaction of satellite cells, the immune system, growth factors, and hormones with the individual muscle fibers of each muscle. Although our goals as fitness professionals and personal trainers motivates us to learn new and more effective ways of training the human body, the basic understanding of how a muscle fiber adapts to an acute and chronic training stimulus is an important educational foundation of our profession.


Table 1. Structural Changes that Occur as a Result of Muscle Fiber Hypertrophy
Increase in actin filaments
Increase in myosin filaments
Increase in myofibrils
Increase in sarcoplasm
Increase in muscle fiber connective tissue
Source: Wilmore, J.H. and D. L. Costill. Physiology of Sport and Exercise (2nd Edition).Champaign, IL: Human Kinetics, 1999.


References

1. Russell, B., D. Motlagh,, and W. W. Ashley. Form follows functions: how muscle shape is regulated by work. Journal of Applied Physiology 88: 1127-1132, 2000.

2. Hawke, T.J., and D. J. Garry. Myogenic satellite cells: physiology to molecular biology. Journal of Applied Physiology. 91: 534-551, 2001.

3. Shephard, R. J. and P.N. Shek. Immune responses to inflammation and trauma: a physical training model. Canadian Journal of Physiology and Pharmacology 76: 469-472, 1998.

4. Pedersen, B. K. Exercise Immunology. New York: Chapman and Hall; Austin: R. G. Landes, 1997.

5. Pedersen, B. K. and L Hoffman-Goetz. Exercise and the immune system: Regulation, Integration, and Adaptation. Physiology Review 80: 1055-1081, 2000.

6. Adams, G.R., and F. Haddad. The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy. Journal of Applied Physiology 81(6): 2509-2516, 1996.

7. Fiatarone Singh, M. A., W. Ding, T. J. Manfredi, et al. Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders. American Journal of Physiology 277 (Endocrinology Metabolism 40): E135-E143, 1999.

8. Yamada, S., N. Buffinger, J. Dimario, et al. Fibroblast Growth Factor is stored in fiber extracellular matrix and plays a role in regulating muscle hypertrophy. Medicine and Science in Sports and Exercise 21(5): S173-180, 1989.

9. Frisch, H. Growth hormone and body composition in athletes. Journal of Endocrinology Investigation 22: 106-109, 1999.

10. Izquierdo, M., K Hakkinen, A. Anton, et al. Maximal strength and power, endurance performance, and serum hormones in middle-aged and elderly men. Medicine and Science in Sports Exercise 33 (9): 1577-1587, 2001.

11. Vermeulen, A., S. Goemaere, and J. M. Kaufman. Testosterone, body composition and aging. Journal of Endocrinology Investigation 22: 110-116, 1999.

12. Robergs, R. A. and S. O. Roberts. Exercise Physiology: Exercise, Performance, and Clinical Applications. Boston: WCB McGraw-Hill, 1997.

13. Kraemer, W. J., S. J. Fleck, and W. J. Evans. Strength and power training: physiological mechanisms of adaptation. Exercise and Sports Science Reviews 24: 363-397, 1996.

14. Carter, S. L., C. D. Rennie, S. J. Hamilton, et al. Changes in skeletal muscle in males and females following endurance training. Canadian Journal of Physiology and Pharmacology 79: 386-392, 2001.

15. Hakkinen, K., W. J. Kraemer, R. U. Newton, et al. Changes in electromyographic activity, muscle fibre and force production characteristics during heavy resistance/power strength training in middle-aged and older men and women. Acta Physiological Scandanavia 171: 51-62, 2001.

16. Schultz, E. Satelite cell behavior during skeletal muscle growth and regeneration. Medicine and Science in Sports and Exercise 21(5): S181-S186, 1989
 
God! You have to love a women who knows about mTor pathways,slow and fast twitch mucle fibers,hypertrophey,hepactocyte growth factor I think Im in love....
 
This is my latest area of interest: Leptin - the articles are from fairly easy to fairly technical


Leptin - Lyle MacDonald

First things first, let me talk about leptin and the hypothalamus. I feel like I’ve been thumping on about leptin for years now, probably because I have. In many ways, it is the single most important hormone when it comes to problems with dieting and body recomposition. Released from body fat (and scaling frighteningly well with body fat levels), leptin signals the brain about two things which are

1. How much fat you’re carrying
2. How much you’re eating

This is important because knowing these two things is crucial for your body to be able to adjust things like metabolic rate, appetite, hormones, etc. Now, originally leptin was thought to exist to prevent obesity; this turns out to be incorrect. Rather, leptin exists to prevent starvation and the fall in leptin is what coordinates most of the bad things that happen on a diet.

Metabolic rate falling, dropping T3, increasing cortisol, increased appetite…all coordinated by the fall in leptin when you diet. Towards this end, while studies have routinely shown that increasing leptin in fat people does little, other studies find that replacing leptin to pre-diet levels on a diet raises metabolic rate and thyroid levels and increases fat loss.

Although leptin affects other tissues such as skeletal muscle, fat cells and the liver, most of its central action occurs in the brain, at the level of the hypothalamus. By exerting its signal there, leptin does what I talked about above. Recent work has also found that leptin can ‘rewire’ the brain (at least in rats) to increase the amount of a compound that does help to inhibit appetite. Outside of cases where leptin is massively elevated chronically (causing problems), leptin is one of the good hormones.



Leptin - by Caleb Stone


As we have discussed briefly, when leptin, the long sought after lipostatic signal, was discovered in 1996, it appeared that the key to solving the epidemic of obesity had been found. Rats with a defect in the gene responsible for its production were profoundly obese, and the administration of recombinant leptin to these rats profoundly decreased food intake and increased energy expenditure as well, resulting in rapid weight loss, which, unlike starvation, was confined solely to adipose tissue -- lean mass was preserved (1). Leptin was quickly anointed as THE anti-obesity hormone (2), and it was only a matter of time and FDA approval before the perfect diet drug would be unleashed upon the gluttonous world.

But, alas, it was not to be. Unfortunately, for the pharmaceutical industry and fat people everywhere, it soon became readily apparent that, rather than suffering from a lack of leptin, obese humans actually exhibited ELEVATED levels (3), thus not only was exogenously administered leptin going to be ineffective as a diet drug, endogenous leptin was not even fulfilling its supposed role as an anti-obesity hormone (4).

Thus, the view of leptin's role shifted, and it is now considered an anti-starvation hormone (5) -- though, it is a lack of leptin, not leptin itself, that sends the starvation signal. It is this role that makes it of paramount importance for the dieting bodybuilder.

Anyone who has dieted for an extended period of time has experienced "hitting the wall", so to speak -- the dreaded slowing, and even complete stoppage, of fat loss.

This is leptin.

Perhaps just as noticeable, or perhaps not -- due to the often fanatical willpower of bodybuilders (or perhaps the fanatical use of EC :) -- is the accompanying increase in appetite, often manifested as true, almost uncontrollable, cravings for food.

This is also leptin.

Then, there is the increased loss of muscle..... And susceptibility to illness..... And fatigue.....

Yep.

Leptin.

Energy Expenditure
Fat loss is sufficiently, if not remarkably, rapid at the beginning of a diet, with two pounds a week being not at all uncommon, even for someone who is fairly lean. However, it soon falls victim to the (not so) wonderful world of evolution. In times of scarcity, the survival advantage of thrifty metabolisms should be fairly self-evident -- Those that had them would be more likely to survive and reproduce than those that needed 5000 calories a day just to keep their skinny asses alive.


Over millions of years, this has become firmly entrenched in the genetic code. Thus, slowly (if you are lucky) but surely, when conditions of scarcity are self-imposed (i.e. when you diet), metabolism, thus fat loss, invariably slows, and if appropriate steps are not taken, it stops completely.

And, just so we do not confine ourselves to anecdotal evidence and conjecture, I will note that, indeed, low leptin levels have been found to be correlated with decreases in resting energy expenditure (6, 7, 8), and the administration of recombinant leptin corrects this in animals with defects in leptin production, as well as preventing or reversing the decline seen with fasting (9).

Appetite
As if that were not enough, your body fights your fat loss efforts furiously on another front as well. Just as with the rate of fat loss, diets generally start out quite favorably in regards to appetite control -- particularly if one is fat or has been on a mass phase for an extended period. A this point, adjusting one's lifestyle around a diet tends to be far more challenging than merely resisting food. However, as the duration of the diet is extended, the tables turn -- cravings start to set in, becoming more and more intense with each passing day, until they dominate one's thoughts.

It has long been recommended that "cheat days" be employed to prevent this -- and rightly so. But, the explanation given is generally in terms of mental well-being -- i.e. a reward for your hard work or a way to overcome a "want what you can't have" mentality. However, contrary to popular belief, and even though it IS technically "all in your head" (i.e. in the hypothalamus), this phenomenon is NOT psychological.

Decreases in leptin are strongly associated with increased voluntary food intake in animals and subjective sensations of hunger, desire to eat, and expected consumption in humans, independent of the degree of changes in adiposity and food intake (10, 11). And, the lower leptin goes, the greater the magnitude. By the same token, The administration of exogenous leptin decreases hunger and food intake in animals with defects in leptin production (12).

In other words, this is not just a matter of willpower -- it is a PHYSIOLOGICAL STARVATION RESPONSE, formed by millions of years of evolution in a world without supermarkets. It is your body commanding you to find food, right now, even if you would rather be sitting on your ass being attended to by a female member of your species.

Your genotype was forged in a world where there existed periods of extreme scarcity, low energy density foods, and a need to actually hunt down your next meal -- in other words, a world where you had to be motivated to put a great deal of effort into merely getting enough food to live. And, since you are alive today, it means this command was (and is) so powerful, that it was sufficient to make every single member of your direct genetic lineage (a lineage stretching millions and millions of years) keep itself alive long enough to reproduce.

This exact same genotype now inhabits a world where an entire day's calories can be procured in half an hour, counting the time it takes to work to earn the money to buy it -- all with very little physical effort.

I think you can see why getting to 6% bodyfat is easier said than done.


The Answer
It has previously been common practice, when the manifestations of low leptin levels become apparent to the dieter, to cut calories even further, increase aerobics, start munching Cytomel, or all of the above, to once again create a calorie deficit, in an effort to get fat loss back on track. This might work for a very short period of time, but it will also decrease leptin even more, making things that much worse.

At this point the dieter will generally do one of two things: 1) they will repeat the steps above, creating a vicious circle, which will ultimately will result in an absolute inability to drop bodyfat, no matter how low calories are taken. And, for the smart guys, or so called smart guys, this is NOT going against the laws of thermodynamics. one still has another ready supply of energy, known to the laymen as "muscle", which the body will be all too ready to utilize in its current hormonal state (this will be the subject of an upcoming installment) or 2) They will give up on dieting altogether, self-righteously declare that big is beautiful, and become a regular poster on alt.support.fat-acceptance :)

But hope is not lost...

What I am now going to suggest that the dieter should do may appear, on the surface, to fly in the face of common sense. In order to keep fat loss going, the dieter needs to eat MORE, not less. And, I do not mean having a slice of pizza or eating maintenance calories for a day. I am talking about what is essentially pigging out for 12-48 hours -- and, to top it off, most of your calories will come from the evil "carbohydrate".

I do not care for the term "cheat day", because it implies that you are doing something wrong. What I am suggesting are PURPOSEFUL, and they are PLANNED -- thus, I use the term "refeeds". "Cheat days" will be left to the glutton.

These refeeds will ideally be done done on a regular basis, BEFORE all of the afore mentioned signs of low leptin become manifest. For that reason, we need to take a look at leptin levels in relation to bodyfat as well as the time table for their fall when dieting before we get into the specifics of the refeed.

Dieting and Leptin Levels
Recall that leptin levels are determined, in the long and short term, by adipose tissue stores and calories balance, respectively. An individual's genetics is also going to play a role in determining leptin level -- This component is depends on the individual's so-called body fat "set point". Generally, someone with a higher genetic setpoint will have lower CNS leptin levels at the same bodyfat and someone with a low setpoint will have higher levels.

In addition, the higher an individual's current bodyfat has become compared their setpoint (from overeating/underexercising), the higher the leptin level will be, and the lower the bodyfat level has become vs. the setpoint (via dieting and/or physical activity, the lower leptin levels will be.

These differences in CNS levels can be a result of of differences in serum levels or differences in transport across the blood brain barrier. As we have noted, it is the latter that is the primary factor in the obese, and probably lean people as well to a lesser extent. This complicates thing greatly, as most of the literature has looked only at serum levels, but leptin transport into the CNS is downregulated by high serum levels as well as by caloric restriction. And, we still do not know to what extent obesity contributed to poor BBB transport and to what extent poor BBB contributes to obesity.

An exact determination of CNS levels is far too invasive to be at all practical. They could be estimated by comparing one's body fat % with data of individuals of similar serum levels and nutritional state whose CNS levels are known, but the lack of CNS data could limit this -- not to mention that such tests are not even available outside of a research setting and would probably not be any more widely utilized than testosterone tests currently are. Thus, another means of estimation is needed.

We shall attempt to make an educated guess based on an analysis of the plethora of data available to us in the literature (average leptin levels for a particularly body fat and studies on the dynamics of leptin levels with changes in calorie balance) combined with your individual setpoint, which you will determine. This will get fairly complicated, but I will try to simplify it as much as possible
$AD$
As mentioned, there is too much information to cover it all in one article without it being totally overwhelming, so today we will look at the average levels for a given bodyfat and the determination of setpoint. In the next installment, we will turn to studies on fasting and dieting, to get an idea of the time-frame and degree of fall of serum levels and BBB transport with different lengths and degrees of caloric deficit, in different populations. We will also look more closely at the refeed.

Leptin Levels
Fortunately, Ruhl and Everhart (13,14) were kind enough to provide the world with an epidemiological study which surveyed serum leptin levels in 3366 women and 2937 and broke them up into cohorts based on body fat percentile.


(Sorry the chart does not copy and paste well)


Assuming you are not obese, your serum level will be a fairly good predictor of your CNS level. If we were not in a society of fat-asses, logic would dictate that where the leptin level of the average person (i.e. those in the 50th percentile) settled would be the level associated with our setpoint. However, lifestyle has shifted bodyfat percentages considerably to the right. A more natural bodyfat for the average person is probably more like the 15th percentile. We will get more into the specifics of the affects of various levels, including trying to pin down a magic number associated with hitting the wall, in the next installment when we look at drops in leptin levels with dieting.

Setpoint
Now, let us talk a little bit about estimating body fat "setpoint". This will determine if you CNS levels fall to the left or the right side of the bell-curve for those at the same body fat level.

The setpoint is the level your body "wants" to exist at, so the best way to figure this out is going to be to pay very close attention to when it fights back against changes in bodyfat level that you have forced upon it. In practical terms: to estimate the low end, you are going to note what body fat levels your body starts showing overt signs of leptin suppression during a diet (appetite, decreased fat loss, increased loss of muscle, susceptibility to illness, irritability/fatigue -- which ones show up first will depend on the individual), and to get the high end, you will note when the fat gain slows and appetite decreases when on a mass phase or when the level you settle at when just eating whatever you want for an extended period. The level halfway in between is a good estimate of your setpoint.

Obviously, this is going to require careful monitoring of both objective and subjective data. Skinfolds should be taken weekly, and a journal should be kept of subjective manifestations. Anything that can increase or decrease appetite will be a confounding variable, so androgens, marijuana, EC, PPA, and prescription or illicit stimulants should, ideally, be avoided while this determination is being made. In addition, the omnipresence of palatable foods could skew things, so vacations and holidays are not an ideal time to make a determination. Boredom, stress, and depression can also influence these parameters. Obviously, it is impossible to totally avoid all confounding variables, so multiple testing periods will result in greater and greater accuracy.

Conclusion
Hopefully, I have not confused you too much. And, even if I have confused you a bit, don't worry, because it should all begin come together when we start looking at the numbers. In the meantime, you can begin figuring out your setpoint or, at the very least, start paying attention and making a mental note of when you notice subjective sign of lower leptin levels.


References
1. Halaas JL, Boozer C, Blair-West J, Fidahusein N, Denton DA, Friedman JM. Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc Natl Acad Sci U S A 1997 Aug 5;94(16):8878-83

2. Spiegelman BM, Flier JS. Adipogenesis and obesity: rounding out the big picture. Cell 1996 Nov 1;87(3):377-89

3. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995 Nov;1(11):1155-61

4. Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS. Nat Med 1995 Dec;1(12):1311-4 Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action.

5. Unger RH. Leptin physiology: a second look. Regul Pept 2000 Aug 25;92(1-3):87-95

6. Doring H, Schwarzer K, Nuesslein-Hildesheim B, Schmidt I. Leptin selectively increases energy expenditure of food-restricted lean mice. Int J Obes Relat Metab Disord 1998 Feb;22(2):83-8

7. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995 Jul 28;269(5223):540-3

8. Doucet E, St Pierre S, Almeras N, Mauriege P, Richard D, Tremblay A. Changes in energy expenditure and substrate oxidation resulting from weight loss in obese men and women: is there an important contribution of leptin? J Clin Endocrinol Metab 2000 Apr;85(4):1550-6

9. Scarpace PJ, Matheny M, Pollock BH, Tumer N. Am J Physiol 1997 Leptin increases uncoupling protein expression and energy expenditure. Jul;273(1 Pt 1):E226-30

10. Brunner L, Nick HP, Cumin F, et al. Leptin is a physiologically important regulator of food intake. Int J Obes Relat Metab Disord 1997;21:1152–60.

11. Keim NL, Stern JS, Havel PJ. Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. Am J Clin Nutr 1998 Oct;68(4):794-801

12. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995 Jul 28;269(5223):546-9

13. Am J Clin Nutr 2001 Sep;74(3):295-301tLeptin concentrations in the United States: relations with demographic and anthropometric measures. Ruhl CE, Everhart JE.

14. Adapted from American College of Sports Medicine Chart -- Subject age: 20-59.

This new research has begun to shed light on leptin’s interplay with various systems in the body. So in this installment we are going to delve much deeper into leptin’s effects. Specifically we are going to discuss how leptin’s direct interaction with various tissues promotes weight loss. However keep in mind that in this installment we are only going to be dealing with leptin’s direct effects on tissues. Much of leptin’s punch occurs because of downstream signals and various changes regulated by leptin’s interaction with the brain and nervous system. So keep that in mind as you read this article. Leptin’s powerful central effects cannot be denied. However to understand how it accomplishes some of this I have tried to ignore any systemic effects in this article. In the next installment we will delve deeper into leptin’s powerful systemic effects. So without further delay…I give you, “Leptin: the Next Big Thing Pt. IV.”

Leptin and Adipose Tissue

When discussing leptin’s effects on fat loss it seems only logical that we should start our discussion with the white adipose cell, a.k.a. fat cells. If you have taken the time to look in to some of the research on leptin and fat cells you would be awestruck. Visions of fat cells shriveling up like raisins in the sun would dance through your head. Seriously, some of these studies are littered with things that seem almost magical—such as fat cells eating away at there own lipid storage depots and spilling glycerol out in to the blood stream (1). Imagine if all you had to do was get a shot of leptin to transform your fat cells in to fat-burning machines. Unfortunately this is one of those times where people don’t behave like rats. Or more specifically, human fat cells behave nothing like mouse or rat fat cells when treated with leptin. When white fat cells extracted from our favorite scientific pet, the rodent, are incubated with a serum of leptin they become quite lipolytic (3,4,5,6). This is not the case with human fat cells however. Treating human white adipose cell lines with leptin does not induce lipolysis; nor does it reduce insulin’s attenuation of lipolysis (2,7).

The story does not end there however. Luckily it seems that leptin does have some positive effects on human white adipose tissue. Namely, leptin is very anti-lipogenic. It has been shown to lower the amount of human fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP) (8). This is further validated by in vivo research conducted on the obese. The obese have plenty of leptin as you already know and the obese have been shown to have lower levels of FAS and SERBP.

Additionally, leptin has a rather remarkable affect on Perosixome Proliferator-Activated Receptor-gamma (PPAR-gamma). PPAR-gamma is an orphan nuclear receptor that is activated when poly-unsaturated fatty acids (PUFA) bind to it. In many ways PPAR-gamma is the master control switch for fat storage. When PPAR-gamma is activated it causes a host of enzymes to be created. The majority of these enzymes serve two purposes. First they promote the esterification of fatty acids, creating triacylglycerides (TAG). Secondly they promote the formation of lipid droplets form TAG. Unfortunately, when leptin was administered to mice it increased the cellular expression of PPAR-gamma by 70-80% (9).

All of this does make sense when you examine it however. Leptin is a multi-function hormone. It serves as an anti-starvation hormone as well as a long-term signal of energy reserves. Well, relatively long term, when compared to neurotransmitters. So it makes sense that leptin would indeed reduce lipogenic enzymes as it is signaling to other cells that there are plenty of caloric reserves, and that the body needn’t bother storing more.

Leptin’s effects on PPAR-gamma activity also makes sense. Specifically this activity is one of the signals that leads pre-adipocytes to differentiate in to full fledged fat cells. Since leptin is signaling that there is ample stored fuel, it logically follows that it would be alerting the pre-fat cells that there may be a need for more fat cells to store these incoming calories because the current cells are already full. This is further validated by studies showing that when pre-adipocytes are incubated in supraphysiological levels of leptin they do indeed differentiate into full-fledged fat cells. Of course, this only happens at extremely high leptin levels such as those seen in the obese.

In normal individuals PPAR-gamma and leptin seem to operate in a negative feedback loop. Leptin signaling at the fat cell upregulates PPAR-gamma as previously stated, however PPAR-gamma activation dramatically lowers leptin production. Thus it would seem that in normal individuals the relationship between leptin and PPAR-gamma is used to evenly distribute nutrients to all of the adipose tissue in the body; it is a sort of short-term regulator of how much fuel each cell should receive.

Additionally, leptin has some positive effects on human adipose tissue, specifically related to insulin stimulated glucose uptake. There are several studies that show leptin to lower glucose uptake in fat cells. This would be of benefit as it would reduce the energy supplied to your fat cells, thus forcing them to use fatty acids to meet their energy demands. Some of the evidence in this category is mixed, however much of that can be attributed to the fact that differing levels of leptin were used in the studies.

The relationship is an “inverted U.” In other words leptin’s effects in this respect appear maximally at low and high leptin concentrations. This makes sense after further examination. When leptin concentration is very low this is a signal that one is in a state of starvation. By reducing glucose uptake into adipose, you make that available to other tissues such as the brain and muscles, which are deemed more important. So, at low concentrations, leptin acts on adipose tissue to prioritize nutrient usage. At very high concentrations this is also to be expected. You see both leptin and insulin have cross talk in their signaling cascade. In other words leptin resistance leads to insulin resistance and insulin resistance leads to leptin resistance. So when one has incredibly high leptin levels it is only logical that insulin sensitivity would suffer, and insulin stimulated glucose uptake would decrease.

So at the very least it would seem that leptin’s effects on human adipose tissue is a mixed bag. Its effects are primarily beneficial, however they are disappointing compared to early animal research. Still, there are many questions left unanswered. In a very rigorous investigation of the current literature, your humble author found that there are approximately 2.34567 gazillion studies on leptin and rodent fat cells. There are however, only a handful conducted on human cell lines. This means that there is still much investigation to be done and hopefully future research will shed some light leptin’s role in the human adipose cellular lifecycle.

Now, you’re probably saying, "But Spook, I read the previous articles, I know leptin is good for fat loss. Are you trying to tell me leptin doesn’t promote fat loss? Did your parents pick you up by the soft spot as a child? Did you fry your brain on In-Rage? Or are you just a commy bastard?" No, no, and no on all accounts. Don't fret; leptin is indeed marvelous for fat loss, at least in the already lean. To understand why, we must look beyond our fat cells. That is exactly what we are going to do in the rest of this article as we examine leptin’s direct effects on the numerous systems of the human body.

Leptin and Muscle Tissue

One way in which leptin aids in fat loss is by its direct effects on skeletal and cardiovascular muscle. Muscle cells express the long form leptin receptor (Ob-R). This is the receptor that is responsible for initiating leptin’s signaling cascade through the JAK pathway when it interacts with various tissues. In very simple terms, leptin causes your muscle cells to utilize fat instead of carbohydrates for energy. To properly address this phenomenon we must digress for a moment to briefly describe the system that regulates substrate utilization at the cellular level.

Inside the muscle cells in your body are small organelles called mitochondria. The mitochondria create the majority of the energy our cells need to operate, in the form of ATP. For various reasons that are to complex to delve in to in this article, our mitochondria tend to use mostly fat or mostly carbohydrates for energy production, but they tend not to use both of them at the same time. This issue is an interesting one that I hope to provide a full examination of in the future, but for now you will just have to take your humble author’s word for it. In essence, your cells will use fat or carbohydrates but not both at the same time.

The choice of fuel selection is controlled in large part by a protein called, acetyl-CoA carboxylase (ACC) (10). On the surface of the mitochondria’s membrane is another protein called carnitine palmitoyl transferase (CPT). You can think of CPT as a doorway for long chain fatty acids to get inside the mitochondria. If CPT can't get those long chain fatty acids in to the mitochondria, then they can't be oxidized (11). CPT transfers a fatty acid in to the mitochondria by binding to the acyl end of a fatty acid acyl complex. Essentially, there is this substance called acytal-CoA that is floating around in your cells. When it comes time to burn fat the acytal-CoA is grafted on to the end of a fatty acid, forming an acyal-FAT complex. CPT latches on to the acyl part and transports the fat into the mitochondria to create around 140 ATP molecules per fatty acid. ACC creates a product called malonyl-CoA by acting on acytal-CoA. Malonyl-CoA is a competitive inhibitor of the acyal-FAT complex. It binds to CPT, thus preventing CPT from doing its job of transporting the real fat into the mitochondria.

As you can see, if we wish for our cells to keep burning fat, we need to make sure there is as little malonyl-CoA as possible. To keep malonyl-CoA content low we need to stop ACC from creating this compound. Luckily our body has a way of doing just that. There is yet another protein called AMP-Activated Protein Kinase (AMPK). This proteins job is to deactivate ACC. In other words:

AMPK activation = ACC deactivation = less malonyl-CoA = more fat oxidation.
AMPK deactivation = ACC activation = more malonyl-CoA = less fat oxidation.

Great, this is just what we were looking for. Now we are ready to see how leptin affects these enzymes and optimizes fatty acid oxidation.

When skeletal muscle was incubated in a serum with leptin, AMP-activated protein kinase (AMPK) was activated (12,13). When AMPK is activated it inhibits ACC thus reducing malonyl-CoA. This reduction in malonyl-CoA frees CPT to do its thing and transfer long chain fatty acids in to the mitochondria where they can be used to produce ATP. Additionally, chronic leptin administration not only activated AMPK but also increased the amount of AMPK in muscle cells. So you can see this is of great benefit. This also makes sense from a physiological perspective, as leptin is signaling the rest of the body that there is ample fuel stored in your fat cells. This signal lets the muscle know that there is ample fat so it should use fat as its primary energy source.

Leptin’s activation of AMPK and concurrent increase of AMPK concentration also promotes a lean physique through mechanisms other than just short-term usage of fat for fuel. Chronic AMPK activation is also implicated in the mechanisms responsible for several of the adaptations muscles undergo in response to chronic exercise. Specifically, chronic AMPK activation upregulates a protein called nuclear respiratory factor-1 (NRF-1). NRF-1 is one of the primary proteins involved in mitochondrial neobiogenesis (16,18). In other words chronic AMPK activation causes cells to grow more mitochondria, thereby increasing ones oxidative potential. Clearly AMPK is not the only protein involved in mitochondrial biogenesis, but it does play a key role.

This behavior is to be expected. You see when you first start a bout of exercise (as in the first few seconds of the first muscle contraction) there is a sharp increase in demand for ATP. This demand cannot be met by oxidative phosphorylation in the mitochondria. So there is a very temporary but very real energy deficit. As AMP-Activated Protein Kinase's (AMPK) name implies it activated by Adenosine Mono-Phosphate (AMP). More specifically, it’s activated by the AMP/ATP ratio. Or even more simply: AMPK is activated when there is an energy deficit. This temporary deficit activates AMPK, which then promotes NRF-1 and PGC-1 production, leading to mitochondrial biogenesis. The entire process of mitochondrial biogenesis is not yet completely understood, but this is certainly an area of interest and something to keep one’s eye on.

AMPK activation also increases cellular concentration of GLUT4 protein (18). The GLUT family of proteins is responsible for transporting carbohydrates into cells. Activation of AMPK may therefore help lower insulin resistance. AMPK is so important for GLUT regulation that its role cannot be overstated. Mice that have their AMPK artificially deactivated are known as “lazy mice” for a reason—there skeletal muscle cannot maintain a store of glycogen and they become incredibly fatigued with even the slightest exertion (19).

Additionally AMPK activation results in the upregulation of Fatty Acid Translocase (FAT/CD36). This protein is to fat as GLUT is to carbohydrates. Its function is to transport free fatty acids across the cellular membrane where they can be used as fuel (12).

An entire article could easily be written about all of AMPK’s various functions. However, considering this article is about leptin and not AMPK we will have to just leave it the explanation where it stands, as further exploration into AMPK is beyond the scope of this article.

Leptin further enhances metabolism by activating the Krebs (TCA) cycle in muscle, as well as pyruvate-dehydrogenase (PDH). PDH is the bridge linking pyruvate decarboxylation to the citric acid cycle. To my knowledge it is not known at this time if this is a direct effect or an indirect one brought about by increased mitochondrial uncoupling (15). Leptin also appears to promote fat oxidation and increased oxygen utilization by some yet undiscovered mechanisms. Specifically, leptin administration induced a large increase in both fat oxidation and oxygen consumption without effecting glucose utilization, AMPK, or ACC in cardiac muscle (14). So, it appears as though all of the pieces of the puzzle have yet to be uncovered.

Furthermore, leptin enhances fatty acid oxidation through some mechanism related to PPAR-alpha. PPAR-alpha is for the most part the opposite of PPAR-gamma. PPAR-alpha, when activated, causes a host of enzymes to be created that elevate fatty acid oxidation. In in vivo studies, PPAR-alpha seems to be linked to leptin’s effects by a yet to be determined mechanism. Specifically, leptin administration to rats increases PPAR-alpha content as well as CPT; it also lowers intra-cellular TAG stored in the muscles and liver. Additionally leptin lowered the amount of ACC present in said tissues.

Clearly this is a near perfect scenario. Leptin is literally priming the pump for fat oxidation to take place. This link between PPAR-alpha and leptin can be verified by experiments conducted on PPAR-alpha knockout mice. When leptin is administered—even at incredibly high level—to these special mice they fail to respond. No increase in fat oxidation, no weight loss, no decrease in ACC, and no decrease in cellular TAG.

Now that’s much better news isn't it? You can officially stop plotting my assassination now, thank you.

Leptin and the Thyroid

Before we dive in and start discussing leptin’s profound effects on the thyroid system, let me first give a very brief review of the hypothalamus-pituitary-thyroid axis.

That wonderful little control center in your brain, the hypothalamus, releases a protein called Thyrotropin-Releasing Hormone (TRH). TRH wanders over to the pituitary gland and causes it to release another hormone called Thyrotropin or Thyroid Stimulating Hormone, but for the remainder of this article we will simply refer to it as TSH. TSH is then relayed to the thyroid gland where the thyroid gland secretes—you guessed it—thyroid hormone.

With that out of the way, we can now discuss leptin’s effects on the thyroid hormone control system. Before I do however, I would like to caution the reader to pay extra close attention to this section and to read it very carefully. I have no idea why but for some reason leptin and the thyroid system have not been discussed in detail in any bodybuilding literature that I am aware of. The reason that I advise you to pay close attention in this section is that, in my opinion, leptin is not some side line player that has only a small effect on the thyroid. It is my contention that leptin is a key player in this system. It may even be the single most important factor governing thyroid hormone levels in healthy individuals.

First let us discuss leptin’s effects on the hypothalamus. When leptin initiates its signal cascade at the hypothalamus it increases TRH output (20). This increase in TRH should cause a concurrent increase in TSH at the pituitary; it should lead to higher levels of thyroid hormone in the blood stream. The literature confirms this as elevated leptin levels are associated with elevated thyroid hormone levels as well. But guess what: that not at all how it works. Now let’s dive deeper in to this system to see why leptin is such a key player in determining thyroid hormone levels (21).

It is true that leptin causes TRH to be released from the hypothalamus. Where things get strange is leptin’s effects on the pituitary gland. As stated previously, one would think that increased TRH results in increased TSH. But this is not the case when one takes leptin’s role in to account. In actuality, the higher the leptin levels are, the lower the level of TSH. This is confusing, I know; it is true however (22). Normally lower TSH means lower thyroid hormone levels—at least in the long run in healthy people. In the short term however TSH and thyroid hormone operate in a negative feedback loop. When thyroid hormone levels get high it causes TSH to go down. When TSH gets too low thyroid hormone levels drop and TSH goes back up. Thus it was thought that TRH is really the main control since TSH and thyroid hormone levels are constantly in oppositional flux.

Leptin throws a monkey wrench into this supposition, however. Specifically, leptin is directly suppressive to TSH release in the pituitary. In fact, it has even been hypothesized that since the pituitary gland creates leptin of its own this is one avenue through which it lowers its own TSH output.

Leptin’s effects on the thyroid gland itself are also very interesting. When leptin signals at the thyroid gland it causes thyroid hormone to be released (23). As you can see this is a pretty complicated relationship. To reiterate: Leptin is positive at the thyroid gland and hypothalamus but negative at the pituitary. This strange relationship is why leptin is such a key player in the control of thyroid hormone levels. Essentially, leptin somewhat overrides the ‘normal’ control system, controlling and in many ways ultimately determining thyroid hormone levels. To shed some light on this paradox, lets stop looking at in vitro research and examine some in vivo studies to see how this really works.

Normally when in caloric restriction, leptin levels and thyroid hormone levels drop. Supplemental leptin administration, given at a replacement dose, brings thyroid hormone levels back within a normal range (24). In a very interesting study rats were starved at 10% below there maintenance calorie levels and monitored for an extended period. During this time—as you would expect—leptin, T3, and T4 levels were all reduced. The researchers then administered the rats with just enough leptin to get them back to their previous pre-dieting levels. As you would expect, thyroid hormone levels returned to normal.

What is interesting is that in a related study, researchers monitored rats that were given supplemental leptin. In these rats TSH was remarkably reduced yet T3/T4 levels were significantly elevated (22). The only viable explanation is that leptin short-circuits the normal negative feedback-loop between the pituitary and the thyroid gland. Essentially, leptin takes control of the thyroid gland and determines the amount of thyroid hormone released.

The link between TSH and leptin is even stronger than one might imagine. TSH not only signals the thyroid gland to make thyroid hormone, it also signals adipose tissue to make leptin (25). It is very potent I might add. In one study researchers took human adipose tissue from elective surgery patients and incubated it with TSH. TSH powerfully stimulated leptin release comparable to that seen by glucose and insulin. Now, that probably comes as a surprise. It appears leptin and TSH operate in a negative feedback loop similar to TSH and thyroid hormone. There is very strong evidence to support this supposition. TSH and leptin blood levels follow the exact same diurnal rhythm. In fact they are so synchronous that there peak blood levels coincide. So it would seem that this negative feedback loop between the two is very efficient and quite powerful (26).

So at this point I think it’s safe to say that leptin is very important for the regulation of the hypothalamus-pituitary-thyroid axis. Further more, it provides some direct insight as to why leptin levels don’t plummet to next to nothing when one’s calories are reduced. You see in the absence of the “feed signal,” TSH output increases due to the drop in thyroid hormone, which in turn serves as a very potent signal to the adipose to secrete leptin.

I know this was a lot of information to take in at once. I suggest you reread it again as, in your humble author’s opinion, the link between thyroid hormones and leptin cannot be overstated.
Of Things to Come

Well that’s all for now. Take some time and ponder the ramifications of all of this. In the next installment of this series we will examine leptin’s effects on various parts of the brain and nervous system, and how it relates to fat loss. This is where things will really start to become interesting, as much of leptin’s power does not come from interacting with various body tissues. Leptin’s primary source of influence comes from its interaction with the brain and the central nervous system. Leptin’s systemic indirect effects are vitally important to its function. These indirect effects are the reason you get the munchies and the reason you can barely get your ass out of bed in the morning while dieting. So tune in next time for the exciting conclusion. Same Spook channel; Same Spook time.

References:

(1) J Biol Chem 1999 Jun 18;274(25):17541
Novel form of lipolysis induced by leptin.
Wang MY, Lee Y, Unger RH.

(2) Horm Res 2002;58(2):88-93
In vitro effects of leptin on human adipocyte metabolism.
Elimam A, Kamel A, Marcus C.

(3) Am J Physiol Endocrinol Metab 2002 Mar;282(3):E593-600
Fatty acid oxidation and triacylglycerol hydrolysis are enhanced after chronic leptin treatment in rats.
Steinberg GR, Bonen A, Dyck DJ.

(4) Cell Signal 2001 Nov;13(11):827-33
Modulation of the leptin-induced white adipose tissue lipolysis by nitric oxide.
Fruhbeck G, Gomez-Ambrosi J.

(5) FASEB J 2001 Feb;15(2):333-40
Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes.
Fruhbeck G, Gomez-Ambrosi J, Salvador J.

(6) J Clin Invest 1997 Dec 1;100(11):2858-64
Direct effects of leptin on brown and white adipose tissue.
Siegrist-Kaiser CA, Pauli V, Juge-Aubry CE, Boss O, Pernin A, Chin WW, Cusin I, Rohner-Jeanrenaud F, Burger AG, Zapf J, Meier CA.

(7) Int J Obes Relat Metab Disord 2001 Oct;25(10):1465
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(8) Am J Physiol Endocrinol Metab 2002 Jan;282(1):E46-51
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(9) Biochem Biophys Res Commun 1998 May 29;246(3):660-7
Leptin regulation of peroxisome proliferator-activated receptor-gamma, tumor necrosis factor, and uncoupling protein-2 expression in adipose tissues.
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(10) Ann N Y Acad Sci 2002 Jun;967:217-35
Regulation of fat metabolism in skeletal muscle.
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(11) Am J Physiol Endocrinol Metab 2002 Jul;283(1):E66-72
Exercise training increases lipid metabolism gene expression in human skeletal muscle.
Tunstall RJ, Mehan KA, Wadley GD, Collier GR, Bonen A, Hargreaves M, Cameron-Smith D.

(12) Biochem Soc Trans 2003 Feb;31(Pt 1):196-201
Role of AMP-activated protein kinase in leptin-induced fatty acid oxidation in muscle.
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(13) Am J Physiol Endocrinol Metab 2003 Mar;284(3):E648-54
AMPK expression and phosphorylation are increased in rodent muscle after chronic leptin treatment.
Steinberg GR, Rush JW, Dyck DJ.

(14) Biol Chem 2002 Aug 16;277(33):29424
Leptin activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinase-acetyl-CoA carboxylase-malonyl-CoA axis.
Atkinson LL, Fischer MA, Lopaschuk GD.

(15) Front Biosci 2001 Jan 1;6:D90-7
The response of skeletal muscle to leptin.
Ceddia RB, William WN Jr, Curi R.

(16) Proc Natl Acad Sci U S A 2002 Dec 10;99(25):15983-7
AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation.
Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI.

(17) Am J Physiol Endocrinol Metab 2001 Dec;281(6):E1340-6
Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis.
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(18) Am J Physiol Endocrinol Metab 2002 May;282(5):E1008-13
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(19) Biochem Soc Trans 2003 Feb;31(Pt 1):236-41
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(20) J Clin Invest 2001 Jan;107(1):111-20
Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling.
Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjoorbaek C, Elmquist JK, Flier JS, Hollenberg AN.

(21) Clin Endocrinol Metab 2002 May;87(5):2391
Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones.
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(22) J Endocrinol 2002 Jul;174(1):121
The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies.
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(23) Int J Mol Med 2002 Jan;9(1):31
Rat thyroid gland expresses the long form of leptin receptors, and leptin stimulates the function of the gland in euthyroid non-fasted animals.
Nowak KW, Kaczmarek P, Mackowiak P, Ziolkowska A, Albertin G, Ginda WJ, Trejter M, Nussdorfer GG, Malendowicz LK.

(24) Clin Endocrinol Metab 2002 May;87(5):2391
Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones.
Rosenbaum M, Murphy EM, Heymsfield SB, Matthews DE, Leibel RL.

(25) J Endocrinol 2003 Jan;176(1):7-12
TSH stimulates leptin secretion by a direct effect on adipocytes.
Menendez C, Baldelli R, Camina JP, Escudero B, Peino R, Dieguez C, Casanueva FF.

(26) J Clin Endocrinol Metab 2001 Jul;86(7):3284
Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling.
Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjoorbaek C, Elmquist JK, Flier JS, Hollenberg AN.
 
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