The following is a chapter excerpt from my Ultimate Diet 2.0, dealing with calorie partitioning. It deals with what controls where calories go when you eat them, and what determines where they come from when you diet. If you read my previous article on AMPk: Master Regulator, it may explain some of the underlying physiology for what's discussed in this chapter. Of course, the rest of the book details an integrated system of nutrition and training to take advantage of this information, to make sure that you pull calories out of fat cells when you diet, and put them back into muscle when you overfeed; with the goal of losing fat while maintaining or gaining muscle at the same time.
Why is it so hard?
At a very fundamental level, the problem natural bodybuilders and athletes have is one of partitioning. At its simplest, partitioning refers to where the calories go (into muscle or fat cells) when you eat more of them or come from (from muscle or fat cells) when you eat less of them.
In an ideal universe, every calorie you ate would go to muscle tissue, with none going into fat cells; you'd gain 100% muscle and no fat. In that same ideal universe, every calorie used during dieting would come from fat stores; you'd lose 100% fat and no muscle. Unfortunately, we don't live in an ideal universe.
As I mentioned early in this book, some hapless individuals will lose as much as one pound of muscle for every 2-3 pounds of fat that they lose when they diet. Typically, those same individuals will put on about the same amount of fat and muscle when they gain weight. Thus is the balance of the universe maintained. More genetically advantaged individuals tend to put more calories into muscle (meaning less into fat) when they overeat and pull more calories out of fat cells (and less out of muscle) when they diet. They stay naturally lean and have few problems dieting. Once again, you aren't one of them, or you wouldn't be reading this book.
When talking about calorie partitioning, researchers refer to something called the P-ratio. Essentially, P-ratio represents the amount of protein that is either gained (or lost) during over (or under) feeding. So a low P-ratio when dieting would mean you used very little protein and a lot of fat. A high P-ratio would mean that you used a lot of protein and very little fat. It looks like, for the most part, P-ratio is more or less the same for a given individual: they will gain about same amount of muscle when they overfeed as they lose when they diet. P-ratio can vary between individuals, of course, but for any given person, it appears to be relatively constant.
So what controls P-ratio? As depressing as this is, the majority of of the P-ratio is out of our control; it's mostly genetic. We can control maybe 15-20% of it with how we eat or train. Supraphysiological amounts of certain compounds (supplements) and, of course, drugs, can also affect the P-ratio. Exercise is perhaps the most significant weapon we have in battling with our body and affecting P-ratio.
So what are the main determinants of calorie partitioning? Hormones are crucially important. High testosterone levels tend to have positive partitioning effects (more muscle, less fat) while chronically high levels of cortisol have the opposite effect (less muscle, more fat). Thyroid and nervous system activity affect not only metabolic rate but also fat burning. Thyroid also affects protein synthesis. Optimal levels of these hormones not only mean better fat loss (and less muscle loss) when you diet but better muscular gains (and less fat gain) when you gain weight. Unfortunately, levels of these hormones are basically "set" by our genetics; the only way to change them significantly is with supplements or drugs. Beyond that, there's not a whole lot we can do to control them.
Another factor controlling P-ratio is insulin sensitivity which refers to how well or how poorly a given tissue responds to the hormone insulin. High insulin sensitivity means that a small amount of insulin will generate a large response; insulin resistance indicates that it takes more insulin to cause the same effects to occur.
Now, insulin is a storage hormone, affecting nutrient storage in tissues such as liver, muscle and fat cells. In that same ideal world, we'd have high insulin sensitivity in skeletal muscle (as this would tend to drive more calories into muscle) and poor insulin sensitivity in fat cells (making it harder to store calories there). This is especially true when you're trying to gain muscle.
When you diet, it's actually better to be insulin resistant (note that two of the most effective diet drugs, GH and clenbuterol/ephedrine cause insulin resistance). By limiting the muscle's use of glucose for fuel, insulin resistance not only spares glucose for use by the brain, but also increases the muscles use of fatty acids for fuel.
In addition to hormonal advantages, it's likely that the genetic elite have high skeletal muscle insulin sensitivity. They store tremendous amounts of calories in their muscles, which leaves less to go to fat cells. Their bodies also don't have to release as much insulin in response to food intake.
In contrast, individuals with poor skeletal muscle insulin sensitivity tend to overproduce insulin, don't store calories in muscle well (this is part of why they have trouble getting a pump: poor glycogen storage in muscle cells) and tend to spill calories over to fat cells more effectively.
So what controls insulin sensitivity? As always, there are a host of factors. One is simply genetic, folks can vary 10 fold in their sensitivity to insulin even if everything about them is the same. Another is diet. Diets high in carbohydrates (especially highly refined carbohydrates), saturated fats and low in fiber tend to impair insulin sensitivity. Diets with lowered carbohydrates (or less refined sources), healthier fats (fish oils and monounsaturated fats like olive oil) and higher fiber intakes tend to improve insulin sensitivity.
Another major factor is activity which influences insulin sensitivity in a number of ways. The first is that muscular contraction itself improves insulin sensitivity, facilitating glucose uptake into the cell. Glycogen depletion (remember this, it's important) improves insulin sensitivity as well.
So what else controls the P-ratio? As it turns out, the primary predictor of P-ratio during over- and underfeeding is bodyfat percentage. The more bodyfat you carry, the more fat you tend to lose when you diet (meaning less muscle loss) and the leaner you are, the less fat you tend to lose (meaning more muscle loss). The same goes in reverse: naturally lean (but not folks who have dieted down) individuals tend to gain more muscle and less fat when they overfeed and fatter individuals tend to gain more fat and less muscle when they overfeed.
The question is why, why does bodyfat percentage have such a profound impact on P-ratio? There are a few easy answers. One is that bodyfat and insulin sensitivity tend to correlate: the fatter you get, the more insulin resistant you tend to get and the leaner you are the more insulin sensitive you tend to be.
A second is that, the fatter you are, the more fatty acids you have available for fuel. In general, when fatty acids are available in large amounts, they get used. This spares both glucose and protein. By extension, the leaner you get, the more problems you tend to have; as it gets harder to mobilize fatty acids, the body has less to use. Since there is less glucose available (because you're dieting) this increases the reliance on amino acids (protein) for fuel. The original Ultimate Diet advocated medium chain triglycerides (a special type of fatty acid that is used more easily for fuel than standard fats) and this can be a good strategy under certain circumstances. I'll mention some other options later on in the book.
But that's not all. It turns out that bodyfat percentage is controlling metabolism to a much greater degree than just by providing fatty acids. Research over the past 10 years or so has identified fat cells as an endocrine tissue in their own right, secreting numerous hormones and proteins that have major effects on other tissues. Perhaps the most important, and certainly the one most talked about is leptin, but that's far from the only one. Tumor necrosis factor-alpha, the various interleukins, adiponectin and other compounds released from fat cells are sending signals to other tissues in the body which affect metabolism.
Without getting into all of the nitpicky details (many of which haven't been worked out yet), I just want to talk a little about leptin (if you read my last book, this will all be familiar ground).
Leptin, the short course
Leptin is a protein released primarily from fat cells although other tissues such as muscle also contribute slightly. Leptin levels primarily correlate with bodyfat percentage, the more fat you have the more leptin you tend to have (note: different depots of fat, visceral versus subcutaneous, show different relationships with leptin). At any given bodyfat percentage, women typically produce 2-3 times as much leptin as men.
In addition to being related to the amount of bodyfat you have, leptin levels are also related to how much you're eating. For example, in response to dieting, leptin levels may drop by 50% within a week (or less) although you obviously haven't lost 50% of your bodyfat. After that initial rapid drop, there is a slower decrease in leptin related to the loss of bodyfat that is occurring. In response to overfeeding, leptin tends to rebound equally quickly (much faster than you're gaining bodyfat). In the short-term at least, and contrary to what you might think, it looks like leptin production by fat cells is mainly determined by glucose availability (you'd think it was fat intake). So whenever you start pulling glucose out of the fat cell (dieting), leptin levels go down; when you drive glucose into fat cells, it goes up.
Basically, leptin represents two different variables: how much bodyfat you're carrying and how much you're eating. That is, it acts as a signal to the rest of your body about your energy stores. I'll come back to this in a second.
Like most hormones in the body, leptin has effects on most tissues in the body. Leptin receptors have been found all over the place, in the liver, skeletal muscle, in immune cells; you name a site in the body and there are probably leptin receptors there. There are also leptin receptors in the brain but I'll come back to that below. For now, let's look at a few of the effects that leptin has on other tissues in the body.
In the liver, leptin tends to reduce insulin secretion from the beta-cells. In skeletal muscle, leptin promotes fat burning and tends to spare glucose (and therefore amino acid use). In fat cells, leptin may promote fat oxidation as well as making the fat cell somewhat insulin resistant. Leptin also affects immune cell function, decreasing leptin impairs the body's ability to mount an immune response. Now you know at least part of the reason you tend to get sick more when you diet. On and on it goes. An entire book could and should be written about leptin.
Leptin and the brain
Now, I want you to think back to the first couple of chapters of this book, where I talked about the evolutionary reasons it's so hard to get extremely lean. To your body, becoming too lean is a very real threat to your survival. From a physiological standpoint, that means that your body needs a way to "know" how much energy you have stored.
As you may have guessed, or known from my last book, leptin is one of the primary signals (along with many others including ghrelin, insulin, peptide YY and other as of yet undiscovered compounds) that "tells" the brain about how much energy you have stored and how much you're eating.
All of these hormones send an integrated signal to a part of the brain called the hypothalamus that "tell" it what's going on elsewhere in your body. Changes in levels of these hormones causes shifts in various neurochemicals such as neuropeptide-Y (NPY), corticotrophin releasing hormone (CRH), pro-opiomelanocortin (POMC) and several others to occur. These neurochemicals regulate metabolic rate, hunger and appetite, hormones and a host of other processes.
So when you restrict calories, causing changes in all of the hormones and neurochemicals mentioned above, a number of physiological processes change, mostly for the worse. Levels of thyroid stimulating hormone, leutinizing hormone and follicle stimulating hormone (TSH, LH and FSH respectively) go down.
This results in lowered levels of thyroid and testosterone. Levels of growth hormone releasing hormone (GHRH) go down meaning GH output can be impaired. Sympathetic nervous system activity goes down which, along with the drop in thyroid, has a huge impact on metabolic rate. Cortisol levels go up as does hunger and appetite. You get the idea. What you end up seeing is an all purposes systems crash when you try to take bodyfat to low levels. I should note that these processes are occurring to one degree or another during all diets, they simply become more pronounced at the extreme low levels of body fat.
Ideally, the opposite effects should occur when you raise calories.
However, for reasons I detailed in my last book, the system is asymmetrical: falling leptin (and changes in all of the other hormones) has a much larger impact on the body's metabolism than raising leptin does (unless you're raising it back to normal). So the body ends up fighting weight loss to a far greater degree than weight gain. Generally speaking, people find that it a lot easier to get fat than to get lean. Of course, there are exceptions, folks who seem to resist obesity (or weight gain altogether). Research will probably find that they are extremely sensitive to the effects of leptin (and other hormones), so when calories go up, they simply burn off the excess calories without getting fat.
Most of us aren't that lucky. Rather, like insulin sensitivity discussed above, researchers will probably find that leptin sensitivity is a huge factor influencing how changes in caloric intake affect metabolism. Someone with good leptin sensitivity will tend to stay naturally lean and have an easy time dieting; folks with poor leptin sensitivity (leptin resistance) won't.
You might be thinking that the quick and dirty solution would be leptin injections. As I pointed out in my last book, injectable leptin is a pipe-dream at this point, an effective dose costs nearly $1000/day (not to mention requiring twice daily injections). Using bromocriptine or other dopamine agonists seem to fix at least part of the problem by sending a false signal to the brain by making it think leptin levels are normal.
Recent studies that have given injectable leptin to dieters show that the fall in leptin is one of the primary signals in initiating the adaptation to dieting. However, unlike in rats, injecting leptin into humans doesn't fix all of the problems.
This is because, in humans, there is more of an integrated response to both over- and underfeeding. To understand this better, I want to take a snapshot of what happens when you either reduce or increase calories.
So you decide to diet, reducing carbs, calories or both. Vary rapidly, blood glucose and insulin levels are going to be reduced. This is good as it releases the "block" on fat mobilization. Additionally, catecholamine release typically goes up (at least initially), further increasing fat mobilization from fat cells. This causes blood fatty acid levels to increase which is also good, as it tends to promote fat burning in tissues such as liver and muscle. The effect is facilitated if you deplete liver and muscle glycogen, as glycogen depletion tends to increase the use of fatty acids for fuel. The increase in blood fatty acid levels also has the short-term effect of causing insulin resistance. As I mentioned, this is a good thing on a diet since it spares glucose and helps promote fat oxidation. So far, so good, right?
Unfortunately, along with these good effects, a lot of bad things start to happen. I already described many of the central adaptations above: changes in leptin, ghrelin, Peptide YY (and certainly other hormones) "tell" your brain that you're not eating enough. This causes changes in the various neurochemicals stimulating a number of negative adaptations. I want to note that the response is not immediate, there is a lag time between the changes in all of these hormones and the body's response. But that's not all.
There are also many other adaptations which occur when you diet, so let's look at some of those. First and foremost, the drop in leptin directly affects liver, skeletal muscle and fat cell metabolism, mostly for the worse.
While the drop in insulin mentioned above causes better fat mobilization, it causes other problems. One is that testosterone will bind to sex-hormone binding globulin (SHBG) better, lowering free testosterone levels (this is in addition to the drop in total testosterone).
As well, insulin is anti-catabolic to muscle, inhibiting muscle breakdown. The increase in cortisol that occurs with dieting enhances protein breakdown as well as stimulating the conversion of protein to glucose in the liver. Additionally, a fall in energy state of the muscle impairs protein synthesis (although it increases fatty acid oxidation). The mechanism behind this is more detail than I want to get into here. But the combined effect of these processes is to decrease protein synthesis and increase protein breakdown; this causes muscle loss.
On top of that, high blood fatty acid levels tend to impair the uptake of T4 (inactive thyroid) into the liver. There are also changes in liver metabolism that impair the conversion of T4 to T3 (active thyroid). Both of these processes cause decreased blood levels of T3. There is some evidence that high blood fatty acid levels causes tissues to become resistant to thyroid hormone itself (this is part of why just taking extra thyroid on a diet doesn't fix all of the problems). After the initial increase, there is also a drop in nervous system output (that can occur in as little as 3-4 days after you start a diet). Along with the drop in thyroid, insulin and leptin, this explains a majority of the metabolic slowdown that occurs. The change in liver metabolism (and the reduction in insulin) also impairs the production of IGF-1 from GH.
All of these adaptations serve two main purposes. The first is to slow the rate of fat loss, as this will ensure your survival as long as possible. Related to that, the body tends to shut down calorically costly activities. This includes protein synthesis, reproduction and immune function; there's little point keeping any of these functioning when you're starving to death. The drop in leptin, and the changes in hormones that occur are a huge part of why men tend to lose their sex drive (and ability) and women lose their period when they get lean/diet hard.
The second is to prime your body to put fat back on at an accelerated rate when calories become available again. Decreased metabolic rate and fat burning, along with improved caloric storage all conspire to put the fat back on when you start eating again. As I mentioned earlier, this makes perfect evolutionary sense, even if it presents a huge pain in the ass to us.
I haven't even mentioned the hunger and appetite issue which is a topic worthy of an entire book. The combination signal sent by leptin, ghrelin, insulin, glucose, and a host of other hormones (cholecystokinin, glucagon-like peptide 1 and 2, bombesin and many, many others) are all involved in both hunger and appetite. The changes that occur with dieting tend to make both shoot through the roof: you tend to get and stay hungry, thinking about food nearly constantly. Bodybuilders and athletes may have unbelievable food control but it still sucks being hungry constantly when you try to diet.
Ok, enough about dieting, what about overfeeding?
To a great degree, most of the adaptations that occur with dieting reverse when you overeat. Actually, that depends a lot on the situation. As I mentioned above, the body as a whole tends to defend against underfeeding better than it does against overfeeding which is why it's generally easier to gain weight than to lose it. Studies where leptin has been increased above normal (i.e. to try and cause weight loss in overweight individuals) have generally borne this out: except at massive doses, raising leptin above normal does very little.
There are a couple of theories as to why this might be the case. One theory is that normal leptin levels send essentially a 100% signal, that is they tell the body that all systems are normal. It should seem clear that raising leptin above 100% isn't going to do much. Another possibility is related to something I alluded to above: leptin sensitivity and resistance. It's thought that people have varying degrees of leptin resistance which means, in essence, that they don't respond as well to leptin as they should. On top of this, when leptin levels go up, it appears to stimulate resistance to itself. That is, when leptin gets and stays high, it causes you to become resistant to its effects.
Both explanations for the failure of high leptin levels to defend against weight gain make good evolutionary sense. Your body doesn't want to be lean but it doesn't really mind getting fat. This is because, during our evolution, being fat was never a risk, while being lean was. If anything, getting fat was a benefit which is why our bodies tend to be so good at it. It's only in modern times when people can get and, more importantly, stay fat for extended periods, that being fat is a problem. Ten thousand years from now, perhaps we will evolve defenses against being fat.
Anyhow, if calories are available all the time, it would make little sense for you to get full and/or start burning them off. This is what would happen if you were extremely sensitive to leptin (and does happen in a small percentage of individuals). So high levels of leptin induce resistance to itself, keeping you hungry and eating while the food is available. Leptin can induce resistance to itself in only a few days of overeating.
But we're not really talking about raising leptin above normal here, we're talking about reversing or preventing the drop that occurs with dieting. In that situation, many of the above adaptations to dieting will reverse to one degree or another. What degree will depend on how lean you are, how long you diet, and how long you overeat.
So now you increase your calories and carbs. Let's look at some of what happens when you do so. First there are all of the central adaptations that occurred during dieting, that will reverse to some degree while overfeeding. Leptin will go up (noting again that it goes up more quickly than bodyfat comes on) along with insulin and peptide YY, ghrelin goes down. This signals the hypothalamus that you're eating again telling the body to reverse the adaptations that had occurred in the first place.
In addition, the increase in insulin will reverse the binding of testosterone to SHBG; cortisol also goes down. With increased carbohydrates, you increase both liver and muscle glycogen. While this decreases fat oxidation in the muscle, you get improved protein synthesis (the increase in insulin and testosterone and the drop in cortisol have an additional effect).
Of course, with increasing insulin, there is a decrease in blood fatty acid concentrations which improves insulin sensitivity. Skeletal muscle insulin sensitivity is enhanced even more by exercise.
The decrease in blood fatty acids, along with changes in liver metabolism will improve both the uptake and conversion of T4 to T3; along with improvements in nervous system output, this will help to increase metabolism. You get the idea: with overfeeding, the body reverses the basic adaptations that occurred to dieting in the first place.
Summing up for now
Looking at the chart below, you may start to appreciate the problems involved, especially for the genetically normal. Underfeeding is necessary for fat loss but will always have a negative impact on muscle mass. Dieting also induces a number of adaptations that tend to limit or slow further fat loss. Overfeeding is necessary to gain muscle but will always have a negative impact on fat mass. However, it can reverse many of the adaptations that occur with dieting.
Table 1: Summary of changes with dieting and overfeeding
|Protein||Up||No change or up|
|Total testosterone||Up or no change||Down|
|Cellular energy state||Up||Down|
|Net effect||Body is systemically anabolic||Body is systemically anabolic|
A final note on leptin
Hopefully the above sections have made you realize that there is far more to the adaptations to either dieting or overfeeding than just leptin. Rather, there is an integrated response involving leptin, insulin, ghrelin, fatty acids, liver, fat cell and skeletal muscle adaptations, and probably factors that haven't been discovered yet. This probably explains why injecting leptin into dieting humans reverses only some but not all of the adaptations to dieting.
For example, just injecting leptin would be expected to fix a defect in TSH (and thyroid output) and it does do this. But injectable leptin won't fix the problems with conversion that occur at the liver. Similarly, while injecting leptin would normalize LH and FSH output, it won't correct the problem with increased binding of testosterone to SHBG caused by lowered insulin. Hopefully you get the picture. Now we know the problem. What's the solution?
What I've basically done over the previous pages is make a long-winded argument for cyclical dieting, that is periods where you alternate a low-calorie intake with a high-calorie intake. More specifically I'm describing a diet where you alternate between periods of low calories/carbs with periods of high calories/carbs to alternate between periods of anabolism (tissue building) and catabolism (tissue breakdown). Of course, this is nothing new.
There have been numerous other schemes over the years that alternated periods of low and high calories. DiPasquale's Anabolic Diet, Rob Faigan's NHE and many others have come and gone over the years.
Several years ago, when I first started making some of the connections between leptin and everything else, this really pointed out the need to do periodic refeeds (or cheat days or whatever you want to call them) on a diet. I think it explains part of why people got better results with the Bodyopus diet: it wasn't the ketogenic phase so much as the two day carb-load which refilled muscle glycogen, maybe instilled an anabolic response, and reversed some of the adaptations inherent to dieting.
Since the Bodyopus days, a number of approaches have come and gone. In general, short refeeds, lasting from 5 to 24 hours done anywhere from once per week to every other day (depending on such variables as bodyfat percentage and how hard you're dieting) while dieting have been used. I've tried them all with varying degrees of success.
One of the factors I've been considering lately has to do with the duration of the overfeeding period. While it's true that 5 (or 12 or 24) hours of concentrated overfeeding will raise leptin, the more important question is whether that's sufficient to "tell" the brain that you're fed. While data (especially in humans) is nonexistent, my hunch is that it is not.
My basic reasoning is this: there's a lag time of several days between the drop in leptin and the drop in metabolic rate (nervous system output) for example; I'd be surprised if a mere 12 or 24 hours was sufficient to reverse this. Rather, I'd expect it to take a similar amount of time for the reversal to occur. The more extended logic of my reasoning is beyond what I want to put in this book, email me if you must know.
Now, this isn't to say that short carb-loads/refeeds aren't of benefit. They refill glycogen, turn off catabolism briefly and maybe induce an anabolic response to boot. They also let you eat some of the crap you're really craving which helps psychologically. But I doubt they are sufficient to affect metabolism very much. Instead, a longer refeed is most likely necessary. The drawback, of course, is that longer refeeds have a tendency to put too much bodyfat back on which goes against the entire goal of dieting.
Perhaps the biggest problem with many cyclical dieting approaches is that they don't coordinate training with the diet. Bodyopus was an exception but, for various reasons, I think the workout plan was screwy. If anything, it was backwards, putting tension workouts on low-calorie/low-carb days (where you aren't very anabolic) and glycogen depletion workouts before you are eating a lot. This seemed wrong to me years ago and more wrong to me now that I've delved into it in more detail. This will make more sense as you read the next chapters.
Ultimately, all of this introductory stuff, brings us to the final question: how do we optimize a diet to maximize fat loss with either muscle maintenance or muscle gain (or, if you're a performance athlete, how do we generate fat loss while maintaining performance)? To understand that, I need to get into a few more details regarding muscle gain and fat loss, which will help you to understand the overall system.