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Leptin: The Next Big Thing in Body Composition, Part 2

A refeed (or cheat day) may appear to fly in the face of common sense, but in order to keep fat loss going, you?ll benefit from eating more, not less.

Last month you learned about leptin and the fed state'and why they are of paramount importance in building your ideal physique. Let's apply that knowledge to training, diet and supplementation so you can tailor a program to your biochemistry, your genetic body type and your personal fitness goals.

Here's a recap of Part 1:

'Leptin is the primary hormonal signal indicating the nutritional state of the cell and, thus the body.

'Adequate leptin signaling'and the fed state'are associated with anabolism and high rates of fatty acid oxidation.

'A decrease in leptin causes the slowing of fat loss, increase in hunger and cravings, loss of energy and general malaise that accompany prolonged dieting.

'Leptin is signaled by fat stores as well as by nutrient intake'specifically, various foodstuffs and their metabolic by-products.

'Thanks to evolution, there's a hierarchy of nutrient uptake that favors lean tissue over fat.

'Micronutrients are far more important than macronutrients

'When bodyfat levels are above about 15 percent for men and 20 percent for women, leptin resistance becomes a major player in body composition. Fortunately, there's ample opportunity to use that information to optimize your individual biochemistry via diet, training and supplementation in order to keep your body in the fed state without letting nutrients spill over into bodyfat cells. It can be of tremendous benefit in your efforts to keep your bodybuilding progress efficient and continuous.

On its own leptin expression and signaling will invariably fall when you restrict calories. Even so, your starting place and the rate of change will be based on genetics, previous lifestyle and your current regimen, so there's no point in getting into microgram-per-liter detail. Assays for determining an individual's leptin levels aren't readily available anyway, so general guidelines combined with monitoring your experience will be your primary tool for rational manipulation.

Nutrient Signals

With regard to leptin expression and the fed state, you can manipulate a number of nutrient-signaling categories. The major categories include the hexosamine biosynthetic pathway, whole-body protein synthesis, cell volume, ion transport, second messengers, inflammation response, ATP, metabolic cofactors, nutrient flow, mood chemicals and leptin sensitivity. I'll discuss them in terms of diet, exercise and supplementation, pinpointing which categories you can manipulate with each part of your program. There will be some crossover, but I'll try to make things simple. Endomorphs have cellular biochemistry similar to that of the obese, whose adipostat is broken, so I'll cover them separately. The general recommendations apply to mesomorphs and ectomorphs, or the muscular and the skinny.


Because of the evolutionary hierarchy of nutrient flow, you want to avoid chronic overfeeding, which quickly fills the cells of the muscle and other lean tissues but subsequently shifts the body toward fat storage. For the same reason you also want to avoid large, acute fluxes of nutrients, except when blood flow to lean tissues is greatly elevated, such as after training. So your starting point is a balanced diet, at near maintenance, with plenty of fiber to ensure a moderate, steady flow of nutrients.

Assuming you aren't at very low bodyfat levels, you already have plenty of fatty acids to supply energy, so we want a lowfat diet. Drop fat intake to 10 percent or so, but since that's a bit too much of a calorie deficit without proper supplementation, bump up your carbs to 50 to 60 percent of total calories, as they're the substrate for hexosamine synthesis (more on that later). Unprocessed, lower-glycemic-index carbohydrate foods tend to have far more of the all-important micronutrients, so stick with those as much as possible.

You should be getting the standard one gram of protein per pound of bodyweight. You can also experiment with higher intakes, as protein stimulates CCK, which is quite synergistic with leptin.

Certain fatty acids are strong mediators of nutrient signaling, so this is a lowfat diet with a twist. Small amounts of oleic acid will help with nutrient uptake in muscle, so you want 10 grams or so per day from nuts or olive oil. Fish oils will do wonders for leptin sensitivity and fatty acid oxidation, so if you like salmon or mackerel, dig in.

Finally, some so-called bad fats, such as those found in eggs and meat, are precursors for prostaglandins, which mediate inflammation-type anabolic responses and increases in protein synthesis. They can also drive more nutrients into the hexosamine pathway. So be bad: Have a few yolks or an ounce of cheese, and don't skimp on the lean red meat.


Hexosamines are by-products of carbohydrates, with glucosamine and galactosamine being particularly important. Research shows that 1 to 3 percent of glucose enters the hexosamine pathway. I've seen no data on galactose, but it's probably similar. The two substances are very potent stimulators of leptin expression'and until very recently they looked to be the nutrient factor for leptin levels.

Other research shows that diets that consist of 60 to 70 percent fat or sucrose lead to significantly lower leptin levels than those that contain calorically equivalent amounts of starch, and both the high-fat and high-sugar plans have negative effects on nutrient uptake in muscle. So, as a rule, don't go the low-carb route, go easy on the fructose and processed-carb sources, and have some skim milk with your meals or MRPs. Refeeds

A refeed (or cheat day) may appear to fly in the face of common sense, but in order to keep fat loss going, you'll benefit from eating more, not less. And I don't mean having a slice of pizza or eating maintenance calories for a day. I'm talking about pigging out for 12 to 24 hours'and to top it off, most of the calories you take in will come from the evil carbohydrates. It's basically a rational, efficient version of the so-called cheat day that has been around forever. I don't care for that term, however, because it implies that you're doing something wrong. This is planned, so I call it a refeed. The psychological component is important, as pleasure chemicals such as dopamine, beta-endorphin and serotonin are strong mediators of nutrient uptake and the fed state, but it isn't the only, or even most important, aspect. Your goal on refeed day is to increase leptin with excess food intake.

Because of the importance of hexosamines, you load carbohydrates, limiting fructose to 50 to 100 grams. Fat and protein should be similar to what you eat on your normal diet, minus the bad fats, unless fat loss is much easier for you than muscle gain.

Frequency and length of refeeds depend on bodyfat levels and body type. The longer and more severely you have dieted'and so the lower leptin has fallen'the more frequently you'll need to refeed. Ideally you want to do it on a regular basis, before all of the signs of low leptin (cravings, fatigue, irritability) show up.

You probably won't benefit from refeeds if you're above 15 percent bodyfat, and for naturally lean people that limit could be as low as 10 percent. Again, there are lots of variables, so the best approach is to pay attention to your body. I am a fan of short, fairly intense refeeds, which keeps lipogenic enzymes from having time to upregulate, so I recommend eating about 50 percent more calories per unit of time than on diet days, done for about eight to 12 hours. You start about four hours before a workout in order to direct substrate flow to anabolic processes in muscle rather than fat.

If you're at 15 percent bodyfat, refeeding every five to seven days should be adequate. Schedule it around a workout that includes squats or deadlifts. As the diet progresses and bodyfat lowers, you will notice yourself needing refeeds more frequently. When you get to 12 percent bodyfat, you may need them every three to four days, and when that drops to less than 10 percent, you may find yourself doing them every second or third day. My personal favorite split was to diet for 36 hours and refeed for 12, timing it around legs, back and then chest training on days 2, 4 and 6, respectively, then hit legs again on day 8. I now keep my cells fed via supplementation, so I refeed a lot less often, but that approach was extremely effective and easy to stick with.


Despite its effectiveness, the refeed is not the ideal approach. Even if you do it perfectly, you're still halting fat loss while overeating, and for many people the outcome is far worse than that. If you don't do the workout, the excess calories are likely to spill over into fat. Many people just lose it once they start eating, and they end up on a two-day sugar-and-fat binge, canceling out days of discipline and progress.

Such cycling also tends to promote binge behaviors in general'if you're prone to that and you aren't careful. That can carry over into drugs and alcohol, thrill seeking, sex or whatever your poison may be. They all share the same reward and reinforcement pathways. Combined with the fact that dieting increases receptor sensitivity to reward, you could find yourself cuckoo for Cocoa Puffs (or halfway through a 30-pack of Marlboro Reds) before you know what hit you.

For that reason I recommend mitigating the extremes of this calorie cycling by shooting for consistent repartitioning. In practical terms that means you stop the overeating and replace the lost nutrients'fed signaling'with supplements, which have far fewer calories for the same degree of nutrient signaling. That point becomes especially important as you get lean and need more refeeds.

Regarding the nutrient-signaling categories listed above, there are a number of supplements, readily available, that can help with each:

Hexosamine biosynthetic pathway: Glucosamine, galactose, chondroitin (contains galactosamine)
Whole-body protein synthesis: Essential amino acids, BCAAs, leucine
Cell volume: Taurine, glycine, glutamine, sodium, creatine
Ion transport: Potassium, chloride, calcium
Second messengers/signal Transduction: IP6, inositol
Inflammation response: Egg phospholipids, arachidonic acid, safflower oil
ATP: Malate, succinate, citrate, acetate
Metabolic cofactors: Zinc, magnesium, antioxidants (especially sulphur-containing thiols, such as NAC, lipoic acid and glutathione)
Mood chemical precursors: l-tyrosine, D,L-phenylalanine, 5-HTP, DMAE, lecithin
Leptin sensitivity: Fish oil, synephrine, acetyl-l-carnitine, histadine


There are data and reasoning in support of several different approaches to training for leptin manipulation. A weight-training workout generally doesn't burn a great number of calories, yet resistance training is the single biggest initiator of nutrient repartitioning you have at your disposal. The reasons are twofold:

1) Protein synthesis and cell repair are extremely energy-greedy processes, with fatty acids supplying most of the energy.

2) Weight training specifically increases substrate flow to muscle over fat, via increases in blood flow, as well as through AMPK activation.

High tension on the muscle, particularly in the eccentric phase, or negative part of the rep, is the key to damaging the muscle sufficiently to set off the chemical cascade that leads to growth. So you need to move some decent weights, and you need to spend at least three to four seconds on the lowering portion of each rep. The use of plyometric-type training can also be useful for inducing a great amount of mechanical tension on muscle fibers.

Unfortunately, significant muscle damage inhibits nutrient uptake as a protective measure. The inflammation response is already great from this type of training, and the metabolism of further substrates within the cell could potentially increase the inflammation to where it's toxic to the cell. So there's a trade-off.

On the other hand, volume training done with higher reps greatly increases blood flow to the working muscle while creating a metabolic demand in muscle cells, without the excess muscle damage provoked by heavy negatives. The outcome: The partitioning of nutrients is optimized. You will still create adequate tension on the fiber, muscle damage and so on to trigger the growth response.

If you do high reps at high intensity, you'll also strongly activate AMPK and the sympathetic nervous system, which preferentially increases the use of fatty acids for fuel, sparing glucose and even facilitating increases in glycogen stores in the muscle. Interestingly, leptin has tissue-specific effects on muscle quite similar to those, and, not coincidentally, AMPK and the sympathetic nervous system are major components of leptin sensitivity.

So which is the best workout style for you? Because of nutrient uptake and partitioning issues, when you're incorporating refeeds, the higher-volume, lower-damage approach is without question superior. There are a number of programs in that category, from GVT to glycogen-depletion workouts, so use the one(s) you like.

If you're not using refeeds, then it comes down to your schedule and personal preference. Heavy negatives will help you initiate the anabolic response in far less time than would volume training, so if you're busy or don't really like working out, a couple of heavy sets followed by drop sets to failure to increase blood flow will get you in and out of the gym in 20 to 30 minutes with nice results. The heavy poundages are also fun for the ego.

On the other hand, if you have two hours a day to dedicate to the gym (and also take care of nutritional needs in and around the workout), you can do some truly remarkable things for body composition with longer workouts and high-volume training. That's because you can preferentially direct so much substrate flow through the muscle rather than fat; that's ultimately what nutrient repartioning is all about.

The Endomorph

The biochemistry of an endomorph is similar to that of someone who consistently overeats. The system is not broken yet, as it is in an obese person, but there are hints, and endomorphs are much more susceptible to creating problems with abuse. If you're an endomorph, you'll have much less difficulty maintaining leptin levels and an anabolic state and much greater chance for spillover of nutrients to fat. The answer is to cut calories more severely (including carbs), stay away from the 'bad' fats and fructose, and refeed less frequently and intensely (24 hours of 10 to 20 percent over maintenance every one to two weeks).

Increasing leptin sensitivity is a high priority, so you'll want to swallow fish oil capsules like a madman. I wouldn't consider 20 to 40 caps a day excessive. That will increase beta oxidation, so supplementation with antioxidants, such as vitamins E and C and the thiols is a must. Ideally, you'll be doing higher-volume training, with short rest periods, to activate AMPK and increase overall induction and utilization of fatty acids.

I hope my tour of the wonderful world of leptin has been informative and enjoyable. By necessity, I've left out huge amounts of detail and data. A PubMed search of 'leptin' in the Medline database returns 6,500-plus studies, so if you're interested in learning more, you'll find yourself in research heaven. IM

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