Ever since The Cheat to Lose Diet interview posted here a few weeks ago, the requests have been rolling in from readers wanting to know more about the hormone leptin. As such, I decided to write my most comprehensive leptin article to date detailing the findings of the available leptin research along with some practical application to boot.

In the pages to follow, I'll address everything from what leptin is and does, how blood levels are mediated, how the hormone affects your dieting and fat loss efforts, it's correlation with specific macronutrients, its affect on appetite and metabolism, leptin resistance, and most importantly how you can get this powerful hormone working for you as you diet to keep metabolism and fat loss at its peak, week after week.

An In-Depth Look at Leptin

A leptin molecule looks a lot like a mangled telephone cord.

You probably know that leptin is a hormone, and you may even have heard it referred to as the "anti-starvation" hormone, but let's dig a little deeper. Leptin (derived from the Greek word leptos, meaning thin) was discovered just over 10 years ago by Jeffrey M. Friedman and his team of researchers at Rockefeller University. A 167-amino acid protein-based hormone, leptin is secreted by adipose tissue (fat cells) and communicates one's nutritional status to the body through its associated receptors.

The bulk of leptin receptors are located in the body's "feeding center" within the hypothalamus of the brain, but there are also receptors elsewhere throughout the body, such as in hepatic (liver) and skeletal muscle cells.

Leptin levels are mediated by two things. One is your level of body fat. (1 - 7, 11, 14, 17, 19, 23, 24, 27, 28, 33, 37, 44, 55, 65 - 67, 69) All else being equal, people with higher levels of body fat will have higher leptin levels than those with lower levels of body fat and vice versa. Because leptin is secreted by fat cells, it makes sense that under normal conditions there is a direct correlation between leptin levels and the amount of fat one is carrying.

Unfortunately, when you're attempting to lose fat and begin to restrict calories, conditions are anything but "normal," and the body responds accordingly by lowering leptin levels. This is because the second mediator of serum leptin is your calorie intake. Lower your calorie intake and leptin will fall, independent of body fat. (26, 44, 55, 56, 58, 59, 65 - 67)

So what happens when leptin levels fall and why the heck does it matter? Again, under normal conditions leptin levels are normal and because there's plenty of binding occurring to the receptors of the hypothalamus, the brain gets the signal loud and clear that nutrition intake is adequate. Metabolism is high and the internal environment of the body is one very conducive to fat burning.

An environment conducive to fat burning.

Until you start dieting.

When you go on a diet, leptin levels quickly plummet (by 50%+ after only one week [1, 59]), sending a signal to the body that you're semi-starved and not consuming enough calories. This puts the breaks on metabolism and creates a hormonal environment extremely conducive to fat storage. Thyroid hormones respond by taking a dive and the abdominal fat-storing stress hormone cortisol skyrockets measurably. And if that wasn't bad enough, the appetite-stimulating hormones ghrelin, neuropeptide-Y, and anandamide all hop on board to make your life even more miserable.

Despite having a pretty good reason for its reaction, it's pretty ironic that our bodies are primed for fat loss at every other time exceptwhen we're trying to lose fat. Wouldn't it be great if we could maintain high leptin levels and a body primed for fat burning while dieting? It would seemingly solve all of our problems. In order to do this, though, we'd somehow have to keep leptin levels high as we attempt to lose those extra pounds.

So Can't We Just Take Some Leptin or Something?

Well, technically you can, but there are a couple of problems. First, recall that leptin is a protein based hormone, so that rules out a leptin pill and oral administration. This leaves the method of exogenous leptin administration to injection. And leptin injections do indeed work, reversing the metabolic adaptations to dieting and "starvation" even while continuing to restrict calories.

- In 1996, Ahima et al. used exogenous leptin to reverse starvation-induced neuroendrocrine adaptations in mice. (35)

Before regular leptin injections, this mouse thought he had to stay hungry.

"Well, that's nice and all," you're probably saying, "but I'm not a mouse, I'm a human!" Fair enough. Research with rodents doesn't always correlate to similar findings in humans, however:

• In 1999, Heymsfield et al. performed a double-blind placebo controlled study analyzing weight loss over a 24-week period in 73 obese humans. Subjects either injected daily with leptin or a placebo. At the end of the 24-week period, the leptin group lost significantly more weight than the placebo group and a higher percentage of fat vs. lean body mass. (70)

• In 2002, Rosenbaum et al. administered low-dose leptin to subjects (male and female) who had dieted to a 10% decrease in body weight. During the diet period, thyroid hormone levels (T3 and T4), 24-hr energy expenditure, and other metabolic markers substantially decreased. The result of the exogenous leptin replacement therapy? "All of these endocrine changes were reversed..." Thyroid output and daily calorie burn increased back to pre-diet levels. (8)

• In 2003, Fogteloo et al. showed that exogenous leptin injections "tended to reduce the decline of energy expenditure associated with energy restriction, whereas the tendency of energy intake to increase back to baseline levels in placebo-treated subjects was largely prevented in subjects treated with leptin." In other words, not only did the leptin group experience less of a decline in energy expenditure, but they were also less hungry, allowing them to more easily adhere to the prescribed dietary regimen. (60)

• In 2004, Welt et al. reported that leptin administered to women with secondary hypothalamic amenorrhea due to reduced fat mass reversed the decline in hypothalamic-pituitary-gonadal axis function and raised circulating concentrations of both T3 and T4. (71)

• In 2005, Rosenbaum and company were at it again, showing that energy expenditure, skeletal muscle work efficiency, sympathetic nervous system tone, and circulating concentrations of T3 and T4 returned to pre-weight-loss levels with exogenous leptin. (84)

So, as theorized, keeping leptin levels high during a diet does indeed solve our dilemma by avoiding the negative metabolic (and perhaps behavioral) adaptations that calorie restriction perpetuates. The problem? Daily leptin injections are far too expensive, costing thousands and thousands of dollars per week. So, we can pretty much forget about exogenous leptin as a solution (which is probably moot anyway considering that not too many people are going to voluntarily plunge a needle into their skin daily).

Leptin addicts easily spend thousands of dollars a week to feed their habit.

Another (Better) Option

Now that we know that exogenous leptin isn't going to save us, let's talk about the possibility of manipulating endogenous leptin levels (your body's natural production of leptin). And the good news is, this indeed can be done, and without involving needles or thousands of dollars. And even better, it's achievable with the help of two things you're sure to enjoy: more calories and more carbs.

We know that leptin levels decrease by about 50% after only one week of energy restriction, but fortunately, it doesn't take nearly that long for leptin to bump back up with a substantial increase in caloric intake. In fact, research has shown that it only takes about 12-24 hours. (27, 55, 61) So, the answer to the fat loss catch-22 lies within strategic dietary cheating.

A strategic cheat meal will boost leptin levels, helping you to lose fat.

By strategically cheating with high calorie foods (and yes, even stuff like pizza, ice cream, wings, cookies, burgers, fries, etc.), you can give leptin and metabolism a major boost mid-diet which sets you up for plenty of subsequent fat loss when you resume your reduced calorie eating regimen. This means greater net fat loss week after week, and ultimately, a much more realistic, maintainable way to bring you to your leanest condition.

So what's so special about carbs? Well, leptin, carbohydrate, and insulin have been shown to have very strong ties. (3, 11, 58, 16, 18, 23, 32, 56, 62, 68) Calories alone don't get the job done, as research shows that overfeeding on protein and fat has little effect on leptin. (11, 15, 32, 68)

In order to get a strong leptin response from overfeeding, there needs to be plenty of carbs in the mix. In fact, the relationship is so strong that research conducted by Boden et al. at the Temple University School of Medicine shows that leptin levels will not fall even in response to all-out fasting so long as insulin and glucose are intravenously maintained. (16) Pretty interesting stuff!

Because of this carbohydrate-insulin-leptin relationship, it makes sense that foods combining both carbs and fat (like those mentioned above) work best for reversing the adaptations caused by calorie restriction because of the synergistic insulin response they produce. But even more importantly, this relationship gives us an indicator of just how important and useful carbohydrates are on "diet" days.

By manipulating carbohydrates strategically on diet days, it should be possible to counteract or at least slow down the leptin decline when returning to dieting. And I'll take this opportunity to shamelessly plug my book, as this type of strategic carbohydrate cycling combined with higher-calorie Cheat Days is exactly what I outline in detail in The Cheat to Lose Diet.

Want to boost your leptin levels? Better buy this book!

Leptin and Cheating FAQ

So if high leptin levels really jack up metabolism and fat burning, why are obese people with the highest leptin levels still so fat?

The most obvious reason is because these people don't spend any time in a caloric deficit, so fat loss isn't going to happen even when leptin is high. Still, it is, or at least it can be a little more complex than that simple explanation, so let's take a look.

When leptin was initially discovered, it was hypothesized that obesity was the result of some sort of genetic leptin deficiency in overweight individuals. After all, a genetic disorder in which very little or no leptin is being produced would cause the body to think it's literally always in a state of starvation, resulting in permanently slowed metabolism and increased fat storage (pretty much the ideal recipe for obesity). So, it made sense.

Unfortunately, when they actually moved forward and analyzed blood samples of obese subjects, instead of the theorized shortage of leptin, there was leptin galore, baby. Welcome to the world of leptin resistance. Just like with a type II diabetic (not type I, as theorized) whose insulin feedback system is no longer functioning properly, leptin receptors become desensitized over time as a result of long-term poor dietary habits and high levels of body fat. While overweight individuals do indeed have high levels of circulating leptin because of the high amount of body fat they possess, these high levels don't mean much when they're not able to communicate effectively with the hormone's receptors.

Welcome to the world of leptin resistance.

The good news is that leptin resistance can be reversed through improvements in diet and exercise habits, and re-sensitizing leptin receptors is actually the major purpose of the Priming Phase of The Cheat to Lose Diet.

I've seen studies that show a decrease in serum leptin as a result of exercise. What gives?

Exercise has been shown to increase leptin sensitivity, (72-83) which will in turn decrease the amount of leptin that is needed to send the "fed" signal to the brain. So, decreased baseline levels of leptin are actually a positive adaptation in this instance.

I saw a study that showed high leptin levels are correlated with low Testosterone levels. Come on, this is T-Nation, the epitome of high T levels!

Take a closer look next time. The study you're referring to (85) analyzes the T levels of obese, leptin resistant individuals. Need I say more?

Isn't cheating on my diet just going to cause tons of water retention and weight gain? I'm not trying to negate all of my weekly progress.

A large increase in calorie intake after spending days in even a moderately calorie restricted state will always result in water retention and weight gain (with maybe even a smidgeon of fat gain? It's not inconceivable).

Cheating on your diet: it doesn't mean what you think it means.

When you take a look at net weight loss from week to week, however, you will see that weight and body fat will consistently decline, and that you're consistently looking leaner and leaner.

Daily measurements mean nothing, and it's very counterproductive psychologically to measure immediately after a Cheat Day. Don't do it. Keep track of weekly measurements and as long as they're decreasing (and they should be), you're on the right track.

Wrap Up

I hope this article has equipped you with a great deal of new dietary and leptin-related knowledge. It's always fun to explore the scientific side of things, as the more we learn, the closer we're able to come to our biggest physique goals. Until next time, enjoy your quest to the fastest fat loss, and most importantly, happy cheating!

About Joel Marion

Joel Marion, CISSN, NSCA-CPT, and 2001 Body-for-Life Champion, is an authority on the use of dietary cheating tactics to accelerate fat loss. His ideas and theories have reached people all across the globe through his frequent contributions to popular health and fitness magazines, both in print and on the Web. Additionally, he's a highly sought-after consultant to doctors, lawyers, athletes, and models as well as the average Joe and Jane looking to improve his or her appearance.

His debut book, The Cheat to Lose Diet, published by Random House, Inc. is now available at all bookstores and online retailers nationwide. To learn more, visit Joel's web site and the Cheat to Lose Diet site.

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