Leptin, Weight Loss, and Health Improvement

You've probably heard you could reverse your diabetes if you lost weight. And if you have lost a lot of weight and kept it off, you've probably learned this claim is bunk.

Despite the intensity which which this claim is made by doctors, my experience and that of dozens of people who responded to my weight loss poll has been that weight loss, even large amounts of weight loss do little or nothing to change our ability to metabolize glucose.

You might wonder then why there is so much data suggesting that weight loss prevents diabetes. I've given this some thought, and my conclusion is that in the large population studies used to support the "weight loss prevents diabetes" meme what we are really seeing is something else entirely: Fat people who can lose weight easily are most likely those who do not have the fatally disturbed glucose metabolisms characteristic of Type 2 diabetes.

I have never seen a prospective study in which people positive for the genes associated with diabetes were able to prevent diabetes by losing weight. I have seen studies where thin people with diabetic genes already demonstrated defects in energy metabolism and mitochondrial function that made it much easier for them to gain weight.

But even though losing weight will not heal diabetes, weight loss does have some benefits beyond the obvious vanity ones. Everyone knows that weight loss decreases blood pressure--the other major cause of heart disease besides elevated blood sugar.

What they may not know is that weight loss may also decrease systemic inflammation--the inflammation, measured with the CRP (C-Reactive Protein) test that has been strongly associated with heart disease.

One reason that weight loss has these benefits is because of its impact on leptin, a hormone that has a major impact on whether our body stores or releases fat. I'm not going to go into the details of how leptin functions on the body here. It's a fascinating topic I've just started researching. A lot of hooey has been written about it by people selling miracle weight loss cures, so it will take me some time to sort the hype from the truth.

But some fascinating findings about leptin are these: When leptin is high, CRP rises, platelets tend to clot aggressively, and blood pressure rises--all factors contributing to heart disease. Some of the studies documenting this are:

Serum Leptin Level in Hypertensive Middle-Aged Obese Women de Moraes, Camila. The Endocrinologist. July/August 2005 - Volume 15 - Issue 4 - pp 219-221

and

Effects of Physiological Leptin Administration on Markers of Inflammation, Platelet Activation, and Platelet Aggregation during Caloric Deprivation Bridget Canavan et al. The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 10 5779-5785

There are a couple reliable ways of lowering leptin. One is by losing a lot of weight. All studies show that by the time an overweight person loses 10% of their starting weight their leptin levels have dropped dramatically. Interestingly, further weight loss appears to have no further effect on leptin level.

But significant weight loss is only one way of lowering leptin. As the Canavan study demonstrates, in normal people, at least, you can also lower leptin with a one day complete fast, even if no significant weight loss occurs. The graph on page 5 of the pdf version of the Canavan study shows leptin dropping from about 11 ng/ml to slightly above 3 ng/ml. Over three more days of fasting leptin does not drop much further.

By now my alert, physiologically aware readers are probably seeing where this is going. Because one thing we know about ketogenic diets is that physiologically they mimic starvation, i.e. fasting. Which suggests very strongly that it may be possible to get the leptin lowering effects of a fast from a ketogenic diet--i.e. a diet whose level of carbohydrates is low enough to switch muscles from burning glucose to burning ketones and, eventually, free fatty acids.

The actual carbohydrate intake that corresponds to a ketogenic diet varies with body size and probably with other physiological idiosyncrasies. One size does not fit all despite what you may have read. But you can tell when you've crossed the ketogenic boundary with your own diet when you lose or gain 2-4 lbs of water in a single day. This water fluctuation represents the draining or refilling of your body's glycogen stores. You can learn more about carbohydrate intake, water, and glycogen storage HERE.

For me, the boundary where I start to refill glycogen is at an intake of about 70 grams of carbs a day. I weigh around 142 lbs. A larger person may not hit that boundary until they take in 100 g of carbs.

There's some suggestion in the research that people on a ketogenic low carb diet do experience the same impact on leptin as do people who fast. To find the data exploring the relationship of leptin to a low carbohydrate diet is not easy, because the majority of studies in high impact journals which discuss "low carbohydate diets" do not describe true, ketogenic, low carb diets. For example, a famous study published in The New England Journal of Medicine which purported to show that the so-called Mediterranean diet was more effective than the Low Carb diet used a "Low Carb" diet where people were eating 120 g of carbs a day after the first few weeks. You can read the details of that diet HERE.

But there is a small amount of research tracking what happens to leptin on a low carb diet and it is quite impressive. You can read about this research in this metastudy published in Nature's journal Obesity Research:

Cardiovascular and Hormonal Aspects of Very-Low-Carbohydrate Ketogenic Diets. Jeff S. Volek and Matthew J. Sharman. Obesity Research (2004) 12, 115S–123S; doi: 10.1038/oby.2004.276

That study found:

There were greater reductions in leptin after the VLCKD [Very Low Carb Diet] (-50%) than the low-fat diet (-17%). The ratio of leptin/total fat mass also decreased more after the VLCKD (-45%) than the low-fat diet (-21%).

This impact on leptin, which occurs very fast during a ketogenic diet because of its physiological similarity to the fasting state may explain the dramatic drop in blood pressure many people experience during the early stages of a low carb diet.

It also suggests that the low carb diet, independent of weight loss, might also have a positive effect on lower CRP and help decrease inflammation and the tendency of blood to clot.

There is one more take away message from this research. One that is lost on many doctors and the health media. Even on the worst weight loss diets--like the famed medically supervised controlled fasts where people are fed mostly on vitamin enriched fluids containing protein, sucrose and omega-6 vegetable oil, which make up an alarming about of mainstream 1990s obesity research--weight loss stops lowering leptin levels once 10% of weight has been lost.

So no matter how fat you are, you should be getting the leptin-related benefits of weight loss, whatever they are, from a weight loss of no more than 10% of your starting weight. And as most low carb weigh loss dieters have learned, while it is difficult and often impossible to get to goal on even a perfect low carb diet, it is easy to lose that 10% of starting weight. Most heavy low carb dieters can easily achieve 20% weight loss, though after that it gets tough-to-impossible, depending on how damaged your metabolism might be.

There's a down side to this, of course. Because when leptin levels drop our metabolisms slow and our brains start hunting for food. Boosting leptin, which many pop diet gurus advocate, may not be the answer, given the negative cardiovascular effects associated with boosting leptin especially the dramatic rise in CRP it causes.

So there's no miracle cure here, folks, but a lot to think about.