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Why do some people lose 100 pounds on a diet that other people follow faithfullywith the result of weight gain? The answer is simpler than you might think.

One of the mysteries at the heart of modern obesity research is that two different people can follow the same weight loss diet with entirely different results. One dieter who sticks to a diet plan may lose 50 pounds in three months. Another dieter who sticks to the same diet plan may gain 10 pounds. This is even sometimes true when the two dieters are of the same race, same gender, same socioeconomic class, and same age. High-protein, high-carb, low-fat, high-fat, no diet works for everyone. Why should this be?

Obesity Is Not a Single Disease

Even though some American doctors still consider obesity to be a moral failing, it's really disease, or, more accurately, a collection of diseases. Some studies even claim that obesity is a genetic disease. Two people can have the same amount of excess weight, but they may have put it on for very different reasons. As Dr. Lee Kaplan, director of the obesity, metabolism and nutrition institute at Massachusetts General Hospital and Harvard Medical School says, insisting that there is just one cause and one way to fight obesity (by banning sugary soft drinks, clearing out snack foods from convenience stores, or helping people get more sleep, for example) makes no more sense than using sunscreen to prevent lung cancer.

Dr. Kaplan believes that there are at least 59 different types of obesity.

Some of these 59 types of obesity can be linked to mutations in up to 25 different genes. Having a mutation in just one of these 25 genes is enough to guarantee that you will be obese. Some of these genes interfere with the ability of fat cells to generate the hormone leptin, which tells the brain that they have stored enough excess calories. Some of these these genes interfere with the ability of the brain to make the messenger molecules after it receives leptin that suppress appetite and slow down the storage of excess carbohydrate calories in the liver.

However, it isn't just 25 genes that can cause obesity. There are 300 more genes that can cause a tendency toward some weight gain. A combination of mutations in these genes can add up to overweight or obesity. That's a total of at least 325 ways that you can be destined to gain weight from birth. But there are other factors beyond simple overeating that lead to weight gain.

Certain Medications Can Interfere with Your Weight Loss Diet

Medication is another culprit in weight gain. Insulin helps your cells receive sugar from the bloodstream, but it also keeps them from using fat for fuel. Any medication diabetics take for lowering blood sugar levels typically will also increase weight.

Certain antipsychotic drugs stimulate weight gain. Beta-blockers for high blood pressure slow the heart rate so that it is necessary to consume even fewer calories to lose weight. Steroids to control inflammation interfere with water and weight loss and make it impossible to lose weight fast.

Certain Health Conditions Also Force You to Cut More Calories to Lose Weight

Hypothyroidism causes weight loss battle: it slows down the body's process of burning carbohydrates. Tumors of the hypothalamus interfere with the body's "thermostat" so fewer calories are burned. Any condition that limits mobility (arthritis, for example, or obesity itself) also primes weight gain.

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  • Frank M. Sacks, M.D., George A. Bray, M.D., Vincent J. Carey, Ph.D., Steven R. Smith, M.D., Donna H. Ryan, M.D., Stephen D. Anton, Ph.D., Katherine McManus, M.S., R.D., Catherine M. Champagne, Ph.D., Louise M. Bishop, M.S., R.D., Nancy Laranjo, B.A., Meryl S. Leboff, M.D., Jennifer C. Rood, Ph.D., Lilian de Jonge, Ph.D., Frank L. Greenway, M.D., Catherine M. Loria, Ph.D., Eva Obarzanek, Ph.D., and Donald A. Williamson, Ph.D. Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates. N Engl J Med 2009. 360:859-873February 26, 2009DOI: 10.1056/NEJMoa0804748.
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