Tuesday, June 23, 2009

Interesting Information on the Survival Advantage from Having the Metabolic Syndrome

Check out this interesting article in JAMA by Jesse Roth about the genetic link between being fat and simultaneously being protected against tuberculosis (TB). Since readers may not have a subscription to JAMA, the Disease Management Care Blog is pleased to provide this Cliffsnotes summary about a disorder that we still have much to learn about.

One of the issues with obesity has been its link to the 'metabolic syndrome,' which is typically accompanied by increased 'background' inflammation. Experts have suspected that this in turn leads to chronic molecular 'wear and tear' that subsequently leads to chronic diseases such as diabetes, atherosclerosis and cancer. While the ability to preserve energy and store fat makes evolutionary sense for humans that have been at risk for famine, scientists have been mystified by the accompanying genetic programing that leads to ongoing cellular damage. Why would having a turbocharged immune system offer a survival benefit?

The answer may be the scourge of TB. Until antibiotics came along, this was an infection that, once established, could never be cured and frequently led to death. It's been estimated that TB has caused more than a billion deaths in the course of human history. For who survived, victims harbored the disease in a subacute or latent form for the rest of their lives. Having increased amounts of visceral fat leading to elevated levels of adipokines, tumor necrosis factor and other pro-inflammatory proteins may have given big bellied people a chance to beat or at least combat the infection.

It was long observed that persons with poor nutritional status seemed to be more prone to TB and were more likely to die from the disease. That's because starvation generally impairs immunity to the point where more persons succumb from just about any infection than from the weight loss itself. In contrast, persons with excess weight have heightened immunity with inflammation. While the link between the two conditions is still being unraveled, Dr. Roth speculates overweight allowed individuals to have the kind of heightened immune response that made them more likely to survive an encounter with TB. As a result, big people had a survival advantage.

Interestingly, high amounts of LDL are also involved in the immune response. Little wonder, then, that physicians in the pre-antibiotic era prescribed sedentary behavior in their sanatoriums with high calorie diets.

Individuals of Indian or Japanese heritage appear to develop the metabolic syndrome at lower levels of obesity. The Inuits, on the other hand, have historically low rates of obesity and seem to be especially prone to TB. This suggests the genetic trigger for inflammation may vary from gene pool to gene pool. These observations are leading scientists to look for the genetic and metabolic triggers for the inflammation that may be modifiable with yet-to-be-discovered medications.

Now that TB is largely absent in the U.S. and much of the West, the metabolic advantage that served us so well for tens of thousands of years is causing chronic illness.

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