Is excess weight hazardous to health, or can it actually be protective? This question has provoked intense debate in the academic community, in some cases even leading researchers to angrily denounce the work of others (1). There is good evidence to suggest that excess body fat increases the risk of specific diseases, including many of our major killers: diabetes, heart attack, stroke, heart failure, cancer, and kidney failure (2). Yet strangely, the studies relating excess weight to the total risk of dying-- an overall measure of health that's hard to argue with-- are inconsistent. Why?
These studies typically rely on a measure of body fatness called the body mass index (BMI), which essentially captures weight-for-height. A BMI of less than 18.5 is considered underweight, 18.5-25 is normal weight, 25-30 is overweight, 30-35 is obese, and greater than 35 is very obese. Most studies agree that underweight and obese people have an elevated risk of death. Yet when we look in the overweight range, the picture is less clear: some studies suggest that lean people are healthiest (3, 4), while others suggest that overweight people are actually healthiest, particularly at older ages (5). The latter conclusion contradicts the message we often hear from public health authorities and in the doctor's office, so it seems like an important question to resolve.
The studies involved in this debate are all observational, meaning researchers simply observed people of different BMIs and attempted to determine the average death risk of each BMI category. But as we know, observational studies come with important caveats. A big one is that it's difficult to be certain that a person's BMI actually caused their health status, rather than BMI being associated with something else that caused their health status (a "confounding factor"). This is one of the main reasons observational studies are considered less convincing than controlled trials, where people are randomized into treatment groups.
In the case of BMI and mortality, we have at least two obvious confounding factors: smoking and illness-induced weight loss (6). People who smoke cigarettes tend to be leaner than nonsmokers, and they also tend to die more because tobacco smoke is toxic. People who are ill tend to lose weight, and they also tend to die more frequently than people who aren't ill. Both of these confounding factors would tend to make leanness appear more hazardous than it really is, and by comparison, make overweight and obesity appear healthier. Studies have attempted to correct for these major confounds, and those that do the best job of it tend to support the idea that lean people are healthiest (7, 8). However, the corrections made for illness-induced weight loss tend to be crude because they can only correct for known illness.
Recently, a University of Pennsylvania graduate student named Andrew Stokes published a paper that examined this question in a groundbreaking way (9). Instead of simply relating current BMI to mortality risk, he related maximum BMI to mortality risk. In other words, what was the highest BMI for each individual between 1988 and 2004, and how does that relate to the risk of dying over the same time period? The advantage of this measure is that it's resistant to confounding by illness-induced weight loss, because the maximum recorded BMI is likely to have occurred at a time prior to the onset of illness. The limitation in this case is that maximum BMI was self-reported rather than objectively measured by investigators.
He also excluded people who had ever smoked regularly, reducing the risk of confounding due to smoking-induced weight loss.
Here are two graphs I created to illustrate his main findings. Similar to previous studies, in Stokes' data set, current BMI was only weakly related to mortality risk (OW=overweight; OB=obese; VOB=very obese). This is the type of result that led Dr. Arya Sharma to refer to BMI as a "meaningless integer".
Yet when he examined maximum BMI, a different picture emerged (same scale in both graphs):
This analysis uncovered a much stronger relationship between BMI and death risk, suggesting that previous observational studies may have been seriously confounded, and as a result, may have greatly underestimated the health impact of excess body fat. This is the main finding of the paper.
Another fascinating tidbit is his estimate of the percentage of total US deaths that can be attributed to excess BMI. When using current BMI, only 5 percent of deaths in this group of people can be attributed to excess BMI. When using maximum BMI, 33 percent of deaths are attributable to excess BMI. Another way of putting this is that excess weight may be linked to one out of three deaths among US adults age 50-84. This could resolve the apparent paradox that excess weight promotes deadly diseases, yet doesn't seem to be strongly associated with the risk of dying.
Presumably, the explanation for the paradox is that people often lose weight before dying, so their death is associated with a lower BMI group, despite the fact that their former excess weight contributed to their demise. This is consistent with Stokes' additional finding that people who had lost the most weight were at the highest risk of death.
I spoke with Stokes about his paper on Monday. He is cautiously optimistic about the finding, and he feels that its primary limitation is the fact that maximum BMI was self-reported. BMI measurement error has the potential to either strengthen or weaken the BMI-mortality association, depending on whether people tend to under-report or over-report their maximum weight. He would like to repeat his analysis using existing data sets in which maximum weight was objectively measured by investigators rather than self-reported. If confirmed, his findings may suggest that excess weight is the single most important public health concern in the United States.
Stokes recently accepted a faculty position at Boston University in the Department of Global Health. I hope he'll be able to continue his work on this important question.