JAMA meta-analysis confirms link between premature mortality and obesity
Tuesday, January 8, 2013. The January 2, 2013 issue of the Journal of the American Medical Association (JAMA) reported the outcome of a meta-analysis conducted by researchers at the National Center for Health Statistics, Centers for Disease Control and Prevention in Hyattsville, Maryland, which reaffirmed the link between being obese and having a greater risk of dying from all causes over follow-up.
Katherine M. Flegal, PhD and her associates reviewed 97 studies that included a total of over 2.88 million individuals, among whom there were 270,000 deaths. Subjects were considered normal weight if their body mass index (BMI) was between 18.5 and less than 25, and those with a BMI between 25 and less than 30 were classified as overweight. (Body mass index is calculated by dividing weight in kilograms by height in meters squared.) Among those considered obese, a BMI ranging from 30 to less than 35 was classified as grade 1, a BMI of 35 to less than 40 was categorized as grade 2 and grade 4 was applied to subjects with a BMI of 40 or higher.
Obese men and women had a 5 percent higher risk of dying over follow up in comparison with those whose BMI was normal. Interestingly, when obesity was examined according to grade, having grade 2 and 3 obesity was associated with a 29 percent higher risk of dying, but being classified as grade 1 was associated with a 5 percent lower risk. Being overweight but not obese was similarly associated with a lower risk of mortality over follow-up. "Possible explanations have included earlier presentation of heavier patients, greater likelihood of receiving optimal medical treatment, cardioprotective metabolic effects of increased body fat, and benefits of higher metabolic reserves," the authors suggest.
"Our study also has limitations," they note. "It addresses only all-cause mortality and not morbidity or cause-specific mortality. It addresses only findings related to BMI and not to other aspects of body composition such as visceral fat or fat distribution."
In an accompanying editorial, Steven B. Heymsfield, MD, and William T. Cefalu, MD observe that "The presence of a wasting disease, heart disease, diabetes, renal dialysis, or older age are all associated with an inverse relationship between BMI and mortality rate, an observation termed the obesity paradox or reverse epidemiology. The optimal BMI linked with lowest mortality in patients with chronic disease may be within the overweight and obesity range. Even in the absence of chronic disease, small excess amounts of adipose tissue may provide needed energy reserves during acute catabolic illnesses, have beneficial mechanical effects with some types of traumatic injuries, and convey other salutary effects that need to be investigated."
Despite the possibility of a protective effect for excess weight in some cases, Drs Heymsfield and Cefalu remark that in addition to BMI, traditional risk factors such as blood pressure, lipid levels, fasting glucose and waist circumference, as well as more newly recognized markers including those that assess inflammation could improve the identification of those at risk of early mortality.
In an article published online on December 6, 2012 in the journal Science, Eric Verdin of the University of California, San Francisco and his associates report their finding of a mechanism via which a low carbohydrate, calorie restricted diet delays the effects of aging. This pattern of eating results in the production of ketone bodies that include beta-hydroxybutyrate (βOHB) which, when present in low levels, may help protect the body from the effects of damaging oxidative stress.
In experiments in human and animal cells, calorie restriction stimulated βOHB production, which blocked the activity of enzymes known as histone deacetylases (HDACs). These enzymes prevent the activation of two genes that boost cellular oxidative stress resistance. "Over the years, studies have found that restricting calories slows aging and increases longevity—however the mechanism of this effect has remained elusive" Dr Verdin stated. "Here, we find that βOHB—the body's major source of energy during exercise or fasting—blocks a class of enzymes that would otherwise promote oxidative stress, thus protecting cells from aging."
"This breakthrough also greatly advances our understanding of the underlying mechanism behind HDACs, which had already been known to be involved in aging and neurological disease," noted coauthor Katerina Akassoglou, PhD. "The findings could be relevant for a wide range of neurological conditions, such as Alzheimer's, Parkinson's, autism and traumatic brain injury—diseases that afflict millions and for which there are few treatment options."
"Identifying βOHB as a link between caloric restriction and protection from oxidative stress opens up a variety of new avenues to researchers for combating disease," added lead author Tadahiro Shimazu. "In the future, we will continue to explore the role of βOHB—especially how it affects the body's other organs, such as the heart or brain—to confirm whether the compound's protective effects can be applied throughout the body."
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