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  1. Quoting a decent chunk from Wikipedia as background: Indeed, simply eliminating people with any history of smoking from an analysis of BMI vs. future risk of death from any cause nearly eliminates the "J-shaped" elevation in mortality amongst people with low body mass indexes: This was an especially powerful study, too, as it is a meta-analysis of 57 prospective epidemiological studies using individual patient data from over 900,000 subjects. The amazingly huge number of subjects makes it powerful, as is the fact that they used the actual, numerical data for each patient extracted from each study's raw data, than (for instance) pooling studies' "high" and "low" categories as is usually done; as the Cochrane Collaboration acknowledges, although most Cochrane analyses do not take the extra trouble to perform individual patient-data analysis, doing so "can improve the quality of data and the type of analyses that can be done and produce more reliable results (Stewart and Tierney 2002). For this reason they are considered to be a ‘gold standard’ of systematic review." Taking this trouble with the individual data from more than 900,000 people is an enormous scientific labor, and the investigators are to be congratulated. Another important factor is the degenerative aging process itself. The National Institute on Aging's Baltimore Longitudinal Study of Aging (BLSA), the "most comprehensive and longest running longitudinal examination of human aging in the world," has reported that Quote Nearly no epidemiological studies on body weight/BMI have even run for long enough to account for a 9 year trajectory of disease-related weight loss. Most such studies either fail to exclude any early deaths that are likely related to undiagnosed disease onset, or exclude no more than 3 years of such deaths (I have never seen more than 5 years excluded). Aging itself is linked to unintended weight loss, as this graph from the Framingham Heart Study (2) shows: ▲ = Females; ◻ = Males What's more informative is that both men and women who go on to be long-lived have lifelong trajectories of lower body weight than normally-lived people: (Males) (Females) ▲ = Long-lived (survived to age 80 for males and age 83 for females); ◻ = medium-lived (i.e., individuals whose age at death was between the ages of 65 and 80 for males and 65 and 83 for females). Also from the Framinham Heart Study (2). References 1: Alley DE, Metter EJ, Griswold ME, Harris TB, Simonsick EM, Longo DL, Ferrucci L. Changes in weight at the end of life: characterizing weight loss by time to death in a cohort study of older men. Am J Epidemiol. 2010 Sep 1;172(5):558-65. doi: 10.1093/aje/kwq168. Epub 2010 Aug 2. PubMed PMID: 20682520; PubMed Central PMCID: PMC3025636. 2: Yashin AI, Akushevich IV, Arbeev KG, Akushevich L, Ukraintseva SV, Kulminski A. Insights on aging and exceptional longevity from longitudinal data: novel findings from the Framingham Heart Study. Age (Dordr). 2006 Dec;28(4):363-374. PubMed PMID: 17895962; PubMed Central PMCID: PMC1994150. 3: Prospective Studies Collaboration, Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009 Mar 28;373(9669):1083-96. doi: 10.1016/S0140-6736(09)60318-4. Epub 2009 Mar 18. PubMed PMID: 19299006; PubMed Central PMCID: PMC2662372.
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