Lean for Life Linked to Lowest Mortality, With Some Nuances

Marcia Frellick

May 12, 2016

Three studies published recently contribute new information on the links between body mass index (BMI) and risk of premature death.

One is the first work to inform on the link between body size over a lifetime and mortality and finds — perhaps unsurprisingly — that people who maintained a stable lean body shape throughout life had the lowest mortality. Mingyang Song, MD, ScD, a research fellow at Harvard Medical School, Boston, Massachusetts, and colleagues, published their paper May 4 in the BMJ.

Using a trajectory approach, Dr Song and team also showed that heavy body shape, from ages 5 to 50, and especially the increase in middle life, was associated with higher mortality.

A second study, also published in the BMJ, suggests there is an optimal BMI for lowest mortality likely to apply to European and North American populations, but that this will vary by confounding factors, say Dagfinn Aune, a PhD student and research associate at the Department of Public Health and General Practice, Norwegian University of Science and Technology, in Trondheim, Norway, and colleagues.

Finally, an analysis published in the May 10 issue of the Journal of the American Medical Association, based on data from Denmark, indicates that the BMI linked with the lowest all-cause mortality has increased from 23.7 to 27 over the years from 1976–1978 to 2003–2013.

The researchers, led by Shoaib Afzal, MD, PhD, of Copenhagen University Hospital, Denmark, and colleagues, suggest one potential explanation for their finding is that, while improved treatment for cardiovascular risk factors or complicating diseases has reduced mortality in all weight classes, the effects may have been greater at higher BMI levels than at lower BMI levels.

However, senior author Borge G Nordestgaard, MD, DMSc, told Medscape Medical News that this is "pure speculation" and there are currently no data to support this hypothesis. If the findings with regard to the BMI associated with lowest mortality are confirmed in other studies, "a group of experts headed by the WHO should decide if the exact BMI cut points used to define overweight need to be revised," he observed.

Weight Gain in Midife Is Most Hazardous

In their research, Dr Song and colleagues used US data on more than 80,000 women who took part in the Nurses' Health Study and more than 36,000 men in the Health Professionals Follow-up Study who recalled their body shape at age 5, 10, 20, 30, and 40 years and provided BMI at age 50 and who were followed from age 60 over a median of 15 years for all-cause and cause-specific death.

Researchers compared five distinct body shapes: lean-stable; lean-moderate increase; lean-marked increase; medium-stable/increase; and heavy-stable/increase.

Those who were lean all their lives had a 15-year risk of death of 11.8% in women and 20.3% in men.

In comparison, those who reported being heavy as children and who stayed heavy or gained more weight, especially during middle age, had a 15-year risk of death of 19.7% in women and 24.1% in men.

"These results indicate the important of weight management across the lifespan," stress Dr Song and colleagues.

"A life-course perspective is crucial to better understanding of the health consequences of overweight and obesity and to development of effective prevention strategies targeting the life period at which excess body weight has a predominant influence on future risk of disease or death," they add.

"Our findings provide further scientific rationale for recommendations on weight management, especially avoidance of weight gain in middle life, for long-term health benefit," they conclude.

Writing in an accompanying editorial, Sarah Wild, PhD, professor of epidemiology at the Centre for Population Health Sciences, University of Edinburgh, United Kingdom, and Christopher Byrne, PhD, professor of endocrinology and metabolism at the University of Southampton, Southampton, applaud the research.

"The study by Song and colleagues is an important step forward in furthering our understanding of how weight gain over the life course, particularly in midlife, is likely to influence health and mortality," they note.

Adiposity Ups Risk of Premature Death: Lowest Mortality at BMI 25

In the second BMJ paper, Mr Aune and colleagues performed a meta-analysis of 230 prospective studies with more than 3.74 million deaths among more than 30.3 million participants, "providing further evidence that adiposity (measured by BMI) increases the risk of premature death," say Drs Wild and Byrne in their editorial.

The lowest mortality was observed with a BMI of around 25, although this varied by risk factors and confounding, with the lowest mortality seen in participants who had a BMI of 23 to 24 and never smoked and at a BMI of 20 to 22 among never-smokers with at least 20 years of follow-up.

"The findings show the importance of smoking and comorbidity in confounding the association between BMI and mortality," state the editorialists (smoking can reduce body weight but increases risk of death).

Regarding both studies, Drs Wild and Byrne conclude: "Major challenges remain in finding effective ways to prevent weight gain, support weight loss, and prevent weight regain, in both individuals and populations."

Danish Study: Is There a Need to Revise Overweight Category?

Finally, in their study, Dr Afzal and colleagues examined whether the BMI value that is associated with the lowest all-cause mortality has increased in the general population over a period of 3 decades.

Previous findings indicate that while average BMI has increased over time in most countries, the prevalence of cardiovascular risk factors may be decreasing among obese individuals. Thus, the BMI associated with lowest all-cause mortality may have changed over time, they speculate.

The study included three groups from the same general population enrolled at different times: the Copenhagen City Heart Study in 1976–1978 (n=13,704) and 1991–1994 (n=9482) and the Copenhagen General Population Study in 2003–2013 (n=97,362). All participants were followed up from inclusion in the studies to November 2014, emigration, or death, whichever came first.

Seemingly in contradiction to the findings from the two BMJ studies, the researchers found that the BMI value associated with the lowest all-cause mortality has increased by 3.3 over 3 decades from 1976–1978 to 2003–2013, from 23.7 to 27.

In addition, the risk for all-cause mortality that was associated with BMI of 30 or greater vs BMI of 18.5 to 24.9 decreased from an adjusted hazard ratio of 1.3 to 1.0 over this 30-year period.

BMI Associated with Lowest Mortality by Type of Mortality


All-cause mortality

Cardiovascular mortality














These data mean that the optimal BMI in relation to mortality is placed in the overweight category in the most recent 2003–2013 cohort.

And while the authors speculate about reasons, they observe: "Further investigation is needed to understand the reason for this change and its implications.

"If this finding is confirmed in other studies, it would indicate a need to revise the WHO categories currently used to define overweight, which are based on data from before the 1990s," they conclude.

The Aune et al study was funded by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Imperial College National Institute of Health Research Biomedical Research Centre. The Song et al study was supported by the National Institutes of Health and Boston Obesity Nutrition Research Center. Regarding the Afzal et al study, the Copenhagen General Population Study and Copenhagen City Heart Study are supported by the Danish Heart Foundation, Danish Medical Research Council, Copenhagen County Foundation, and Herlev and Gentofte Hospital, and Copenhagen University Hospital. The authors report no relevant financial relationships.

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BMJ. Published online May 4, 2016. Song study, Aune study, Editorial

JAMA. 2016;315:1989-1996. Abstract


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