Editorial

See corresponding article on page 999.

A narrow view of optimal weight for health generates the

obesity paradox1,2
John B Dixon and Garry J Egger

The ‘‘obesity paradox’’ is represented by a range of observa- not altered by age, sex, ethnicity, or state of health. The assumption
tions that suggest a lower risk of mortality in individuals who that adults have an optimal weight range for health appears sound
have a weight (adjusted for height) in the overweight or class but that this weight range (corrected for height) is the same for
I obese range rather than in the normal weight range. Mortality all individuals under all conditions is biologically challenging,
curves for a given BMI for any population are generally U-shaped as this study shows. The state of health—in this case, cancer—has
with increased mortality at both ends. There is debate as to where changed the context, and a higher weight, presumably associated

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the nadir of mortality for BMI lies in the general adult community with higher FM and FFM, is associated with a survival advantage.
and the degree of increased risk, if any, that is associated with Given the serious consequences of cancer cachexia for those
overweight or class I obesity when compared with the normal commencing chemotherapy, it appears that additional weight
weight range (1, 2). The issues revolve around the selection of provides biological resilience and an advantage under these
included studies, granularity of the BMI cutoffs selected, and altered circumstances. We would argue therefore that this is
how to adjust for potential bias associated with unintentional not a paradox.
weight loss (reverse causation) and selective survival advantage Obesity, a chronic condition, is strongly associated with an in-
(3). However, there are now a broad range of conditions in adults creased risk of cardiovascular disease, type 2 diabetes, and many
that are clearly associated with improved survival in overweight cancers and reduces the quality and length of life (7). Yet, these 3
and class I obese adults. The article by Gonzalez et al (4) in this chronic disease consequences of obesity are included in the grow-
issue of the Journal provides another example of the obesity ing list of chronic conditions that show an upward shift in the
paradox, this time in patients with cancer who are commencing BMI for mortality nadir (8). In addition, normal aging provides
chemotherapy, and provides interesting insights into the impor- a similar alteration to the mortality-to-BMI relation, with people
tance of nutrition and body composition for survival. over the age of 70 y in the overweight or class I obese range
The observational study, which follows 175 cancer patients, having the lowest mortality (9). The concept of a flexible optimal
examined survival in relation to BMI classification and bioelec- weight that can be adapted to the individual’s age, ethnicity, and
trical impedance analysis–derived estimates of fat-free mass state of health is biologically plausible, perhaps logical, but pres-
(FFM) and fat mass (FM) to identify obesity and sarcopenia ents us with public health and clinical dilemmas.
through an FM index and FFM index, respectively (5). The Intentional weight loss is broadly recommended for overweight
study has several author-acknowledged weaknesses, such as that and class I obese individuals, especially if they have a high risk of
developing, or have developed, type 2 diabetes or cardiovascular
body composition was measured by using bioelectrical imped-
disease, but we have no evidence of a mortality advantage. With
ance analysis, a methodology that needs to be validated in the
established type 2 diabetes and cardiovascular disease alone, or in
population being studied and is highly dependent on the algo-
combination, there are a series of interventional and observational
rithm and assumptions being used (6). And we know nothing of
studies that have not found reductions in mortality or major car-
the patients’ weight trajectories immediately before enrollment
diovascular events with weight loss. The Look AHEAD (Action
in the study. There was, however, clear evidence of an obesity
for Health in Diabetes) Study found that an intensive diet and
paradox, with survival better in patients who were BMI-classi-
exercise program resulting in weight loss did not reduce cardio-
fied as overweight and obese at baseline. In addition, sarcopenia
vascular events (10). Intentional weight loss using the medication
at baseline was problematic. Overweight and obesity as mea-
sibutramine increased the risk of nonfatal cardiovascular events
sured by BMI appeared to be associated with adequate FFM, and did not alter overall mortality (11). A post hoc analysis of
because all individuals with sarcopenia were found in under- and
normal-weight BMI categories. It is therefore clear that BMI 1
From the Baker IDI Heart & Diabetes Institute, Melbourne, Australia
was a strong predictor of survival and FFM is important, espe-
(JBD), and Southern Cross University, Lismore, Australia (GJE).
cially in those with a BMI (in kg/m2) ,25. 2
Address correspondence to JB Dixon, Baker IDI Heart & Diabetes In-
The so-called obesity paradox appears to have arisen through stitute, PO Box 6492, St Kilda Road Central, Melbourne Victoria 8008,
a flawed concept whereby the lowest mortality for adults lies in Australia. E-mail: [email protected].
a single ‘‘normal BMI range’’ of 18.5–25 and that this range is First published online March 26, 2014; doi: 10.3945/ajcn.114.086470.

Am J Clin Nutr 2014;99:969–70. Printed in USA. Ó 2014 American Society for Nutrition 969
970 EDITORIAL

pioglitazone or placebo, as additions to patients’ concurrent di- 2. Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L,
abetes medications, from a large randomized controlled trial MacInnis RJ, Moore SC, Tobias GS, Anton-Culver H, Freeman LB,
et al. Body-mass index and mortality among 1.46 million white adults.
showed an inverse association between baseline BMI and mortal-
N Engl J Med 2010;363:2211–9.
ity. In addition, weight loss was associated with increased mor- 3. Flegal KM, Graubard BI, Williamson DF, Cooper RS. Reverse causation
tality, whereas weight gain was not (12). The only evidence that and illness-related weight loss in observational studies of body weight
mortality is reduced with intentional weight loss comes from and mortality. Am J Epidemiol 2011;173:1–9.
bariatric surgical studies in which the preintervention BMI 4. Gonzalez MC, Pastore CA, Orlandi SP, Heymsfield SB. Obesity paradox
in cancer: new insights provided by body composition. Am J Clin Nutr
is .35 (13).
2014;99:999–1005.
Chronic diseases, malignancy, and aging are associated with 5. Kyle UG, Pirlich M, Lochs H, Schuetz T, Pichard C. Increased length of
reductions in lean body mass and especially muscle mass, lower hospital stay in underweight and overweight patients at hospital admis-
bone mineral density, compromised nutrition, impaired physical sion: a controlled population study. Clin Nutr 2005;24:133–42.
function, and frailty. Overweight and class I obesity may provide 6. Alvarez VP, Dixon JB, Strauss BJ, Laurie CP, Chaston TB, O’Brien PE.
Single frequency bioelectrical impedance is a poor method for deter-
biological resilience under these circumstances, with preserva- mining fat mass in moderately obese women. Obes Surg 2007;17:
tion of FFM one of several putative mechanisms. We need to bet- 211–21.
ter understand these mechanisms. Meanwhile, individualized 7. Dixon JB. The effect of obesity on health outcomes. Mol Cell Endocrinol
lifestyle and behavioral programs with a focus on quality nutri- 2010;316:104–8.
tion, physical activity, fitness, and maintaining function (ie, fo- 8. Carnethon MR, Rasmussen-Torvik LJ, Palaniappan L. The obesity par-
adox in diabetes. Curr Cardiol Rep 2014;16:446.
cusing more on the ‘‘environmental causes’’ of obesity than 9. Oreopoulos A, Kalantar-Zadeh K, Sharma AM, Fonarow GC. The obe-
obesity per se) may be biologically preferable in overweight sity paradox in the elderly: potential mechanisms and clinical implica-
or class I obese people who are older or who suffer from malig- tions. Clin Geriatr Med 2009;25:643–59, viii.
nancy or chronic disease, rather than trying to achieve a normal 10. Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow

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(for healthy younger adults) weight. RS, Curtis JM, Egan CM, Espeland MA, et al. Cardiovascular effects of
intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;
JBD receives competitive research grant funding from Allergan Inc. He 369:145–154.
was a consultant for Allergan Health and Bariatric Advantage and is a mem- 11. James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni
ber of the Optifast Medical Advisory Board for Nestlé Health, Australia. He AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, et al.
is on the speakers bureaus for Eli Lilly and iNova Pharmaceuticals and has Effect of sibutramine on cardiovascular outcomes in overweight and
developed educational material for Novartis and iNova Pharmaceuticals. obese subjects. N Engl J Med 2010;363:905–17.
12. Doehner W, Erdmann E, Cairns R, Clark AL, Dormandy JA, Ferrannini
GJE had no conflicts of interest.
E, Anker SD. Inverse relation of body weight and weight change with
mortality and morbidity in patients with type 2 diabetes and cardiovas-
cular co-morbidity: an analysis of the proactive study population. Int J
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