The obesity paradox is the finding in some studies of a lower mortality rate for overweight or obese people within certain subpopulations.
The paradox has been observed in people with
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
and cancer. Explanations for the paradox range from excess weight being protective to the statistical association being caused by methodological flaws such as confounding, detection bias, reverse causality, or selection bias.
Description
The terminology "reverse epidemiology" was first proposed by
Kamyar Kalantar-Zadeh
Kamyar Kalantar-Zadeh (born October 1963) is an Iranian-American physician doing research in nephrology, kidney dialysis, nutrition, and epidemiology. He is best known as a specialist in kidney disease nutrition and chronic kidney disease and f ...
in the journal ''
Kidney International
''Kidney International'' is a monthly peer-reviewed medical journal covering all aspects of nephrology. It was established in 1972 and is published by Elsevier on behalf of the International Society of Nephrology, of which it is the official journa ...
'' in 2003 and in the ''
Journal of the American College of Cardiology
The ''Journal of the American College of Cardiology'' is a peer-reviewed medical journal covering all aspects of cardiovascular disease, including original clinical studies, translational investigations with clear clinical relevance, state-of-the-a ...
'' in 2004.
It is a contradiction to prevailing medical concepts of prevention of
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...
and
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
; however, active
prophylactic treatment of heart disease in otherwise healthy,
asymptomatic
In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asy ...
people has been and is controversial in the medical community for several years.
The mechanism responsible for this reversed association is unknown, but it has been theorized that, in
chronic kidney disease
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...
patients, "The common occurrence of persistent
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
and protein energy wasting in advanced CKD
hronic kidney diseaseseems to a large extent to account for this paradoxical association between traditional risk factors and CV
ardiovascularoutcomes in this patient population." Other research has proposed that the paradox also may be explained by
adipose tissue
Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular e ...
storing
lipophilic
Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipop ...
chemicals that would otherwise be toxic to the body.
The obesity paradox (excluding the cholesterol paradox) was first described in 1999 in overweight and obese people undergoing
hemodialysis
Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
,
and has subsequently been found in those with
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
,
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
,
acute coronary syndrome
Acute coronary syndrome (ACS) is a syndrome (a set of signs and symptoms) due to decreased blood flow in the coronary arteries such that part of the heart muscle is unable to function properly or dies. The most common symptom is centrally loca ...
,
chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
(COPD),
pulmonary embolism
Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
s, and in older
nursing home
A nursing home is a facility for the residential care of elderly or disabled people. Nursing homes may also be referred to as skilled nursing facility (SNF) or long-term care facilities. Often, these terms have slightly different meanings to in ...
residents.
While obese people have twice the risk of developing heart failure compared to individuals with a normal BMI,
once a person experiences heart failure, those with a BMI between 30.0 and 34.9 had lower mortality than those with a normal BMI. This has been attributed to the fact that people often lose weight when they have severe and chronic illness (a syndrome called
cachexia
Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart f ...
).
Similar findings have been made in other types of heart disease. Among people with heart disease, those with class I obesity do not have greater rates of further heart problems than people of normal weight. In people with greater degrees of obesity, however, risk of further events is increased. Even after
cardiac bypass surgery, no increase in mortality is seen in the overweight and obese. One study found that the improved survival could be explained by the more aggressive treatment obese people receive after a cardiac event. Another found that if one takes into account COPD in those with
peripheral artery disease
Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular diseas ...
, the benefit of obesity no longer exists.
The obesity paradox is also relevant in discussion of
weight loss
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
as a preventative health measure – weight-cycling (a repeated pattern of losing and then regaining weight) is more common in obese people, and has health effects commonly assumed to be caused by obesity, such as
hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
,
insulin resistance
Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
, and cardiovascular diseases.
Criticisms
Methodology
The obesity paradox has been criticized on the grounds of being an
artifact arising from
biases
Bias is a disproportionate weight ''in favor of'' or ''against'' an idea or thing, usually in a way that is closed-minded, prejudicial, or unfair. Biases can be innate or learned. People may develop biases for or against an individual, a group, ...
in
observational studies
In fields such as epidemiology, social sciences, psychology and statistics, an observational study draws inferences from a sample (statistics), sample to a statistical population, population where the dependent and independent variables, independ ...
. Strong confounding by
smoking
Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...
has been noted by several researchers, although others have suggested that smoking does not account for the observed patterns. Since smokers, who are subject to higher mortality rates, also tend to be leaner, inadequate adjustment for smoking would lead to underestimations of the risk ratios associated with the overweight and obese categories of BMI among non-smokers. In an analysis of 1.46 million individuals, restriction to never-smoking participants greatly reduced the mortality estimates in the underweight group, as well as strengthening the estimates in the overweight and obese groups.
This study concluded that, for non-Hispanic white adults who have never smoked, the BMI range of 20.0 to 24.9 was associated with the lowest mortality rates.
A similar 2016 study found that, of the BMI ranges studied (which ranged from 18.5 to >30), the "normal" 18.5–22.4 BMI range combined with healthy eating, high levels of physical activity, not smoking, and no more than moderate alcohol consumption was associated with the lowest risk of premature death.
[Veronese, Nicola; Li, Yanping; Manson, JoAnn E; Willett, Walter C; Fontana, Luigi; Hu, Frank B. (2016) "Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study", ''BMJ'', v355. doi]
Another concern is reverse causation due to illness-induced weight loss. That is, it may not be low BMI that is causing death (and thereby making obesity seem protective) but rather imminent death causing low BMI. Indeed, unintentional weight loss is an extremely significant predictor of mortality. Terminally ill individuals often undergo weight loss before death, and classifying those individuals as lean greatly inflates the mortality rate in the normal and underweight categories of BMI, while lowering the risk in the higher BMI categories. Studies that employ strategies to reduce reverse causation such as excluding sick individuals at baseline and introducing time lag to exclude deaths at the beginning of follow-up
have yielded estimates of increased risk for body mass indices above 25 kg/m
2.
The obesity paradox may therefore result from people becoming lean due to smoking, sedentary lifestyles, and unhealthy diets – all factors which also negatively impact health.
Critics of the paradox have also argued that studies supporting its existence almost always use BMI as the only measure of obesity. However, because BMI is an imperfect method of measuring obesity, critics argue that studies using other measures of obesity in addition to BMI, such as
waist circumference
The waist is the part of the Human abdomen, abdomen between the rib cage and Hip (anatomy), hips. On people with slim bodies, the waist is the narrowest part of the torso.
''Waistline'' refers to the horizontal line where the waist is narrowe ...
and
waist to hip ratio
The waist is the part of the abdomen between the rib cage and hips. On people with slim bodies, the waist is the narrowest part of the torso.
''Waistline'' refers to the horizontal line where the waist is narrowest, or to the general appearan ...
, render the existence of the paradox questionable.
One probable methodological explanation for the obesity paradox in regards to cardiovascular disease is
collider
A collider is a type of particle accelerator which brings two opposing particle beams together such that the particles collide. Colliders may either be ring accelerators or linear accelerators.
Colliders are used as a research tool in particle ...
stratification
Stratification may refer to:
Mathematics
* Stratification (mathematics), any consistent assignment of numbers to predicate symbols
* Data stratification in statistics
Earth sciences
* Stable and unstable stratification
* Stratification, or str ...
bias, which commonly emerges when one restricts or stratifies on a factor (the "collider") that is caused by both the exposure (or its descendants) of an unmeasured variable and the outcome (or its ancestors / risk factors). In the example of the obesity-cardiovascular disease relationship, the obesity is the collider, the outcome is cardiovascular disease, and the unmeasured variables are environmental and genetic factors – given that obesity and cardiovascular disorders are often associated with each other, medical professionals may be reluctant to consider both other causes of cardiovascular disease or other causes of protection against said diseases.
A study from 2018 found that the reason why overweight or obese patients supposedly live longer with cardiovascular disease than people of normal weight is simply because overweight / obese patients get cardiovascular disease at an earlier age, meaning while they survive more years with it, non-obese patients don't get cardiovascular disease at all up until later in life. In fact, the obese have shorter lifespans because they get cardiovascular disease at an early age and have to live a longer proportion of their life with it. This also shows an misunderstanding regarding the paradox: While survival rate once sick is indeed higher for those with obesity than for those few non-obese that have cardiovascular disease, people without obesity usually do not get cardiovascular disease in the first place.
Ties to Coca Cola
It has also been noted that
Coca Cola
Coca-Cola, or Coke, is a carbonated soft drink manufactured by the Coca-Cola Company. Originally marketed as a temperance drink and intended as a patent medicine, it was invented in the late 19th century by John Stith Pemberton in Atlanta ...
has promoted the hypothesis and funded researchers who agree with the hypothesis, which has raised questions about what research the company supports and why.
Weight stigma
Dixon ''et al.'' have proposed that a paradox does not actually exist, as people can be healthy at a range of sizes. As one study puts it, "There is no 'obesity paradox' to explain, if we accept the premise that varying ideal weight ranges apply to individuals over different stages of the life span, accordingly allowing us to abandon the rigid biologically implausible concept of a single 'ideal weight' (for height) or weight range."
See also
*
French paradox
The French paradox is an apparently paradoxical epidemiological observation that French people have a relatively low incidence of coronary heart disease (CHD), while having a diet relatively rich in saturated fats, in apparent contradicti ...
*
Israeli paradox
*
Low birth-weight paradox {{Short description, Statistical quirk of babies' birth weights
The low birth-weight paradox is an apparently paradoxical observation relating to the birth weights and mortality rate of children born to tobacco smoking mothers. Low birth-weight chi ...
(Low birth-weight babies born to smokers have a lower mortality than low birth-weight babies born to non-smokers, because other causes of low birth-weight are more harmful than smoking.)
*
Katherine Flegal
Katherine Mayhew Flegal is an American epidemiologist and senior scientist at the Center for Disease Control and Prevention's National Center for Health Statistics. She is one of the most highly cited scientists in the field of the epidemiology ...
*
Social stigma of obesity
Social stigma of obesity is broadly defined as bias or discriminatory behaviors targeted at overweight and obese individuals because of their weight. Such social stigmas can span one's entire life, as long as excess weight is present, starting ...
References
Further reading
*
*{{cite journal , doi=10.1001/jama.2012.9776 , pmid=22871873 , title=Beyond the Obesity Paradox in Diabetes: Fitness, Fatness, and Mortality , year=2012 , journal=JAMA , volume=308 , issue=6 , pages=619–620, first1=Hermes , last1=Florez , first2=Sumaya , last2=Castillo-Florez
Epidemiology
Hypotheses
Obesity
Health paradoxes