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1.  Short- and long-term reliability of adult recall of vegetarian dietary patterns in the Adventist Health Study-2 (AHS-2) 
Past dietary patterns may be more important than recent dietary patterns in the aetiology of chronic diseases because of the long latency in their development. We developed an instrument to recall vegetarian dietary patterns during the lifetime and examined its reliability of recall over 5·3 and 32·6 years on average. The short-term/5-year recall ability study (5-RAS) was done using 24 690 participants from the cohort of the Adventist Health Study-2 (mean age 62·2 years). The long-term/33-year recall ability study (33-RAS) included an overlap population of 1721 individuals who joined the Adventist Health Study-1 and Adventist Health Study-2 (mean age 72·5 years). Spearman correlation coefficients for recall of vegetarian status were 0·78 and 0·72 for the 5-RAS and 33-RAS, respectively, when compared with ‘reference’ data. For both time periods sensitivity and positive predictive values were highest for the lacto-ovo-vegetarian and non-vegetarian patterns (vegans, lacto-ovo-vegetarians, pesco-vegetarians, semi-vegetarians and non-vegetarians). In the 5-RAS analyses, male, non-black, younger, and more educated participants, lifetime Adventists, and those with more stability of consumption of animal products generally showed higher recall ability. Somewhat similar tendencies were shown for the 33-RAS analyses. Our findings show that the instrument has higher reliability for recalled lacto-ovo-vegetarian and non-vegetarian than for vegan, semi- and pesco-vegetarian dietary patterns in both short- and long-term recalls. This is in part because these last dietary patterns were greatly contaminated by recalls that correctly would have belonged in the adjoining category that consumed more animal products.
PMCID: PMC4462762  PMID: 26097699
Long-term reliability; Vegetarian diets; Dietary patterns; Adventists; Dietary recall; AHS-1, Adventist Health Study-1 ; AHS-2, Adventist Health Study-2 ; HHF, hospitalisation history form ; HHF-3, third hospitalisation history form ; PPV, positive predictive value ; 5-RAS, short-term/5-year recall ability study ; 33-RAS, long-term/33-year recall ability study ; S-Stab, score of stability
2.  A pooled analysis of body mass index and pancreatic cancer mortality in African Americans 
Pancreatic cancer is a leading cause of cancer-related mortality in the U.S. and both incidence and mortality are highest in African Americans. Obesity is also disproportionately high in African Americans, but limited data are available on the relation of obesity to pancreatic cancer in this population.
Seven large prospective cohort studies pooled data from African American participants. Body mass index (BMI) was calculated from self-reported height and weight at baseline. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for levels of BMI relative to BMI 18.5–24.9, with adjustment for covariates. Primary analyses were restricted to participants with ≥5 years of follow-up because weight loss prior to diagnosis may have influenced baseline BMI in cases who died during early follow-up.
In follow-up of 239,597 participants, 897 pancreatic cancer deaths occurred. HRs were 1.08 (95% CI, 0.90–1.31) for BMI 25.0–29.9, 1.25 (95% CI, 0.99–1.57) for BMI 30.0–34.9, and 1.31 (95% CI, 0.97–1.77) for BMI ≥35.0 among those with ≥5 years of follow-up (Ptrend = 0.03). The association was evident among both sexes and was independent of a history of diabetes. A stronger association was observed among never-smokers (BMI ≥30 vs. referent: HR = 1.44; 95% CI, 1.02–2.03) than among smokers (HR = 1.16; 95% CI, 0.87–1.54; Pinteraction = 0.02).
The findings suggest that obesity is independently associated with increased pancreatic cancer mortality in African Americans.
Interventions to reduce obesity may also reduce risk of pancreatic cancer mortality, particularly among never-smokers.
PMCID: PMC4184984  PMID: 25017247
body mass index; obesity; pancreatic cancer mortality; African American
3.  Body Size and Multiple Myeloma Mortality: a pooled analysis of 20 prospective studies 
British journal of haematology  2014;166(5):667-676.
Multiple myeloma (MM) is a rare but highly fatal malignancy. High body weight is associated with this cancer, but several questions remain regarding the aetiological relevance of timing and location of body weight. To address these questions, we conducted a pooled analysis of MM mortality using 1.5 million participants (including 1,388 MM deaths) from 20 prospective cohorts in the National Cancer Institute Cohort Consortium. Proportional hazards regression was used to calculate pooled multivariate hazard ratios (HRs) and 95% confidence intervals (CIs). Associations with elevated MM mortality were observed for higher early-adult body mass index (BMI; HR=1.22, 95% CI: 1.09–1.35 per 5 kg/m2) and for higher cohort-entry BMI (HR 1.09, 95% CI: 1.03–1.16 per 5 kg/m2) and waist circumference (HR= 1.06, 95% CI: 1.02–1.10 per 5 cm). Women who were the heaviest, both in early adulthood (BMI 25+) and at cohort entry (BMI 30+) were at greater risk compared to those with BMI 18.5–<25 at both time points (HR=1.95, 95% CI: 1.33–2.86). Waist-to-hip ratio and height were not associated with MM mortality. These observations suggest that overall, and possibly also central, obesity influence myeloma mortality, and women have the highest risk of death from this cancer if they remain heavy throughout adulthood.
PMCID: PMC4134758  PMID: 24861847
multiple myeloma; prospective cohort study; pooled analysis; body mass index; anthropometry
4.  Regression Calibration When Foods (Measured With Error) Are the Variables of Interest: Markedly Non-Gaussian Data With Many Zeroes 
American Journal of Epidemiology  2012;175(4):325-331.
Regression calibration has been described as a means of correcting effects of measurement error for normally distributed dietary variables. When foods are the items of interest, true distributions of intake are often positively skewed, may contain many zeroes, and are usually not described by well-known statistical distributions. The authors considered the validity of regression calibration assumptions where data are non-Gaussian. Such data (including many zeroes) were simulated, and use of the regression calibration algorithm was evaluated. An example used data from Adventist Health Study 2 (2002–2008). In this special situation, a linear calibration model does (as usual) at least approximately correct the parameter that captures the exposure-disease association in the “disease” model. Poor fit in the calibration model does not produce biased calibrated estimates when the “disease” model is linear, and it produces little bias in a nonlinear “disease” model if the model is approximately linear. Poor fit will adversely affect statistical power, but more complex linear calibration models can help here. The authors conclude that non-Gaussian data with many zeroes do not invalidate regression calibration. Irrespective of fit, linear regression calibration in this situation at least approximately corrects bias. More complex linear calibration equations that improve fit may increase power over that of uncalibrated regressions.
PMCID: PMC3271814  PMID: 22268227
bias (epidemiology); foods; measurement error; power; regression calibration
5.  Variables Associated with Cognitive Function in Elderly California Seventh-day Adventists 
American journal of epidemiology  1996;143(12):1181-1190.
From a cohort of white, non-Hispanic California Seventh-day Adventists, 99 subjects over age 75 years in 1991 were randomly selected. Dietary habits and educational status had been measured in 1976. Subjects completed the Mini-Mental State Examination (MMSE) in 1991, and at that time, they or caregivers also gave information on current medical problems and drug therapy. Those who ate more calories in 1976 had lower MMSE scores in 1991 (p = 0.03), an association strengthened by excluding those with previous stroke or Parkinson’s disease by 1991. This raises the possibility that higher consumption of calories in middle age may accelerate the decline in cognitive function seen with aging, as apparently occurs in some animals. Less-educated subjects had lower MMSE scores, especially among the very elderly. The statistical model predicts that the negative association between use of psychotropic drugs and MMSE score (p = 0.004) is particularly potent in those cognitively impaired for other reasons. If causal, this suggests that physicians should use these agents very cautiously in such subjects.
PMCID: PMC3463954  PMID: 8651216
caloric intake; dementia; education; psychotropic drugs; Seventh-day Adventists
6.  Prevalence of hyperthyroidism according to type of vegetarian diet 
Public health nutrition  2014;18(8):1482-1487.
Vegetarian diets may be associated with low prevalence of autoimmune disease, as observed in rural sub-Saharan Africans. Graves’ disease, an autoimmune disorder, is the most common cause of hyperthyroidism. We studied prevalence of hyperthyroidism according to dietary pattern in a population with a high proportion of vegetarians.
Cross-sectional prevalence study. The association between diet and prevalence of hyperthyroidism was examined using multivariate logistic regression analyses controlling for sociodemographic characteristics and salt use.
The Adventist Health Study-2 conducted in the USA and Canada.
Church members (n 65 981) provided demographic, dietary, lifestyle and medical history data by questionnaire.
The prevalence of self-reported hyperthyroidism was 0·9 %. Male gender (OR=0·32; 95 % CI 0·26, 0·41) and moderate or high income (OR=0·67; 95 % CI 0·52, 0·88 and OR=0·73; 95 % CI 0·58, 0·91, respectively) protected against hyperthyroidism, while obesity and prevalent CVD were associated with increased risk (OR=1·25; 95 % CI 1·02, 1·54 and OR=1·92; 95 % CI 1·53, 2·42, respectively). Vegan, lacto-ovo and pesco vegetarian diets were associated with lower risk compared with omnivorous diets (OR=0·49; 95 % CI 0·33, OR=0·72, 0·65; 95 % CI 0·53, 0·81 and OR=0·74; 95 % CI 0·56, 1·00, respectively).
Exclusion of all animal foods was associated with half the prevalence of hyperthyroidism compared with omnivorous diets. Lacto-ovo and pesco vegetarian diets were associated with intermediate protection. Further study of potential mechanisms is warranted.
PMCID: PMC4377303  PMID: 25263477
Diet; Vegetarianism; Vegan; Thyroid
7.  Vegetarian Dietary Patterns and the Risk of Colorectal Cancers 
JAMA internal medicine  2015;175(5):767-776.
Colorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable. The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established.
To evaluate the association between vegetarian dietary patterns and incident colorectal cancers.
The Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96 354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007. Follow-up varied by state and was indicated by the cancer registry linkage dates. Of these participants, an analytic sample of 77 659 remained after exclusions. Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. The analysis was conducted between June 1, 2014, and October 20, 2014.
Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern.
The relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages.
During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented. The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64–0.95) for all colorectal cancers, 0.81 (95%CI, 0.65–1.00) for colon cancer, and 0.71 (95% CI, 0.47–1.06) for rectal cancer. The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59–1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65–1.02); in pescovegetarians, 0.57 (95% CI, 0.40–0.82); and in semivegetarians, 0.92 (95% CI, 0.62–1.37) compared with nonvegetarians. Effect estimates were similar for men and women and for black and nonblack individuals.
Vegetarian diets are associated with an overall lower incidence of colorectal cancers. Pescovegetarians in particular have a much lower risk compared with nonvegetarians. If such associations are causal, they may be important for primary prevention of colorectal cancers.
PMCID: PMC4420687  PMID: 25751512
8.  Reliability of Meat, Fish, Dairy, and Egg Intake Over a 33-Year Interval in Adventist Health Study 2 
Nutrition and cancer  2014;66(8):1315-1321.
We studied Adventist Health Study 2 (AHS-2) cohort members to determine the reliability of long-term recall of adult dietary intake that occurred 33 years ago. Establishing the reliability of these measures supports studies of how dietary exposure across the life course affects risk of cancer and other noncommunicable disease outcomes. Among 1816 AHS-2 cohort members, we conducted a statistical comparison of long-term recall of meat, fish, dairy, and eggs at AHS-2 baseline with their report of current diet 33 years before AHS-2 baseline at an age of 30–60 years. Major findings are as follows: 1) a high correlation for frequency of red meat (R = 0.71), poultry (R = 0.67), and fish (R = 0.60); lower correlations for dairy (R = 0.19) and eggs (R = 0.28); 2) good concordance for dichotomous measures of red meat [sensitivity: 0.70; specificity: 0.92; positive predictive value (PPV): 0.91], poultry (sensitivity: 0.76; specificity: 0.87; PPV: 0.83), fish (sensitivity: 0.61; specificity: 0.93; PPV: 0.89), dairy (sensitivity: 0.95; specificity: 0.57; PPV: 0.99), and eggs (sensitivity: 0.95; specificity: 0.41; PPV: 0.96); negative predictive value for dairy and eggs was poor. Among older AHS-2 cohort members, we found good reliability of recall of red meat, poultry, and fish intake that occurred 33 years earlier.
PMCID: PMC4381800  PMID: 25298211
9.  Legumes and meat analogues consumption are associated with hip fracture risk independently of meat intake among Caucasian men and women: the Adventist Health Study-2 
Public health nutrition  2013;17(10):2333-2343.
In contrast to non-vegetarians, vegetarians consume more legumes and meat analogues as sources of protein to substitute for meat intake. The present study aimed to assess the association between foods with high protein content (legumes, meat, meat analogues) by dietary pattern (vegetarians, non-vegetarians) and hip fracture incidence, adjusted for selected lifestyle factors.
A prospective cohort of Adventist Health Study-2 (AHS-2) enrollees who completed a comprehensive lifestyle and dietary questionnaire between 2002 and 2007.
Every two years after enrolment, a short questionnaire on hospitalizations and selected disease outcomes including hip fractures was sent to these members.
Respondents (n 33 208) to a baseline and a follow-up questionnaire.
In a multivariable model, legumes intake of once daily or more reduced the risk of hip fracture by 64% (hazard ratio=0·36, 95% CI 0·21, 0·61) compared with those with legumes intake of less than once weekly. Similarly, meat intake of four or more times weekly was associated with a 40% reduced risk of hip fracture (hazard ratio=0·60, 95% CI 0·41, 0·87) compared with those whose meat intake was less than once weekly. Furthermore, consumption of meat analogues once daily or more was associated with a 49% reduced risk of hip fracture (hazard ratio=0·51, 95% CI 0·27, 0·98) compared with an intake of less than once weekly.
Hip fracture incidence was inversely associated with legumes intake and, to a lesser extent, meat intake, after accounting for other food groups and important covariates. Similarly, a high intake of meat analogues was associated with a significantly reduced risk of hip fracture.
PMCID: PMC4125560  PMID: 24103482
Legumes; Meat analogues; Vegetable protein; Hip fracture; Dietary protein
10.  Missing Data in a Long Food Frequency Questionnaire 
Epidemiology (Cambridge, Mass.)  2009;20(2):289-294.
Missing data are a common problem in nutritional epidemiology. Little is known of the characteristics of these missing data, which makes it difficult to conduct appropriate imputation.
We telephoned, at random, 20% of subjects (n = 2091) from the Adventist Health Study–2 cohort who had any of 80 key variables missing from a dietary questionnaire. We were able to obtain responses for 92% of the missing variables.
We found a consistent excess of “zero” intakes in the filled-in data that were initially missing. However, for frequently consumed foods, most missing data were not zero, and these were usually not distinguishable from a random sample of nonzero data. Older, black, and less-well-educated subjects had more missing data. Missing data are more likely to be true zeroes in older subjects and those with more missing data. Zero imputation for missing data may create little bias except for more frequently consumed foods, in which case, zero imputation will be suboptimal if there is more than 5%–10% missing.
Although some missing data represent true zeroes, much of it does not, and data are usually not missing at random. Automatic imputation of zeroes for missing data will usually be incorrect, although there is a little bias unless the foods are frequently consumed. Certain identifiable subgroups have greater amounts of missing data, and require greater care in making imputations.
PMCID: PMC2745716  PMID: 19177024
11.  Obesity and Life Expectancy Among Long-Lived Black Adults 
In samples of African Americans and the elderly adults, obesity is often not found to be a risk factor for mortality. These data contradict the evidence linking obesity to chronic disease in these groups. Our objective was to determine whether obesity remains a risk factor for mortality among long-lived black adults.
The Adventist Health Study 2 is a large prospective cohort study of Seventh-day Adventist church members who are encouraged by faith-based principles to avoid tobacco, alcohol, and meat consumption. We conducted an attained age survival analysis of 22,884 U.S. blacks of the cohort—half of whom attained an age of 58–108 years during the follow-up (adult life expectancy of 84 years in men, 89 years in women).
Women in the highest body mass index quintile (>33.8) experienced a significant 61% increase (hazard ratio [95% CI] = 1.62 [1.23, 2.11] relative to the middle quintile) in mortality risk and a 6.2-year (95% CI = 2.8–10.2 years) decrease in life expectancy. Men in the highest body mass index quintile (>30.8) experienced a significant 87% increase (hazard ratio [95% CI] = 1.87 [1.28, 2.73] relative to the middle quintile) in mortality risk and 5.9-year (95% CI = 2.1– 9.5 years) decrease in life expectancy. Obesity (>30) was a significant risk factor relative to normal weight (18.5–24.9) in never-smokers. Instantaneous hazards indicated excess risk from obesity was evident through at least age 85 years. The nonobese tended to follow plant-based diets and exercise vigorously.
Avoiding obesity promotes gains in life expectancy through at least the eighth decade of life in black adults. Evidence for weight control through plant-based diets and active living was found in long-lived nonobese blacks.
PMCID: PMC3859363  PMID: 23682156
Aging; Black*; African American; Caribbean; Southern; Obesity; BMI.
12.  Nutrient Profiles of Vegetarian and Non Vegetarian Dietary Patterns 
Differences in nutrient profiles between vegetarian and non vegetarian dietary patterns reflect nutritional differences that may contribute to the development of disease.
To compare nutrient intakes between dietary patterns characterized by consumption or exclusion of meat and dairy products.
Cross-sectional study of 71751 subjects (mean age 59 years) from the Adventist-Health-Study-2. Data was collected between 2002 and 2007. Participants completed a 204-item validated semi-quantitative food frequency questionnaire. Dietary patterns compared were: non vegetarian, semi vegetarian, pesco vegetarian, lacto-ovo vegetarian and strict vegetarian. ANCOVA was used to analyze differences in nutrient intakes by dietary patterns and were adjusted for age, and sex and race. BMI and other relevant demographic data were reported and compared by dietary pattern using chi-square tests and ANOVA.
Many nutrient intakes varied significantly between dietary patterns. Non vegetarians had the lowest intakes of plant proteins, fiber, β-Carotene, and Mg than those following vegetarian dietary patterns and the highest intakes of saturated, trans, arachidonic, and docosahexaenoic fatty acids. The lower tails of some nutrient distributions in strict vegetarians suggested inadequate intakes by a portion of the subjects. Energy intake was similar among dietary patterns at close to 2000 kcal/d with the exception of semi vegetarians that had an intake of 1713 kcal/d. Mean BMI was highest in non-vegetarians (mean; standard deviation [SD]) (28.7; [6.4]) and lowest in strict vegetarians (24.0; [4.8]).
Nutrient profiles varied markedly between dietary patterns that were defined by meat and dairy intakes. These differences can be of interest in the etiology of obesity and chronic diseases.
PMCID: PMC4081456  PMID: 23988511
Dietary Pattern; Nutrient Profile; Vitamins; Minerals; Vegetarian
13.  Patterns of food consumption among vegetarians and non-vegetarians 
The British journal of nutrition  2014;112(10):1644-1653.
Vegetarian dietary patterns have been reported to be associated with a number of favourable health outcomes in epidemiological studies, including the Adventist Health Study 2 (AHS-2). Such dietary patterns may vary and need further characterisation regarding foods consumed. The aims of the present study were to characterise and compare the food consumption patterns of several vegetarian and non-vegetarian diets. Dietary intake was measured using an FFQ among more than 89 000 members of the AHS-2 cohort. Vegetarian dietary patterns were defined a priori, based on the absence of certain animal foods in the diet. Foods were categorised into fifty-eight minor food groups comprising seventeen major food groups. The adjusted mean consumption of each food group for the vegetarian dietary patterns was compared with that for the non-vegetarian dietary pattern. Mean consumption was found to differ significantly across the dietary patterns for all food groups. Increased consumption of many plant foods including fruits, vegetables, avocados, non-fried potatoes, whole grains, legumes, soya foods, nuts and seeds was observed among vegetarians. Conversely, reduced consumption of meats, dairy products, eggs, refined grains, added fats, sweets, snack foods and non-water beverages was observed among vegetarians. Thus, although vegetarian dietary patterns in the AHS-2 have been defined based on the absence of animal foods in the diet, they differ greatly with respect to the consumption of many other food groups. These differences in food consumption patterns may be important in helping to explain the association of vegetarian diets with several important health outcomes.
PMCID: PMC4232985  PMID: 25247790
Dietary patterns; Vegetarians; Foods
14.  Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2 
JAMA internal medicine  2013;173(13):1230-1238.
Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established.
To evaluate the association between vegetarian dietary patterns and mortality.
Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders.
Adventist Health Study 2 (AHS-2), a large North American cohort.
A total of 96 469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73 308 participants remained after exclusions.
Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo–vegetarian, and vegan.
Main Outcome and Measure
The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index.
There were 2570 deaths among 73 308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82–6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs non-vegetarians was 0.88 (95% CI, 0.80–0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73–1.01); in lacto-ovo–vegetarians, 0.91 (95% CI, 0.82–1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69–0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75–1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women.
Conclusions and Relevance
Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.
PMCID: PMC4191896  PMID: 23836264
15.  Association between Class III Obesity (BMI of 40–59 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies 
PLoS Medicine  2014;11(7):e1001673.
In a pooled analysis of 20 prospective studies, Cari Kitahara and colleagues find that class III obesity (BMI of 40–59) is associated with excess rates of total mortality, particularly due to heart disease, cancer, and diabetes.
Please see later in the article for the Editors' Summary
The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity.
Methods and Findings
In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19–83 y at baseline, classified as obese class III (BMI 40.0–59.9 kg/m2) compared with those classified as normal weight (BMI 18.5–24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976–2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40–44.9, 45–49.9, 50–54.9, and 55–59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7–7.3), 8.9 (95% CI: 7.4–10.4), 9.8 (95% CI: 7.4–12.2), and 13.7 (95% CI: 10.5–16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report.
Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight.
Please see later in the article for the Editors' Summary
Editors' Summary
The number of obese people (individuals with an excessive amount of body fat) is increasing rapidly in many countries. Worldwide, according to the Global Burden of Disease Study 2013, more than a third of all adults are now overweight or obese. Obesity is defined as having a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of more than 30 kg/m2 (a 183-cm [6-ft] tall man who weighs more than 100 kg [221 lbs] is obese). Compared to people with a healthy weight (a BMI between 18.5 and 24.9 kg/m2), overweight and obese individuals (who have a BMI between 25.0 and 29.9 kg/m2 and a BMI of 30 kg/m2 or more, respectively) have an increased risk of developing diabetes, heart disease, stroke, and some cancers, and tend to die younger. Because people become unhealthily fat by consuming food and drink that contains more energy (kilocalories) than they need for their daily activities, obesity can be prevented or treated by eating less food and by increasing physical activity.
Why Was This Study Done?
Class III obesity (extreme, or morbid, obesity), which is defined as a BMI of more than 40 kg/m2, is emerging as a major public health problem in several high-income countries. In the US, for example, 6% of adults are now morbidly obese. Because extreme obesity used to be relatively uncommon, little is known about the burden of disease, including total and cause-specific mortality (death) rates, among individuals with class III obesity. Before we can prevent and treat class III obesity effectively, we need a better understanding of the health risks associated with this condition. In this pooled analysis of prospective cohort studies, the researchers evaluate the risk of total and cause-specific death and the years of life lost associated with class III obesity. A pooled analysis analyzes the data from several studies as if the data came from one large study; prospective cohort studies record the characteristics of a group of participants at baseline and follow them to see which individuals develop a specific condition.
What Did the Researchers Do and Find?
The researchers included 20 prospective (mainly US) cohort studies from the National Cancer Institute Cohort Consortium (a partnership that studies cancer by undertaking large-scale collaborations) in their pooled analysis. After excluding individuals who had ever smoked and people with a history of chronic disease, the analysis included 9,564 adults who were classified as class III obese based on self-reported height and weight at baseline and 304,011 normal-weight adults. Among the participants with class III obesity, mortality rates (deaths per 100,000 persons per year) during the 30-year study period were 856.0 and 663.0 in men and women, respectively, whereas the mortality rates among normal-weight men and women were 346.7 and 280.5, respectively. Heart disease was the major contributor to the excess death rate among individuals with class III obesity, followed by cancer and diabetes. Statistical analyses of the pooled data indicate that the risk of all-cause death and death due to heart disease, cancer, diabetes, and several other diseases increased with increasing BMI. Finally, compared with having a normal weight, having a BMI between 40 and 59 kg/m2 resulted in an estimated loss of 6.5 to 13.7 years of life.
What Do These Findings Mean?
These findings indicate that class III obesity is associated with a substantially increased rate of death. Notably, this death rate increase is similar to the increase associated with smoking among normal-weight people. The findings also suggest that heart disease, cancer, and diabetes are responsible for most of the excess deaths among people with class III obesity and that having class III obesity results in major reductions in life expectancy. Importantly, the number of years of life lost continues to increase for BMI values above 50 kg/m2, and beyond this point, the loss of life expectancy exceeds that associated with smoking among normal-weight people. The accuracy of these findings is limited by the use of self-reported height and weight measurements to calculate BMI and by the use of BMI as the sole measure of obesity. Moreover, these findings may not be generalizable to all populations. Nevertheless, these findings highlight the need to develop more effective interventions to combat the growing public health problem of class III obesity.
Additional Information
Please access these websites via the online version of this summary at
The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (in English and Spanish)
The World Health Organization provides information on obesity (in several languages); Malri's story describes the health risks faced by an obese child
The UK National Health Service Choices website provides information about obesity, including a personal story about losing weight
The Global Burden of Disease Study website provides the latest details about global obesity trends
The US Department of Agriculture's website provides a personal healthy eating plan; the Weight-Control Information Network is an information service provided for the general public and health professionals by the US National Institute of Diabetes and Digestive and Kidney Diseases (in English and Spanish)
MedlinePlus provides links to other sources of information on obesity (in English and Spanish)
PMCID: PMC4087039  PMID: 25003901
16.  Body Mass Index at Age 20 and Subsequent Childbearing: The Adventist Health Study-2 
Journal of Women's Health  2013;22(5):460-466.
Some epidemiological, clinical, and laboratory studies suggest that underweight and obesity impact fertility.
This is cross-sectional study of 33,159 North American Adventist women, who were nulliparous at age 20 years and who, as a group, have a healthy lifestyle. Logistic regression analysis was used to assess how body mass index (BMI, kg/m2) at age 20 was related to never becoming pregnant, never giving birth to a living child, or not giving birth to a second or third child.
A total of 4954 (15%) of the women reported never becoming pregnant (nulligravidity) and 7461 (23%) women remained nulliparous. Underweight (BMI<18.5 kg/m2) at age 20 was associated with approximately 13% increased risk of nulligravidity or nulliparity. Women with BMI≥32.5 kg/m2 when aged 20 had 2.5 (95% CI: 2.0, 3.1) times increased odds of nulliparity compared to women with BMI 20–24.9 kg/m2. Increased risk was found for all groups of overweight women (BMI≥25 kg/m2). However, if the women gave birth to one live child after age 20, BMI≥32.5 kg/m2 at age 20 had less impact (OR 1.6 [95% CI: 1.2, 2.2]) on the likelihood of not delivering a second child. In women who delivered two living children, obesity at age 20 had no bearing on the odds of having a third child.
Obesity and, to a lesser extent, underweight at age 20 increases the nulliparity rate. The results underscore the importance of a healthy weight in young women.
PMCID: PMC3653375  PMID: 23611121
17.  Soy isoflavone intake and the likelihood of ever becoming a mother: the Adventist Health Study-2 
As little is known about the possible relationship between the intake of phytoestrogens and female fertility, we investigated the relationship between soy isoflavone intake and the risk of nulliparity and nulligravidity.
A cross-sectional study of 11,688 North American Adventist women aged 30–50 years old with data regarding childbearing. These women were, as a group, characterized by a high proportion (54%) of vegetarians and a healthy lifestyle with a very low prevalence of smoking and alcohol use.
The mean isoflavone intake (17.9 mg per day) was very high compared to other Western populations. Only 6% of the women indicated no intake of isoflavones. We found, after adjustment for age, marital status, and educational level, an inverse relationship (P=0.05) between isoflavone intake and the likelihood of ever having become a mother. In women with high (≥40 mg/day) isoflavone intake (12% of this group of women), the adjusted lifetime probability of giving birth to a live child was reduced by approximately 3% (95% CI: 0, 7) compared to women with low (<10 mg/day) intake. No relationships were found between the isoflavone intake and parity or age at first delivery in parous women. A similar inverse relationship (P=0.03) was found between the isoflavone intake and the risk of nulligravidity with a 13% (95% CI: 2, 26) higher risk of never have been pregnant in women with high (≥40 mg/day) isoflavone intake. These relationships were found mainly in women who reported problems becoming pregnant.
The findings suggest that a high dietary isoflavone intake may have significant impact on fertility.
PMCID: PMC3982974  PMID: 24741329
soybeans; phytoestrogens; isoflavones; fertility; Seventh-Day Adventist
18.  Tree Nuts Are Inversely Associated with Metabolic Syndrome and Obesity: The Adventist Health Study-2 
PLoS ONE  2014;9(1):e85133.
To examine the relationships of nut consumption, metabolic syndrome (MetS), and obesity in the Adventist Health Study-2, a relatively healthy population with a wide range of nut intake.
Research Design and Methods
Cross-sectional analysis was conducted on clinical, dietary, anthropometric, and demographic data of 803 adults. MetS was defined according to the American Heart Association and the National Heart, Lung, and Blood Institute diagnostic criteria. We assessed intake of total nuts, tree nuts and peanuts, and also classified subjects into low tree nut/low peanut (LT/LP), low tree/high peanut (LT/HP), high tree nut/high peanut (HT/HP), and high tree/low peanut (HT/LP) consumers. Odds ratios were estimated using multivariable logistic regression.
32% of subjects had MetS. Compared to LT/LP consumers, obesity was lower in LT/HP (OR = 0.89; 95% CI = 0.53, 1.48), HT/HP (OR = 0.63; 95% CI = 0.40, 0.99) and HT/LP (OR = 0.54; 95% CI = 0.34, 0.88) consumers, p for trend = 0.006. For MetS, odds ratios (95% CI) were 0.77 (0.47, 1.28), 0.65 (0.42, 1.00) and 0.68 (0.43, 1.07), respectively (p for trend = 0.056). Frequency of nut intake (once/week) had significant inverse associations with MetS (3% less for tree nuts and 2% less for total nuts) and obesity (7% less for tree nuts and 3% less for total nuts).
Tree nuts appear to have strong inverse association with obesity, and favorable though weaker association with MetS independent of demographic, lifestyle and dietary factors.
PMCID: PMC3885676  PMID: 24416351
19.  Religious Engagement in a Risky Family Model Predicting Health in Older Black and White Seventh-day Adventists 
In a structural equation model, associations among latent variables – Child Poverty, Risky Family exposure, Religious Engagement, Negative Social Interactions, Negative Emotionality, and Perceived Physical Health – were evaluated in 6,753 Black and White adults aged 35–106 years (M = 60.5, SD = 13.0). All participants were members of the Seventh-day Adventist church surveyed in the Biopsychosocial Religion and Health Study (BRHS). Child Poverty was positively associated with both Risky Family exposure (conflict, neglect, abuse) and Religious Engagement (intrinsic religiosity, religious coping, religiousness). Risky Family was negatively associated with Religious Engagement and positively associated with both Negative Social Interactions (intrusive, failed to help, insensitive, rejecting) and Negative Emotionality (depression, negative affect, neuroticism). Religious Engagement was negatively associated with Negative Emotionality and Negative Social Interactions at a given level of risky family. Negative Social Interactions was positively associated with Negative Emotionality, which had a direct, negative effect on Perceived Physical Health. All constructs had indirect effects on Perceived Physical Health through Negative Emotionality. The effects of a risky family environment appear to be enduring, negatively affecting one’s adult religious life, emotionality, social interactions, and perceived health. Religious engagement, however, may counteract the damaging effects of early life stress.
PMCID: PMC3613156  PMID: 23560134
religious engagement; risky family; emotionality; physical health
20.  Validation of Recall of Body Weight over a 26 year Period in Cohort Members of Adventist Health Study 2 
Annals of epidemiology  2012;22(10):744-746.
PMCID: PMC3459141  PMID: 22863312
Recall Bias; Correlation Coefficient; Overweight; Elderly; Body Mass Index
21.  Validation of soy protein estimates from a food-frequency questionnaire with repeated 24-h recalls and isoflavonoid excretion in overnight urine in a Western population with a wide range of soy intakes2 
Evidence of the benefits of soy on cancer risk in Western populations is inconsistent, in part because of the low intake of soy in these groups.
We assessed the validity of soy protein estimates from food-frequency questionnaires (FFQs) in a sample of Adventist Health Study-2 participants with a wide range of soy intakes.
We obtained dietary intake data from 100 men and women (43 blacks and 57 nonblacks). Soy protein estimates from FFQs were compared against repeated 24-h recalls and urinary excretion of daidzein, genistein, total isoflavonoids (TIFLs), and equol (measured by HPLC/photodiode array/mass spectrometry) as reference criteria. We calculated Pearson and Spearman correlation coefficients (with 95% CIs) for FFQ–24-h recall, 24 h-recall–urinary excretion, and FFQ–urinary excretion pairs.
Among soy users, mean (± SD) soy protein values were 12.12 ± 10.80 g/d from 24-h recalls and 9.43 ± 7.83 g/d from FFQs. The unattenuated correlation (95% CI) between soy protein estimates from 24-h recalls and FFQs was 0.57 (0.32, 0.75). Correlation coefficients between soy protein intake from 24-h recalls and urinary isoflavonoids were 0.72 (0.43, 0.96) for daidzein, 0.67 (0.43, 0.91) for genistein, and 0.72 (0.47, 0.98) for TIFLs. Between FFQs and urinary excretion, these were 0.50 (0.32, 0.65), 0.48 (0.29, 0.61), and 0.50 (0.32, 0.64) for daidzein, genistein, and TIFLs, respectively.
Soy protein estimates from questionnaire were significantly correlated with soy protein from 24-h recalls and urinary excretion of daidzein, genistein, and TIFLs. The Adventist Health Study-2 FFQ is a valid instrument for assessing soy protein in a population with a wide range of soy intakes.
PMCID: PMC3564955  PMID: 18469267
22.  Self-Reported Physical Health, Mental Health, and Comorbid Diseases Among Women With Irritable Bowel Syndrome, Fibromyalgia, or Both Compared With Healthy Control Respondents 
Physicians often encounter patients with functional pain disorders such as irritable bowel syndrome (IBS), fibromyalgia (FM), and their co-occurrence. Although these diseases are diagnosed exclusively by patients’ report of symptoms, there are few comparative studies about patients’ perceptions of these diseases.
To compare perceptions of these conditions among 4 groups—3 clinical groups of older women with IBS, FM, or both disorders (IBS plus FM) and 1 similarly aged control group of women with no IBS or FM—using their responses to survey questions about stressful life events, general physical and mental health, and general medical, pain, and psychiatric comorbidities.
Using data from the Biopsychosocial Religion and Health Study survey, responses from women were compared regarding a number of variables. To compare stress-related and physical-mental health profiles across the 4 groups, 1-way analyses of variance and χ2 tests (with Tukey-Kramer and Tukey post hoc tests, respectively) were used, with α set to .05.
The present study comprised 3811 women. Participants in the control group, the IBS group, the FM group, and the IBS plus FM group numbered 3213 (84.3%), 366 (9.6%), 161 (4.2%), and 71 (1.9%), respectively, with a mean (standard deviation) age of 62.4 (13.6), 64.9 (13.7), 63.2 (10.8), and 61.1 (10.9) years, respectively. In general, participants in the control group reported fewer lifetime traumatic and major life stressors, better physical and mental health, and fewer comorbidities than respondents in the 3 clinical groups, and these differences were both statistically significant and substantial. Respondents with IBS reported fewer traumatic and major life stressors and better health (ratings and comorbidity data) than respondents with FM or respondents with IBS plus FM. Overall, respondents with both diseases reported the worst stressors and physical-mental health profiles and reported more diagnosed medical, pain, and psychiatric comorbidities.
The results revealed statistically significant, relatively large differences in perceptions of quality of life measures and health profiles among the respondents in the control group and the 3 clinical groups.
PMCID: PMC3542981  PMID: 23139343
23.  Correlates of Perceived Pain-Related Restrictions among Women with Fibromyalgia 
Pain medicine (Malden, Mass.)  2010;11(11):1698-1706.
To identify correlates of perceived pain-related restrictions in a community sample of women with fibromyalgia.
The fibromyalgia group was composed of white women with a self-reported, physician-given fibromyalgia diagnosis (N = 238) from the Biopsychosocial Religion and Health Study (BRHS). BRHS respondents had participated in the larger Adventist Health Study-2. To identify associations with pain-related restrictions, we used hierarchical linear regression. The outcome measure was subjects' pain-related restrictions (one SF-12 version 2 item). Predictors included age, education, body mass index (BMI), sleep apnea, and fibromyalgia treatment in the last year, as well as standardized measures for trauma, major life stress, depression, and hostility. To better interpret the findings, pain-related restrictions also were predicted in women with osteoarthritis and no fibromyalgia.
Women with fibromyalgia reporting the more severe pain-related restrictions were those who had experienced trauma accompanied by physical pain, were older, less educated, more depressed, more hostile, had high BMI scores, and had been treated for fibromyalgia in the last 12 months (adjusted R2 = 0.308). Predictors in women with osteoarthritis were age, BMI, treatment in the last 12 months, experience of a major life stressor, and greater depression symptom severity (adjusted R2 = 0.192).
In both groups, age, BMI, treatment in the last 12 months, and depression predicted pain-related restrictions. Experience of a traumatic event with physical pain was the strongest predictor in the fibromyalgia group. These findings may be useful in constructing novel treatments and prevention strategies for pain-related morbidity in fibromyalgia patients.
PMCID: PMC3539411  PMID: 21044260
Fibromyalgia; Osteoarthritis; Pain; Central Nervous System; Trauma; Stress
24.  Utilization of Prostate Cancer Screening According to Dietary Patterns and Other Demographic Variables. The Adventist Health Study-2 
Journal of Cancer  2013;4(5):416-426.
Background: Prostate-specific antigen test and digital rectal examination are considered important screening methods for early detection of prostate cancer. However, the utilization of prostate cancer screening varies widely and there is limited knowledge of the predictors of utilization.
Methods: Self-reported prostate cancer screening utilization within the last 2 years was investigated among 11,162 black and non-black North American Seventh-day Adventist men, aged 50-75 years, with different dietary patterns and lifestyle characteristics.
Results: Blacks were more likely to screen for prostate cancer than non-blacks (Odds Ratio (OR)=1.38 (95% confidence interval (CI): 1.20-1.57).
Those with a vegetarian diet, especially vegans, were less likely to follow screening guidelines, particularly among non-Blacks: vegans (OR=0.47, 0.39-0.58), lacto-ovo-vegetarians (OR=0.75, 0.66-0.86), and pesco-vegetarians (OR=0.74, 0.60-0.91) compared to non-vegetarians after adjusting for age, BMI, marital status, education, income, and family history of cancer. Trends for dietary patterns remained unchanged after stratification on age, family history of cancer, education, personal income, marital status, and BMI.
Among black men, diet patterns showed no significant associations with utilization of prostate cancer screening, although vegans tended to underutilize screening compared to non-vegetarians (OR=0.70, 0.44-1.10).
Conclusions: Vegetarians, especially non-black vegans, are less likely to follow recommended prostate cancer screening guidelines. The effect of diet was attenuated, and not statistically significant, among black men.
Impact: Since only about 60% of US men follow prostate cancer screening guidelines, it is important to study reasons for non-compliance in order to increase utilization of preventive measures against prostate cancer.
PMCID: PMC3701811  PMID: 23833686
PSA; digital rectal exam; prostate cancer screening; lifestyle predictors; dietary pattern; vegetarian; vegan; black men.
25.  Obesity at age 20 and the risk of miscarriages, irregular periods and reported problems of becoming pregnant: the Adventist Health Study-2 
European Journal of Epidemiology  2012;27(12):923-931.
In a group of 46,000 North-American Adventist women aged 40 and above, we investigated the relationships between body mass index (BMI, kg/m2) at age 20 and the proportion of women who reported at least one miscarriage, periods with irregular menstruation or failing to become pregnant even if trying for more than one straight year. Approximately 31, 14 and 17 %, respectively, reported the three different problems related to reproduction. Positive age- and marital status adjusted relationships were found between BMI at age 20 and periods with irregular menstruation or failing to become pregnant even if trying for more than 1 year, but not with the risk of miscarriages. Women with BMI ≥ 32.5 kg/m2 when aged 20 had approximately 2.0 (95 % CI: 1.6, 2.4) and 1.5 (95 % CI: 1.3, 1.9) higher odds for irregular periods or failing to get pregnant, respectively, than women with BMI in the 20–24.9 kg/m2 bracket. These relationships were consistently found in a number of strata of the population, including the large proportion of the women who never had smoked or never used alcohol. Underweight (BMI < 18.5 kg/m2) when aged 20 marginally (approximately 15 %) increased the risk of failing to get pregnant within a year. Thus, obesity at age 20 increases the risk of reporting some specific reproductive problems, but not the risk of miscarriages.
Electronic supplementary material
The online version of this article (doi:10.1007/s10654-012-9749-8) contains supplementary material, which is available to authorized users.
PMCID: PMC3539069  PMID: 23224589
Obesity; Menstruation; Abortion, spontaneous; Fertility; Seventh-day adventist

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