A large body of evidence has shown that higher red meat consumption, especially processed red meat, is associated with an increased risk of type 2 diabetes,1 cardiovascular disease,2 certain types of cancer, including colorectal cancer,3 and mortality.45 Consumption of processed red meat (eg, bacon, hot dogs, and sausages) has been associated with additional health outcomes, including chronic obstructive pulmonary disease,6 heart failure,7 and hypertension.8 Components of red and processed meats such as proatherosclerotic lipids (eg, saturated fat),9 potential carcinogens (eg, polycyclic aromatic hydrocarbons),10 sodium, and preservatives could contribute to adverse health outcomes.
Red meat is a major component of dietary patterns in Western populations. The average consumption of red meat in the United States has decreased in recent decades, but it remains more than twice the global average.11 Several epidemiological studies have analyzed the relation between red meat consumption and mortality risk. In this study, we examined whether changes in red meat intake are associated with subsequent risk of total and cause-specific mortality.
Analyze of the association of changes in red meat consumption over eight years with mortality risk during the subsequent eight years. Participants were US women from the Nurses’ Health Study and US men from the Health Professionals Follow-up Study.
The Dietary Guidelines for United States 2015-2020 include the recommendation: “Strategies to increase the variety of protein foods include incorporating seafood as the protein foods choice in meals . . . and using legumes or nuts and seeds in mixed dishes instead of some meat or poultry.”12 Therefore, we used statistical models to estimate the effects of replacing red meat with equivalent amounts of other protein sources, such as nuts, poultry, fish, dairy, eggs, and legumes, and whole grains and vegetables.
Study population
The Nurses’ Health Study is a prospective cohort study of 121 700 US registered female nurses aged 30-55 at enrollment. The study started in 1976 and nurses completed a baseline questionnaire about demographic factors, diet habits, lifestyle, and medical history. The Health Professionals Follow-up Study was established in 1986 when 51 529 US male health professionals aged 40-75 returned a baseline questionnaire about detailed medical history, lifestyle, and usual diet. In both cohorts, questionnaires were completed biennially after baseline to collect and update information on lifestyle and occurrence of new-onset diseases. The follow-up rates were approximately 90% for both cohorts. Detailed descriptions of the cohorts have been published elsewhere.1314
The baseline of the current analysis was set as 1994, which is eight years after 1986 when detailed information on diet, physical activity, and other lifestyle factors was collected for both cohorts. The end of follow-up was 2010. The researchers excluded participants who had a history of heart disease, stroke or cancer, missing information on diet and lifestyle covariates, extreme energy intake (men: <800 or >4200 kcal/day; women: <500 or >3500 kcal/day; 1 kcal=4.18 kJ=0.00418 MJ), or those who died before baseline (that is, 1994). The final analysis included 53 553 women and 27 916 men.
Dietary assessment
The two cohorts completed a validated semiquantitative food frequency questionnaire in 1986 and every four years thereafter. Participants were asked how often, on average, they consumed a standard portion of each food in the past year. Frequency response categories ranged from never or less than once a month, to six or more times each day. Questionnaire items on unprocessed red meat (one serving, 85 g) included beef, pork, and lamb as a main dish; hamburger; and beef, pork, or lamb as a sandwich or mixed dish. Items on processed red meat included bacon (one serving, two slices, 13 g), hot dogs (one serving, one hot dog, 45 g), and sausage, salami, bologna, and other processed red meats (one serving, one piece, 28 g). Total red meat included unprocessed and processed red meat. The reproducibility and validity of the food frequency questionnaire have been described elsewhere151617 and show good correlations with several weeks of food records.16 For the Health Professionals Follow-up Study, the corrected correlation coefficients between the food frequency questionnaire and multiple dietary records were 0.59 for unprocessed red meat and 0.52 for processed red meat18; we observed similar correlations for the Nurses’ Health Study.16 In a subcohort of the Nurses’ Health Study (n=3690), higher red meat consumption was associated with unfavourable plasma concentrations of inflammatory and glucose metabolic biomarkers.19 In the current study, we calculated a modified diet score of the alternative healthy eating index to assess overall diet quality after removing the red meat components.17
Ascertainment of mortality
Death from any cause was the primary outcome of this analysis. We identified deaths by using the state vital statistics records, the national death index, reports by families, and the postal system.20 Using these methods, we ascertained 98% of deaths in each cohort.20 We sought death certificates for all deaths, and when appropriate, requested permission from the next of kin to review medical records. A physician reviewed death certificates and medical records and determined the underlying cause of death according to the ICD-8 and ICD-9 (international classification of diseases, eighth and ninth revisions). We grouped causes of death into six major categories.
Covariates measurement
Information on potential confounders was assessed and updated biennially. These confounders included age, race, family history of myocardial infarction, diabetes or cancer, weight, smoking status, aspirin use, multivitamin use, menopausal status and postmenopausal hormone therapy use for women, physical activity, and physician-diagnosed hypertension, diabetes, or hypercholesterolemia. Alcohol consumption was assessed and updated from the food frequency questionnaire every four years. Height and weight were used to calculate body mass index. Detailed descriptions of the validity and reproducibility of self-reported body weight, physical activity, and alcohol consumption have been published elsewhere.212223
Statistical analysis
Researchers calculated the follow-up person-years from the date of returning the 1994 questionnaire to the date of death or the end of follow-up, whichever came first. Updated eight-year change in red meat consumption was used as the time-varying exposure. We used time-dependent Cox proportional hazards regression to estimate the hazard ratios and 95% confidence intervals of total and cause-specific mortality in the subsequent eight years; that is, changes in red meat consumption between 1986 and 1994 predicted mortality in 1994-2002, and changes in red meat consumption between 1994 and 2002 predicted mortality in 2002-10. We divided participants into five categories based on their changes in red meat consumption: two increase categories (increase of >0.5 serving per day or 3.5 servings per week; increase of 0.15-0.5 serving per day or 1-3.5 servings per week); two decrease categories (decrease of >0.5 serving per day or 3.5 servings per week; decrease of 0.15-0.5 serving per day or 1-3.5 servings per week), and one reference category (increase or decrease of <0.15 serving per day or <1 serving per week). We also calculated hazard ratios and the corresponding 95% confidence intervals for changes in red meat consumption.
We adjusted multivariable models for initial age, calendar year as the underlying time scale, race (white v other), family history of myocardial infarction, diabetes, or cancer (yes v no), initial aspirin use (yes v no), and initial multivitamin use (yes v no). We also adjusted for initial consumption of red meat (in fifths); body mass index categories (<23, 23-24.9, 25-29.9, 30-34.9, and ≥35); menopausal status and hormone therapy use in women (premenopausal, postmenopausal and hormone therapy never user, postmenopausal and hormone therapy current user, postmenopausal and hormone therapy past user, or missing indicator); simultaneous changes in smoking status (never to never, never to current, former to former, former to current, current to former, current to current, or missing indicator); initial and simultaneous changes in physical activity, alcohol consumption, total energy intake, and other main food groups, including vegetables, fruits, whole grains, and sugar-sweetened beverages (all in fifths). In an additional model, we further adjusted for initial history of hypertension, hypercholesterolemia, or diabetes (all yes v no), and simultaneous weight change (in fifths), which were potential mediators of the association between red meat changes and mortality. Unprocessed and processed red meat changes were also estimated separately. Stratified analyses were performed a priori by treating total red meat change as a continuous variable according to initial age, body mass index, smoking status, physical activity, alcohol consumption, and modified the alternative healthy eating index. The significance of the interaction terms was tested by including cross-product terms for each category and change in red meat consumption in the multivariable models.
As well the risk of death examined associated with a decrease in red meat by one serving per day and a simultaneous increase of one serving per day of poultry (no skin), fish, dairy products, eggs, legumes, nuts, whole grains, or vegetables (no legumes). Concurrent changes were included in all these food sources, in addition to red meat, in the same multivariable model. The difference in the β coefficients for change in red meat and change in the alternative food was used to estimate the hazard ratio; the corresponding variances and covariance were used to estimate 95% confidence intervals.24
In secondary analyses, short term (four years) and long term (12 years) changes in red meat consumption for associations were estimated with total mortality (four-year change in red meat consumption predicted four-year follow-up and 12-year change in red meat consumption predicted 12-year follow-up). Researchers also modelled associations of a decrease of one serving per day of red meat substituted with an alternative food over four years with total mortality in the subsequent four years and the same substitution over 12 years with total mortality in the subsequent 12 years.
We calculated hazard ratios and 95% confidence intervals from the different models separately for each cohort, and then we pooled the results by using an inverse variance weighted meta-analysis with the fixed effects model. Analyses were performed with SAS version 9.4 for UNIX (SAS Institute, Cary, NC). Statistical tests were two sided and a P value less than 0.05 was considered statistically significant.
Patient and public involvement
No patients were involved in setting the research question or the outcome measures, nor were they involved in the design and implementation of the study. No plans exist to involve patients in dissemination.
In the Nurses’ Health Study, 8426 deaths were identified during the follow-up (804 685 person-years): 1774 deaths from cardiovascular disease, 3138 from cancer, 939 from neurodegenerative diseases, 751 from respiratory diseases, and 1824 from other causes. In the Health Professionals Follow-up Study, we identified 5593 deaths during follow-up (409 073 person-years): 1754 deaths from cardiovascular disease, 1754 from cancer, 434 from respiratory diseases, 375 from neurodegenerative diseases, and 1276 from other causes.
Source: BMJ
