Publications by authors named "Walter C Willett"

1,156 Publications

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The Study of Dietary Patterns: Righting the Remedies.

Am J Health Promot 2021 Jul;35(6):875-878

Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.

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http://dx.doi.org/10.1177/08901171211016191bDOI Listing
July 2021

Sugar-Sweetened Beverages, Artificially Sweetened Beverages, and Breast Cancer Risk: Results From 2 Prospective US Cohorts.

J Nutr 2021 Jun 10. Epub 2021 Jun 10.

Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, and Harvard Medical School, Boston, MA, USA.

Background: Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with the risk of breast cancer is of public health interest.

Objectives: We sought to evaluate associations between consumption of SSBs and ASBs and risks of total and subtype-specific breast cancer.

Methods: We followed 82,713 women from the Nurses' Health Study (1980 to 2016) and 93,085 women from the Nurses' Health Study II (1991 to 2017). Cumulatively averaged intakes of SSBs and ASBs from FFQs were tested for associations with incident breast cancer cases and subtypes using Cox regression models. We also evaluated the associations stratified by menopausal status, physical activity, BMI, and alcohol intake.

Results: We documented 11,379 breast cancer cases during 4,655,153 person-years of follow-up. Consumption of SSBs or ASBs was not associated with total breast cancer risk: pooled HRs comparing extreme categories (≥1/day compared with <1/month) were 1.03 (95% CI, 0.95-1.12) and 0.96 (95% CI, 0.91-1.02), respectively. We observed a suggestive interaction by BMI using pooled data (P-interaction = 0.08), where a modestly higher risk of breast cancer with each serving per day increment of SSBs was found in lean women (HR, 1.06; 95% CI, 1.01-1.11) but not among overweight or obese women (HR, 1.00; 95% CI, 0.95-1.06). Moreover, in the pooled, fully adjusted analysis, compared to infrequent consumers (<1/month), those who consumed ≥1 serving of ASBs per day had a lower risk of luminal A breast tumors (HR, 0.90; 95% CI, 0.80-1.01; P-trend = 0.02).

Conclusions: Although no significant associations were observed overall, consumption of SSBs was associated with a slightly higher risk of breast cancer among lean women. This finding could have occurred by chance and needs confirmation. Our findings also suggest no substantial increase in the risk of breast cancer with consumption of ASBs.
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http://dx.doi.org/10.1093/jn/nxab172DOI Listing
June 2021

Diabetes Risk Reduction Diet and Survival After Breast Cancer Diagnosis.

Cancer Res 2021 Jun 9. Epub 2021 Jun 9.

Channing Division of Network Medicine, Brigham and Women's Hospital.

Type 2 diabetes is associated with poor breast cancer prognosis. To study the association between a diabetes risk reduction diet (DRRD) and survival following breast cancer, we followed 8,482 women with breast cancer from two large cohort studies. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. The DRRD includes 9 components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated/saturated fat ratio; and lower glycemic index, trans fat, sugar-sweetened beverages, and red meat. Cumulative average DRRD score was calculated using repeated measures of post-diagnostic diet. Deaths were assessed by family members or via National Death Index. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. During a median of 14 years of follow-up since diagnosis, 2,600 deaths occurred among participants, 1,042 of which were due to breast cancer. Women with higher post-diagnostic DRRD score had a 20% lower risk of breast cancer-specific mortality (top vs. bottom quintile HR =0.80; 95%CI=0.65-0.97; p-trend=0.02) and 34% lower risk of all-cause mortality (HR=0.66; 95%CI=0.58-0.76; p-trend <0.0001). Compared with women who consistently had lower score ({less than or equal to}median) before and after diagnosis, those whose score improved from low to high had a lower risk of breast cancer-specific mortality (HR =0.77; 95%CI=0.62-0.95) and overall mortality (HR =0.85; 95%CI=0.74-0.97). These findings demonstrate that greater adherence to DRRD was associated with better survival, suggesting post-diagnosis dietary modification consistent with Type 2 diabetes prevention may be important for breast cancer survivors.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0256DOI Listing
June 2021

Response to the letter to the editor: "The link between Vitamin D and COVID-19".

Contemp Clin Trials 2021 06 29;105:106418. Epub 2021 May 29.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1016/j.cct.2021.106418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163558PMC
June 2021

Dietary yogurt is distinct from other dairy foods in its association with circulating lipid profile: Findings from the Million Veteran Program.

Clin Nutr ESPEN 2021 Jun 20;43:456-463. Epub 2021 Mar 20.

Massachusetts Veterans Epidemiology and Research Information Center (MAVERIC), Boston Veterans Affairs Healthcare System, Boston, MA, USA; Division of Aging, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.

Background & Aims: Dyslipidemia is a major cardiovascular disease risk factor. Research has proposed mechanisms whereby yogurt may improve circulating lipid concentrations. However, at the population level, the association of yogurt, as distinct from other dairy foods, with these important risk factors is poorly understood. This study aimed to determine whether the circulating lipid profile associated with yogurt is different to the circulating lipid profile that is associated with non-yogurt dairy products, specifically milk and cheese.

Methods: The current study included the 192,564 US Veterans enrolled in the Million Veteran Program who reported frequency of yogurt consumption (assessed via food frequency questionnaire) and had lipid concentrations assessed. Trends were evaluated with linear regression. Mean age was 65 (SD = 11) years [20, 100 years].

Results: A one serve/day higher yogurt consumption was positively associated (coefficient ± SE) with the concentration of high-density lipoprotein cholesterol (HDLC) in individuals who were not (0.26 ± 0.12 mg/dL, P value = 0.025), and who were (0.25 ± 0.09, P value = 0.004), using antilipemic agents. Furthermore, higher yogurt consumption was inversely associated with the concentration of triglycerides, but only in individuals who were not using antilipemic agents (-1.46 ± 0.58, P value = 0.012).

Conclusion: These apparent beneficial associations of yogurt with HDLC and triglycerides were independent of consumption of non-yogurt dairy foods and were not observed for consumption of either milk or cheese. In this prospective cohort study of U.S. Veterans, we found a beneficial relationship between higher frequency of yogurt consumption with circulating HDLC and triglyceride concentrations that was distinct from non-yogurt dairy foods.
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http://dx.doi.org/10.1016/j.clnesp.2021.02.022DOI Listing
June 2021

Long-term Intake of Gluten and Cognitive Function Among US Women.

JAMA Netw Open 2021 May 3;4(5):e2113020. Epub 2021 May 3.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Gluten avoidance has been suggested as having a benefit to cognitive health among the general population, given the link between gluten and cognitive impairment in patients with celiac disease. However, data are lacking in individuals without celiac disease.

Objective: To examine whether gluten intake is associated with cognitive function in women without celiac disease.

Design, Setting, And Participants: This cohort study included US women who participated in the longitudinal, population-based Nurses' Health Study II and had not previously or subsequently been diagnosed with celiac disease. Dietary data were collected from 1991 to 2015, and data on cognitive function were collected from 2014 to 2019. Data analysis was conducted from October 2020 to April 2021.

Exposures: Energy-adjusted gluten intake, cumulatively averaged across questionnaire cycles prior to cognitive assessment.

Main Outcomes And Measures: Three standardized cognitive scores assessed by the validated Cogstate Brief Battery: (1) psychomotor speed and attention score, (2) learning and working memory score, and (3) global cognition score. Higher scores indicated better performance.

Results: The cohort included 13 494 women (mean [SD] age, 60.6 [4.6] years). The mean (SD) gluten intake was 6.3 (1.6) g/d. After controlling for demographic and lifestyle risk factors in linear regression, no significant differences in standardized cognitive scores (mean [SD], 0 [1]) by quintile of gluten intake were found across highest and lowest quintiles of gluten intake (psychomotor speed and attention: -0.02; 95% CI, -0.07 to 0.03; P for trend = .22; learning and working memory: 0.02; 95% CI, -0.03 to 0.07; P for trend = .30; global cognition: -0.002; 95% CI, -0.05 to 0.05; P for trend = .78). The null associations persisted after additional adjustment for major sources of dietary gluten (ie, refined grains or whole grains), comparing decile categories of gluten intake, using gluten intake updated at each previous questionnaire cycle, or modeling changes in gluten intake. Similarly, these associations were not materially altered in sensitivity analyses that excluded women who had reported cancer or dementia diagnosis or had not completed all dietary assessments.

Conclusions And Relevance: In this study, long-term gluten intake was not associated with cognitive scores in middle-aged women without celiac disease. Our results do not support recommendations to restrict dietary gluten to maintain cognitive function in the absence of celiac disease or established gluten sensitivity.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.13020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140370PMC
May 2021

International Scientific Collaboration Is Needed to Bridge Science to Society: USERN2020 Consensus Statement.

SN Compr Clin Med 2021 May 11:1-5. Epub 2021 May 11.

http://usern.org.

Scientific collaboration has been a critical aspect of the development of all fields of science, particularly clinical medicine. It is well understood that myriads of benefits can be yielded by interdisciplinary and international collaboration. For instance, our rapidly growing knowledge on COVID-19 and vaccine development could not be attained without expanded collaborative activities. However, achieving fruitful results requires mastering specific tactics in collaborative efforts. These activities can enhance our knowledge, which ultimately benefits society. In addition to tackling the issue of the invisible border between different countries, institutes, and disciplines, the border between the scientific community and society needs to be addressed as well. International and transdisciplinary approaches can potentially be the best solution for bridging science and society. The Universal Scientific Education and Research Network (USERN) is a non-governmental, non-profit organization and network to promote professional, scientific research and education worldwide. The fifth annual congress of USERN was held in Tehran, Iran, in a hybrid manner on November 7-10, 2020, with key aims of bridging science to society and facilitating borderless science. Among speakers of the congress, a group of top scientists unanimously agreed on The USERN 2020 consensus, which is drafted with the goal of connecting society with scientific scholars and facilitating international and interdisciplinary scientific activities in all fields, including clinical medicine.
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http://dx.doi.org/10.1007/s42399-021-00896-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111052PMC
May 2021

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes.

Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status.

Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models.

Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d).

Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
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http://dx.doi.org/10.1093/ajcn/nqab097DOI Listing
May 2021

Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women.

Gut 2021 May 6. Epub 2021 May 6.

Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

Objective: Sugar-sweetened beverage (SSB) consumption had substantially increased across successive US birth cohorts until 2000, and adolescents and young adults under age 50 years have the highest consumption. However, the link between SSBs and early-onset colorectal cancer (EO-CRC) remains unexamined.

Design: In the Nurses' Health Study II (1991-2015), we prospectively investigated the association of SSB intake in adulthood and adolescence with EO-CRC risk among 95 464 women who had reported adulthood beverage intake using validated food frequency questionnaires (FFQs) every 4 years. A subset of 41 272 participants reported beverage intake at age 13-18 years using a validated high school-FFQ in 1998. Cox proportional hazards models were used to estimate relative risks (RRs) with 95% CIs.

Results: We documented 109 EO-CRC cases. Compared with individuals who consumed <1 serving/week of SSBs in adulthood, women who consumed ≥2 servings/day had a more than doubled risk of EO-CRC (RR 2.18; 95% CI 1.10 to 4.35; p=0.02), with a 16% higher risk (RR 1.16; 95% CI 1.00 to 1.36) per serving/day increase. Each serving/day increment of SSB intake at age 13-18 years was associated with a 32% higher risk of EO-CRC (RR 1.32; 95% CI 1.00 to 1.75). Replacing each serving/day of adulthood SSB intake with that of artificially sweetened beverages, coffee, reduced fat milk or total milk was associated with a 17%-36% lower risk of EO-CRC.

Conclusion: Higher SSB intake in adulthood and adolescence was associated with a higher risk of EO-CRC among women. Reduction of SSB consumption among adolescents and young adults may serve as a potential strategy to alleviate the growing burden of EO-CRC.
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http://dx.doi.org/10.1136/gutjnl-2020-323450DOI Listing
May 2021

Consumption of sugar-sweetened and artificially sweetened beverages and breast cancer survival.

Cancer 2021 May 4. Epub 2021 May 4.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Background: The activation of insulin pathways is hypothesized to promote tumor growth and worsen breast cancer survival. Sugar-sweetened beverages (SSBs) can lead to a higher risk of insulin resistance and may affect survival. The authors prospectively evaluated the relation of postdiagnostic SSB and artificially sweetened beverage (ASB) consumption with mortality among women with breast cancer.

Methods: In total, 8863 women with stage I through III breast cancer were identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and Nurses' Health Study II (NHSII; 1991-2011). Women completed a validated food frequency questionnaire every 4 years after diagnosis and were followed until death or the end of follow-up (2014 for the NHS and 2015 for the NHSII). Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific and all-cause mortality after adjusting for measures of adiposity and other potential predictors of cancer survival.

Results: With a median follow-up of 11.5 years, 2482 deaths were prospectively documented, including 1050 deaths from breast cancer. Compared with women who had no consumption, women who had SSB consumption after diagnosis had higher breast cancer-specific mortality (>1 to 3 servings per week: HR, 1.31 [95% CI, 1.09-1.58]; >3 servings per week: HR, 1.35 [95% CI, 1.12-1.62]; P = .001) and all-cause mortality (>1 to 3 servings per week: HR, 1.21 [95% CI, 1.07-1.37]; >3 servings per week: HR, 1.28 [95% CI, 1.13-1.45]; P = .0001). In contrast, ASB consumption was not associated with higher breast cancer-specific or all-cause mortality. Furthermore, replacing 1 serving per day of SSB consumption with 1 serving per day of ASB consumption was not associated with a lower risk of mortality.

Conclusions: Higher postdiagnostic SSB consumption among breast cancer survivors was associated with higher breast cancer-specific mortality and death from all causes.
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http://dx.doi.org/10.1002/cncr.33461DOI Listing
May 2021

The Structure of Relationships between the Human Exposome and Cardiometabolic Health: The Million Veteran Program.

Nutrients 2021 Apr 19;13(4). Epub 2021 Apr 19.

Massachusetts Veterans Epidemiology and Research Information Center (MAVERIC), Boston Veterans Affairs Healthcare System, Boston, MA 02130, USA.

The represents the array of dietary, lifestyle, and demographic factors to which an individual is exposed. Individual components of the exposome, or groups of components, are recognized as influencing many aspects of human physiology, including cardiometabolic health. However, the influence of the whole exposome on health outcomes is poorly understood and may differ substantially from the sum of its individual components. As such, studies of the complete exposome are more biologically representative than fragmented models based on subsets of factors. This study aimed to model the system of relationships underlying the way in which the diet, lifestyle, and demographic components of the overall exposome shapes the cardiometabolic risk profile. The current study included 36,496 US Veterans enrolled in the VA Million Veteran Program (MVP) who had complete assessments of their diet, lifestyle, demography, and markers of cardiometabolic health, including serum lipids, blood pressure, and glycemic control. The cohort was randomly divided into training and validation datasets. In the training dataset, we conducted two separate exploratory factor analyses (EFA) to identify common factors among exposures (diet, demographics, and physical activity) and laboratory measures (lipids, blood pressure, and glycemic control), respectively. In the validation dataset, we used multiple normal regression to examine the combined effects of exposure factors on the clinical factors representing cardiometabolic health. The mean ± SD age of participants was 62.4 ± 13.4 years for both the training and validation datasets. The EFA revealed 19 Exposure Common Factors and 5 Physiology Common Factors that explained the observed (measured) data. Multivariate regression in the validation dataset revealed the structure of associations between the Exposure Common Factors and the Physiology Common Factors. For example, we found that the factor for fruit consumption was inversely associated with the factor summarizing total cholesterol and low-density lipoprotein cholesterol (LDLC, = 0.008), and the latent construct describing light levels of physical activity was inversely associated with the blood pressure latent construct ( < 0.0001). We also found that a factor summarizing that participants who frequently consume whole milk are less likely to frequently consume skim milk, was positively associated with the latent constructs representing total cholesterol and LDLC as well as systolic and diastolic blood pressure ( = 0.0006 and <0.0001, respectively). Multiple multivariable-adjusted regression analyses of exposome factors allowed us to model the influence of the exposome as a whole. In this metadata-rich, prospective cohort of US Veterans, there was evidence of structural relationships between diet, lifestyle, and demographic exposures and subsequent markers of cardiometabolic health. This methodology could be applied to answer a variety of research questions about human health exposures that utilize electronic health record data and can accommodate continuous, ordinal, and binary data derived from questionnaires. Further work to explore the potential utility of including genetic risk scores and time-varying covariates is warranted.
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http://dx.doi.org/10.3390/nu13041364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073795PMC
April 2021

Body-Mass Index and Mortality among Adults with Incident Myocardial Infarction.

Am J Epidemiol 2021 Apr 27. Epub 2021 Apr 27.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

The relation between body mass index (BMI, kg/m2) and mortality among survivors of myocardial infarction (MI) remains controversial. We examined the relationship of BMI before and after MI, and change in weight, with all-cause mortality among participants of the Nurses' Health Study (1980-2016) and Health Professionals Follow up Study (1988-2016) cohorts. During up to 36 years of follow-up, we documented 4856 incident nonfatal MI cases, among whom 2407 died. For the pre-MI and post-MI BMI, overweight was not associated with lower mortality. Obesity (BMI ≥ 30 kg/m2) was associated with higher risk of mortality. Compared to participants with post-MI BMI of 22.5-24.9, HRs were 1.16, 95% CI: 1.01, 1.34 for BMI 30-34.9 and 1.52, 95% CI: 1.27, 1.83 for BMI ≥ 35; Ptrend<0.001. Compared to stable weight from before to after MI, reduction of > 4 BMI units was associated with increased mortality, HR=1.53, 95%: CI 1.28, 1.83. This increase was only among participants who lost weight without improving physical activity or diet. Our findings showed no survival benefit of excess adiposity in relation to risk of mortality. Weight loss from before to after MI without lifestyle improvement may reflect reverse causation and disease severity.
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http://dx.doi.org/10.1093/aje/kwab126DOI Listing
April 2021

Overview of the Microbiome Among Nurses study (Micro-N) as an example of prospective characterization of the microbiome within cohort studies.

Nat Protoc 2021 Jun 21;16(6):2724-2731. Epub 2021 Apr 21.

Harvard Chan Microbiome in Public Health Center, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses' Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort's ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out.
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http://dx.doi.org/10.1038/s41596-021-00519-zDOI Listing
June 2021

Building better guidelines for healthy and sustainable diets.

Am J Clin Nutr 2021 Apr 19. Epub 2021 Apr 19.

Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.

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http://dx.doi.org/10.1093/ajcn/nqab079DOI Listing
April 2021

DIETARY GLUTEN INTAKE IS NOT ASSOCIATED WITH RISK OF INFLAMMATORY BOWEL DISEASE IN U.S. ADULTS WITHOUT CELIAC DISEASE.

Clin Gastroenterol Hepatol 2021 Mar 25. Epub 2021 Mar 25.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA; Clinical and Translation Epidemiology, Massachusetts General Hospital and Harvard Medical School, Boston MA; Broad Institute of MIT and Harvard, Cambridge MA 02142. Electronic address:

Background & Aims: Diet is thought to play a role in the development of inflammatory bowel disease (IBD), though the relationship between gluten intake and risk of IBD has not been explored. The aim of this study was to determine the relationship between gluten intake and risk of incident Crohn's disease (CD) and ulcerative colitis (UC).

Methods: We performed a prospective cohort study of 208,280 US participants from the Nurses' Health Study (NHS; 1986-2016), NHSII (1991-2017), and Health Professionals Follow-up Study (1986-2016) who did not have IBD at baseline or celiac disease, and who completed semi-quantitative food frequency questionnaires. We used Cox proportional hazards modeling to estimate the risk of IBD according to quintiles of cumulative average energy-adjusted dietary gluten intake over follow-up period.

Results: We documented 337 CD cases and 447 UC cases over 5,115,265 person-years of follow-up. Dietary gluten intake was not associated with risk of IBD. Compared to participants in the lowest quintile of gluten intake, the adjusted hazard-ratios and 95% confidence intervals (CI) for participants in the highest quintile of gluten intake were 1.16 (95% CI: 0.82-1.64; P = 0.41) for CD and 1.04 (95% CI: 0.75-1.44; P = 0.64) for UC. Adjusting for primary sources of gluten intake did not materially change our estimates.

Conclusions: In three large adult US prospective cohorts, gluten intake was not associated with risk of CD or UC. Our findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases.
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http://dx.doi.org/10.1016/j.cgh.2021.03.029DOI Listing
March 2021

Post-diagnostic coffee and tea consumption and breast cancer survival.

Br J Cancer 2021 May 24;124(11):1873-1881. Epub 2021 Mar 24.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: We examined the role of post-diagnostic coffee and tea consumption in relation to breast cancer-specific and all-cause mortality among women with breast cancer in prospective cohort studies.

Methods: We identified 8900 women with stage I-III breast cancer from 1980 through 2010 in the Nurses' Health Study (NHS) and from 1991 through 2011 in the NHSII. Post-diagnostic coffee and tea consumption was assessed by a validated food frequency questionnaire every 4 years after diagnosis.

Results: During up to 30 years of follow-up, we documented 1054 breast cancer-specific deaths and 2501 total deaths. Higher post-diagnostic coffee consumption was associated with a lower breast cancer-specific mortality: compared with non-drinkers, >3 cups/day of coffee was associated with a 25% lower risk (hazard ratio (HR) = 0.75, 95% confidence interval (CI) = 0.59-0.96; P = 0.002). We also observed a lower all-cause mortality with coffee consumption: compared with non-drinkers, >2 to 3 cups/day was associated with a 24% lower risk (HR = 0.76, 95% CI = 0.66-0.87) and >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.63-0.87, P < 0.0001). Post-diagnostic tea consumption was associated with a lower all-cause mortality: compared with non-drinkers, >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.58-0.95; P = 0.04).

Conclusions: Among breast cancer survivors, higher post-diagnostic coffee consumption was associated with better breast cancer and overall survival. Higher post-diagnostic tea consumption may be related to better overall survival.
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http://dx.doi.org/10.1038/s41416-021-01277-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144620PMC
May 2021

Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors.

Gastroenterology 2021 Mar 19. Epub 2021 Mar 19.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Background & Aims: Recent increasing trends in early-onset colorectal cancer (CRC) strongly supports that early-life diet is involved in CRC development. However, data are lacking on the relationship with high sugar intake during early life.

Methods: We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses' Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for clustered data.

Results: During follow-up, 2909 conventional adenomas (758 high-risk) and 2355 serrated lesions were identified (mean age at diagnoses, 52.2 ± 4.3 years). High sugar and SSB intake during adolescence was positively associated with risk of adenoma, but not serrated lesions. Per each increment of 5% of calories from total fructose intake, multivariable ORs were 1.17 (95% CI, 1.05-1.31) for total and 1.30 (95% CI, 1.06-1.60) for high-risk adenoma. By subsite, ORs were 1.12 (95% CI, 0.96-1.30) for proximal, 1.24 (95% CI, 1.05-1.47) for distal, and 1.43 (95% CI, 1.10-1.86) for rectal adenoma. Per 1 serving/day increment in SSB intake, ORs were 1.11 (95% CI, 1.02-1.20) for total and 1.30 (95% CI, 1.08-1.55) for rectal adenoma. Contrary to adolescent intake, sugar and SSB intake during adulthood was not associated with adenoma risk.

Conclusions: High intake of simple sugars and SSBs during adolescence was associated with increased risk of conventional adenoma, especially rectal adenoma.
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http://dx.doi.org/10.1053/j.gastro.2021.03.028DOI Listing
March 2021

Association of folate intake and colorectal cancer risk in the postfortification era in US women.

Am J Clin Nutr 2021 Mar 19. Epub 2021 Mar 19.

Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.

Background: Folate may play a preventive role in the early stages of colorectal carcinogenesis, but long latencies may be needed to observe a reduction in colorectal cancer (CRC) incidence. In addition, concerns have been raised about the potential for cancer promotion with excessive folate intake, especially after the mandatory folic acid fortification in the United States in 1998.

Objective: We aimed to examine the association between folate intake in different chemical forms and CRC risk, especially in the postfortification era in the United States.

Design: We prospectively followed 86,320 women from the Nurses' Health Study (1980-2016). Folate intake was collected by validated food frequency questionnaires. CRC was self reported and confirmed by review of medical records. The association between the folate intake and CRC risk was assessed using Cox proportional hazards regression.

Results: We documented 1988 incident CRC cases during follow-up. Analyzing folate intake as a continuous variable, greater total folate intake 12-24 y before diagnosis was associated with lower risk of CRC (per increment of 400 dietary folate equivalents (DFE)/d, HR: 0.93, 95% CI: 0.85, 1.01 for 12-16 y; HR: 0.83, 95% CI: 0.75, 0.92 for 16-20 y; and HR: 0.87, 95% CI: 0.77, 0.99 for 20-24 y); and greater synthetic folic acid intake 16-24 y before diagnosis was also associated with a lower CRC risk (per increment of 400 DFE/d, HR: 0.91, 95% CI: 0.84, 0.99 for 16-20 y and HR: 0.91, 95% CI: 0.83-1.01 for 20-24 y). In the postfortification period (1998-2016), intake of total or specific forms of folate was not associated with CRC risk, even among multivitamin users.

Conclusions: Folate intake, both total and from synthetic forms, was associated with a lower risk of overall CRC after long latency periods. There was no evidence that high folate intake in the postfortification period was related to increased CRC risk in this US female population.
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http://dx.doi.org/10.1093/ajcn/nqab035DOI Listing
March 2021

Quality of Plant-Based Diet and Risk of Total, Ischemic, and Hemorrhagic Stroke.

Neurology 2021 04 10;96(15):e1940-e1953. Epub 2021 Mar 10.

From the Department of Nutrition (M.Y.B., Z.S., F.W., Y.L., E.B.R., W.C.W., F.B.H.), Department of Epidemiology (J.E.M., E.B.R., W.C.W., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Metabolic Medicine (M.Y.B.), Osaka University Graduate School of Medicine, Japan; Channing Division of Network Medicine (J.E.M., W.C.W., F.B.H.), Department of Medicine, Division of Preventive Medicine (J.E.M.), Department of Medicine, and Division of Women's Health (K.M.R.), Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.

Objective: To determine whether a healthful plant-based diet is related to lower stroke risk, we examined the associations of plant-based diet quality with risk of total, ischemic, and hemorrhagic stroke.

Methods: The participants were 73,890 women in Nurses' Health Study (NHS; 1984-2016), 92,352 women in NHSII (1991-2017), and 43,266 men in Health Professionals Follow-Up Study (1986-2012) without cardiovascular disease and cancer at baseline. Plant-based diet quality was evaluated by the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Participants who reported that their meat and/or fish intakes were 0 or <1 serving per month were categorized as vegetarians, and others were classified as nonvegetarians. Strokes with available medical records were subtyped as ischemic or hemorrhagic.

Results: During the follow-up, 6,241 total stroke cases (including 3,015 ischemic and 853 hemorrhagic strokes) were documented. Compared to participants with the lowest PDIs, among participants with the highest PDIs, the hazard ratios (HRs) for total stroke were 0.94 (95% confidence interval 0.86-1.03) for PDI, 0.90 (0.83-0.98) for hPDI, and 1.05 (0.96-1.15) for uPDI. Participants in the highest hPDI showed marginally lower HR for ischemic stroke (0.92 [0.82-1.04]) and no consistent associations for hemorrhagic stroke. We observed no association between a vegetarian diet and total stroke (1.00 [0.76-1.32]), although the number of cases was small.

Conclusion: Lower risk of total stroke was observed by those who adhered to a healthful plant-based diet.
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http://dx.doi.org/10.1212/WNL.0000000000011713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166423PMC
April 2021

TV viewing during childhood and adult type 2 diabetes mellitus.

Sci Rep 2021 Mar 4;11(1):5157. Epub 2021 Mar 4.

Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Elsässerstr. 2, 79110, Freiburg, Germany.

We examined whether regular television (TV) viewing at ages 3-5 and 5-10 years is related to the incidence of type 2 diabetes mellitus (T2D) in adult women. We used data from 34,512 mother-nurse daughter dyads in the Nurses' Health Study (NHS) II and the Nurses' Mothers' Cohort Study. Mothers of NHS II participants completed a questionnaire on their pregnancy with the nurse and her early life experience. During 391,442 person-years of follow-up from 2001 to 2013, 1515 nurses developed T2D. Increasing levels of TV viewing at 3-5 years of age retrospectively reported by the mothers were related to a greater risk of T2D in adulthood: multivariable-adjusted hazard ratios (HRs) for ≤ 1, 2, and ≥ 3 h/day vs. no TV viewing were 1.11 [95% confidence interval (CI) 0.96-1.28], 1.20 (95% CI 1.02-1.41), and 1.35 (95% CI 1.11-1.65), p trend = 0.002, respectively, after adjustment for early life variables, including childhood physical activity and adiposity. Retrospectively reported TV viewing for ≥ 3 h/day at 5-10 years of age was associated with a 34% greater risk of adult T2D (HR 1.34, 95% CI 1.05-1.70, p trend < 0.001). Additional adjustments for adult variables, including adult TV viewing and current BMI attenuated the effect estimates (≥ 3 h/day TV viewing at 3-5 years: HR 1.22, 95% CI 0.99-1.49, p trend = 0.07; TV viewing at 5-10 years: 1.16, 95% CI 0.91-1.49, p trend = 0.09). The present study suggests that TV viewing during early childhood increases risk of T2D in adult women; adult BMI explains part of this association. Further research is required to confirm this observation and understand the mediating pathways.
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http://dx.doi.org/10.1038/s41598-021-83746-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933176PMC
March 2021

Fruit and Vegetable Intake and Mortality: Results From 2 Prospective Cohort Studies of US Men and Women and a Meta-Analysis of 26 Cohort Studies.

Circulation 2021 Apr 1;143(17):1642-1654. Epub 2021 Mar 1.

Channing Division for Network Medicine (D.D.W., S.N.B., B.A.R., Q.S., E.L.G., E.B.R., J.E.M., W.C.W., M.J.S., F.B.H.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Background: The optimal intake levels of fruit and vegetables for maintaining long-term health are uncertain.

Methods: We followed 66 719 women from the Nurses' Health Study (1984-2014) and 42 016 men from the Health Professionals Follow-up Study (1986-2014) who were free from cardiovascular disease (CVD), cancer, and diabetes at baseline. Diet was assessed using a validated semiquantitative food frequency questionnaire at baseline and updated every 2 to 4 years. We also conducted a dose-response meta-analysis, including results from our 2 cohorts and 24 other prospective cohort studies.

Results: We documented 33 898 deaths during the follow-up. After adjustment for known and suspected confounding variables and risk factors, we observed nonlinear inverse associations of fruit and vegetable intake with total mortality and cause-specific mortality attributable to cancer, CVD, and respiratory disease (all <0.001). Intake of ≈5 servings per day of fruit and vegetables, or 2 servings of fruit and 3 servings of vegetables, was associated with the lowest mortality, and above that level, higher intake was not associated with additional risk reduction. In comparison with the reference level (2 servings/d), daily intake of 5 servings of fruit and vegetables was associated with hazard ratios (95% CI) of 0.87 (0.85-0.90) for total mortality, 0.88 (0.83-0.94) for CVD mortality, 0.90 (0.86-0.95) for cancer mortality, and 0.65 (0.59-0.72) for respiratory disease mortality. The dose-response meta-analysis that included 145 015 deaths accrued in 1 892 885 participants yielded similar results (summary risk ratio of mortality for 5 servings/d=0.87 [95% CI, 0.85-0.88]; <0.001). Higher intakes of most subgroups of fruits and vegetables were associated with lower mortality, with the exception of starchy vegetables such as peas and corn. Intakes of fruit juices and potatoes were not associated with total and cause-specific mortality.

Conclusions: Higher intakes of fruit and vegetables were associated with lower mortality; the risk reduction plateaued at ≈5 servings of fruit and vegetables per day. These findings support current dietary recommendations to increase intake of fruits and vegetables, but not fruit juices and potatoes.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084888PMC
April 2021

Alcohol intake in early adulthood and risk of colorectal cancer: three large prospective cohort studies of men and women in the United States.

Eur J Epidemiol 2021 Mar 15;36(3):325-333. Epub 2021 Feb 15.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Heavy alcohol consumption in mid-adulthood is an established risk factor of colorectal cancer (CRC). Alcohol use in early adulthood is common, but its association with subsequent CRC risk remains largely unknown. We prospectively investigated the association of average alcohol intake in early adulthood (age 18-22) with CRC risk later in life among 191,543 participants of the Nurses' Health Study ([NHS], 1988-2014), NHSII (1989-2015) and Health Professionals Follow-Up Study (1988-2014). Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), which were pooled using random effects models. We documented 2,624 CRC cases. High alcohol consumption in early adulthood (≥ 15 g/day) was associated with a higher CRC risk (multivariable HR 1.28, 95% CI 0.99-1.66, P = 0.02; P = 0.44), after adjusting for potential confounding factors in early adulthood. Among never/light smokers in early adulthood, the risk associated with high alcohol consumption in early adulthood was elevated (HR 1.53, 95% CI 1.04-2.24), compared with those who had < 1 g/day of alcohol intake. The suggestive higher CRC risk associated with high alcohol consumption in early adulthood was similar in those who had < 15 g/day (HR 1.35, 95% CI 0.98-1.86) versus ≥ 15 g/day of midlife alcohol intake (HR 1.35, 95% CI 0.89-2.05), compared with nondrinkers in both life stages. The findings from these large prospective cohort studies suggest that higher alcohol intake in early adulthood may be associated with a higher risk of developing CRC later in life.
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http://dx.doi.org/10.1007/s10654-021-00723-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168576PMC
March 2021

The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk.

Nat Med 2021 02 11;27(2):333-343. Epub 2021 Feb 11.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome.
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http://dx.doi.org/10.1038/s41591-020-01223-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186452PMC
February 2021

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

Nutrients 2021 Feb 3;13(2). Epub 2021 Feb 3.

Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer's disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.
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http://dx.doi.org/10.3390/nu13020499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913332PMC
February 2021

Changes in Plant-Based Diet Indices and Subsequent Risk of Type 2 Diabetes in Women and Men: Three U.S. Prospective Cohorts.

Diabetes Care 2021 Mar 13;44(3):663-671. Epub 2021 Jan 13.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA

Objective: We evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes.

Research Design And Methods: We prospectively followed 76,530 women in the Nurses' Health Study (NHS) (1986-2012), 81,569 women in NHS II (1991-2017), and 34,468 men in the Health Professionals Follow-up Study (1986-2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis.

Results: We documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (>10%) in PDI and hPDI over 4 years had a 12-23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7-9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0-35.6% of the associations between changes in PDI and hPDI and diabetes risk.

Conclusions: Improving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk.
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http://dx.doi.org/10.2337/dc20-1636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896264PMC
March 2021

THE RELATIONSHIP BETWEEN INFLAMMATORY DIETARY PATTERN AND INCIDENCE OF PERIODONTITIS.

Br J Nutr 2021 Jan 8:1-36. Epub 2021 Jan 8.

Department of Epidemiology, Harvard T.H. Chan School of Public Health 677 Huntington Ave, Boston, MA02115, USA.

The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food based, reduced rank regression (RRR) derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34,940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years, and dietary data through validated semi-quantitative food frequency questionnaires every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) to the lowest quintile was 0.99 (95% confidence interval: 0.89 -1.10, p-value for trend = 0.97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile to the lowest was 1.39 (95% confidence interval: 0.98 -1.96, p-value for trend = 0.03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated EDIP was significantly associated with increased risk of periodontitis only among nonsmokers who were obese. Hence, this association must be interpreted with caution.
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http://dx.doi.org/10.1017/S0007114520005231DOI Listing
January 2021