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1.
Effects of vitamin D, omega-3 and a simple strength exercise programme in cardiovascular disease prevention: The DO-HEALTH randomized controlled trial.
Gaengler, S, Sadlon, A, De Godoi Rezende Costa Molino, C, Willett, WC, Manson, JE, Vellas, B, Steinhagen-Thiessen, E, Von Eckardstein, A, Ruschitzka, F, Rizzoli, R, et al
The journal of nutrition, health & aging. 2024;(2):100037
Abstract
BACKGROUND The effects of non-pharmaceutical interventions in the prevention of cardiovascular diseases (CVD) in older adults remains unclear. Therefore, the aim was to investigate the effect of 2000 IU/day of vitamin D3, omega-3 fatty acids (1 g/day), and a simple home strength exercise program (SHEP) (3×/week) on lipid and CVD biomarkers plasma changes over 3 years, incident hypertension and major cardiovascular events (MACE). METHODS The risk of MACE (coronary heart event or intervention, heart failure, stroke) was an exploratory endpoint of DO-HEALTH, incident hypertension and change in biomarkers were secondary endpoints. DO-HEALTH is a completed multicentre, randomised, placebo-controlled, 2 × 2 × 2 factorial design trial enrolling 2157 Europeans aged ≥70 years. RESULTS Participants' median age was 74 [72, 77] years, 61.7% were women, 82.5% were at least moderately physically active, and 40.7% had 25(OH)D < 20 ng/mL at baseline. Compared to their controls, omega-3 increased HDL-cholesterol (difference in change over 3 years: 0.08 mmol/L, 95% CI 0.05-0.10), decreased triglycerides (-0.08 mmol/L, (95%CI -0.12 to -0.03), but increased total- (0.15 mmol/L, 95%CI 0.09; 0.2), LDL- (0.11 mmol/L, 0.06; 0.16), and non-HDL-cholesterol (0.07 mmol/L, 95%CI 0.02; 0.12). However, neither omega-3 (adjustedHR 1.00, 95%CI 0.64-1.56), nor vitamin D3 (aHR 1.37, 95%CI 0.88-2.14), nor SHEP (aHR 1.18, 95%CI 0.76-1.84) reduced risk of MACE or incident hypertension compared to control. CONCLUSION Among generally healthy, active, and largely vitamin D replete, older adults, treatment with omega-3, vitamin D3, and/or SHEP had no benefit on MACE prevention. Only omega-3 supplementation changed lipid biomarkers, but with mixed effects. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER NCT01745263.
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2.
Consumption of 100% Fruit Juice and Body Weight in Children and Adults: A Systematic Review and Meta-Analysis.
Nguyen, M, Jarvis, SE, Chiavaroli, L, Mejia, SB, Zurbau, A, Khan, TA, Tobias, DK, Willett, WC, Hu, FB, Hanley, AJ, et al
JAMA pediatrics. 2024;(3):237-246
Abstract
IMPORTANCE Concerns have been raised that frequent consumption of 100% fruit juice may promote weight gain. Current evidence on fruit juice and weight gain has yielded mixed findings from both observational studies and clinical trials. OBJECTIVE To synthesize the available evidence on 100% fruit juice consumption and body weight in children and adults. DATA SOURCES MEDLINE, Embase, and Cochrane databases were searched through May 18, 2023. STUDY SELECTION Prospective cohort studies of at least 6 months and randomized clinical trials (RCTs) of at least 2 weeks assessing the association of 100% fruit juice with body weight change in children and adults were included. In the trials, fruit juices were compared with noncaloric controls. DATA EXTRACTION AND SYNTHESIS Data were pooled using random-effects models and presented as β coefficients with 95% CIs for cohort studies and mean differences (MDs) with 95% CIs for RCTs. MAIN OUTCOMES AND MEASURES Change in body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was assessed in children and change in body weight in adults. RESULTS A total of 42 eligible studies were included in this analysis, including 17 among children (17 cohorts; 0 RCTs; 45 851 children; median [IQR] age, 8 [1-15] years) and 25 among adults (6 cohorts; 19 RCTs; 268 095 adults; median [IQR] age among cohort studies, 48 [41-61] years; median [IQR] age among RCTs, 42 [25-59]). Among cohort studies in children, each additional serving per day of 100% fruit juice was associated with a 0.03 (95% CI, 0.01-0.05) higher BMI change. Among cohort studies in adults, studies that did not adjust for energy showed greater body weight gain (0.21 kg; 95% CI, 0.15-0.27 kg) than studies that did adjust for energy intake (-0.08 kg; 95% CI, -0.11 to -0.05 kg; P for meta-regression <.001). RCTs in adults found no significant association of assignment to 100% fruit juice with body weight but the CI was wide (MD, -0.53 kg; 95% CI, -1.55 to 0.48 kg). CONCLUSION AND RELEVANCE Based on the available evidence from prospective cohort studies, in this systematic review and meta-analysis, 1 serving per day of 100% fruit juice was associated with BMI gain among children. Findings in adults found a significant association among studies unadjusted for total energy, suggesting potential mediation by calories. Further trials of 100% fruit juice and body weight are desirable. Our findings support guidance to limit consumption of fruit juice to prevent intake of excess calories and weight gain.
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3.
BMI and breast cancer risk around age at menopause.
Von Holle, A, Adami, HO, Baglietto, L, Berrington de Gonzalez, A, Bertrand, KA, Blot, W, Chen, Y, DeHart, JC, Dossus, L, Eliassen, AH, et al
Cancer epidemiology. 2024;:102545
Abstract
BACKGROUND A high body mass index (BMI, kg/m2) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology. METHODS We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy. RESULTS The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO. CONCLUSION The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.
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4.
International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.
Timmins, IR, Jones, ME, O'Brien, KM, Adami, HO, Aune, D, Baglietto, L, Bertrand, KA, Brantley, KD, Chen, Y, Clague DeHart, J, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024;(8):927-939
Abstract
PURPOSE There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. CONCLUSION This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.
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Portfolio Diet Score and Risk of Cardiovascular Disease: Findings From 3 Prospective Cohort Studies.
Glenn, AJ, Guasch-Ferré, M, Malik, VS, Kendall, CWC, Manson, JE, Rimm, EB, Willett, WC, Sun, Q, Jenkins, DJA, Hu, FB, et al
Circulation. 2023;(22):1750-1763
Abstract
BACKGROUND The plant-based Portfolio dietary pattern includes recognized cholesterol-lowering foods (ie, plant protein, nuts, viscous fiber, phytosterols, and plant monounsaturated fats) shown to improve several cardiovascular disease (CVD) risk factors in randomized controlled trials. However, there is limited evidence on the role of long-term adherence to the diet and CVD risk. The primary objective was to examine the relationship between the Portfolio Diet Score (PDS) and the risk of total CVD, coronary heart disease (CHD), and stroke. METHODS We prospectively followed 73 924 women in the Nurses' Health Study (1984-2016), 92 346 women in the Nurses' Health Study II (1991-2017), and 43 970 men in the Health Professionals Follow-up Study (1986-2016) without CVD or cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every 4 years using a PDS that positively ranks plant protein (legumes), nuts and seeds, viscous fiber sources, phytosterols (mg/day), and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and cholesterol. RESULTS During up to 30 years of follow-up, 16 917 incident CVD cases, including 10 666 CHD cases and 6473 strokes, were documented. After multivariable adjustment for lifestyle factors and a modified Alternate Healthy Eating Index (excluding overlapping components), comparing the highest with the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled hazard ratio [HR], 0.86 [95% CI, 0.81-0.92]; Ptrend<0.001), CHD (pooled HR, 0.86 [95% CI, 0.80-0.93]; Ptrend=0.0001), and stroke (pooled HR, 0.86 [95% CI, 0.78-0.95]; Ptrend=0.0003). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR, 0.92 [95% CI, 0.89-0.95]), CHD (pooled HR, 0.92 [95% CI, 0.88-0.95]), and stroke (pooled HR, 0.92 [95% CI, 0.87-0.96]). Results remained consistent across sensitivity and most subgroup analyses, and there was no evidence of departure from linearity for CVD, CHD, or stroke. In a subset of participants, a higher PDS was associated with a more favorable blood lipid and inflammatory profile. CONCLUSIONS The PDS was associated with a lower risk of CVD, including CHD and stroke, and a more favorable blood lipid and inflammatory profile, in 3 large prospective cohorts.
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6.
Sugar-sweetened beverage consumption and weight gain in children and adults: a systematic review and meta-analysis of prospective cohort studies and randomized controlled trials.
Nguyen, M, Jarvis, SE, Tinajero, MG, Yu, J, Chiavaroli, L, Mejia, SB, Khan, TA, Tobias, DK, Willett, WC, Hu, FB, et al
The American journal of clinical nutrition. 2023;(1):160-174
Abstract
BACKGROUND Sugar-sweetened beverages (SSBs) have been implicated in fueling the obesity epidemic. OBJECTIVES This study aimed to update a synthesis of the evidence on SSBs and weight gain in children and adults. METHODS MEDLINE, Embase, and Cochrane databases were searched through September 8, 2022, for prospective cohort studies and randomized controlled trials (RCTs) that evaluated intake of SSBs in relation to BMI and body weight in children and adults, respectively. Eligible interventions were compared against a noncaloric control. Study-level estimates were pooled using random-effects meta-analysis and presented as β-coefficients with 95% CIs for cohorts and weighted mean differences (MDs) with 95% CIs for RCTs. RESULTS We identified 85 articles including 48 in children (40 cohorts, n = 91,713; 8 RCTs, n = 2783) and 37 in adults (21 cohorts, n = 448,661; 16 RCTs, n = 1343). Among cohort studies, each serving/day increase in SSB intake was associated with a 0.07-kg/m2 (95% CI: 0.04 kg/m2, 0.10 kg/m2) higher BMI in children and a 0.42-kg (95% CI: 0.26 kg, 0.58 kg) higher body weight in adults. RCTs in children indicated less BMI gain with SSB reduction interventions compared with control (MD: -0.21 kg/m2; 95% CI: -0.40 kg/m2, -0.01 kg/m2). In adults, randomization to addition of SSBs to the diet led to greater body weight gain (MD: 0.83 kg; 95% CI: 0.47 kg, 1.19 kg), and subtraction of SSBs led to weight loss (MD: -0.49 kg; 95% CI: -0.66 kg, -0.32 kg) compared with the control groups. A positive linear dose-response association between SSB consumption and weight gain was found in all outcomes assessed. CONCLUSIONS Our updated systematic review and meta-analysis expands on prior evidence to confirm that SSB consumption promotes higher BMI and body weight in both children and adults, underscoring the importance of dietary guidance and public policy strategies to limit intake. This meta-analysis was registered at the International Prospective Register of Systematic Reviews as CRD42020209915.
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Racial and ethnic heterogeneity in diets of low-income adult females in the United States: results from National Health and Nutrition Examination Surveys from 2011 to 2018.
Stephenson, BJK, Willett, WC
The American journal of clinical nutrition. 2023;(3):625-634
Abstract
BACKGROUND Poor diet is a major risk factor of cardiovascular and chronic diseases, particularly for low-income female adults. However, the pathways by which race and ethnicity plays a role in this risk factor have not been fully explored. OBJECTIVES This observational study aimed to identify dietary consumption differences by race and ethnicity of US female adults living at or below the 130% poverty income level from 2011 to 2018. METHODS A total of 2917 adult females aged 20 to 80 years from the National Health and Nutrition Examination Survey (2011-2018) living at or below the 130% poverty income level with at least one complete 24-hour dietary recall were classified into 5 self-identified racial and ethnic subgroups (Mexican, other Hispanic, non-Hispanic [NH]-White, NH-Black, and NH-Asian). Dietary consumption patterns were defined by 28 major food groups summarized from the Food Pattern Equivalents Database and derived via a robust profile clustering model, which identifies foods that share consumption patterns across all low-income female adults and foods that differ in consumption patterns based on the racial and ethnic subgroups. RESULTS All food consumption patterns were identified at the local level, defined by racial and ethnic subgroups. Legumes and cured meats were the most differentiating foods identified across all racial and ethnic subgroups. Higher consumption levels of legumes were observed among Mexican-American and other Hispanic females. Higher consumption levels of cured meat were observed among NH-White and Black females. NH-Asian females had the most uniquely characterized patterns with a higher consumption of prudent foods (fruits, vegetables, and whole grains). CONCLUSIONS Differences among the consumption behaviors of low-income female adults were found along racial and ethnic lines. Efforts to improve the nutritional health of low-income female adults should consider racial and ethnic differences in diets to appropriately focus interventions.
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Effects of Vitamin D, Omega-3 Fatty Acids and a Home Exercise Program on Prevention of Pre-Frailty in Older Adults: The DO-HEALTH Randomized Clinical Trial.
Gagesch, M, Wieczorek, M, Vellas, B, Kressig, RW, Rizzoli, R, Kanis, J, Willett, WC, Egli, A, Lang, W, Orav, EJ, et al
The Journal of frailty & aging. 2023;(1):71-77
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Abstract
BACKGROUND The benefits of supplemental vitamin D3, marine omega-3 fatty acids, and a simple home exercise program (SHEP) on frailty prevention in generally healthy community-dwelling older adults are unclear. OBJECTIVE To test the effect of vitamin D3, omega-3s, and a SHEP, alone or in combination on incident pre-frailty and frailty in robust older adults over a follow-up of 36 months. METHODS DO-HEALTH is a multi-center, double-blind, placebo-controlled, 2x2x2 factorial randomized clinical trial among generally healthy European adults aged 70 years or older, who had no major health events in the 5 years prior to enrollment, sufficient mobility and intact cognitive function. As a secondary outcome of the DO-HEALTH trial, among the subset of participants who were robust at baseline, we tested the individual and combined benefits of supplemental 2,000 IU/day of vitamin D3, 1 g/day of marine omega-3s, and a SHEP on the odds of being pre-frail and frail over 3 years of follow-up. RESULTS At baseline, 1,137 out of 2,157 participants were robust (mean age 74.3 years, 56.5% women, mean gait speed 1.18 m/s). Over a median follow-up time of 2.9 years, 696 (61.2%) became pre-frail and 29 (2.6%) frail. Odds ratios for becoming pre-frail were not significantly lower for vitamin D3, or omega 3-s, or SHEP, individually, compared to control (placebo for the supplements and control exercise). However, the three treatments combined showed significantly decreased odds (OR 0.61 [95% CI 0.38-0.98; p=0.04) of becoming pre-frail compared to control. None of the individual treatments or their combination significantly reduced the odds of becoming frail. CONCLUSION Robust, generally healthy and active older adults without major comorbidities, may benefit from a combination of high-dose, supplemental vitamin D3, marine omega-3s, and SHEP with regard to the risk of becoming pre-frail over 3 years.
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Effects of non-nutritive sweeteners on the BMI of children and adolescents: a systematic review and meta-analysis of randomised controlled trials and prospective cohort studies.
Espinosa, A, Mendoza, K, Laviada-Molina, H, Rangel-Méndez, JA, Molina-Segui, F, Sun, Q, Tobias, DK, Willett, WC, Mattei, J
The Lancet. Global health. 2023;:S8
Abstract
BACKGROUND Considering the biological variation across subgroups during periods of growth, the role of non-nutritive sweeteners in weight-related outcomes among children and adolescents is unclear. We did a systematic review and meta-analysis to summarise the evidence on experimental and habitual consumption of non-nutritive sweeteners and prospective changes in BMI in paediatric populations. METHODS We searched eligible (ie, lasting a minimum of 4 weeks) randomised controlled trials of the effect of non-nutritive sweeteners versus non-caloric or caloric comparators on BMI change and prospective cohort studies reporting multivariable-adjusted coefficients for non-nutritive sweetener intake and BMI in children (aged 2-9 years) and adolescents (aged 10-24 years). We generated pooled estimates using random effects meta-analysis and did secondary stratified analyses to explore heterogeneity by study-level and subgroup characteristics. We further evaluated the quality of the included evidence and classified industry-funded studies, or those whose authors were related to the food industry, as having potential conflicts of interest. FINDINGS From 2789 results, we included five randomised controlled trials (n=1498 participants; median follow-up 19·0 weeks [IQR 13·0-37·5]); three [60%] with potential conflicts of interest), and eight prospective cohort studies (n=35 340 participants; median follow-up 2·5 years [IQR 1·7-6·3]; two [25%] with potential conflicts of interest). Random allocation to intake of non-nutritive sweeteners (25-2400 mg/day, from food and beverages) suggested less BMI gain (standardised mean difference -0·42 kg/m2 [95% CI -0·79 to -0·06]; I2=89%) compared with intake of sugar from food and beverages. Stratified estimates were significant only in adolescents, participants with obesity at baseline, consumers of a mixture of non-nutritive sweeteners, longer trials, and trials not found to have potential conflicts of interest. No randomised controlled trials tested beverages containing non-nutritive sweeteners versus water. Prospective cohorts reported a non-significant association between consumption of beverages containing non-nutritive sweeteners and BMI gain (0·05 kg/m2 [95% CI -0·02 to 0·12]; I2=67%; per daily serving of 355 mL), which was accentuated for adolescents, boys, and cohorts with longer follow-ups. Removing studies with potential conflicts of interest attenuated the estimates. Evidence was predominantly classified as of low to moderate quality. INTERPRETATION Intake of non-nutritive sweeteners versus sugar in randomised controlled trials resulted in less BMI gain in adolescents and participants with obesity. Better designed studies should contrast beverages containing non-nutritive sweeteners with water. Long-term prospective analyses with changes in repeated measures might clarify the effect of intake of non-nutritive sweeteners on BMI changes in childhood and adolescence. FUNDING None.
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Prevalence of healthy aging among community dwelling adults age 70 and older from five European countries.
Schietzel, S, Chocano-Bedoya, PO, Sadlon, A, Gagesch, M, Willett, WC, Orav, EJ, Kressig, RW, Vellas, B, Rizzoli, R, da Silva, JAP, et al
BMC geriatrics. 2022;(1):174
Abstract
BACKGROUND To compare the prevalence of healthy aging among adults age 70 and older from 5 European countries recruited for the DO-HEALTH clinical trial. Participants were selected for absence of prior major health events. METHODS Cross-sectional analysis of DO-HEALTH baseline data. All 2,157 participants (mean age 74.9, SD 4.4; 61.7% women) were included and 2,123 had data for all domains of the healthy aging status (HA) definition. HA was assessed based on the Nurses` Health Study (NHS) definition requiring four domains: no major chronic diseases, no disabilities, no cognitive impairment (Montreal Cognitive Assessment, MoCA ≥25), no mental health limitation (GDS-5 <2, and no diagnosis of depression). Association between HA and age, BMI, gender, and physical function (sit-to-stand, gait speed, grip strength) was assessed by multivariate logistic regression analyses adjusting for center. RESULTS Overall, 41.8% of DO-HEALTH participants were healthy agers with significant variability by country: Austria (Innsbruck) 58.3%, Switzerland (Zurich, Basel, Geneva) 51.2%, Germany (Berlin) 37.6%, France (Toulouse) 36.7% and Portugal (Coimbra) 8.8% (p <0.0001). Differences in prevalence by country persisted after adjustment for age. In the multivariate model, younger age (OR = 0.95, 95% CI 0.93 to 0.98), female gender (OR = 1.36, 95% CI 1.03 to 1.81), lower BMI (OR = 0.94, 95% CI 0.91 to 0.96), faster gait speed (OR = 4.70, 95% CI 2.68 to 8.25) and faster performance in sit-to-stand test (OR = 0.90, 95% CI 0.87 to 0.93) were independently and significantly associated with HA. CONCLUSIONS Despite the same inclusion and exclusion criteria preselecting relatively healthy adults age 70 years and older, HA prevalence in DO-HEALTH varied significantly between countries and was highest in participants from Austria and Switzerland, lowest in participants from Portugal. Independent of country, younger age, female gender, lower BMI and better physical function were associated with HA. TRIAL REGISTRATION DO-HEALTH was registered under the protocol NCT01745263 at the International Trials Registry ( clinicaltrials.gov ), and under the protocol number 2012-001249-41 at the Registration at the European Community Clinical Trial System (EudraCT).