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Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review.
Diaz, C, Rezende, LFM, Sabag, A, Lee, DH, Ferrari, G, Giovannucci, EL, Rey-Lopez, JP
Advances in nutrition (Bethesda, Md.). 2023;(4):710-717
Abstract
The consumption of artificially sweetened beverages (ASBs) is increasing in some countries. However, some meta-analyses have found that habitual consumers of ASBs (compared with low or no consumption) had an increased risk on some health outcomes. We performed an umbrella review of meta-analyses to grade the credibility of the evidence of claimed observational associations between ASBs and health outcomes. Data were searched in Web of Science, Embase, and PubMed for systematic reviews published up to 25 May 2022, examining association between ASBs and any health outcomes. Certainty of the evidence for each health outcome was obtained based on statistical results of tests used in umbrella reviews. The AMSTAR-2 tool (16 items) was used to identify high-quality systematic reviews. Answers of each item were rated as yes, no, or partial yes (for a partial adherence to the standard). We included data from 11 meta-analyses with unique population, exposure, comparison group, outcome obtained from 7 systematic reviews (51 cohort studies and 4 case-control studies). ASBs were associated with higher risk of obesity, type 2 diabetes, all-cause mortality, hypertension, and cardiovascular disease incidence (supported by highly suggestive evidence). Evidence for other outcomes (colorectal cancer, pancreatic cancer, gastrointestinal cancer, cancer mortality, cardiovascular mortality, chronic kidney disease, coronary artery disease, and stroke) was weak. Results of the quality assessment of systematic reviews using AMSTAR-2 showed some notable deficiencies: unclear sources of funding of eligible studies and lack of predefined study protocols to guide authors. The consumption of ASBs was associated with a higher risk of obesity, type 2 diabetes, all-cause mortality, hypertension, and cardiovascular disease incidence. However, further cohort studies and clinical trials in humans are still needed to understand the impact of ASBs on health outcomes.
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Cheese consumption and multiple health outcomes: an umbrella review and updated meta-analysis of prospective studies.
Zhang, M, Dong, X, Huang, Z, Li, X, Zhao, Y, Wang, Y, Zhu, H, Fang, A, Giovannucci, EL
Advances in nutrition (Bethesda, Md.). 2023;(5):1170-1186
Abstract
This umbrella review aims to provide a systematic and comprehensive overview of current evidence from prospective studies on the diverse health effects of cheese consumption. We searched PubMed, Embase, and Cochrane Library to identify meta-analyses/pooled analyses of prospective studies examining the association between cheese consumption and major health outcomes from inception to August 31, 2022. We reanalyzed and updated previous meta-analyses and performed de novo meta-analyses with recently published prospective studies, where appropriate. We calculated the summary effect size, 95% prediction confidence intervals, between-study heterogeneity, small-study effects, and excess significance bias for each health outcome. We identified 54 eligible articles of meta-analyses/pooled analyses. After adding newly published original articles, we performed 35 updated meta-analyses and 4 de novo meta-analyses. Together with 8 previous meta-analyses, we finally included 47 unique health outcomes. Cheese consumption was inversely associated with all-cause mortality (highest compared with lowest category: RR = 0.95; 95% CI: 0.92, 0.99), cardiovascular mortality (RR = 0.93; 95% CI: 0.88, 0.99), incident cardiovascular disease (CVD) (RR = 0.92; 95% CI: 0.89, 0.96), coronary heart disease (CHD) (RR = 0.92; 95% CI: 0.86, 0.98), stroke (RR = 0.93; 95% CI: 0.89, 0.98), estrogen receptor-negative (ER-) breast cancer (RR = 0.89; 95% CI: 0.82, 0.97), type 2 diabetes (RR = 0.93; 95% CI: 0.88, 0.98), total fracture (RR = 0.90; 95% CI: 0.86, 0.95), and dementia (RR = 0.81; 95% CI: 0.66, 0.99). Null associations were found for other outcomes. According to the NutriGrade scoring system, moderate quality of evidence was observed for inverse associations of cheese consumption with all-cause and cardiovascular mortality, incident CVD, CHD, and stroke, and for null associations with cancer mortality, incident hypertension, and prostate cancer. Our findings suggest that cheese consumption has neutral to moderate benefits for human health.
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Is early-onset cancer an emerging global epidemic? Current evidence and future implications.
Ugai, T, Sasamoto, N, Lee, HY, Ando, M, Song, M, Tamimi, RM, Kawachi, I, Campbell, PT, Giovannucci, EL, Weiderpass, E, et al
Nature reviews. Clinical oncology. 2022;(10):656-673
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Abstract
Over the past several decades, the incidence of early-onset cancers, often defined as cancers diagnosed in adults <50 years of age, in the breast, colorectum, endometrium, oesophagus, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, bone marrow, pancreas, prostate, stomach and thyroid has increased in multiple countries. Increased use of screening programmes has contributed to this phenomenon to a certain extent, although a genuine increase in the incidence of early-onset forms of several cancer types also seems to have emerged. Evidence suggests an aetiological role of risk factor exposures in early life and young adulthood. Since the mid-20th century, substantial multigenerational changes in the exposome have occurred (including changes in diet, lifestyle, obesity, environment and the microbiome, all of which might interact with genomic and/or genetic susceptibilities). However, the effects of individual exposures remain largely unknown. To study early-life exposures and their implications for multiple cancer types will require prospective cohort studies with dedicated biobanking and data collection technologies. Raising awareness among both the public and health-care professionals will also be critical. In this Review, we describe changes in the incidence of early-onset cancers globally and suggest measures that are likely to reduce the burden of cancers and other chronic non-communicable diseases.
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Post-Diagnosis Vitamin D Supplement Use and Survival among Cancer Patients: A Meta-Analysis.
Chen, QY, Kim, S, Lee, B, Jeong, G, Lee, DH, Keum, N, Manson, JE, Giovannucci, EL
Nutrients. 2022;(16)
Abstract
Vitamin D administered pre-diagnostically has been shown to reduce mortality. Emerging evidence suggests a role of post-diagnosis vitamin D supplement intake for survival among cancer patients. Thus, we conducted a meta-analysis to evaluate the relationship. PubMed and Embase were searched for relevant observational cohort studies and randomized trials published through April 2022. Summary relative risk (SRR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The SRR for post-diagnosis vitamin D supplement use vs. non-use, pooling cohort studies and randomized trials, was 0.87 (95% CI, 0.78-0.98; p = 0.02; I2 = 0%) for overall survival, 0.81 (95% CI, 0.62-1.06; p = 0.12; I2 = 51%) for progression-free survival, 0.86 (95% CI, 0.72-1.03; p = 0.10; I2 = 0%) for cancer-specific survival, and 0.86 (95% CI, 0.64-1.14; p = 0.29; I2 = 0%) for relapse. Albeit not significantly heterogeneous by variables tested, a significant inverse association was limited to cohort studies and supplement use during cancer treatment for overall survival, and to studies with ≤3 years of follow-up for progression-free survival. Post-diagnosis vitamin D supplement use was associated with improved overall survival, but not progression-free or cancer-specific survival or relapse. Our findings require confirmation, as randomized trial evidence was insufficient to establish cause-and-effect relationships.
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Role of Diet in Colorectal Cancer Incidence: Umbrella Review of Meta-analyses of Prospective Observational Studies.
Veettil, SK, Wong, TY, Loo, YS, Playdon, MC, Lai, NM, Giovannucci, EL, Chaiyakunapruk, N
JAMA network open. 2021;(2):e2037341
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Abstract
IMPORTANCE Several meta-analyses have summarized evidence for the association between dietary factors and the incidence of colorectal cancer (CRC). However, to date, there has been little synthesis of the strength, precision, and quality of this evidence in aggregate. OBJECTIVE To grade the evidence from published meta-analyses of prospective observational studies that assessed the association of dietary patterns, specific foods, food groups, beverages (including alcohol), macronutrients, and micronutrients with the incidence of CRC. DATA SOURCES MEDLINE, Embase, and the Cochrane Library were searched from database inception to September 2019. EVIDENCE REVIEW Only meta-analyses of prospective observational studies with a cohort study design were eligible. Evidence of association was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. RESULTS From 9954 publications, 222 full-text articles (2.2%) were evaluated for eligibility, and 45 meta-analyses (20.3%) that described 109 associations between dietary factors and CRC incidence were selected. Overall, 35 of the 109 associations (32.1%) were nominally statistically significant using random-effects meta-analysis models; 17 associations (15.6%) demonstrated large heterogeneity between studies (I2 > 50%), whereas small-study effects were found for 11 associations (10.1%). Excess significance bias was not detected for any association between diet and CRC. The primary analysis identified 5 (4.6%) convincing, 2 (1.8%) highly suggestive, 10 (9.2%) suggestive, and 18 (16.5%) weak associations between diet and CRC, while there was no evidence for 74 (67.9%) associations. There was convincing evidence of an association of intake of red meat (high vs low) and alcohol (≥4 drinks/d vs 0 or occasional drinks) with the incidence of CRC and an inverse association of higher vs lower intakes of dietary fiber, calcium, and yogurt with CRC risk. The evidence for convincing associations remained robust following sensitivity analyses. CONCLUSIONS AND RELEVANCE This umbrella review found convincing evidence of an association between lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat. More research is needed on specific foods for which evidence remains suggestive, including other dairy products, whole grains, processed meat, and specific dietary patterns.
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Muscle-strengthening activities and risk of cardiovascular disease, type 2 diabetes, cancer and mortality: A review of prospective cohort studies.
Giovannucci, EL, Rezende, LFM, Lee, DH
Journal of internal medicine. 2021;(4):789-805
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Abstract
The benefits of aerobic moderate-to-vigorous physical activity (MVPA) on major non-communicable diseases (NCDs) are well established. However, much less is known whether muscle-strengthening activities (i.e., resistance/weight/strength training) confer similar benefits. Herein, we conducted a narrative literature review and summarized the existing evidence from large prospective cohort studies on muscle strengthening activities and risk of major chronic diseases and mortality in adults generally free of major NCDs at baseline. Current epidemiologic evidence suggests that engagement in muscle-strengthening activities over 1-2 sessions (or approximately 60-150 min) per week was associated with reduced risk of cardiovascular disease (seven studies; approximately 20%-25% reduction), type 2 diabetes (four studies; approximately 30% reduction), cancer mortality (four studies; approximately 15%-20% reduction) as well as all-cause mortality (six studies; approximately 20%-25% reduction). For diabetes, the risk appears to lower further with even higher levels of muscle-strengthening activities, but some studies for cardiovascular and all-cause mortality suggest a reversal whereby higher levels (≥2.5 h/week) have less benefit, or are even harmful, relative to lower levels of activity. The likely mechanisms contributing to a benefit include improvement in body composition, lipid profile, insulin resistance and inflammation. The evidence supports engaging in 1-2 sessions (up to 2.5 h) per week, preferably performed complementary to the recommended levels of aerobic MVPA. Although data are limited, caution is suggested for training exceeding 2.5 h per week. Further studies are required to better understand the influence of frequency, duration and intensity of muscle-strengthening activities on major NCDs and mortality in diverse populations.
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Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials.
Patikorn, C, Roubal, K, Veettil, SK, Chandran, V, Pham, T, Lee, YY, Giovannucci, EL, Varady, KA, Chaiyakunapruk, N
JAMA network open. 2021;(12):e2139558
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IMPORTANCE Several meta-analyses of randomized clinical trials (RCTs) have demonstrated the many health benefits of intermittent fasting (IF). However, there has been little synthesis of the strength and quality of this evidence in aggregate to date. OBJECTIVE To grade the evidence from published meta-analyses of RCTs that assessed the associations of IF (zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating) with obesity-related health outcomes. EVIDENCE REVIEW PubMed, Embase, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Data analysis was conducted from April 2021 through July 2021. Meta-analyses of RCTs investigating effects of IF in adults were included. The effect sizes of IF were recalculated using a random-effects model. We assessed the quality of evidence per association by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) as high, moderate, low, and very low. FINDINGS A total of 11 meta-analyses comprising 130 RCTs (median [IQR] sample size, 38 [24-69] participants; median [IQR] follow-up period, 3 [2-5] months) were included describing 104 unique associations of different types of IF with obesity-related health outcomes (median [IQR] studies per association, 4 [3-5]). There were 28 statistically significant associations (27%) that demonstrated the beneficial outcomes for body mass index, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure. IF was found to be associated with reduced fat-free mass. One significant association (1%) supported by high-quality evidence was modified alternate-day fasting for 1 to 2 months, which was associated with moderate reduction in body mass index in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease compared with regular diet. Six associations (6%) were supported by moderate quality evidence. The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence. CONCLUSIONS AND RELEVANCE In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity. More clinical trials with long-term follow-up are needed to investigate the effects of IF on clinical outcomes such as cardiovascular events and mortality.
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Tea Consumption and Risk of Cancer: An Umbrella Review and Meta-Analysis of Observational Studies.
Kim, TL, Jeong, GH, Yang, JW, Lee, KH, Kronbichler, A, van der Vliet, HJ, Grosso, G, Galvano, F, Aune, D, Kim, JY, et al
Advances in nutrition (Bethesda, Md.). 2020;(6):1437-1452
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Tea is one of the most widely consumed beverages, but its association with cancer risk remains controversial and unclear. We performed an umbrella review to clarify and determine the associations between tea consumption and various types of cancer by summarizing and recalculating the existing meta-analyses. Meta-analyses of observational studies reporting associations between tea consumption and cancer risk were searched on PubMed and Embase. Associations found to be statistically significant were further classified into levels of evidence (convincing, suggestive, or weak), based on P value, between-study heterogeneity, prediction intervals, and small study effects. Sixty-four observational studies (case-control or cohort) corresponding to 154 effect sizes on the incidence of 25 types of cancer were included. Forty-three (27.9%) results in 15 different types of cancer were statistically significant. When combining all studies on the same type of cancer, 19 results in 11 different types of cancer showed significant associations with lower risk of gastrointestinal tract organ cancer (oral, gastric, colorectal, biliary tract, and liver cancer), breast cancer, and gynecological cancer (endometrial and ovarian cancer) as well as leukemia, lung cancer, and thyroid cancer. Only the reduced risk of oral cancer in tea-consuming populations (OR = 0.62; 95% CI: 0.55, 0.72; P value < 10-6) was supported by convincing evidence. Suggestive evidence was found for 6 results on biliary tract, breast, endometrial, liver, and oral cancer. To summarize, tea consumption was shown to have protective effects on some types of cancer, particularly oral cancer. More well-designed prospective studies are needed with consideration of other factors that can cause biases.
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Global patterns in excess body weight and the associated cancer burden.
Sung, H, Siegel, RL, Torre, LA, Pearson-Stuttard, J, Islami, F, Fedewa, SA, Goding Sauer, A, Shuval, K, Gapstur, SM, Jacobs, EJ, et al
CA: a cancer journal for clinicians. 2019;(2):88-112
Abstract
The prevalence of excess body weight and the associated cancer burden have been rising over the past several decades globally. Between 1975 and 2016, the prevalence of excess body weight in adults-defined as a body mass index (BMI) ≥ 25 kg/m2 -increased from nearly 21% in men and 24% in women to approximately 40% in both sexes. Notably, the prevalence of obesity (BMI ≥ 30 kg/m2 ) quadrupled in men, from 3% to 12%, and more than doubled in women, from 7% to 16%. This change, combined with population growth, resulted in a more than 6-fold increase in the number of obese adults, from 100 to 671 million. The largest absolute increase in obesity occurred among men and boys in high-income Western countries and among women and girls in Central Asia, the Middle East, and North Africa. The simultaneous rise in excess body weight in almost all countries is thought to be driven largely by changes in the global food system, which promotes energy-dense, nutrient-poor foods, alongside reduced opportunities for physical activity. In 2012, excess body weight accounted for approximately 3.9% of all cancers (544,300 cases) with proportion varying from less than 1% in low-income countries to 7% or 8% in some high-income Western countries and in Middle Eastern and Northern African countries. The attributable burden by sex was higher for women (368,500 cases) than for men (175,800 cases). Given the pandemic proportion of excess body weight in high-income countries and the increasing prevalence in low- and middle-income countries, the global cancer burden attributable to this condition is likely to increase in the future. There is emerging consensus on opportunities for obesity control through the multisectoral coordinated implementation of core policy actions to promote an environment conducive to a healthy diet and active living. The rapid increase in both the prevalence of excess body weight and the associated cancer burden highlights the need for a rejuvenated focus on identifying, implementing, and evaluating interventions to prevent and control excess body weight.
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Body composition and mortality in the general population: A review of epidemiologic studies.
Lee, DH, Giovannucci, EL
Experimental biology and medicine (Maywood, N.J.). 2018;(17-18):1275-1285
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Current understanding of the association of body composition on mortality in the general population is limited. This review evaluated the available epidemiologic studies on body composition and mortality that leveraged diverse approaches to estimate body composition. Although studies showed inconsistent results, there was evidence suggesting that high fat mass and low lean body mass may be independently associated with mortality in the general population. This review may help partially explain the "obesity paradox" phenomenon and facilitate further studies to advance the understanding of the association of body composition on health in the general and patient populations.