Can Artificial Sweeteners Increase the Risk of Cancer Incidence and Mortality: Evidence from Prospective Studies.
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SUBMITTER: Yan S
PROVIDER: S-EPMC9506029 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
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Can Artificial Sweeteners Increase the Risk of Cancer Incidence and Mortality: Evidence from Prospective Studies.
Yan Shoumeng S Yan Feifei F Liu Liping L Li Bo B Liu Shuxiang S Cui Weiwei W
Nutrients 20220910 18
Cancer has become a major challenge in the global disease burden. Artificial sweeteners are a class of chemical compounds that are used as food and beverage addition agent to replace sugar. However, the health effects of consuming artificial sweeteners are still unclear. This meta-analysis was performed to evaluate the role of artificial sweeteners on cancer. The databases PubMed, Cochrane Library, MEDLINE, Web of Science and EMBASE were searched up until July 2022. A Newcastle−Ottawa scale (NOS ...[more]
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Project description:BackgroundArtificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM).MethodsThis study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed.ResultsIn our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%.ConclusionsOur findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior.
| S-EPMC11225337 | biostudies-literature
Project description:Background:In recent decades, data from certain observational studies have stirred controversy over artificial sweeteners by linking them with certain malignancies. As the incidences of artificial sweetener consumption and thyroid cancer are both increasing, our study aimed to determine any possible association between them. Methods:This retrospective observational study enrolled 50 patients (group 1) with proven diagnosis of well-differentiated thyroid cancer (WDTC) and 50 control subjects (group 2) diagnosed as having benign thyroid nodule by fine-needle aspiration. The survey questionnaire included the total amount and duration of intake of artificial sweeteners. Results:Increased consumption of artificial sweeteners was noted in group 1 as compared to group 2, which was statistically significant (76% vs. 24%, P < 0.01). This study suggested that the use of an average of four packets (4 g) per day of artificial sweetener for an average duration of 5 years is associated with WDTC. Conclusions:Our study emphasizes the significance of artificial sweetener consumption as a potential risk factor for WDTC and increase in public awareness regarding this association if other studies in future report similar findings.
| S-EPMC7430875 | biostudies-literature
Project description:ObjectiveTo study the relationships between artificial sweeteners, accounting for all dietary sources (total and by type of artificial sweetener) and risk of type 2 diabetes (T2D), in a large-scale prospective cohort.Research design and methodsThe analyses included 105,588 participants from the web-based NutriNet-Santé study (France, 2009-2022; mean age 42.5 ± 14.6 years, 79.2% women). Repeated 24-h dietary records, including brands and commercial names of industrial products, merged with qualitative and quantitative food additive composition data, enabled artificial sweetener intakes to be accurately assessed from all dietary sources. Associations between artificial sweeteners (total, aspartame, acesulfame potassium [K], and sucralose) and T2D were investigated using Cox proportional hazard models adjusted for potential confounders, including weight variation during follow-up.ResultsDuring a median follow-up of 9.1 years (946,650 person-years, 972 incident T2D), compared with nonconsumers, higher consumers of artificial sweeteners (i.e., above the sex-specific medians of 16.4 mg/day in men and 18.5 mg/day in women) had higher risks of developing T2D (hazard ratio [HR] 1.69; 95% CI 1.45-1.97; P-trend <0.001). Positive associations were also observed for individual artificial sweeteners: aspartame (HR 1.63 [95% CI 1.38-1.93], P-trend <0.001), acesulfame-K (HR 1.70 [1.42-2.04], P-trend <0.001), and sucralose (HR 1.34 [1.07-1.69], P-trend = 0.013).ConclusionsPotential for reverse causality cannot be eliminated; however, many sensitivity analyses were computed to limit this and other potential biases. These findings of positive associations between artificial sweetener intakes and increased T2D risk strengthen the evidence that these additives may not be safe sugar alternatives. This study provides important insights in the context of on-going reevaluation of artificial sweeteners by health authorities worldwide.
| S-EPMC10465821 | biostudies-literature
Project description:ObjectivesTo study the associations between artificial sweeteners from all dietary sources (beverages, but also table top sweeteners, dairy products, etc), overall and by molecule (aspartame, acesulfame potassium, and sucralose), and risk of cardiovascular diseases (overall, coronary heart disease, and cerebrovascular disease).DesignPopulation based prospective cohort study (2009-21).SettingFrance, primary prevention research.Participants103 388 participants of the web based NutriNet-Santé cohort (mean age 42.2±14.4, 79.8% female, 904 206 person years). Dietary intakes and consumption of artificial sweeteners were assessed by repeated 24 h dietary records, including brand names of industrial products.Main outcomes measuresAssociations between sweeteners (coded as a continuous variable, log10 transformed) and cardiovascular disease risk, assessed by multivariable adjusted Cox hazard models.ResultsTotal artificial sweetener intake was associated with increased risk of cardiovascular diseases (1502 events, hazard ratio 1.09, 95% confidence interval 1.01 to 1.18, P=0.03); absolute incidence rate in higher consumers (above the sex specific median) and non-consumers was 346 and 314 per 100 000 person years, respectively. Artificial sweeteners were more particularly associated with cerebrovascular disease risk (777 events, 1.18, 1.06 to 1.31, P=0.002; incidence rates 195 and 150 per 100 000 person years in higher and non-consumers, respectively). Aspartame intake was associated with increased risk of cerebrovascular events (1.17, 1.03 to 1.33, P=0.02; incidence rates 186 and 151 per 100 000 person years in higher and non-consumers, respectively), and acesulfame potassium and sucralose were associated with increased coronary heart disease risk (730 events; acesulfame potassium: 1.40, 1.06 to 1.84, P=0.02; incidence rates 167 and 164; sucralose: 1.31, 1.00 to 1.71, P=0.05; incidence rates 271 and 161).ConclusionsThe findings from this large scale prospective cohort study suggest a potential direct association between higher artificial sweetener consumption (especially aspartame, acesulfame potassium, and sucralose) and increased cardiovascular disease risk. Artificial sweeteners are present in thousands of food and beverage brands worldwide, however they remain a controversial topic and are currently being re-evaluated by the European Food Safety Authority, the World Health Organization, and other health agencies.Trial registrationClinicalTrials.gov NCT03335644.
| S-EPMC9449855 | biostudies-literature
Project description:Here we provide a comprehensive meta-analysis to summarize and appraise the quality of the current evidence on the associations of tea drinking in relation to cancer risk. PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched up to June 2020. We reanalyzed the individual prospective studies focused on associations between tea drinking and cancer risk in humans. We conducted a meta-analysis of prospective studies and provided the highest- versus lowest-category analyses, dose-response analyses, and test of nonlinearity of each association by modeling restricted cubic spline regression for each type of tea. We graded the evidence based on the summary effect size, its 95% confidence interval, 95% prediction interval, the extent of heterogeneity, evidence of small-study effects, and excess significance bias. We identified 113 individual studies investigating the associations between tea drinking and 26 cancer sites including 153,598 cancer cases. We assessed 12 associations for the intake of black tea with cancer risk and 26 associations each for the intake of green tea and total tea with cancer risk. Except for an association between lymphoid neoplasms with green tea, we did not find consistent associations for the highest versus lowest categories and dose-response analyses for any cancer. When grading current evidence for each association (number of studies ≥2), weak evidence was detected for lymphoid neoplasm (green tea), glioma (total tea, per 1 cup), bladder cancer (total tea, per 1 cup), and gastric and esophageal cancer (tea, per 1 cup). This review of prospective studies provides little evidence to support the hypothesis that tea drinking is associated with cancer risk. More well-designed studies are still needed to identify associations between tea intake and rare cancers.
| S-EPMC8009746 | biostudies-literature
Project description:BackgroundThe food industry uses artificial sweeteners in a wide range of foods and beverages as alternatives to added sugars, for which deleterious effects on several chronic diseases are now well established. The safety of these food additives is debated, with conflicting findings regarding their role in the aetiology of various diseases. In particular, their carcinogenicity has been suggested by several experimental studies, but robust epidemiological evidence is lacking. Thus, our objective was to investigate the associations between artificial sweetener intakes (total from all dietary sources, and most frequently consumed ones: aspartame [E951], acesulfame-K [E950], and sucralose [E955]) and cancer risk (overall and by site).Methods and findingsOverall, 102,865 adults from the French population-based cohort NutriNet-Santé (2009-2021) were included (median follow-up time = 7.8 years). Dietary intakes and consumption of sweeteners were obtained by repeated 24-hour dietary records including brand names of industrial products. Associations between sweeteners and cancer incidence were assessed by Cox proportional hazards models, adjusted for age, sex, education, physical activity, smoking, body mass index, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, and baseline intakes of energy, alcohol, sodium, saturated fatty acids, fibre, sugar, fruit and vegetables, whole-grain foods, and dairy products. Compared to non-consumers, higher consumers of total artificial sweeteners (i.e., above the median exposure in consumers) had higher risk of overall cancer (n = 3,358 cases, hazard ratio [HR] = 1.13 [95% CI 1.03 to 1.25], P-trend = 0.002). In particular, aspartame (HR = 1.15 [95% CI 1.03 to 1.28], P = 0.002) and acesulfame-K (HR = 1.13 [95% CI 1.01 to 1.26], P = 0.007) were associated with increased cancer risk. Higher risks were also observed for breast cancer (n = 979 cases, HR = 1.22 [95% CI 1.01 to 1.48], P = 0.036, for aspartame) and obesity-related cancers (n = 2,023 cases, HR = 1.13 [95% CI 1.00 to 1.28], P = 0.036, for total artificial sweeteners, and HR = 1.15 [95% CI 1.01 to 1.32], P = 0.026, for aspartame). Limitations of this study include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.ConclusionsIn this large cohort study, artificial sweeteners (especially aspartame and acesulfame-K), which are used in many food and beverage brands worldwide, were associated with increased cancer risk. These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally.Trial registrationClinicalTrials.gov NCT03335644.
| S-EPMC8946744 | biostudies-literature
Project description:Although there are reports that artificial sweeteners (AS) are safe, the relationship between artificial sweeteners and cancer remains controversial. The purpose of the study is to evaluate whether the consumption of artificial sweeteners is associated with the risk of cancers. We conducted a comprehensive search of multiple databases, including MEDLINE, EMBASE, Web of Science, and Cochrane Library. We found all the literature that studied the relationship between artificial sweeteners and cancer. Ten case-control studies were included in the meta-analysis. Our findings indicated that the consumption of artificial sweeteners was not associated with an increase in cancer when all types of cancers are analyzed comprehensively (OR 0.91, 95% CI 0.75-1.11). Interestingly, the use of artificial sweeteners is inversely related to urinary system cancer risk when analyzing women individually (OR 0.76, 95% CI 0.60-0.97). Our meta-analysis found that these is no correlation between artificial sweeteners and occurrence of cancer except urinary system cancer in women. Considering some limitations found in this study, additional data from large clinical trials are needed.
| S-EPMC8358351 | biostudies-literature
Project description:Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control patients. The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5×10(-8). Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer.
| S-EPMC4643630 | biostudies-literature
Project description:Epidemiological studies have suggested inconclusive associations between 25-hydroxyvitamin D and total cancer incidence and mortality. The aim of this study was to quantitatively assess these associations by combining results from prospective cohort studies. A systematic literature search was implemented in PubMed and Scopus databases in April 2019. Comparing the highest with the lowest categories, the multivariate-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled using a random-effects model. A trend estimation was performed using a two-stage, dose-response, meta-analysis method. Twenty-three independent prospective studies were included for data synthesis. Eight studies investigated the association between 25-hydroxyvitamin D and the risk of cancer incidence (7511 events and 70,018 participants), and the summary estimate showed that 25-hydroxyvitamin D is marginally associated with cancer risk (Summary RR = 0.86; 95% CI: 0.73, 1.02; I2 = 70.8%; p = 0.001). Sixteen studies investigated the association between 25-hydroxyvitamin D and the risk of cancer mortality (8729 events and 101,794 participants), and a higher 25-hydroxyvitamin D concentration was inversely associated with the risk of cancer mortality (Summary RR = 0.81; 95% CI: 0.71, 0.93; I2 = 48.8%, p = 0.012). Dose-response analysis indicated that the risk of cancer incidence was reduced by 7% (RRs = 0.93; 95% CI: 0.91, 0.96), and the risk of cancer mortality was reduced by 2% (RRs = 0.98; 95% CI: 0.97, 0.99), with each 20 nmol/L increment of 25-hydroxyvitamin D concentration. This meta-analysis provides evidence that a higher 25-hydroxyvitamin D concentration is associated with a lower cancer incidence and cancer mortality.
| S-EPMC6835972 | biostudies-literature
Project description:The prevalence of obesity is increasing, and the origins of obesity and metabolic dysfunction may be traced back to fetal life. Currently, overweight pregnant women are advised to substitute sugar-sweetened beverages with diet drinks containing artificial sweeteners. Recent evidence suggests that the consumption of artificial sweeteners during pregnancy increases the risk of obesity in the child, but the mechanism is unknown. We hypothesized the transportation of artificial sweeteners across the placenta into the fetal circulation and the amniotic fluid. We included 19 pregnant women who were given an oral dose of acesulfame, cyclamate, saccharin, and sucralose immediately before a planned caesarean section. Nine women were included as controls, and they refrained from an intake of artificial sweeteners. The maternal and fetal blood and amniotic fluid were collected during the caesarean section, and concentrations of artificial sweeteners were measured using mass spectrometry. We found a linear relationship between the fetal plasma concentrations of artificial sweeteners and the maternal plasma concentrations, with adjusted coefficients of 0.49 (95% CI: 0.28-0.70) for acesulfame, 0.72 (95% CI: 0.48-0.95) for cyclamate, 0.51 (95% CI: 0.38-0.67) for saccharin, and 0.44 (95% CI: 0.33-0.55) for sucralose. We found no linear relationship between amniotic fluid and fetal plasma concentrations, but there were positive ratios for all four sweeteners. In conclusion, the four sweeteners investigated all crossed the placenta and were present in the fetal circulation and amniotic fluid.
| S-EPMC10181363 | biostudies-literature