Can Artificial Sweeteners Increase the Risk of Cancer Incidence and Mortality: Evidence from Prospective Studies

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) was used to estimate the study quality. A total of 25 observational studies were included with a total of 3,739,775 subjects. The intake of artificial sweeteners had no apparent association with overall cancer incidence and mortality. However, in Europe, artificial sweeteners’ intake could increase the risk of cancer incidence (HR/RR = 1.07, 95% CI = [1.02, 1.12], I2 = 25.8%, P = 0.223), which appears to be related to a shift in nutritional behaviors in the countries. Significant results were also observed in subgroups with aspartame and a mixed intake of artificial sweeteners. Moreover, higher risk was observed for artificial sweeteners intake in all-cause mortality (HR/RR =1.13, 95% CI = [1.03, 1.25], I2 = 79.7%, p < 0.001) and a J-shaped association between them was found. More data from well-conducted studies and clinical trials are required.

[1]  A. Tjønneland,et al.  Sweetened beverages are associated with a higher risk of differentiated thyroid cancer in the EPIC cohort: a dietary pattern approach , 2022, European Journal of Nutrition.

[2]  K. Dokova,et al.  Nutrition Transition in Europe: East-West Dimensions in the Last 30 Years—A Narrative Review , 2022, Frontiers in Nutrition.

[3]  Kevin Kantono,et al.  Changes in temporal sensory profile, liking, satiety, and postconsumption attributes of yogurt with natural sweeteners , 2022, Journal of food science.

[4]  Sungeun Cho,et al.  The Effect of Steviol Glycosides on Sensory Properties and Acceptability of Ice Cream , 2022, Foods.

[5]  Dan Liu,et al.  Association of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Coffee Consumption With All-Cause and Cause-Specific Mortality , 2022, Annals of Internal Medicine.

[6]  M. Touvier,et al.  Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study , 2022, PLoS medicine.

[7]  Vijay Kumar Chattu,et al.  Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019 , 2021, JAMA oncology.

[8]  N. Narula,et al.  Intake of artificial sweeteners among adults is associated with reduced odds of gastrointestinal luminal cancers: a meta-analysis of cohort and case-control studies , 2021, Nutrition research.

[9]  J. Meyerhardt,et al.  Sugar-sweetened beverage, artificially sweetened beverage and sugar intake and colorectal cancer survival , 2021, British Journal of Cancer.

[10]  Kehu Yang,et al.  Association of soft drink and 100% fruit juice consumption with all-cause mortality, cardiovascular diseases mortality, and cancer mortality: A systematic review and dose-response meta-analysis of prospective cohort studies , 2021, Critical reviews in food science and nutrition.

[11]  W. Willett,et al.  Sugar-Sweetened Beverages, Artificially Sweetened Beverages, and Breast Cancer Risk: Results From 2 Prospective US Cohorts. , 2021, The Journal of nutrition.

[12]  W. Willett,et al.  Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women , 2021, Gut.

[13]  W. Willett,et al.  Consumption of sugar‐sweetened and artificially sweetened beverages and breast cancer survival , 2021, Cancer.

[14]  M. Schulze,et al.  Soft Drink and Juice Consumption and Renal Cell Carcinoma Incidence and Mortality in the European Prospective Investigation into Cancer and Nutrition , 2021, Cancer Epidemiology, Biomarkers & Prevention.

[15]  A. Pan,et al.  Association of Consumption of Sugar-Sweetened Beverages or Artificially Sweetened Beverages with Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. , 2020, Advances in nutrition.

[16]  A. Pan,et al.  Association of sugar-sweetened beverage and artificially sweetened beverage intakes with mortality: an analysis of US National Health and Nutrition Examination Survey , 2020, European Journal of Nutrition.

[17]  D. English,et al.  Consumption of sugar‐sweetened and artificially sweetened soft drinks and risk of cancers not related to obesity , 2020, International journal of cancer.

[18]  J. Pell,et al.  The associations of sugar-sweetened, artificially sweetened and naturally sweet juices with all-cause mortality in 198,285 UK Biobank participants: a prospective cohort study , 2020, BMC Medicine.

[19]  J. Boer,et al.  Association Between Soft Drink Consumption and Mortality in 10 European Countries. , 2019, JAMA internal medicine.

[20]  M. Touvier,et al.  Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort , 2019, BMJ.

[21]  W. Willett,et al.  Long-Term Consumption of Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Mortality in US Adults , 2019, Circulation.

[22]  J. Manson,et al.  Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women’s Health Initiative , 2019, Stroke.

[23]  Jennifer J. Otten,et al.  Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association , 2018, Circulation.

[24]  W. Willett,et al.  Associations of artificially sweetened beverage intake with disease recurrence and mortality in stage III colon cancer: Results from CALGB 89803 (Alliance) , 2018, PloS one.

[25]  D. English,et al.  Consumption of sugar-sweetened and artificially sweetened soft drinks and risk of obesity-related cancers , 2018, Public Health Nutrition.

[26]  Michelle Pearlman,et al.  The Association Between Artificial Sweeteners and Obesity , 2017, Current Gastroenterology Reports.

[27]  K. Rother,et al.  Trends in the consumption of low-calorie sweeteners , 2016, Physiology & Behavior.

[28]  F. Clavel-Chapelon,et al.  Sweet-beverage consumption and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). , 2016, The American journal of clinical nutrition.

[29]  E. Funkhouser,et al.  Dietary carbohydrate intake, glycaemic load, glycaemic index and ovarian cancer risk in African-American women. , 2016, The British journal of nutrition.

[30]  A. Tjønneland,et al.  Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort , 2016, European Journal of Nutrition.

[31]  K. Stanhope.  Sugar consumption, metabolic disease and obesity: The state of the controversy , 2016, Critical reviews in clinical laboratory sciences.

[32]  P. Vineis,et al.  Dietary glycemic index and glycemic load and risk of colorectal cancer: results from the EPIC‐Italy study , 2015, International journal of cancer.

[33]  N. Wareham,et al.  Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages , 2015, Diabetologia.

[34]  Jennifer G. Robinson,et al.  Diet Drink Consumption and the Risk of Cardiovascular Events: A Report from the Women’s Health Initiative , 2015, Journal of General Internal Medicine.

[35]  M. McCullough,et al.  Artificially and sugar-sweetened carbonated beverage consumption is not associated with risk of lymphoid neoplasms in older men and women. , 2014, The Journal of nutrition.

[36]  A. Uçar,et al.  A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not? , 2014, Cytotechnology.

[37]  J. Cerhan,et al.  Sugar-Sweetened Beverage Intake and the Risk of Type I and Type II Endometrial Cancer among Postmenopausal Women , 2013, Cancer Epidemiology, Biomarkers & Prevention.

[38]  S. Swithers.  Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements , 2013, Trends in Endocrinology & Metabolism.

[39]  J. Jaworska-Adamu,et al.  Effects of aspartame metabolites on astrocytes and neurons. , 2013, Folia neuropathologica.

[40]  W. Willett,et al.  Consumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. , 2012, The American journal of clinical nutrition.

[41]  F. Clavel-Chapelon,et al.  Dietary glycemic index and glycemic load and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). , 2012, The American journal of clinical nutrition.

[42]  M. Tonelli,et al.  A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes , 2011, BMC medicine.

[43]  C. Beglinger,et al.  Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides. , 2011, The British journal of nutrition.

[44]  M. Soffritti,et al.  Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. , 2010, American journal of industrial medicine.

[45]  Karen L Jones,et al.  Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects , 2010, British Journal of Nutrition.

[46]  M. Bellon,et al.  Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. , 2009, American journal of physiology. Gastrointestinal and liver physiology.

[47]  J. Manson,et al.  Sweetened beverage consumption and risk of coronary heart disease in women. , 2009, The American journal of clinical nutrition.

[48]  K. Hunt,et al.  Fueling the Obesity Epidemic? Artificially Sweetened Beverage Use and Long‐term Weight Gain , 2008, Obesity.

[49]  C. Kawas,et al.  Non-alcoholic beverage and caffeine consumption and mortality: the Leisure World Cohort Study. , 2007, Preventive medicine.

[50]  P. Hartge,et al.  Consumption of Aspartame-Containing Beverages and Incidence of Hematopoietic and Brain Malignancies , 2006, Cancer Epidemiology Biomarkers & Prevention.

[51]  L. Lambertini,et al.  First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats , 2005, Environmental health perspectives.

[52]  V. Diehl,et al.  Artificial sweeteners--do they bear a carcinogenic risk? , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[53]  M. Thun,et al.  American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity , 2002, CA: a cancer journal for clinicians.

[54]  R. Tweedie,et al.  A Nonparametric “Trim and Fill” Method of Accounting for Publication Bias in Meta-Analysis , 2000 .

[55]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[56]  P. Tugwell,et al.  The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses , 2014 .

[57]  C. Heppner.  DRAFT Scientific Opinion on the re-evaluation of aspartame ( E 951 ) as a food additive , 2013 .

[58]  M. Thun,et al.  American Cancer Society guidelines on nutrition and physical activity for cancer prevention , 2002, CA: a cancer journal for clinicians.

[59]  Fernando Aguilar,et al.  Re‐evaluation of stannous chloride (E 512) as food additive , 2018, EFSA journal. European Food Safety Authority.