Consumption of Aspartame-Containing Beverages and Incidence of Hematopoietic and Brain Malignancies

Background: In a few animal experiments, aspartame has been linked to hematopoietic and brain cancers. Most animal studies have found no increase in the risk of these or other cancers. Data on humans are sparse for either cancer. Concern lingers regarding this widely used artificial sweetener. Objective: We investigated prospectively whether aspartame consumption is associated with the risk of hematopoietic cancers or gliomas (malignant brain cancer). Methods: We examined 285,079 men and 188,905 women ages 50 to 71 years in the NIH-AARP Diet and Health Study cohort. Daily aspartame intake was derived from responses to a baseline self-administered food frequency questionnaire that queried consumption of four aspartame-containing beverages (soda, fruit drinks, sweetened iced tea, and aspartame added to hot coffee and tea) during the past year. Histologically confirmed incident cancers were identified from eight state cancer registries. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression that adjusted for age, sex, ethnicity, body mass index, and history of diabetes. Results: During over 5 years of follow-up (1995-2000), 1,888 hematopoietic cancers and 315 malignant gliomas were ascertained. Higher levels of aspartame intake were not associated with the risk of overall hematopoietic cancer (RR for ≥600 mg/d, 0.98; 95% CI, 0.76-1.27), glioma (RR for ≥400 mg/d, 0.73; 95% CI, 0.46-1.15; P for inverse linear trend = 0.05), or their subtypes in men and women. Conclusions: Our findings do not support the hypothesis that aspartame increases hematopoietic or brain cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1654–9)

[1]  J. Fraumeni,et al.  Cancer epidemiology and prevention. , 2006 .

[2]  J. Stanford,et al.  Carbonated soft drink consumption and risk of esophageal adenocarcinoma. , 2006, Journal of the National Cancer Institute.

[3]  Ulrike Peters,et al.  Is It Time to Abandon the Food Frequency Questionnaire? , 2005, Cancer Epidemiology Biomarkers & Prevention.

[4]  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.

[5]  C. Kruchko,et al.  Consensus conference on cancer registration of brain and central nervous system tumors. , 2005, Neuro-oncology.

[6]  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.

[7]  Frances E. Zollers,et al.  The European Food Safety Authority: Towards coherence in food safety policy and practice , 2004 .

[8]  C. la Vecchia,et al.  Cigarette smoking and risk of Hodgkin's disease , 2004, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[9]  Raymond J Carroll,et al.  A comparison of a food frequency questionnaire with a 24-hour recall for use in an epidemiological cohort study: results from the biomarker-based Observing Protein and Energy Nutrition (OPEN) study. , 2003, International journal of epidemiology.

[10]  N. Day,et al.  Are imprecise methods obscuring a relation between fat and breast cancer? , 2003, The Lancet.

[11]  E. Jaffe Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues , 2003 .

[12]  D. Midthune,et al.  Using intake biomarkers to evaluate the extent of dietary misreporting in a large sample of adults: the OPEN study. , 2003, American journal of epidemiology.

[13]  K. McMartin,et al.  Aspartame: review of safety. , 2002, Regulatory toxicology and pharmacology : RTP.

[14]  J. Bruner,et al.  Consensus Conference on Brain Tumor Definition for registration. November 10, 2000. , 2002, Neuro-oncology.

[15]  D. Hossfeld E.S. Jaffe, N.L. Harris, H. Stein, J.W. Vardiman (eds). World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues , 2002 .

[16]  J. Jobe,et al.  Cognitive research enhances accuracy of food frequency questionnaire reports: results of an experimental validation study. , 2002, Journal of the American Dietetic Association.

[17]  A F Subar,et al.  Design and serendipity in establishing a large cohort with wide dietary intake distributions : the National Institutes of Health-American Association of Retired Persons Diet and Health Study. , 2001, American journal of epidemiology.

[18]  W. Stargel,et al.  Aspartame: scientific evaluation in the postmarketing period. , 2001, Regulatory toxicology and pharmacology : RTP.

[19]  B. Rosner,et al.  Measurement error correction in nutritional epidemiology based on individual foods, with application to the relation of diet to breast cancer. , 2001, American journal of epidemiology.

[20]  H. Kemper,et al.  Longitudinal trends in and tracking of energy and nutrient intake over 20 years in a Dutch cohort of men and women between 13 and 33 years of age: The Amsterdam growth and health longitudinal study , 2001, British Journal of Nutrition.

[21]  A F Subar,et al.  Is shorter always better? Relative importance of questionnaire length and cognitive ease on response rates and data quality for two dietary questionnaires. , 2001, American journal of epidemiology.

[22]  G. Williams,et al.  Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repair assay. , 2000, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[23]  D O Stram,et al.  Calibration of the dietary questionnaire for a multiethnic cohort in Hawaii and Los Angeles. , 2000, American journal of epidemiology.

[24]  J. Henkel Sugar substitutes. Americans opt for sweetness and lite. , 1999, FDA consumer.

[25]  V. Duffy,et al.  Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners. , 1998, Journal of the American Dietetic Association.

[26]  S. Preston‐Martin,et al.  Aspartame consumption in relation to childhood brain tumor risk: results from a case-control study. , 1997, Journal of the National Cancer Institute.

[27]  E. Spitznagel,et al.  Increasing Brain Tumor Rates: Is There a Link to Aspartame? , 1996, Journal of neuropathology and experimental neurology.

[28]  A F Subar,et al.  Improving food frequency questionnaires: a qualitative approach using cognitive interviewing. , 1995, Journal of the American Dietetic Association.

[29]  G. Colditz,et al.  The nurses' health study: a cohort of US women followed since 1976. , 1995, Journal of the American Medical Women's Association.

[30]  D Feskanich,et al.  Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. , 1993, Journal of the American Dietetic Association.

[31]  K. Wakabayashi,et al.  Mutagenic activity of peptides and the artificial sweetener aspartame after nitrosation. , 1993, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[32]  G A Colditz,et al.  Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. , 1992, American journal of epidemiology.

[33]  J H Lubin,et al.  On power and sample size for studying features of the relative odds of disease. , 1990, American journal of epidemiology.

[34]  A. Miller,et al.  A study of repeatability of dietary data over a seven-year period. , 1989, American journal of epidemiology.

[35]  L. Lambertini,et al.  Aspartame induces lymphomas and leukaemias in rats a L'aspartame induce linfomi e leucemie nei ratti , 2005 .

[36]  E. Berg,et al.  World Health Organization Classification of Tumours , 2002 .

[37]  J. Ross Brain tumors and artificial sweeteners? A lesson on not getting soured on epidemiology. , 1998, Medical and pediatric oncology.

[38]  V. Duffy,et al.  Position of the American Dietetic Association: use of nutritive and nonnutritive sweeteners. , 2004, Journal of the American Dietetic Association.

[39]  E Riboli,et al.  Validation and calibration of dietary intake measurements in the EPIC project: methodological considerations. European Prospective Investigation into Cancer and Nutrition. , 1997, International journal of epidemiology.

[40]  Flamm Wg Increasing brain tumor rates: is there a link to aspartame?". , 1997 .

[41]  R A Goldbohm,et al.  Reproducibility of a food frequency questionnaire and stability of dietary habits determined from five annually repeated measurements. , 1995, European journal of clinical nutrition.

[42]  M. Singer,et al.  Nutritional Epidemiology , 2020, Definitions.

[43]  B. W. Lichtenstein,et al.  Neoplasms in the nervous system. , 1949 .