Primary Care Corner with Geoffrey Modest MD: Stroke and dementia, and artificial sweeteners

by Dr Geoffrey Modest

Two studies came out from the Framingham Heart Study database by the same authors in 2 different journals, one on the association between consuming artificially-sweetened beverages and the later development of stroke and dementia, and the other on sugary beverages and preclinical Alzheimer’s disease. I will divide these into 2 blogs.

An evaluation of the Framingham Heart Study Offspring cohort, with data from 1971 and evaluated over 9  examination cycles, found that artificially-sweetened soft drink consumption was associated with a higher risk of stroke and dementia (see DOI: 10.1161/STROKEAHA.116.016027).



— 2888 participants >45yo were evaluated for incident stroke;  1484 who were >60yo were evaluated for incident dementia

— mean age 62 for the younger group and 45% men, 69 for the older group and 46% men

— beverage intake was quantified at cohort examinations 5 (1991-5), 6 (1995-8), and 7 (1998-2001). Total sugar-sweetened beverages included soft drinks, fruit juice, and fruit drinks.

— surveillance for incident events began at examination 7 and continued for 10 years

— there were 97 cases of incident stroke (82 ischemic), and 81 cases of incident dementia (63 consistent with Alzheimer’s)



— controlling for age, sex, education (for the dementia cohort), calorie intake, diet quality, physical activity, and smoking; when compared to a daily cumulative intake of 0 artificially-sweetened drinks per week:

— hazard ratio for ischemic stroke was 2.96 (1.26-6.97), p=0.01 (ie, about 3x higher). Relationship was strongest for ischemic stroke

— hazard ratio for Alzheimer’s disease 2.89 (1.18-7.07), p=0.02. There was also an association with all-cause dementia of similar magnitude, 2.47 (1.15-5.30), p=0.02. Both were statistically significant in the group having at least one drink per day.

— sugar-sweetened beverages were not associated with the stroke or dementia, only artificially-sweetened soft drinks

— the curves for event-free survival for both of these outcomes continued to decrease through year 10 (i.e. it was not plateauing), and there was a dose-response curve with the more artificially-sweetened soft drinks, the lower the event-free survival

— there was no interaction in the above analyses with waist-to-hip ratio, diabetes mellitus, or with the presence of apolipoprotein E4

— there was not much change in the associations when excluding diabetes from the analysis, given the potential interaction of those with diabetes drinking more artificially-sweetened beverages (diabetes was found to be only a partial mediator of the association).



— the Nurses’ Health Study and Health Professionals Follow-Up Study both reported a higher risk of incident stroke with greater consumption of sugar-and artificially-sweetened beverages. The above study is reported to be the 1st showing association between artificially-sweetened drinks and an increase in both all-cause dementia and Alzheimer’s.

— The above study predated the approval of Stevia

— there are studies which have shown that artificial sweeteners cause glucose intolerance in mice by altering the gut microbiome, and they are associated with glucose intolerance in humans. See here for a detailed review of these animal and human studies.

— Generalizability of these results: the Framingham study served as a model for epidemiologic studies given its long-term nature (began in 1948) and in the regular intensive follow-ups done over the years. However, it was limited by the lack of ethnic variation. It also was an observational study which limits drawing conclusions regarding causality.


So, bottom line (again): these no-calorie artificial sweeteners seem to be associated with significant problems, including glucose intolerance (despite the fact that we used to push diabetic patients to drink these over regular sodas). And there are suggestive data that they do not help even with weight loss (see here ). so, all in all, we should be promoting water as the best drink….

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