Artificially sweetened beverages are not associated with an increased risk for heart attacks

The same day as the last post on diet beverages and metabolic syndrome, another relevant paper was published in Circulation by the Harvard group. This is the same group using the same cohort that found no link to artificial sweeteners and diabetes last year. This time they analyzed for heart attacks as the endpoint, which is more similar to the recent paper that found a positive association with cardiovascular events, so it is worth commenting on.

Design

The Health Professionals Follow-up is a prospective cohort of males started in 1986, and at baseline and every 4 years participants filled out a (validated, fairly close with food journals) food frequency questionnaire that asked about usual intake of sugar-sweetened and artificially-sweetened beverages. This analysis contained 42,883 participants, and a subset of these (18,225) gave a blood sample between 1993 and 1995 (relevant data from these are total, HDL, and LDL cholesterol, triglycerides, HbA1c, CRP, IL-6, TNF-1 & 2, ICAM-1, VCAM-1, adiponectin, and leptin). Participants/family reported non-fatal and fatal heart attacks (incident coronary heart disease) by questionnaire and these were confirmed with medical records.

For the analyses, time-dependent proportional hazard modeling was used with cumulative beverage and diet intakes updated every 4 years. A second analysis compared with only baseline diet data. Keep that in mind as compared to the study that found a positive association with cardiovascular events only collected a baseline food frequency questionnaire. Beverage consumption was divided into quartiles and modeling was adjusted for smoking, physical activity, alcohol intake, multivitamin use, family history of coronary heart disease, pre-enrollment weight gain, weight loss, low-calorie diet adherence, total energy intake, and BMI. Importantly, the also controlled for diet pattern with the Healthy Eating Index which scores by intake of fruit, vegetables, nuts/soy, cereal fiber, PUFA/sat fat ratio, white/red meat ratio, alcohol intake, multivitamin use, and trans fat intake.

Results

Again prior to statistical adjustments, relationships of beverage consumption with lifestyle variables is interesting; people who consumed sugar-sweetened drinks, smoked more, had lower physical activity, lower overall diet quality (HEI), but a decreased family history of coronary heart disease. They also had higher weight gain prior to enrollment and decreased weight loss, and lower adherence to a low-calorie diet. Consumers of artificially sweetened beverages tended to smoke less, have a higher physical activity, but a greater coronary heart disease family history. Although overall diet quality was higher and they were more active, they tended to have greater incidence of high triglycerides, cholesterol, and blood pressure- small differences but still there. Strange.

3683 incidence coronary heart disease cases over 22 years (790,852 person years) occurred. Prior to adjusting for covariates, comparing the quartile of most consumption for both sugar-sweetened drinks and artificially sweetened drinks, they found a RR of 1.21 for sugary drinks (95% CI, 1.10-1.33 p for trend < 0.01) and a RR of 1.04 for artificial sweeteners (0.96-1.15 which is not significant). Another good lesson of the complexities comes from the results after adjustment. Adjusting for smoking, physical activity, alcohol intake, multivitamins, and family history slightly reduced the risk for sugar beverages, but increased the risk for artificial beverages into significance (RR = 1.10, see table below for CI and p values). Further adjusting for pre-enrollment weight change lowered this back into non-significance, then adjusting for dietary factors raised it to significance again, and adjusting one last time for BMI removed it! Final adjustment for past diabetes, high lipids, and high blood pressure didn’t much effect. So the increased risk of heart attacks with sugar beverages in the upper quartile (median 6.5 servings per week) was about 20% compared to not drinking any, while there was no risk with artificially sweetened beverages. Also note the lack of significance at other quartiles, even for sugar sweetened beverages with a median of 2 drinks per week. And, converting the RR to absolute risk after all adjustments in quartile 4 for sugar beverages, this is only going from a .47% risk per year to .55% risk pear year of heart attacks in this population if my math is right. Not so scary!

The results were similar when intake was treated as continuous (except for carbonated non-colas which was consumed less & doesn’t really make sense here). Importantly, artificially sweetened colas did not increase risk of coronary heart disease. So 1 serving per day of a sugar-sweetened beverage increases coronary heart disease risk by about 20%, but we cannot say that artificially sweetened beverages increase risk.

They did the analyses again only baseline beverage intake associations were similar when coronary heart disease incidences in the first 4 years were removed (not done in the other study), as well as when diet was updated every 8 years- good to know for future research I imagine.

Among the previously mentioned blood markers, 1 sugar-sweetened beverage serving was associated with a significantly increase in triglycerides, CRP, IL-6, TNFalpha1 & 2 (all inflammatory factors which corroborate other research with sugar), lower HDL, Lp(a), and leptin, whereas artificial beverages did not reach significance in any.

Though there are some limitations to these types of designs, we have increasing confidence that the original positive associations between artificially sweetened beverages and cardiometabolic diseases were the result of insufficient controlling for confounding variables.

Reference

Lawrence de Koning, Vasanti S. Malik, Mark D. Kellogg, Eric B. Rimm, Walter C. Willett, & Frank B. Hu (2012). Sweetened Beverage Consumption, Incident Coronary Heart Disease and Biomarkers of Risk in Men Circulation : 10.1161/​CIRCULATIONAHA.111.067017

  • http://www.rae-gellner.de/ Fachanwalt Medizinrecht

    Very interesting study, although I am not quite convinced, as the side effects “increased weight gain” and “lower physical activity” could very well increase the risk for a heart attack!