Long‐term Consumption of Artificial Sweeteners Does not Affect Cardiovascular Function but May Cause Cardiac Electrophysiological Abnormalities in Rats

Abstract

Introduction Artificial sweeteners are commonly used as sugar substitutes. Because they have virtually no calories, they are believed to be useful in combatting obesity, metabolic syndrome, and diabetes. However, there is still uncertainty about their potential health problems. Recent population studies have suggested that consumption of artificial sweeteners was associated with adverse cardiovascular events - in particular, increasing coronary artery disease, stroke and all-cause mortality. Nevertheless, those population association studies cannot establish a causal relationship. We hypothesized that long-term consumption of artificial sweeteners could cause cardiovascular dysfunction. Thus, in this study we investigated the effect of long-term (1 year) consumption of artificial sweeteners (Equal and Splenda, 2 commonly used artificial sweeteners) in drinking water on cardiovascular health in rats. Methods Adult Sprague-Dawley rats (both sexes, 4-5 months old) were randomized into the following 3 groups: control group (n=21), artificial sweetener Equal group (n=21) and Splenda group (n=18). In the artificial sweetener groups, Equal or Splenda (at concentration of 2 packs per cup of water) was added to the drinking water, while drinking water alone was used in the control rats. The treatment was administered for 12 months. At the end of the treatment, blood pressure, pulse wave velocity (an index of arterial stiffness), left ventricular pressure and cardiac function were measured using catheter approach and echocardiography. ECG and cardiac electrophysiology was determined using intracardiac catheter approach. Blood glucose and lipids levels were also measured. Results Rats consistently consumed more sweetened water in both Equal and Splenda groups than that in the control group (e.g., 45±6ml in control, 72±5ml in Equal and 74±14ml in Splenda groups at 2 week treatment, P<0.01). The body weight was comparable among the 3 groups. The blood pressure and pulse wave velocity were not altered after 1-year treatment. There were no significant differences in left ventricular wall thicknesses, chamber dimension and cardiac function evaluated with cardiac echocardiography and left ventricular hemodynamic at the end of the experiment. There were no differences in blood lipids and glucose levels. Artificial sweeteners did not affect heart rate and atrial effective refractory period. However, rats in both Equal and Splenda groups had longer PR intervals (63±5ms in Equal, 68±6 ms in Splenda, vs 56±8ms in control, p<0.01) and a tendency of increased atrial fibrillation inducibility (60% in Equal, 70% in Splenda vs 31% in control). The survival (15/21 in Equal, 10/18 in Splenda, and 16/21 in control) was not significantly affected by the 1-year treatment. Conclusions Long-term consumption of artificial sweeteners in drinking water did not affect blood glucose and lipids levels. The artificial sweeteners did not affect blood pressure and cardiovascular function but caused some electrophysiological abnormalities with prolonged PR interval and a tendency of increased atrial fibrillation inducibility in rats. The 1-year survival was not significantly affected in these animals.