Metabolic disturbances and worsening of atherosclerotic lesions in ApoE(-/-) mice after cola beverages drinking

BACKGROUND: Atherosclerosis is a major health burden. Metabolic disorders had been associated with large consumption of soft drinks. The rising incidence of atherosclerosis and metabolic alterations warrants the study of long-term soft drink consumption’ effects on metabolism and atherosclerosis in genetic deficiency of apolipoprotein E which typically develops spontaneous atherosclerosis and metabolic alterations. METHODS: ApoE(-/-) mice were randomized in 3 groups accordingly with free access to: water (W), regular cola (C) or light cola (L). After 8 weeks, 50% of the animals in each group were euthanized (Treatment: W(8), C(8), L(8)). The remaining mice (all groups) drank water for 8 weeks and were euthanized (Washout: W(16), C(16), L(16)). Body weight and food and drink consumption were periodically measured. Blood was collected (biochemistry). At autopsy, transverse aortic sinus sections were serially cut and stained (histomorphometry); livers and kidneys were processed (microscopy). MANOVA (identification of variance factors) was followed by ANOVA and LSD tests (within-factor differences between levels). Conventionally a p< 0.05 was considered significant. RESULTS: Treatment increased drinking volumes (vs W(8): 4 fold C(8), p<0.0001; +47% L(8), p<0.02). Only C reduced eating amounts (–54%, p<0.05 vs W(8)). I). Compared with W(8): C(8) developed hyperglycemia (+43%, p<0.03) and increased non-HDL cholesterol (+54%, p<0.05); L(8) showed decreased glycemia (–15%, p<0.05 vs W(8)) and increased creatinine (2.5 fold, p<0.04), urea (+74, p<0.03) and aspartate-aminotransferase (2.8 fold, p<0.05). Hypercreatininemia was observed in L(16) (2.7 fold vs W(16), p<0.05). Hypertriglyceridemia (+91%, p<0.008) and hyperuremia (+68%, p<0.03) developed over time of study (age). II). Treatment caused plaque area increase (vs W(8): 28% C(8), p<0.02 and 50% L(8), p<0.01; vs W(16): 43% C(16), p<0.05 and 68% L(16), p<0.02) and stenosis (vs W(8): 38% C(8), p<0.04 and 57% L(8), p<0.01; vs W(16): 71% C(16), p<0.01 and 46% L(16), p<0.04). Age also caused plaque area increase (56%, p<0.04). Treatment- and age-effects on plaque enlargement were additive. CONCLUSION: Cola beverages caused atherosclerotic lesions’ enlargement with metabolic (C) or non metabolic disturbances (L). ApoE(-/-) mice were particularly sensitive to L treatment. These findings may likely relate to caramel colorant and non-nutritive sweeteners in cola drinks and have potential implications in particularly sensitive individuals.