Effects of Cranberry Juice Supplementation on Cardiovascular Disease Risk Factors in Adults with Elevated Blood Pressure: A Randomized Controlled Trial

Abstract

Emerging cardiovascular disease (CVD) risk factors, including central vascular function and HDL efflux, may be modifiable with food-based interventions such as cranberry juice. A randomized, placebo-controlled, crossover trial was conducted in middle-aged adults with overweight/obesity (n = 40; mean BMI: 28.7 ± 0.8 kg/m²; mean age: 47 ± 2 years) and elevated brachial blood pressure (mean systolic/diastolic BP: 124 ± 2/81 ± 1 mm Hg). Study participants consumed 500 mL/d of cranberry juice (~16 fl oz; 27% cranberry juice) or a matched placebo juice in a randomized order (8-week supplementation periods; 8-week compliance break), with blood samples and vascular measurements obtained at study entry and following each supplementation period. There was no significant treatment effect of cranberry juice supplementation on the primary endpoint of central systolic blood pressure or central or brachial diastolic pressure. Cranberry juice significantly reduced 24-h diastolic ambulatory BP by ~2 mm Hg compared to the placebo (p = 0.05) during daytime hours. Cranberry juice supplementation did not alter LDL-C but significantly changed the composition of the lipoprotein profile compared to the placebo, increasing the concentration of large LDL-C particles (+29.5 vs. -6.7 nmol/L; p = 0.02) and LDL size (+0.073 vs. -0.068 nm; p = 0.001). There was no effect of treatment on ex vivo HDL efflux in the total population, but exploratory subgroup analyses identified an interaction between BMI and global HDL efflux (p = 0.02), with greater effect of cranberry juice in participants who were overweight. Exploratory analyses indicate that baseline C-reactive protein (CRP) values may moderate treatment effects. In this population of adults with elevated blood pressure, cranberry juice supplementation had no significant effect on central systolic blood pressure but did have modest effects on 24-h diastolic ambulatory BP and the lipoprotein profile. Future studies are needed to verify these findings and the results of our exploratory analyses related to baseline health moderators.

Keywords: LDL-C; arterial stiffness; blood pressure; inflammatory markers; lipids.

Figure 1

Schematic of participant recruitment and exclusion.

Figure 2

Change in ambulatory diastolic blood pressure following supplementation (n = 40). Change scores were calculated by subtracting study-entry baseline values from each post-supplementation measure. Values are means ± SEM (n = 40; 25 M, 15 F) and were compared using the MIXED models procedure (SAS version 9.4; SAS Institute Inc., Cary, NC, USA) to test the effects of treatment, period, and treatment by period interactions. Baseline values were included as covariates for each endpoint. p-values represent significant main effects of treatment.

Figure 3

Changes in lipoprotein sub-fractions and characteristics following supplementation. Change scores were calculated by subtracting study-entry baseline values from each post-supplementation measure. Values are means ± SEM (n = 40; 25 M, 15 F) and were compared using the MIXED models procedure (SAS version 9.4; SAS Institute Inc., Cary, NC, USA) to test the effects of treatment, period, and treatment by period interactions. Baseline values were included as covariates for each endpoint. p-values represent treatment effects, and * indicates a significant change from baseline (p = 0.05).

Figure 4

Change in ex vivo measures of HDL-C efflux following supplementation. Change scores were calculated by subtracting study-entry baseline values from each post-supplementation measure. Values are means ± SEM (n = 40; 25 M, 15 F) and were compared using the MIXED models procedure (SAS version 9.4; SAS Institute Inc., Cary, NC, USA) to test the effects of treatment, period, and treatment by period interactions. Baseline values were included as covariates for each endpoint. * indicates a significant change from baseline (p < 0.05).

Figure 5

Change in global HDL efflux (+cAMP) following supplementation according to BMI category. Change scores were calculated by subtracting study-entry baseline values from each post-supplementation measure. Values are means ± SEM (n = 40; 25 M, 15 F) and were compared using the MIXED models procedure (SAS version 9.4; SAS Institute Inc., Cary, NC, USA) to test the effects of treatment, period, and treatment by period interactions. Baseline values were included as covariates for each endpoint. p-values represent unadjusted post hoc comparisons, and * indicates a significant change from baseline (p ≤ 0.05).

Figure 6

Significant changes in vascular function according to baseline CRP status. Change scores were calculated by subtracting study-entry baseline values from each post-supplementation measure. Values are means ± SEM (n = 40; 25 M, 15 F) and were compared using the MIXED models procedure (SAS version 9.4; SAS Institute Inc., Cary, NC, USA). Baseline values were included as covariates for each endpoint. CRP status was defined based on the median baseline CRP value of 1.3 mg/L. p-values indicate unadjusted post hoc comparisons, and * indicates a significant change from baseline (p ≤ 0.05).