A pilot study to evaluate the potential cardioprotective effects of grape juice in survivors of childhood cancer.

Abstract

Childhood cancer is a rare, yet devastating disease, which was almost uniformly fatal 50 years ago. Fortunately, with the tremendous advance of cancer therapies, the 5-year relative survival rate for children under age 15 years has increased to 80%. Research into the late effects of cancer treatment has revealed that there are consequences of the cure. Childhood cancer survivors are at an increased risk of premature cardiovascular disease (CVD), and few interventions have been tested to delay or mitigate progression of disease in this population. Dietary strategies have been evaluated as potential means to prevent, attenuate, or reverse the CVD process in adults. Notably, there is considerable interest in the cardioprotective properties of red wine, which are primarily attributed to flavonoids, a class of polyphenols present in most plant foods. Purple grape juice (PGJ) is a rich source of flavonoids with antioxidant properties that has been shown in adults to reduce oxidative stress and improve endothelial function, a key measure of vascular health. The effects of supplementing meals with PGJ on endothelial function and oxidative stress were examined in 24 cancer survivors ages 10 to 21 years in a randomized controlled crossover study consisting of two 4 week intervention periods, each preceded by a 4 week washout period. Subjects were randomly assigned to 6 ounces twice daily of PGJ or clear apple juice (AJ, similar in calories but lower in flavonoids). Clinical measurements and blood samples were obtained before and after each supplementation period. Change in microvascular endothelial function, assessed using peripheral arterial tonometry in the fingertips, and change in plasma markers of oxidative stress (oxidized LDL (oxLDL), myeloperoxidase (MPO)) and inflammation (high sensitivity C-Reactive Protein (hs-CRP)) were evaluated using mixed effects analysis of variance.</DISS_para> <DISS_para>PGJ did not improve endothelial function compared with AJ (mean change: PGJ 0.06, AJ 0.22; difference of mean change (95% CI): -0.16 (-0.42 to 0.11), p = 0.25). There were no significant improvements in biomarkers of oxidative stress (mean change: oxLDL (U/L): PGJ 4.66, AJ 1.57, p=0.29; MPO (ng/mL): PGJ 0.95, AJ 1.03 p=0.15) or inflammation (mean change: hs-CRP (mg/L): PGJ 1.42, AJ 1.06, p=0.37). There were no adverse effects on fasting glucose or insulin, or blood pressure during either juice supplementation; however, there was a statistically significant increase in weight and BMI during the apple juice supplementation (median change: weight: 0.70, p=0.01; BMI: 0.26, p=0.03). Additionally, there was a 5 mg/dL decrease in HDL cholesterol during the apple juice supplementation (p=0.001). Our study was the first to examine the effects of purple grape juice on endothelial function in cancer survivors. The intervention was well-tolerated by study participants and all 24 subjects randomized to the juice intervention completed the four month study. After four weeks of daily consumption of flavonoid-rich purple grape juice, no measurable improvement in vascular health was observed in adolescent and young adult cancer survivors. However, these young survivors were relatively healthy with few cardiovascular risk factors, which may have precluded identifying measurable improvement. An important next step in childhood cancer survivorship research is to be able to identify those cancer survivors most at risk before vascular disease is clinically evident. Future studies might consider targeting the major risk factors for CVD, such as obesity, insulin resistance or diabetes, or hypertension, which directly or indirectly may also affect endothelial function.