Effects of Cranberry Extract (Vaccinium macrocarpon) Supplementation on Lipid Peroxidation and Inflammation in Patients with Chronic Kidney Disease (Stages 3-4): A Randomized Controlled Trial

Abstract

Background: Growing evidence suggests that bioactive compounds in berry fruits may mitigate inflammation in patients with chronic kidney disease (CKD).

Objectives: To evaluate cranberry (Vaccinium macrocarpon) supplementation effects on modulation of transcription factors involved in inflammation and oxidative stress in nondialysis (stages 3 and 4) patients with CKD. Design/Participants. A randomized, double-blind, placebo-controlled study was performed with 30 patients to receive capsules containing cranberry extract (1000 mg/day) or placebo (1000 mg/day of corn starch) for two months. Measurements. The mRNA expression of nuclear factor-erythroid 2-related factor-2 (Nrf2) and nuclear factor-kB (NF-kB) was evaluated in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction. Thiobarbituric acid reactive substances (TBARS) were measured in the plasma to assess oxidative stress. Interleukin-6 (IL-6) plasma levels were assessed by enzyme-linked immunosorbent assay and C-reactive protein (CRP) by immunoturbidimetric method.

Results: Twenty-five patients completed the study: 12 in the cranberry group (56.7 ± 7.5 years and body mass index (BMI) of 29.6 ± 5.5 kg/m²) and 13 in the placebo group (58.8 ± 5.1 years and BMI 29.8 ± 5.4 kg/m²). There were no differences in NF-kB or Nrf2 mRNA expressions (p = 0.99 and p = 0.89) or TBARS, CRP, and IL-6 plasma levels after cranberry supplementation.

Conclusions: The cranberry extract administration (1000 mg/day) did not affect Nrf2 and NF-kB mRNA expression, oxidative stress, or inflammatory markers levels in nondialysis CKD patients. This trial is registered with NCT04377919.

Figure 1

Body index mass (BMI) (a) and glomerular filtration rate (GFR) (b) before and after two months of placebo and cranberry supplementation. There were no differences in body index mass (BMI) (a) and glomerular filtration rate (GFR) (b) after two months of intervention in both groups. The sample distributions of data in grey are represented in boxplots and strip plots. In black, the central circle represents the mean expected marginal effect for each group estimated from linear mixed-effects models. The fixed effects in the models were the intervention group, the time, its interaction, and the confounding variables: sex, age, systemic arterial hypertension (SAH), and diabetes mellitus (DM). Individuals were included as a random effect. Black horizontal bars represent the 95% confidence intervals of the expected mean marginal effects by the group. p values were corrected for the number of contrasts/two-by-two comparisons by Tukey's honest significant difference (HSD) method.

Figure 2

C-reactive protein (CRP) (a), thiobarbituric acid reactive substances (TBARS) (b), and interleukin-6 (IL-6) (c) plasma levels and their respective differences before and after two months of placebo and cranberry supplementation. We found no evidence of C-reactive protein (CRP) (a), thiobarbituric acid reactive substances (TBARS) (b), and interleukin-6 (IL-6) (c) plasma level differences after intervention in cranberry and placebo groups. The sample distributions of data in grey are represented in boxplots and strip plots. In black, the center circle represents the mean expected marginal effect for each group estimated from linear mixed-effects models. The fixed effects in the models were the intervention group, the time, its interaction, and the confounding variables sex, age, systemic arterial hypertension (SAH), and diabetes mellitus (DM). Individuals were included as a random effect. Black horizontal bars represent the 95% confidence intervals of the expected mean marginal effects by the group. p values were corrected for the number of contrasts/two-by-two comparisons by Tukey's honest significant difference (HSD) method.

Figure 3

mRNA expression of nuclear factor erythroid 2-related factor-2 (Nrf2) (a) and nuclear factor-kappa B (NF-κB) and their respective differences before and after two months of placebo and cranberry supplementation. There was no evidence of mRNA expression of nuclear factor erythroid 2-related factor-2 (Nrf2) (a) and nuclear factor-kappa B (NF-κB) (b) differences after intervention in cranberry and placebo groups. The sample distributions of data in grey are represented in boxplots and strip plots. In black, the center circle represents the mean expected marginal effect for each group estimated from linear mixed-effects models. The fixed effects in the models were the intervention group, the time, its interaction, and the confounding variables: sex, age, systemic arterial hypertension (SAH), and diabetes mellitus (DM). Individuals were included as a random effect. Black horizontal bars represent the 95% confidence intervals of the expected to mean marginal effects by the group. p values were corrected for the number of contrasts/two-by-two comparisons by Tukey's honest significant difference (HSD) method.