Objectives: We sought to determine whether cranberry juice consumption would ameliorate laboratory and clinical measurements of disease activity in people with rheumatoid arthritis receiving fish oil supplementation.Methods: A prospective study was performed with 62 people with rheumatoid arthritis. We analyzed C-reactive protein modification of the Disease Activity Score-28 (DAS28-CRP) and inflammatory markers. The first group was assigned to eat their typical diet, a second group was asked to consume 3 g of fish oil -3 fatty acids daily, and a third group received both 3 g of fish oil n-3 fatty acids and 500 mL of reduced-calorie cranberry juice daily.Results: Compared with baseline values, the group receiving both fish oil and cranberry juice showed reductions in erythrocyte sedimentation rate (P = 0.033), C-reactive protein (P = 0.002), DAS28-CRP (P = 0.001), adiponectin (P = 0.021), and interleukin-6 levels (P = 0.045), whereas the fish oil group showed decreased DAS28-CRP (P = 0.0261) and adiponectin (P = 0.0239). Differences across treatments showed that the group receiving both fish oil and cranberry experienced reductions (P < 0.05) in erythrocyte sedimentation rate and C-reactive protein compared to the control group and the group treated with fish oil alone, and a reduction in DAS28-CRP was verified when the fish oil and cranberry group was compared to the control group.Conclusions: The ingestion of cranberry juice adds beneficial effects to fish oil supplementation, decreasing disease activity and inflammatory biomarkers in people with rheumatoid arthritis.

Background We aimed to evaluate the effect of cranberry supplementation on serum liver enzymes, hepatic steatosis, and cardiometabolic risk factors in patients with non-alcoholic fatty liver (NAFLD). Methods In the present parallel-designed randomized controlled clinical trial, 110 patients with NAFLD were enrolled. The patients were randomized to receive 144 mg cranberry capsule or placebo for 6 months. The primary efficacy of the treatment was lipid profile, glycemic measurements, and liver enzyme levels. Results The data were reported for 46 in the supplementation group and 48 in the placebo group. The patient's mean (SD) age was 43.16 (11.08) years. No significant differences between groups were observed regarding the post-intervention level of liver enzyme. The mean after-intervention levels of total cholesterol (p < 0.001) and triglyceride (p = 0.01) were significantly lower in the intervention group compared with the placebo group. At the end of the study, the mean insulin and HOMA-IR levels were significantly lower in the cranberry group compared with the placebo group. Significantly more patients in the cranberry group experienced a decrease in steatosis level compared with the control group. Conclusion The results of the present study showed that cranberry supplementation had a positive effect on some lipid profiles, insulin resistance, and hepatic steatosis in patients with NAFLD.

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 +or- 0.8 kg/m2; mean age: 47 +or- 2 years) and elevated brachial blood pressure (mean systolic/diastolic BP: 124 +or- 2/81 +or- 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.

Background: Previous studies indicate cardiovascular health benefits of cranberry juice consumption. However, whether daily consumption of whole cranberries will have sustained vascular benefits in healthy individuals is currently unknown. Objective: To investigate the vascular effects of acute and daily consumption of freeze dried whole cranberry in healthy men and how effects relate to circulating cranberry (poly)phenol metabolites. Methods: A double-blind, parallel-group, randomized controlled trial was conducted in 45 healthy male adults randomly allocated to 1 month daily consumption of either cranberry (9 g powder solubilized in water equivalent to 100 g of fresh cranberries, 525 mg total (poly)phenols) or control (9 g powder, no (poly)phenols). Flow-mediated dilation (FMD, primary outcome), pulse wave velocity (PWV), aortic augmentation index (AIx), blood pressure, heart rate, blood lipids, and blood glucose were assessed at baseline and at 2 h on day 1 and after 1 month. Plasma and 24 h-urine were analyzed before and after treatment using targeted quantitative LC-MS methods including 137 (poly)phenol metabolites. Results: Cranberry consumption significantly increased FMD at 2 h and 1-month (1.1% (95% CI: 1.1%, 1.8%); p(treatment) <= 0.001; p(treatment x time) = 0.606) but not PWV, AIx, blood pressure, heart rate, blood lipids, and glucose. Of the 56 and 74 (poly)phenol metabolites quantified in plasma and urine, 13 plasma and 13 urinary metabolites significantly increased 2 h post-consumption and on day 1, respectively, while 4 plasma and 13 urinary metabolites were significantly higher after 1-month of cranberry consumption, in comparison with control. A multi-variable stepwise linear regression analysis showed that plasma cinnamic acid-4 '-glucuronide, 4-hydroxybenzoic acid-3-sulfate, 2,5-dihydroxybenzoic acid, 3 '-hydroxycinnamic acid, and 5-O-caffeoylquinic acid were significant independent predictors of 2 h FMD effects (R-2 = 0.71), while 3 '-hydroxycinnamic acid, 4-methoxycinnamic acid-3 '-glucuronide, 3-(4 '-methoxyphenyl)propanoic acid 3 '-sulfate, and 3-(4 '-methoxyphenyl)propanoic acid 3 '-glucuronide predicted the 1-month FMD effects (R-2 = 0.52). Conclusions: Acute and daily consumption of whole cranberry powder for 1 month improves vascular function in healthy men and this is linked with specific metabolite profiles in plasma. The National Institutes of Health (NIH)-randomized trial records held on the NIH ClinicalTrials.gov website (NCT02764749). https://clinicaltrials.gov/ct2/show/NCT02764749

OBJECTIVES:Studies have shown that cranberry (Vaccinium macrocarpon) has antiinflammatory and antioxidant effects; however, to our knowledge, the effects of cranberry juice consumption have not been studied in patients with rheumatoid arthritis (RA). The aim of this study was to verify the effect of cranberry juice consumption on several inflammatory biomarkers and on the disease activity of patients with RA.METHODS:A prospective study was conducted with 41 women diagnosed with RA. The disease activity measured by Disease Activity Score 28 (DAS28) and anticyclic citrullinated peptide (anti-CCP) antibodies, and several inflammatory and biochemical biomarkers were analyzed. The control group (n = 18) maintained their usual diet. The cranberry group (n = 23) consumed 500 mL/d of low-calorie cranberry juice.RESULTS:Regarding the baseline values, the cranberry group presented a decrease in the values of DAS28 (P = 0.048) and anti-CCP (P = 0.034) after 90 d of treatment, whereas changes in inflammatory biomarkers were not found.CONCLUSION:The present study indicated that cranberry juice decreases disease activity and therefore has beneficial effects for RA patients, although larger and long-term studies are needed to definitively probe this effect and to clarify the mechanisms involved.

PURPOSE: We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. METHODS: 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m2) with abdominal adiposity (waist: hip>0.8 for women and >0.9 for men; waist: height>=0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. RESULTS: Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P<0.05). Interferon-gamma was elevated (P<0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P<0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P<0.05). CONCLUSIONS: An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Background: The aim of this study was to analyze the effect of supplementation with cranberry (Vaccinum macrocarpon) on the levels of pro-inflammatory cytokines, hepcidin and selected markers of iron metabolism in rowers subjected to exhaustive exercise. Methods: This double-blind study included 16 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group (n=9), receiving 1200 mg of cranberry extract for 6 weeks, or to the placebo group (n=7). The participants performed a 2000-m test on a rowing ergometer at the beginning and at the end of the preparatory camp. Blood samples were obtained from the antecubital vein prior to each exercise test, one minute after completing the test, and after a 24-h recovery period. The levels of hepcidin, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), ferritin, iron, soluble transferrin receptor (sTfR) and myoglobin were determined, along with total iron-binding capacity (TIBC), unbound iron-binding capacity (UIBC) and total antioxidant capacity (TAC). Results: Both prior and after the supplementation, a significant post-exercise increase in the concentration of IL-6 was observed in both groups. At the end of the study period, cranberry-supplemented athletes presented with significantly higher resting, post-exercise and post-recovery levels of TAC than the controls. However, a significant exercise-induced increase in the concentrations of TNF-alpha, myoglobin and hepcidin was observed solely in the control group. Conclusion: Supplementation with cranberry extract contributed to a significant strengthening of antioxidant potential in individuals exposed to strenuous physical exercise. However, supplementation did not exert direct effects on other analyzed parameters: inflammatory markers and indices of iron metabolism (TNF-alpha, hepcidin and myoglobin).

SCOPE: Cranberries are rich in potentially bioactive (poly)phenols. The aim of this work was to investigate whether cranberry juice intake can improve vascular function in healthy men in a dose- and time-dependent manner, and to understand which of the circulating (poly)phenol metabolites correlate with vascular effects. METHODS AND RESULTS: A double-blind randomized controlled crossover trial was conducted in 10 healthy males. Flow-mediated dilation (FMD), blood pressure, pulse wave velocity and augmentation index were investigated at baseline, 1, 2, 4, 6, and 8h post-consumption of cranberry juices containing 409, 787, 1238, 1534, and 1910 mg of total cranberry (poly)phenols (TP), and a control drink. Plasma (poly)phenol metabolites were analyzed by UPLC-Q-TOF MS using authentic standards. We observed dose-dependent increases in FMD at 1, 2, 4, 6, and 8h with a peak at 4h and maximal effects with juice containing 1238 mg TP. A total of 60 metabolites were quantified in plasma after cranberry consumption. Twelve (poly)phenol metabolites significantly correlated with the increases in FMD, including ferulic and caffeic acid sulfates, quercetin-3-O-s-D-glucuronide and a gamma-valerolactone sulfate. CONCLUSION: (Poly)phenols in cranberry juice can improve vascular function in healthy males and this is linked to the presence of specific newly identified plasma metabolites.

Flavonoids are important bioactive plant constituents found in abundance in berries, including cranberries. Cranberry beverages have been shown to beneficially impact urinary and cardiovascular health in clinical and observational studies, but their association with anthropometric outcomes is unknown. We examined the association between cranberry juice cocktail (CJC) consumption with flavonoid intake, and cardiometabolic and anthropometric outcomes among adults in the US data for adults (>19 years, n = 10334) were drawn from cross-sectional National Health and Nutrition Examination Survey combined 2005-2008 survey. We hypothesized that CJC consumers will have lower anthropometric measures and healthier cardiometabolic profiles, including lower cholesterol and C-reactive protein (CRP). A CJC consumer (n = 330) was defined as anyone consuming CJC for 2 nonconsecutive 24-hour dietary recalls. We used multivariate linear regression models to examine differences in anthropometric and cardiometabolic outcomes comparing CJC consumers to nonconsumers controlling for important confounders. Consumers drank an average 404 mL (14 fl oz) of CJC for 2 days and did not have higher total energy intakes compared with nonconsumers (mean [SD], 2259 [79] vs 2112 [24], respectively). In fully adjusted models, adult CJC consumers had significantly lower levels of CRP (mean [SD], -0.13 [0.05]; P = .015), results that were strengthened after further adjustment for body mass index (mean [SD], -0.98 [0.04]; P = .027). Trends toward lower weights and lower levels of cholesterol did not reach statistical significance. Intake of cranberry polyphenols may play a role in promoting anti-inflammatory markers among CJC consumers, specifically lowering CRP levels

BACKGROUND: Cardiometabolic risk is the risk of cardiovascular disease (CVD), diabetes, or stroke, which are leading causes of mortality and morbidity worldwide.
OBJECTIVE: The objective of this study was to determine the potential of low-calorie cranberry juice (LCCJ) to lower cardiometabolic risk.
METHODS: A double-blind, placebo-controlled, parallel-arm study was conducted with controlled diets. Thirty women and 26 men (mean baseline characteristics: 50 y; weight, 79 kg; body mass index, 28 kg/m(2)) completed an 8-wk intervention with LCCJ or a flavor/color/energy-matched placebo beverage. Twice daily volunteers consumed 240 mL of LCCJ or the placebo beverage, containing 173 or 62 mg of phenolic compounds and 6.5 or 7.5 g of total sugar per 240-mL serving, respectively.
RESULTS: Fasting serum triglycerides (TGs) were lower after consuming LCCJ and demonstrated a treatment x baseline interaction such that the participants with higher baseline TG concentrations were more likely to experience a larger treatment effect (1.15 +/- 0.04 mmol/L vs. 1.25 +/- 0.04 mmol/L, respectively; P = 0.027). Serum C-reactive protein (CRP) was lower for individuals consuming LCCJ than for individuals consuming the placebo beverage [ln transformed values of 0.522 +/- 0.115 ln(mg/L) vs. 0.997 +/- 0.120 ln(mg/L), P = 0.0054, respectively, and equivalent to 1.69 mg/L vs. 2.71 mg/L back-transformed]. LCCJ lowered diastolic blood pressure (BP) compared with the placebo beverage (69.2 +/- 0.8 mm Hg for LCCJ vs. 71.6 +/- 0.8 mm Hg for placebo; P = 0.048). Fasting plasma glucose was lower (P = 0.03) in the LCCJ group (5.32 +/- 0.03 mmol/L) than in the placebo group (5.42 +/- 0.03 mmol/L), and LCCJ had a beneficial effect on homeostasis model assessment of insulin resistance for participants with high baseline values (P = 0.035).
CONCLUSION: LCCJ can improve several risk factors of CVD in adults, including circulating TGs, CRP, and glucose, insulin resistance, and diastolic BP. This trial was registered at clinicaltrials.gov as NCT01295684.