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Cardiovascular Health and Anti-inflammatory Benefits: Human

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Low-calorie cranberry juice supplementation reduces plasma oxidized LDL and cell adhesion molecule concentrations in men.

Posted
Authors
Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B, Couillard C
Journal
Br J Nutr 99(2):352-9
Abstract

Elevated circulating concentrations of oxidized LDL (OxLDL) and cell adhesion molecules are considered to be relevant markers of oxidative stress and endothelial activation which are implicated in the development of CVD. On the other hand, it has been suggested that dietary flavonoid consumption may be cardioprotective through possible favourable impacts on LDL particle oxidation and endothelial activation. The present study was undertaken to determine the effect of the daily consumption of low-calorie cranberry juice cocktail on plasma OxLDL, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin concentrations in men. Thirty men (mean age 51 (sd 10) years) were recruited and asked to consume increasing daily doses of cranberry juice cocktail (125, 250 and 500 ml/d) over three successive periods of 4 weeks. Plasma OxLDL and adhesion molecule concentrations were measured by ELISA before and after each phase. We noted a significant decrease in plasma OxLDL concentrations following the intervention (P 0.0001). We also found that plasma ICAM-1 (P 0.0001) and VCAM-1 (P 0.05) concentrations decreased significantly during the course of the study. In summary, the present results show that daily cranberry juice cocktail consumption is associated with decreases in plasma OxLDL, ICAM-1 and VCAM-1 concentrations in men.

Plasma matrix metalloproteinase (MMP)-9 levels are reduced following low-calorie cranberry juice supplementation in men

Posted
Authors
Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B and Couillard C
Journal
J Am Coll Nutr 28(6):694-701
Abstract

OBJECTIVE: Matrix metalloproteinase (MMP)-9, also known as gelatinase B, is implicated in the development of hypertension and atherosclerotic plaque vulnerability to rupture, an important step in the etiology of cardiovascular diseases. Studies have suggested that flavonoid consumption may be cardioprotective, and its favorable impact on circulating MMP-9 concentrations could partly explain this association. The aim of the present study was to determine the effect of consuming increasing daily doses of low-calorie cranberry juice cocktail (CJC) on plasma MMP-9 concentrations of abdominally obese men.
METHODS: Thirty men (mean age +/- SD: 51 +/- 10 years) consumed increasing doses of CJC during 3 successive periods of 4 weeks (weeks 1-4: 125 ml/day, weeks 5-8: 250 ml/day, and weeks 9-12: 500 ml/day). Before the study and after each phase, a series of physical and metabolic variables were measured, including MMP-9.
RESULTS: We found that CJC supplementation significantly decreased plasma MMP-9 concentrations (mean +/- SEM: -36% +/- 9%, p 0.0005; week 12 vs. baseline) while baseline plasma MMP-9 concentrations strongly correlated with the changes noted over the entire intervention (r = -0.71, p 0.0001). We also show that the reduction in plasma MMP-9 levels was associated with a change in plasma nitrites/nitrates (NOx) concentration over the entire intervention (r = -0.38, p 0.05; week 12 vs. baseline). Significant correlations were also noted between changes in plasma MMP-9 levels and those of systolic (r = 0.39, p 0.05) and diastolic (r = 0.60, p 0.001) blood pressure during the course of the study (week 12 vs. baseline).
CONCLUSIONS: Our results show that daily CJC consumption is associated with a decrease in plasma MMP-9 concentrations in abdominally obese men. We hypothesize that polyphenolic compounds from cranberries may be responsible for this effect, supporting the notion that the consumption of flavonoid-rich foods can exert cardioprotective effects.

Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants.

Posted
Authors
Vinson JA, Bose P, Proch J, Al Kharrat H, Samman N
Journal
J Agric Food Chem 56(14):5884-91
Abstract

Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.

Effect of cranberry extracts on lipid profiles in subjects with Type 2 diabetes

Posted
Authors
Lee IT, Chan YC, Lin CW, Lee WJ, Sheu WH
Journal
Diabet Med 25(12):1473-7
Abstract

AIM: To examine the effect of cranberry ingestion on lipid profiles in Type 2 diabetic patients taking oral glucose-lowering drugs.

METHODS: Thirty Type 2 diabetic subjects (16 males and 14 females; mean age 65 +/- 1 years) who were taking oral glucose-lowering medication regularly were enrolled in this randomized, placebo-controlled, double-blind study. Changes in lipid profiles, oxidized low-density lipoprotein (ox-LDL), glycaemic control, components of the metabolic syndrome, C-reactive protein (CRP) and urinary albumin excretion (UAE) were assessed after cranberry or placebo treatment for 12 weeks.

RESULTS: Low-density lipoprotein (LDL) cholesterol decreased significantly in the cranberry group (from 3.3 +/- 0.2 to 2.9 +/- 0.2 mmol/l, P = 0.005) and the decrease was significantly greater than that in the placebo group (-0.4 +/- 0.1 vs. 0.2 +/- 0.1 mmol/l, P 0.001). Total cholesterol and total : high-density lipoprotein (HDL) cholesterol ratio also decreased significantly (P = 0.020 and 0.044, respectively) in the cranberry group and the reductions were significantly different from those in the placebo group (P 0.001 and P = 0.032, respectively). However, ox-LDL levels did not change significantly in response to cranberry consumption. Neither fasting glucose nor glycated haemoglobin improved in either group. Changes in components of the metabolic syndrome, UAE and CRP were not significantly different between groups.

CONCLUSIONS: Cranberry supplements are effective in reducing atherosclerotic cholesterol profiles, including LDL cholesterol and total cholesterol levels, as well as total : HDL cholesterol ratio, and have a neutral effect on glycaemic control in Type 2 diabetic subjects taking oral glucose-lowering agents.

The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers.

Posted
Authors
Duthie SJ, Jenkinson AM, Crozier A, Mullen W, Pirie L, Kyle J, Yap LS, Christen P, Duthie GG
Journal
Eur J Nutr 45(2):113-22
Abstract

BACKGROUND: Consumption of fruit and vegetables is associated with a decreased risk of heart disease and cancer. This has been ascribed in part to antioxidants in these foods inactivating reactive oxygen species involved in initiation or progression of these diseases. Non-nutritive anthocyanins are present in significant amounts in the human diet. However, it is unclear whether they have health benefits in humans.

AIM: To determine whether daily consumption of anthocyanin-rich cranberry juice could alter plasma antioxidant activity and biomarkers of oxidative stress.

METHODS: 20 healthy female volunteers aged 18-40 y were recruited. Subjects consumed 750 ml/day of either cranberry juice or a placebo drink for 2 weeks. Fasted blood and urine samples were obtained over 4 weeks. The total phenol, anthocyanin and catechin content of the supplements and plasma were measured. Anthocyanin glycosides were identified by tandem mass spectrometry (MS-MS). Vitamin C, homocysteine (tHcy) and reduced glutathione (GSH) were measured by HPLC. Total antioxidant ability was determined using electron spin resonance (ESR) spectrometry and by the FRAP assay. Plasma total cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol and triglycerides (TG) were measured. Glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities were measured in erythrocytes. Urine was collected for analysis of malondialdehyde (MDA) by HPLC and 8-oxo-deoxyguanosine (8-oxo-dG) by ELISA. Endogenous and induced DNA damage were measured by single cell gel electrophoresis (SCGE) in lymphocytes.

RESULTS: Vitamin C, total phenol, anthocyanin and catechin concentrations and FRAP and ESR values were significantly higher in the cranberry juice compared with the placebo. Cyanidin and peonidin glycosides comprised the major anthocyanin metabolites [peonidin galactoside (29.2%) > cyanidin arabinoside (26.1%) > cyanidin galactoside (21.7%) > peonidin arabinoside (17.5%) > peonidin glucoside (4.1%) > cyanidin glucoside (1.4 %)]. Plasma vitamin C increased significantly (P0.01) in volunteers consuming cranberry juice. No anthocyanins (plasma) or catechins (plasma or urine) were detectable and plasma total phenols, tHcy,TC,TG,HDL and LDL were unchanged. The antioxidant potential of the plasma, GSH-Px, CAT and SOD activities, and MDA were similar for both groups. Supplementation with cranberry juice did not affect 8-oxo-deoxyguanosine in urine or endogenous or H(2)O(2)-induced DNA damage in lymphocytes.

CONCLUSIONS: Cranberry juice consumption did not alter blood or cellular antioxidant status or several biomarkers of lipid status pertinent to heart disease. Similarly, cranberry juice had no effect on basal or induced oxidative DNA damage. These results show the importance of distinguishing between the in vitro and in vivo antioxidant activities of dietary anthocyanins in relation to human health.

A double-blinded, placebo-controlled, randomized trial of the neuropsychologic efficacy of cranberry juice in a sample of cognitively intact older adults: pilot study findings

Posted
Authors
Crews WD Jr, Harrison DW, Griffin ML, Addison K, Yount AM, Giovenco MA and Hazell J.
Journal
J Altern Complement Med 11(2):305-9
Abstract

OBJECTIVES: The aim of this research was to conduct the first known clinical trial of the short-term (i.e., 6 weeks) efficacy of cranberry juice on the neuropsychologic functioning of cognitively intact older adults.PARTICIPANTS: Fifty (50) community-dwelling, cognitively intact volunteers, > or = 60 years old, who reported no history of dementia or significant neurocognitive impairments, participated in this study.DESIGN: A 6-week, double-blind, placebo-controlled, randomized, parallel-group, clinical trial was utilized. Participants were randomly assigned to receive either 32 ounces/day of a beverage containing 27% cranberry juice per volume (n = 25) or placebo (n = 25) for 6 weeks, and administered a series of neuropsychologic tests at both pretreatment baseline and again after 6 weeks of either cranberry juice or placebo treatment to assess treatment-related changes.OUTCOME MEASURES: Efficacy measures consisted of participants' raw scores on the following standardized neuropsychologic tests: Selective Reminding Test, Wechsler Memory Scale-III Faces I and Faces II subtests, Trail Making Test (Parts A and B), Stroop Color and Word Test, and the Wechsler Adult Intelligence Scale- III Digit Symbol-Coding subtest. A subjective Follow-up Self-report Questionnaire was also administered to participants at the conclusion of the end-of-treatment phase assessments.RESULTS: Two-factor, mixed analyses of variance (ANOVA) revealed no significant group (cranberry juice and placebo) by trial (pretreatment baseline and end-of-treatment assessments) interactions across all of the neuropsychologic tests and measures utilized in this study when a Bonferroni corrected alpha level was used to correct for multiple comparisons (i.e., .05/17 group by trial comparisons = .003). Pearson Chi-Square analyses of the groups' self-reported changes over the 6-week treatment phase in their abilities to remember, thinking processes, moods, energy levels, and overall health on the Follow-up Self-report Questionnaire revealed no significant relationships. However, a nonsignificant trend (X2(1) = 2.373, p = 0.123) was noted for participants' self-reported overall abilities to remember from pretreatment baseline to the end-of-treatment assessment. Specifically, more than twice as many participants in the cranberry group (n = 9, 37.5%) rated their overall abilities to remember by treatment end as "improved" as compared to placebo controls (n = 4, 17.4%).CONCLUSIONS: Taken together, no significant interactions were found between the cranberry and placebo groups and their pretreatment baseline and end-of-treatment phase (after 6 weeks) standardized neuropsychologic assessments. A nonsignificant trend was noted, however, on a subjective, self-report questionnaire where twice as many participants in the cranberry group rated their overall abilities to remember by treatment end as "improved" compared to placebo controls.

Comparison of urinary cytokines after ingestion of cranberry juice cocktail in pregnant subjects: a pilot study.

Posted
Authors
Wing DA, Rumney PJ, Leu SY, Zaldivar F
Journal
Am J Perinatol 27(2):137-42
Abstract

Our objective was to evaluate urinary cytokine excretion after daily cranberry or placebo exposure in pregnant women. Four-hour urine samples were collected from 27 pregnant women subjects who were randomized to cranberry juice cocktail or placebo in three treatment arms: A: Cranberry (C) two times daily (C, C; n = 10 pregnant); B: cranberry in the AM, then placebo (P) in the PM (C, P; n = 9 pregnant); and C: placebo two times daily (P, P; n = 8 pregnant). Urinary cytokines were measured using commercially available kits. There was a statistically significant difference in interleukin (IL)-6 of the urinary cytokines between the multiple daily cranberry dosing group (group A [C, C]): median, 3.16 (range, 0.01 to 7.34) and the placebo group (group C [P, P]): 9.32 (0.53 to 29.61 pg/mL; p = 0.038, Kruskal-Wallis test). We concluded that a difference in IL-6 was found in the multiple daily cranberry dosing groups compared with placebo. Lack of differences based on treatment allocation in the other cytokines may be due to beta error. Further studies are planned to evaluate these assays for the assessment of clinical effect.