Cranberry
Phytochemicals

CRANBERRY : THE CARDIOVASCULAR BENEFITS

“Let your food be your medecine and medecine be your food.” Hippocrates (460–370 BC)

INTRODUCTION

Eating a healthy balanced diet, is one of the most important and relevant ways to delay and prevent various health complications including cardiovascular disease (CVD). Among the nutritional factors that have been investigated in recent years, dietary fat intake may be the one that has been most targeted. However, there is also clear epidemiological evidence that increased fruits and vegetables intake can significantly reduce the risk of CVD, an effect that has been suggested to be resulting to a significant extent, from the high polyphenol content of these foods. Numerous polyphenolic compounds such as flavonoids have been identified as having strong antioxidant properties.

Cranberries are one of the most important sources of flavonoids that have a strong antioxidant and anti-inflammatory capacities. Thus, consumption of cranberries or their related products could be of importance not only in the maintenance of health but also in preventing CVD.

Among the 20 most commonly consumed fruits in the American diet, cranberries have the highest total phenol content. These phenolic compounds have a wide range of biological effects including the ability to serve as antioxidants, modulate enzyme activity, and regulate gene expression.

CRANBERRY COMPOSITION

Specific cranberry products, dried sweetened cranberries and cranberry juice cocktail (27% juice), have been recognized by the American Heart Association as “heart healthy” based on their nutrient composition.
Cranberries contain a higher amount of total phenols per serving (507–709 mg gallic acid equivalents/100 g) than other common fruits including blueberries (258–531 mg/100 g), apples (185–347 mg/100 g), red grapes (175–370 mg/100 g), and strawberries (132–368 mg/100g). Most of the phenolics in cranberries are present in a soluble free form: the two major classes of phenolics identified in cranberries are phenolic acids and flavonoids .
The most abundant phenolic acid identified was benzoic acid
The predominant flavonoids present in cranberries include the anthocyanins, flavonols, and flavan-3-ols (particularly proanthocyanidins). In cranberries, the six major anthocyanins are peonidin-3-galactoside, cyanidin-3-galactoside, cyanidin-3-arabinoside, peonidin-3-arabinoside, peonidin-3-glucoside, and cyanidin-3-glucoside.

Cranberries (Vaccinium macrocarpon) and cardiovascular disease risk factors,2007

CRANBERRY JUICE AND HIS EFFECT ON LDL OXIDATION

Experimental in vitro studies suggest phenolics may affect the pathogenesis of CVD by increasing the resistance of low-density lipoproteins (LDL) to oxidation ,preventing platelet aggregation and thrombosis, reducing blood pressure, and/or inhibiting inflammation.
Dietary antioxidants are associated with a reduced risk of CVD and hypertension. The high concentration of phenolic compounds found in cranberries correlates with their high antioxidant capacity.
Several in vitro studies have demonstrated the antioxidant activity of cranberries using assays measuring linoleic acid peroxidation, diene-conjugation formation,or other end products of lipid peroxidation in LDL: Cranberry phenolics, when mixed with plasma or modified serum prior to LDL isolation, remain associated with lipoproteins after their isolation, and subsequently increase the lag time of Cu2 induced LDL oxidation.

Cranberry extract inhibits low density lipoprotein oxidation, 1998

As oxidized LDL (OxLDL) are not recognized by the LDL receptor but rather by scavenger receptors at the surface of sub-endothelial resident macrophages, LDL oxidation favours the unrestricted uptake of cholesterol, thereby leading to the formation of foam cells, which is the first step in the formation of the earliest atherosclerotic lesions.
Migration of monocytes from the bloodstream into the subendothelial space requires that cell adhesion molecules such as the intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin be expressed by endothelial cells.
Cranberries also contain acetylsalicylic acid that possesses anti-inflammatory activity and that has been shown to decrease VCAM-1 expression in vitro

Low-calorie cranberry juice supplementation reduces plasma oxidized LDL and cell adhesion molecule concentrations in men,2008

CRANBERRY JUICE AND HIS USE IN DIABETIC PATIENTS TO PREVENT CVD

Moreover, Cranberry seems to have significant skills in reducing CVD risk factors in type 2 diabetic patients: type 2 diabetic patients are faced with a higher risk of dyslipidemia and cardiovascular disorders, due to, besides the other aspects, plasma/serum glucose level, Apo-lipo protein such as apoA-1, apoB, and the important anti-atherosclerotic enzyme Serum paraoxonase/arylesterase 1
Paraoxonase-1 (PON-1) is an HDL- associated enzyme and has been implicated in many anti- atherogenic processes, such as inhibiting LDL and HDL from oxidation and reducing macrophage cholesterol biosynthesis, attenuating cholesterol and oxidized lipid influx, and stimulating macrophage cholesterol efflux.
Trial findings leads to know that intakes of Cranberry Juice in tipe 2- diabetes patients decrease serum glucose and apo B concentrations and increase apoA-I and PON-1 activity;
this may be beneficial effect in reducing the risk of CVD in diabetic patients and, maybe, in other categories of patients aiming to fight CVD risk.

The effects of cranberry juice on serum glucose, apoB, apoA-I, Lp(a), and Paraoxonase-1 activity in type 2 diabetic male patients, 2012

CRANBERRY JUICE AND WARFARIN

Another interesting aspect concerning the daily use of cranberries relateds producs, such as Cranberry Juice predominantly, is the farmacodynamic interation with a very common drug used by patients with cardiovascular patologies: Warfarin.

Warfarin is one of the main anticoagulants prescribed: common clinical indications for warfarin use are atrial fibrillation the presence of artificial heart valves, deep venous thrombosis, and pulmonary embolism (where the embolized clots first form in veins). Warfarin is also used in antiphospholipid syndrome. It has been used occasionally after heart attacks (myocardial infarctions), but is far less effective at preventing new thromboses in coronary arteries.

It is apparent that consumption of large quantities of cranberry juice (about 1-2 L per day) or cranberry juice concentrates in supplements for an extended time period (>3-4 weeks) may temporally alter the effect of warfarin: cranberry juice may have the potential to interfere in the absorption, metabolism and/or excretion of warfarin via CYP enzymes, in particular CYP3A4 and CYP2C9.
In spite of the in vitro CYP inhibitions or Pgp inhibition produced by cranberry juice, there was no clinical translatability of the evidence in vivo. The summation of the pharmacodynamics data obtained in patients and healthy subjects from the various prospective and controlled clinical trials do not provide overwhelming support for a pharmacodynamic drug interaction with cranberry juice.

Cranberry juice ingestion and clinical drug-drug interaction potentials; review of case studies and perspectives, 2013