Many epidemiological studies have suggested that diets high in fruit and vegetables protect against cardiovascular disease. However, attributing this beneficial effect to single components or classes of phytochemicals has been less well reported and attempts to dissect these from dietary intervention studies have proved both complex and contradictory.

This apparent lack of progress beyond the global statement that “fruit and vegetables help reduce the incidence of cardiovascular disease” is often a result of the complexity of both human diets metabolism/biochemistry and the phytochemical complexity of fruit and vegetables themselves.

To identify which phytochemicals are eliciting the beneficial effects we are collaborating with leaders in the fields of cardiovascular biomedical and clinical research.

Cardiovascular disease is an encompassing terms used to cover disease and their processes and progression. Coronary artery disease, stroke, peripheral vascular disease and hypertension, amongst others, are all examples of cardiovascular disease. Atherosclerosis, a pathological process whereby the arteries thicken (or narrow) leading to elevated blood pressure and ultimately rupture and often death, arises primary due to damage to, or malfunction of the innermost layer of the artery: the endothelium.

One of the key factors leading to endothelial damage is oxidative stress a condition that can arise due to a combination of factors; poor diet, lack of exercise, smoking, illness, trauma in the broadest sense, can all be contributory factors. Oxidative stress interrupts and/or corrupts many of the body’s natural processes leading to the generation of many deleterious and damaging reactions; protein denaturing and precipitation, DNA modification, lipid oxidation and the generation of reactive oxygen species (ROS).

Endothelial cells are particularly susceptible to oxidative stress not only through ROS-mediated cell death but also because the bioavailability of the normally protective mediator, nitric oxide (NO), is compromised through its very rapid reaction with superoxide anion, which is a highly reactive and damaging chemical. Logic dictates that if we elevate the level of antioxidants in our diet and they are bioavailable, that is they can get into the blood stream and subsequently to the other tissues, then they can restrict the damage of oxidative stress and cardiovascular disease and thereby positively influence health.

Collaborations with the Dr Carlene Hamilton, British Heart Foundation Glasgow Cardiovascular Research Centre, into the efficacy of fruit phytochemicals as superoxide scavenger components have shown that the polyphenol enriched extracts of Rubus (predominantly ellagitannins (Figure 1) showed significantly better scavenging ability (Figure 2) than equivalent amounts of vitamin C or other dietary polyphenols, sulphate and glucuronide metabolites of quercetin.

Figure 1: A Raspberry Ellagitannin

Figure 2: Superoxide scavenging ability of Rubus polyphenols in a rat arterial model
The raspberry extract was compared against the common fruit antioxidant, Vitamin C as well as two metabolites (a sulphate and glucuronide) generated following consumption of quercetin, an polyphenolic antioxidant routinely found in many fruit and vegetables(for example, onions).

Subjecting the extracts to a digestion process that closely mimics our own digestion system showed that these polyphenols were robust enough to exhibit significant extensive superoxide scavenging capacity (Figure 3). In addition to these superior superoxide scavenging abilities the Rubus extracts were potent stimulators of nitric oxide (NO), an important molecule responsible in part for maintaining arterial flexibility (Figure 4). In fact on an equivalent activity basis the amount of Rubus extract required to achieve this was significantly less than Vitamin C or other dietary polyphenols.

Figure 3: In vitro digestion of a raspberry extract had only a slight effect on the superoxide scavenging capacity

Figure 4: Impact of raspberry polyphenolics on Nitric oxide bioavailability in an arterial model system: RE – raspberry extract, QG-quercetin-glucuronide, QS – Quercetin-sulphate

Our research on phytochemicals and cardiovascular disease is also translating through to the clinical level. A project funded by Chest, Heart and Stroke Scotland and in collaboration with Professor Jill Belch’s group at the Vascular Diseases Research Unit, University of Dundee, is currently trying to determine the specific effect that Vitamin C and fruit polyphenolics have on markers of cardiovascular disease.

This project aims to evaluate the effects of three different antioxidant-containing fruits (high and low Vitamin C containing blackcurrant fruit and blueberries (virtually zero Vitamin C) on surrogate markers for cardiovascular disease, via dynamic tests of endothelial function, and blood markers for endothelial function in oxidative stress. A no fruit group (flavoured coloured water) will provide a negative control. Within the project Professor Belch’s group are dealing with the intervention and surrogate markers whilst we are analysing the plasma samples for new biomarkers, indications of reduced oxidative stress and to determine the metabolic fate of the fruit phytochemicals.