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Mediterranean blend designed for cardiovascular protection

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Mediterranean blend designed for cardiovascular protection

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A healthy heart is progressively more recognized as a crucial part of healthy ageing.

Consumers are increasingly taking greater ownership of their health, tending to a long-term, preventative approach as opposed to more reactive treatments of ailments. People see health as a crucial part of their wellbeing and are taking responsibility for their own health. Therefore natural supplements that help them ward off damage and disease in later life, are likely to grow.

This is a good opportunity for botanicals with heart health benefits, which are mostly for prevention rather than treatment. They help consumers keep their heart and vascular system in shape, in a natural way.

Cardiovascular disease - A multifactorial problem

Cardiovascular disease (CVD) is a major public health problem contributing substantially to morbidity, mortality, and escalating health care costs throughout the world. In the 2017 European cardiovascular statistics, CVD was the main cause of death, accounting for 45% of all deaths in Europe(1)​. Despite advances in treatment and preventive measures(2) ​, an aging global population and the increased prevalence of diabetes and obesity, CVD deaths are still on the rise(3)​.

CVD is often multifactorial. People suffer from elevated blood pressure, raised cholesterol, high blood glucose, blood clotting problems. These pathologies are all considered modifiable risk factors, that are prevalent in most populations and often coexist.

Improving one or more of these modifiable risk factors in an individual reduces overall cardiovascular risk and thereby reduces CVD mortality and morbidity(4)​. As a result, patients with elevated cardiovascular risk are often prescribed a range of medications to tackle each pathology separately and sometimes extra medication to counter the side effects of the drugs.

The pharmaceutical industry has worked on a way to avoid this; the so called "polypill”. Polypills use fixed-dose combinations of cholesterol- and blood pressure–lowering drugs, several ingredients commonly used to treat heart disease.

Combining several anti-hypertensive drugs at low doses simultaneously targets multiple risk factors for the prevention of cardiovascular events and it is likely more effective and has fewer side-effects than high-dose therapy with a single drug(5)​.

The role of diet is crucial in the development and prevention of CVD, and there is ever more convincing evidence of the favorable effects of the Mediterranean diet in people at high cardiovascular risk(6,7)​. This is why dietary recommendations have been systematically included in clinical practice guidelines on the prevention of CVD (8,9)​. But even during high adherence to the Mediterranean diet, dietary intake of flavonoids and polyphenolic compounds is still low. Epidemiological studies calculated an average dietary intake of flavonoids of merely 20–40 mg/day, which is below requirements for a preventive-dose relationship(10)​. This is where nutritional supplements can be useful to ingest these active compounds in standardized doses that are shown to be appropriate and effective.

There is a rise in strategic natural extract blends, working on even more aspects of cardiovascular protection, and leveraging these complementary actions to support cardiovascular health in a more convenient and more cost-effective way.

A growing interest in natural health solutions means consumers are looking for natural ingredients that can provide similar benefits as pharmaceutical polypills and have beneficial effects on several cardiovascular risk factors.

An ideal synergistic blend should work on supporting cholesterol reduction (or more importantly LDL-cholesterol oxidation), blood pressure regulation as well as inflammation, blood clotting and endothelial function. Clinical efficiency studies will validate the effects and help determine the lowest and most convenient dosage.

The road towards the ideal blend for heart health

Benolea is an olive leaf extract (olea europaea​), acting on several targets of cardiovascular function, namely blood lipid profile and blood pressure regulation. Clinical studies have shown that Benolea is effective at supporting a healthy blood pressure.

Experiments in rats had shown that Benolea leads to a normalization of blood pressure in rats with established hypertension as well as prevented the experimentally induced rise in blood pressure(11)​.

A randomized, controlled clinical trial in monozygotic twin pairs with slightly elevated blood pressure showed it significantly reduced blood pressure after six weeks, in the twin receiving 500mg of Benolea, with a maximal difference between treatment and control of up to 6 mmHg systolic and 5 mmHg diastolic pressure, respectively. A dose increase to 1000 mg Benolea enhanced the effect to a difference of up to 13 mmHg systolic and 5 mmHg diastolic pressure(12)​.

In a double-blind, controlled study the anti-hypertensive effect of Benolea was compared to captopril, a standard therapy for individuals with stage 1 hypertension(13)​. After 8 weeks, both patients receiving 500mg Benolea and those receiving captopril, experienced a significant decrease in systolic and diastolic blood pressure with a comparable effect.

Benolea may work two mechanisms to support a healthy blood pressure. First, it may promote the production of nitric oxide (NO), an important vasodilator. NO can relax the vascular smooth muscles, decreasing blood pressure. Second, the other phenolic substances found in olive leaves can inhibit angiotensin converting enzyme (ACE), decreasing the formation of angiotensin II. Together this can bring about a systematic dilation of blood vessels, further decreasing arterial blood pressure.

Interestingly, in addition to the anti-hypertensive effect, a significant reduction of LDL-cholesterol was observed in the groups consuming Benolea. Such effects were not observed with captopril.


CitroVen Graph 1 Blood pressure & 2 LDL cholesterol levels - green

Figure 1a: Decrease of systolic blood pressure from baseline (*p<0.05, significant differences between groups based on statistical analysis). 1b: Reduction of mean LDL-C concentration compared to baseline, after 4 and 8 weeks of intervention, respectively. Data represent means ± SEM of LDL-C differences within twin pairs of group 1 (500 mg Benolea vs. control) and group 2 (500 vs 1000 mg Benolea) (* p<0.05, significant difference)

Inspired by the positive outcomes of these clinical studies on two major risk factors of CVD, the team developed a specialized blend, CitrOlive. It is a unique and patented synergistic blend of citrus and olive extracts; the combination of the key olive polyphenols oleuropein and hydroxytyrosol with citrus flavonoids from bitter orange (citrus aurantium​) such as naringin and neohesperidin gives CitrOlive a robust antioxidant and anti-inflammatory effect.

CitrOlive has been shown to reduce postprandial triglyceride levels after an oral fat load in animal trials(14)​.

A double-blind trial in humans confirmed this sustained triglyceride-lowering of about 15% after taking a 500 mg supplement of CitrOlive for three months (15)​. Elevated fasting and postprandial triglyceride levels are linked to a higher cardiovascular risk.

Finally, the citrus and olive extract blend successfully decreased oxidized LDL by 38% (p<0.05) in subjects with elevated cholesterol(15)​.

Oxidation of LDL is increasingly used as a marker for cardiovascular risk. The oxidation of LDL occurs after exposure to free radicals which destabilize the LDL molecule. The oxidized LDL itself then becomes reactive with the surrounding tissues. Oxidized LDL plays an important role in atherogenesis by triggering inflammation and lipid deposition in the blood vessel walls(16)​.


CitroVen Graph 3 LDL cholesterol oxidation - green

Figure 2: Change in LDL-C oxidation after 3 months of supplementation of placebo or CitrOlive

Recently the researchers at IFF Health developed a new Mediterranean blend, designed to support multiple aspects of cardiovascular health. The blend called CitroVen has a combination of a few major phytochemicals, providing a synergistic activity on cardiovascular health by combining olive (Olea europaea​), grapefruit (Citrus paradisi​) and bitter orange (Citrus aurantium​) in one product.

It delivers the protective phytonutrients of the Mediterranean diet in a tailor-made optimized blend for support of cardiovascular health.

A recent proprietary clinical study revealed a decrease in oxidized LDL levels (-42%) and an increase in endothelium-dependent vasodilatation (+45%) as compared to baseline levels in healthy subjects, after taking CitroVen daily for 8 weeks(17)​.

Endothelial function has increasingly been recognized as an important prognostic marker for cardiovascular disease, and markers for endothelial dysfunction can point to an early stage of atherosclerosis.

Additionally the clinical study showed CitroVen activity as an anti-oxidant and had positive effects on blood pressure, blood cholesterol and markers of inflammation.


CitroVen Graph 4 LDL cholesterol oxidation & 5 Endothelial function - green

Figure 3: Change in LDL-c oxidation and endothelium-dependent vasodilatation after 8 weeks of supplementation of placebo or CitroVen

Consumers are drawn by ingredients rooted in traditional use, like those from the Mediterranean diet. Not only do they have a long history of use, but it helps consumers feel more connected to their health in a holistic way.

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