‘Remarkable findings’ reported in RCT on citrus and olive polyphenols for heart health

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Eight weeks of supplementation with a combination of citrus flavones and flavanones and olive polyphenols led to “remarkable” improvements in markers of heart health, report Spanish researchers.

Data published in Nutrients showed that the citrus-olive combination led to significant improvements in total cholesterol, LDL-C, and oxidized-LDL (ox-LDL) levels, as well as improvements in markers of inflammation.

Reductions of 40-45% in ox-LDL levels were described as “remarkable”, as were the 38-40% reduction in IL-6 (interleukin-6, a marker of inflammation) by scientists from the Universidad Católica San Antonio de Murcia (UCAM), Nutrafur iff-Health, and the Hospital General Universitario Reina Sofia.

“… the contribution of the active supplement to reduce IL-6 levels (38–40%) after a short-term period of treatment is clinically relevant and, to our knowledge, reduction of plasma levels of IL-6 of this magnitude has not been previously reported in intervention clinical trials with nutritional supplements,” they wrote.

The study used Nutrafur iff-Health’s Citroven ingredient containing a blend of extracts from immature citrus fruits, grapefruit and bitter orange plus an olive leaf extract.

Study details

The Spain-based researchers recruited 96 healthy volunteers to participate in their single-center, randomized, double-blind controlled trial. Participants were randomly assigned to consume either two capsules per day of either placebo or Citroven (500 mg per capsule). According to the researchers, the active supplement contained 250–300 mg of flavanone-glycosides, 175–200 mg of flavones, and 85–90 mg of olive polyphenols.

The results showed that, after eight weeks, flow-mediated vasodilation (FMD - a measure of a blood vessel's healthy ability to relax) increased by an average of 3% in the active group, compared to only 0.5% in the placebo group. The differences between the groups were statistically significant.

In addition, reductions in blood pressure (BP) were observed for both systolic and diastolic blood pressure, but statistical significance between the Citroven and placebo groups was only observed for diastolic blood pressure.

Blood lipid levels were also significantly improved as a result of consuming citrus flavones and flavanones and olive polyphenols, with total cholesterol levels decreasing by 13.57 mg/dL, compared to 6.38 mg/dL  increase in the placebo group. LDL- and HDL-cholesterol levels were also improved by -8.80 mg/dL and +1.65 mg/dL, respectively, while LDL levels increased and HDL levels decreased in the placebo group.

Oxidized-LDL (ox-LDL) were reduced by 342.84 pg/mL, a result that the researchers called “remarkable”.

“In relation to oxidative stress biomarkers, a 62–65% increase in GSH/GSSH ratio and a 30–32% reduction of the protein carbonyl level was obtained, which is consistent with a reduction of ox-LDL as biomarkers of cardiovascular risk reduction,” they added.

Looking at inflammation-related biomarkers, serum levels of IL-6 in the active product group significantly decreased from 1.49 pg/mL at the start of the study to 0.91 pg/mL after eight weeks, while no significant changes were observed in the placebo group.

“This study shows that supplementation with a combination of two citrus fruit extracts, grapefruit (Citrus paradisi Macfad) and bitter orange (Citrus aurantium L.), and one olive leaf extract (Olea europaea L.) during eight weeks improved endothelial function measured by FMD, reduced blood pressure and lipid metabolism-related parameters, and improved antioxidant and inflammatory status,” wrote the researchers.

“All these findings, taken together, suggest a beneficial effect of the nutritional supplement on underlying mechanisms that may interact each other to decrease the cardiovascular risk in healthy people. However, further randomized studies are needed to confirm the present results of this exploratory trial, in particular with a larger study population and consumption of the nutritional supplement over a longer period of time.”

Source: Nutrients

2020, 12(5), 1475; doi: 10.3390/nu12051475

“Effect of a Combination of Citrus Flavones and Flavanones and Olive Polyphenols for the Reduction of Cardiovascular Disease Risk: An Exploratory Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects”

Authors: M. Sánchez Macarro et al.