Mediterranean Diet With Olive Oil Boosted HDL Function: PREDIMED study

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Mediterranean Diet With Olive Oil Boosted HDL Function: PREDIMED
Patrice Wendling February 13, 2017

BARCELONA, SPAIN — More research suggests that a Mediterranean-style diet supplemented with either virgin olive oil or mixed nuts enhances the function of HDL cholesterol[1].

In a subset of 296 patients at high risk of heart disease in the PREDIMED study, cholesterol efflux capacity (CEC), the first step in reverse cholesterol transport, was significantly increased at 1 year compared with baseline in those advised to eat a Mediterranean diet rich in virgin olive oil (VOO) (P=0.018) or mixed nuts (P=0.013) rather than a reduced-fat diet.

In addition, both Mediterranean-diet groups had a trend toward improved antioxidant and endothelial functions of HDL, although the changes were statistically significant only in the Mediterranean diet–VOO group.

“For that reason, we say that especially when the Mediterranean diet is supplemented with virgin olive oil, the HDL quality and function is better,” senior author Dr Montserrat Fito? (Hospital del Mar Medical Research Institute of Barcelona and CIBEROBN Institute, Spain) told heartwire from Medscape.

She noted that the differences in results between the diets were relatively small because the control diet was a healthy one, but smaller studies have also shown that antioxidant-rich foods like olive oil, tomatoes, and berries improve HDL function.

A number of medications that raise HDL-cholesterol levels have failed to improve patient outcomes, although data are not available for HDL function. The landmark PREDIMED study showed that a Mediterranean diet could cut the risk of cardiovascular events by as much as 30%. Exactly how the diet did so isn’t entirely clear.

“From a public-health standpoint, it may not matter—the diet is safe and effective in preventing disease, but from a scientific standpoint it’s really a fascinating question,” Dr Amit V Khera (Massachusetts General Hospital, Harvard Medical School, Boston, MA), who was not involved in the study, told heartwire .

Based on research by Khera and other HDL experts, the prevailing belief is that HDL-C levels are a crude measure of the particles’ function in the body. Notably, HDL-C levels in the present analysis trended lower with all three diets, even as the Mediterranean diets significantly increased CEC, the best-established HDL functionality parameter.

“I expect there will numerous cases where they [PREDIMED investigators] are able to show that the Mediterranean diet improved a circulating biomarker. But which of these changes were responsible for cutting the cardiovascular risk by 30%? It is almost impossible to tell,” Khera commented.

He added, “Nevertheless, the investigators performed careful phenotyping of several HDL functional parameters. This raises the possibility that we might use a panel of such functional parameters when we are looking at new potential therapeutics to help predict which are most likely to have benefit in clinical trials.”

The findings were reported online today in Circulation.

A Small Subsample

The investigators examined stored blood samples from 4% of the 7557 PREDIMED patients (mean age 66 years) before and after 1 year of randomization to a Mediterranean diet supplemented with 4 tbsp of VOO, about a handful of nuts each day, or a low-fat diet.

At 1 year, all three diets increased the percentage of large HDL particles from baseline (P<0.001). Adherence to the Mediterranean diet supplemented with VOO also:

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Decreased cholesteryl ester transfer protein activity (P=0.008 vs baseline; NS vs low-fat diet). Increased the ability of HDL particles to esterify cholesterol (P=0.007 vs baseline; P=0.039 vs low-fat

Increased the arylesterase activity of paraoxonase-1 (NS vs baseline; P=0.012 vs low-fat diet).

Increased HDL vasodilatory capacity through the production of nitric oxide in endothelial cells (NS vs baseline; P=0.026 vs low-fat diet).

When asked why the Mediterranean diet rich in nuts did not have similar effects, Fito? told heartwire , “Olive oil is a very complex food enriched with antioxidant compounds, and our hypothesis is that the antioxidant state and anti-inflammatory state of HDL is improved, and then this particle is more functional.”

She added, “In the case of nuts, they are very rich in omega-3 and very beneficial for other questions, for example, arrhythmias or the lipid profile in general. But in this study for HDL function, we observed a higher benefit when the Mediterranean diet was enriched with olive oil.”

Fito? said they were surprised that the low-fat diet, which was also rich in fruits and vegetables, had a negative impact on HDL’s anti-inflammatory properties, increasing the HDL inflammatory index relative to baseline (P=0.025). The index did not rise with the Mediterranean-diet interventions.

In an accompanying editorial[2], HDL expert Dr Daniel J Rader (University of Pennsylvania, Philadelphia) writes that alcohol consumption may account for some of the observed differences. The Mediterranean-diet groups were told to drink one small glass of red wine per meal when consuming alcohol, but no such instructions were given to the low-fat diet group.

He suggests that other HDL measures may also provide clues as to how the Mediterranean-diet intervention increases CEC. For example, the ratio of HDL-C to apolipoprotein A-1 was significantly decreased only in the Mediterranean-diet groups, suggesting a reduction in core cholesteryl ester relative to surface apolipoprotein A-1. This could signal an increase in hepatic activity of the scavenger receptor class B-1, which promotes CEC and overall reverse cholesterol transport.

“It is intriguing to speculate that [the Mediterranean diet] may result in upregulation of hepatic scavenger receptor class B-1, which would be consistent with many of the findings,” he adds.

Rader also notes that cholesterol esterification, a function of the enzyme lecithin-cholesterol acyltransferase (LCAT), was improved after the Mediterranean diet-VOO diet and that increased LCAT activity is thought to promote reverse cholesterol transport and to potentially be antiatherogenic.

HDL phospholipid content, an important determinant of HDL CEC, was also increased in the Mediterranean diet-VOO group compared with the low-fat diet group.

Rader concluded, “Although efforts to promote HDL CEC through pharmacological means are still in development, these results indicate that a Mediterranean diet is a practical lifestyle-focused approach to improving HDL function and has the proven benefit of reducing cardiovascular risk and the potential to reduce the progression of [age-related macular degeneration] AMD.”

The study was funded by Age?ncia de Gestio? d’Ajuts Universitaris i de Recerca, the Instituto de Salud Carlos III, the Spanish Ministry of Education, Culture, and Sport, and the European Development Fund (ERDF). The researchers and Khera report no relevant financial relationships. Rader is a founder of VascularStrategies.

Follow Patrice Wendling on Twitter: @pwendl. For more, follow us on Twitter and Facebook. References

1. Herna?ez A, Castan?er O, Elosua R, et al. Mediterranean diet improves high-density lipoprotein function in high-cardiovascular-risk individuals: a randomized controlled trial. Circulation 2017; 135:633-643.

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2. Rader DJ. Mediterranean approach to improving high-density lipoprotein function. Circulation 2017; 135:644-647. Editorial

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