Several functions of HDL particles improved by Mediterranean diet
Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals - A Randomized Controlled Trial
Background
The biological functions of high-density lipoproteins (HDLs), such as cholesterol transport, HDL antioxidant properties and HDL vasodilatory capacity, contribute to explaining the cardioprotective role of the lipoproteins, beyond measuring levels only. Several nutrients and food that are part of a traditional Mediterranean diet (TMD) may improve these functions, as shown by previous trials [1-4].
However, no evidence of the effects of a whole TMD on HDL properties has been reported. Therefore, this study assessed whether long-term (1 year) consumption of a TMD, enriched with virgin olive oil or nuts, improved different biological functions of HDL in a random selection of PREDIMED study patients (n=296, 4.14% of total trial). 100 Patients received a TMD diet with supplementary virgin olive oil, 100 with supplementary nuts and 96 a low-fat control diet.
Main results
- Total cholesterol levels declined from baseline after low-fat control diet (P=0.039) and were lower compared to a virgin olive oil diet (P=0.007), as LDL decreased (P=0.019 and P=0.004 relative to baseline and virgin olive oil diet, respectively). HDL-c or Apo-A1 levels did not change. However, HDL-c/ApoA1 ratios significantly decreased in both nuts (P<0.001) and olive oil (P=0.031) enriched diets, relative to baseline.
- Cholesterol efflux capacity increased with both nuts (P=0.013) and olive oil (P=0.018) enriched diets, relative to baseline.
- HDL-c esterification index (ability of HDL particles to esterify cholesterol) increased after TMD diet with virgin olive oil, relative to baseline (P=0.007) and low-fat control diet (P=0.039). CETP activity decreased with virgin olive oil diet (P=0.008), relative to baseline.
- The HDL capacity to directly counteract LDL oxidation increased after the virgin olive oil enriched diet relative to baseline (P=0.004). The HDL inflammatory index (HII) increased from baseline after the low-fat control diet (P=0.025) but not with other diets. HII values after nut diet, relative to low-fat diet were borderline decreased (P=0.06).
- Production of nitric oxide in endothelial cells was not increased by HDL (HDL vasodilatory capacity) with any diet, compared to baseline. However, this was increased after the virgin olive oil diet relative to the low-fat diet (P=0.026).
- HDL oxidation index decreased after virgin olive oil diet and low-fat diet, compared to baseline (P=0.028 and P=0.011, respectively). HDL dynamic resistance against oxidation increased after virgin olive oil diet compared to baseline (P=0.006).
- Triglyceride content in HDL core decreased after both nuts and virgin olive oil diets, compared to low-fat diet (P=0.035 and P=0.027, respectively). Content of phospholipids at HDL surface increased after virgin olive oil diet compared to baseline (P=0.003) and low-fat control diet (P=0.036). Levels of ApoAI, ApoAII, ApoCIII in HDL were not changed.
- All three diets increased levels of large HDL particles from baseline (all P<0.001).
Conclusion
After 1 year, a TMD, especially the one enriched with virgin olive oil, improved several HDL functions, namely cholesterol efflux capacity, cholesterol metabolism, antioxidant/anti-inflammatory properties and vasodilatory capacity, in individuals at high cardiovascular risk. Further studies are warranted to investigate the mechanisms by which a TMD achieves this and whether this results in cardioprotective effects.
Editorial comment
Rader discusses the complexity of the role HDL in cardiovascular diseases in this editorial comment [5]. In this regard, he mentions the ‘HDL flux’ or ‘HDL function’ hypothesis, which “ concept is based on the idea that HDL has a number of putative antiatherogenic functions that may causally affect CVD risk but that are not directly related to simple measures of HDL mass such as HDL-C levels. The best established of the measures of HDL function is HDL cholesterol efflux capacity (CEC), an ex vivo measure of the ability of an individual’s HDL to promote cholesterol efflux from macrophages in cell culture. A number of studies have shown that HDL CEC is inversely associated with prevalent coronary artery disease and incident CVD events even independently of HDL-C levels. Although this is consistent with the concept of a protective effect, it is still only an association that is far from proof of causality.” He notes that interventions that increase CEC are one approach to establish a body of data that CEC could causally protect against atherosclerosis, but that this so far, didn’t yield any rigorous data. Therefore, this dietary study on CEC is of particular interest, he writes. Rader further discusses the results for the low-fat diet group, the differences between the three dietary groups and the mechanisms by which the TMD increases HDL CEC. And he also points out that “it is possible that the TMD, by enhancing HDL function, could slow the progression of AMD in addition to atherosclerosis.” His conclusion is “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 AMD. Whether promotion of HDL CEC causally contributes to the benefits of the Mediterranean diet remains to be established.”
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