It increasingly believed that HDL quality may be as important or even more so than total HDL cholesterol. We reported that HDL functionality can predict cardiovascular disease incidence in a general population (Sanllorente A, Eur J Prev Cardiol. 2022; Soria-Florido MT, Atherosclerosis 2020) and subjects at high cardiovascular disease (Soria-Florido MT, Circulation. 2020). We identified foods the consumption of which improve HDL function (Hernáez A, Mol Nutr Food Res. 2019). We reported that a Mediterranean Diet supplemented with extra virgin olive oil (i.e., PREDIMED study; PREDIMED-Plus study) can improve several HDL functional properties (Hernáez A, Circulation. 2017; Sanllorente A, Am J Clin Nutr. 2021). We also proved that such effect can be mediated by the polyphenol content of olive oil (Hernáez A, Arterioscler Thromb Vasc Biol. 2014). Additionally, transcriptomic studies have been conducted to discover the mechanisms underlying the improvement of HDL functionality (Hernando-Redondo J, Mol Nutr Food Res 2025).
In addition to cellular models used to assess the cardioprotective properties of HDL, standardized models have also been developed to evaluate its neuroprotective functions. Dr. Olga Castañer, awarded by a fellowship from the Global Brain Health Institute, uses these models to explore potential dementia risk factors linked to cardiovascular risk, in alignment with her current research on diet and neurodegeneration. It has been shown that the Mediterranean diet downregulates transcriptomic pathways associated with neuroinflammation, which may influence the development of neurodegenerative diseases (Almanza E, Nutr Neurosci, 2020).
Research is also focusing on the genetic basis of these traits and their causal relationship with cardiovascular disease (Sayols-Baixeras S, Arterioscler Thromb Vasc Biol 2017).
The European Food Safety Authority (EFSA) approved one health claim regarding the protective effects of olive oil phenolic compounds against low-density lipoprotein (LDL) oxidation (EFSA Journal, 2011; 9(4):2033). This approval was mainly based on evidence from the EUROLIVE European study, coordinated by Dr. Covas, which demonstrated the benefits of extra virgin olive oil compared with common olive oil on LDL oxidation (Covas MI, Ann Intern Med, 2006; Covas MI, Free Radic Biol Med, 2006).
Furthermore, we demonstrated that triglyceride-rich lipoproteins are associated with cardiovascular risk, potentially due to their high remnant cholesterol content resulting from the larger size of these lipoproteins (Castañer O, J Am Coll Cardiol. 2020; Hernando-Redondo J, EurJ Prev Cardiol 2026) and that the atherogenicity of LDL could be a residual cardiovascular risk beyond lipoprotein levels (Hernando-Redondo J, Curr Opin Lipidol 2025).
We also found that a Mediterranean diet (Hernáez A, PLoS ONE 2019; Hernáez A, Mol Nutr Food Res 2017) and phenolic compounds of olive oil (Hernáez A, J Nutr. 2015) have a role in decreasing LDL cholesterol concentrations and LDL atherogenicity.
Omega-3 fatty acids (fish, walnuts) are one of the most explored dietary factors in relation to cardiovascular disease. There is an increasing interest in whether they also can promote brain health. Dr. Aleix Sala uses lipidomics to measure omega-3 and other dietary biomarkers in blood and other tissues. We have reported that high blood omega-3 status at the time of a heart attack is related to a lower risk of major adverse cardiovascular events during the next 3 years (Lázaro I, J Am Coll Cardiol. 2020); and that in patients with heart failure, those with lower levels of a specific plant-derived omega-3 have a worse mid-term prognosis compared to those with higher levels (Lázaro I, J Am Coll Cardiol. 2022). He is collaborating with Fundació Pasqual Maragall to explore the link between omega-3 and Alzheimer's disease.
The line of research has recently been expanded following the collaboration agreement between Dr. Iolanda Lázaro and the LiverKids Study. The aim is to study the role of fatty acids in children and adolescents in MASLD, in this study that uses non-invasive imaging techniques in children and adolescents to achieve an early diagnosis of fatty liver disease associated with metabolic dysfunction (MASLD).
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