Review Article

Is Extra Virgin Olive Oil an Ally for Women’s and Men’s Cardiovascular Health?

Table 3

Clinical studies on the effect of EVOO, VOO, OO, leaf extracts, and MPCs.

CompoundsIndividualsDesignMain dataReferences

High MPC EVOO vs moderate and low MPC EVOO200 healthy menMulticenter RC crossover designThe negative association between the oleic/linoleic acid ratio and biomarkers of oxidative stress and improvement of LDL fatty acid profile[296]
EVOO vs saturated fat diet18 healthy postmenopausal womenProspective, longitudinal, studyEVOO decreases the risk to develop the metabolic syndrome and CAD[297]
EVOO vs soya oil41 adult women with excess body fatDouble-blinded RC vs placeboEVOO increases fat loss and reduces DBP and some biochemical parameters[298]
High MPC EVOO vs low MPC EVOO9 men and 11 women with metabolic syndromeRC sequential crossover designAfter EVOO-based breakfast, numerous inflammatory genes involved in factor NF-κB, AP-1, MAPK, and AA pathways are repressed in PBMC[299]
High MPC VOO vs intermediate and low VOO19 men and 30 women with metabolic syndromeRC, crossover designHigh MPC VOO-based breakfast attenuates plasma LPS, TLR4, and SOCS3 proteins, activation of NF-κB and the IL-6 vs low and intermediate oil. In PBMC, postprandial expression of IL-1B, IL-6, and CXCL1 is reduced especially by high MPC VOO[300]
High MPC EVOO vs low MPC EVOO6 healthy men and 6 healthy women; 6 men and 6 women with metabolic syndromePaired studyAcute high MPC EVOO transiently improves glycaemia and insulin sensitivity. It directly modifies the miRNA of PBMC. Acute EVOO poor in MPC is less effective[278]
EVOO vs ROO14 healthy and 14 hypertriacylglycerolemia menBlind RC crossover designEVOO has postprandial anti-inflammatory effects[301]
EVOO26 male and 34 female DM2 patientsRC trialBoth atorvastatin and EVOO reduce plasma lipids and increase HDL with a higher activity of atorvastatin[302]
EVOO17 males and 13 females with impaired fasting glucoseBlind RC crossover designAfter EVOO meal, glucose, TG, ApoB-48, and DPP4 activity decrease, whereas insulin and GLP-1 increase vs meal without EVOO. Chol and HDL do not change after EVOO meal vs meal without EVOO[303]
EVOO vs coconut oil vs unsalted butterHealthy women (67%) and men (33%)RC trialNo changes in BW, BMI, central adiposity, fasting blood glucose, SBP, and DBP for all diets. Butter increases LDL; coconut increases HDL[304]
EVOO vs VOO41 males and females (overweight or obese)Single-blinded RCEVOO decreases SBP and increases anti-CD3/anti-CD28 stimulated T cell proliferation vs VOO[305]
VOO rich in MPC vs ROO11 women at stage 1 of essential hypertension or 13 with normal-high BPDouble-blind RC crossover designVOO rich in MPC decreases SBP, DBP, CRP, LDL, ADMA and increases nitrites/nitrates and hyperemic area after ischemia[306]
Diet enriched with VOO, walnuts, or almonds9 female and 9 male hypercholesterolemic patientsRC crossover designThe VOO, walnut, and almond diets reduce LDL; They reduce LDL, Chol, and LDL/HDL ratio. Other lipid fractions, oxidation, and inflammatory biomarkers do not change[307]
OO rich in MPC vs OO + EGCGPatients with endothelial dysfunction, OO rich in MPC (13 men and 15 women) OO + EGCG (10 men and 14 women)Double-blinded RCThey reduce endothelial dysfunction, but only OO reduces inflammatory biomarkers, white blood cells, monocytes, and lymphocytes[308]
OO enriched with oleanolic acid (OA) vs OO176 individuals of both sexes with impaired fasting glucose and impaired glucose toleranceMulticenter double‐blind RC trialThe intake of OO rich in OA reduces the risk of developing DM in individuals with impaired fasting glucose and impaired glucose tolerance[309]
MedDiet + EVOO vs MedDiet + nut vs control7447 old participants of PREDIMED (43% men and 57% women) at risk for CVDObservational study in primary preventionLong intake of MedDiet + EVOO and MedDiet + nut reduces primary CV events[11]
High MPC EVOO vs moderate and low MPC VOO18 healthy menDouble-blind RC, crossover designHigh PMC EVOO reduces SBP vs basal values and low PMC VOO. It maintains DBP values compared to low MPC VOO. Further, it reduces ACE and NR1H2 gene expressions vs basal and IL-8RA vs low PMC MPC[310]
MeDiet + EVOO vs MeDiet + washed EVOO vs habitual diet26 healthy men and 64 healthy womenRC crossover designIn plasma, MedDiet + EVOO reduces oxidative and inflammatory status. In PBMC, it reduces oxidative stress, the gene expression of INF-γ, Rho GTPase-activating protein 15, IL-7 receptor, adrenergic β2 receptor and polymerase (DNA-directed) k. These effects with the exception of polymerase (DNA-directed) κ are more elevated when EVOO rich in polyphenols was added[311]
High MPC EVOO vs low MPC EVOO46 healthy subjects (14 men and 32 women)RC crossover designNo effect on fasting plasma lipids, oxLDL, and LPO[106]
EVOO vs refined OO24 menRC crossover designOnly EVOO rich in MPCs lowers oxLDL being ineffective vs plasma lipids[312]
High MPC VOO vs moderate and low MPC VOO18 healthy menRC crossover designHigh MPC VOO reduces oxLDL MPC-1, CD40L, IL-23A, IL-7R, IL-8RA, ADRB2, and OLR1 genes, whereas IFNG, IL-7R, IL-23A, CD40L, MCP-1, and IL-8RA decrease with low MPC VOO[313]
High MPC VOO + triterpenes (OVOO) vs OVOO + higher MPC and triterpenes (FOO) vs low MPC and triterpenes (VOO)27 healthy men and 26 healthy womenDouble-blind RC, crossover designUrinary 8-hydroxy-2′-deoxyguanosine, plasma IL-8, and TNF- α decrease more after FOO vs OVOO[314]
High MPC VOO + triterpenes (OVOO) vs OVOO + higher amounts of MPC and triterpenes (FOO) vs low MPC and triterpenes (VOO)27 healthy men and 26 healthy womenDouble-blind RC, crossover designAfter OVOO, HDL increases only in females. Chol increases after FOO and TG after VOO and OVOO. SBP decreases after the VOO and increases after the FOO. DBP and pulse pressure do not vary as well as LDL, sICAM-1, and sVCAM-1. Plasma ET-1 decreases after the VOO, OVOO, and FOO[315]
VOO, VOO + MPC (FVOO), VOO + MPC + Thyme phenols (FVOOT)Hypercholesterolemic men and womenDouble-blind RC crossover designAcute and sustained intake of VOO and FVOO attenuate PON1 protein and increase PON1-associated specific activities, while FVOOT has opposite effects. Only VOO increases PON3 protein[316]
VOO vs VOO + MPC (FVOO) vs VOO + MPC + Thyme phenols (FVOOT) Hypercholesterolemic volunteers: 5 women and 7 menDouble-blind RC, crossover designFVOOT reduces serum oxLDL and elevates gut bifidobacteria vs VOO. FVOO does not change blood lipids and microbial populations but elevates the coprostanone vs FVOOT[317]
VOO vs VOO + MPC (FVOO) VOO + MPC + Thyme phenols (FVOOT)Hypercholesterolemic volunteers:19 men and 14 womenDouble-blind, RC crossover designUrinary HTyr sulfate and thymol sulfate increase after FVOO or after FVOOT, respectively. FVOO and FVOOT do not change glycaemia, TG, LDL, HDL, ApoAI, and ApoB100 vs VOO with the exception of LDL that decreases after FVOO. FVOO and FVOOT change the lipoprotein subclasses profile and decrease insulin resistance index. BP and BMI do not change[318]
VOO vs VOO + MPC (FVOO)Prehypertensive or stage 1 hypertension participants (7 men and 6 women)Double-blind RC crossover designFVOO decreases ischemic reactive hyperemia, oxLDL, postprandial glycaemia, TG, PAI-I, and CRP vs VOO[319]
VOO vs VOO + MPC and VOO + Thyme8 men and 14 women hypercholesterolemic subjectsDouble-blind, RC crossover designIn PBMC, the intake of enriched VOO and VOO + thyme increases the expression of proteins involved in Chol efflux and nuclear receptor-related genes[320]
VOO vs VOO + MPC (FVOO) and VOO + Thyme (FVOOT)Hypercholesterolemic subjects: 19 men and 14 womenDouble-blind, RC crossover designThe 2 enriched oils elevate antioxidants in HDL, whereas α-tocopherol is elevated only after FVOOT[321]
VOO vs VOO + MPC vs VOO + MPC + Thyme phenols19 hypercholesterolemic men and 14 womenDouble-blind RC crossover designTheir consumption of each oil affects the HDL proteome in a cardioprotective mode[322]
Diets with VOO and refined OO vs sunflower or corn oil during washout period24 young women with high-normal BP or stage 1 essential hypertensionDouble-blind RC crossover designOnly VOO decreases SBP and DBP, serum asymmetric dimethylarginine, oxLDL, and CRP. It increases the plasma nitrites/nitrates ratio and hyperemic area after ischemia[306]
High MPC OO enriched breakfast vs low MPC OO breakfast5 hypercholesterolemic men and 16 womenRC design sequential crossoverAfter the high MPC breakfast, FVIIa increases less and PAI-1 activity decreases more than after the low MPC breakfast[169]
OO rich in MPC vs refined OO69 healthy participants of both sexesDouble-blind RC parallel designBoth OO improve the urinary proteomic CAD score but not chronic kidney disease or DM proteomic biomarkers. No differences are measured between the two OO[99]
OO with high vs OO with moderate MPCpre/hypertensive patients 17 men and 6 womenRC crossover designIn white blood cells, high MPC OO increases gene expression of ATP binding cassette transporter-A1, scavenger receptor class B type 1, PPARα, PPARγ, PPAR δ, and CD36 vs moderate MPC OO[323]
High MPC OO vs moderate MPC and low MPC OO30 healthy subjects of unknown sexDouble-blind RC vs placebo- crossover designThe consumption of oil rich in MPCs increases MPCs in LDL-C and decreases oxLDL[324]
High MPC OO vs moderate and low MPC OO12 healthy male subjectsDouble-blind RC, crossover designAll OO promote postprandial increase in F2-isoprostanes whereas the LDL oxidation is inversely linked with MPCs[325]
High MPC OO vs moderate and low MPC OO200 healthy menRC crossover designHDL and Chol increase and decrease linearly with the MPC amounts, respectively. OxLDL and MPC amount are inversely related. TG decrease is not influenced by MPC amount[325]
High MPC OO vs low MPC OO10 menopausal healthy womenRC design crossoverMPC-rich OO diet reduces DNA damage vs low MPC OO whereas plasma antioxidant capacity does not diverge[326]
High MPC OO vs moderate and low MPC OO12 male healthy subjectsDouble-blind, RC crossover designShort-term consumption of MPC-rich OO decreases plasma oxLDL, urinary 8-oxo-dg and increases plasma HDL and GPx vs moderate and low MPC OO[327]
High MPC OOPatients with polymorphism in NOS3 Glu298Asp (rs1799983) of eNOS (22 men, 35 women)RC sequential crossover designSingle administration seems to reduce the deleterious effect of the T allele carrier’s condition[328]
High MPC OO vs moderate and low MPC OO30 healthy men from a religious centerRC, crossover designMPC-rich OO is more effective in protecting LDL oxidation and in raising HDL than OO with lower quantities of MPCs[15]
High MPC OO vs low MPC OO22 mildly dyslipidemic subjectsRC crossover designMPC-rich OO lowers plasma TXB2 and elevates plasma antioxidant capacity vs low MPC OO. Urinary F2-isoprostanes and plasma lipids do not diverge between the two groups[329]
High MPC OO vs low MPC OO enriched breakfast21 hypercholesterolemic subjects (5 men and 16 postmenopausal women)RC crossover designHigh MPC OO protects against postprandial endothelial dysfunction and decreases lipid peroxide and F2-isoprostanes vs low MPC OO[330]
High MPC OO vs low phenolic OO28 individuals with CHD (sex not reported)Double-blind RC placebo-controlled, crossover designEnriched OO decreases IL-6 and CRP being ineffective on soluble sICAM-sVCAM-1 and lipid profile[331]
High MPC OO vs low MPC OO vs corn oil12 healthy menThe study has a Latin square designEnriched OO decreases TXB2 and LTB4 and increases plasma antioxidant capacity[332]
High MPC OO vs low MPC OO40 men with stable CIDRC crossover designMPC-rich OO decreases oxLDL and LPO and increases GPx[333]
OO vs sunflower-seed vs and rapeseed18 healthy menDouble-blind RC crossover designPostprandial lipid and lipoprotein concentrations are not greatly affected versus rapeseed and sunflower-seed oil, while rapeseed and OO diets have the same effect on LDL oxidation[334]
OO18 healthy menRC crossover designOO may attenuate the acute procoagulant effects of fatty meals[335]
OO8 men and 5 women with type DM2Single-blinded RC crossover designIt increases in GLP-1 and GIP[336]
OO (unrefined)23 hypertensive patients of both sexesDouble-blind RC crossover designResting SBP and DBP are significantly lower at the end of the MUFA diet vs the PUFA diet. The cold pressor test and isometric exercise are similar. Daily drug dosage is significantly reduced during the MUFA vs PUFA diet[337]
High MPC OO vs low MPC OOHealthy smokers: 11 men and 14 womenSingle-blind RC crossover designPlasma antioxidant capacity and oxLDL do not differ significantly between the rich and low MPC OO[18]
High MPC OO (HPCOO); low MPC VOO low-MPCOO (LPCOO), refined OO25 healthy menRC parallel, crossover, designHPCOO decreases ApoB-100 and small LDL particles vs baseline and LPCOO. LPCOO increases previous parameters. HPCOO increases the lag time of LDL oxidation, which is not affected by LPCCO. LPL gene expression is not significantly changed by both OO[338]
High MPC OO (HPCOO); VOO low MPC OO (LPCOO); refined OO47 healthy menRC crossover designHPCOO increases HDL cholesterol efflux capacity vs the LPCOO and incorporation of MPC and their metabolites in HDL and HDL2. HPCOO intake decreases HDL3 and the HDL core becomes TG-poor, and HDL fluidity increased[339]
HTyrHealthy subjects (12 men and 16 women)Double-blinded, RC crossover designRegular intake of HTyr improves the antioxidant defense and decreases nitrate and MDA[340]
HTyr21 healthy volunteers (sex not reported)Double-blinded, RC crossover designIn PBMC, it induces miR-193a-5p, which leads to the generation of anti-inflammatory molecules[218]
Oleuropein24 healthy participants (sex not reported)Double-blind RC Latin square designNo effect on postprandial glucose derived from bread, but in solution it attenuates postprandial blood glucose after 25 g sucrose, but has no effect after 50 g of sucrose or glucose[254]
OleuropeinHealthy 10 men and 10 womenDouble-blind RC crossover studyIts intake lowers glycaemia, DPP‐4 activity, soluble NADPH oxidase‐derived peptide activity, 8‐iso‐PGF2α, platelet p47phox phosphorylation and elevates insulin and GLP‐1[341]
Low-fat diet vs high in saturated fat (butter) vs high in monounsaturated fat (EVOO) diets8 women and 5 men with type 1 DMRCT crossover designThe addition of EVOO attenuates the early postprandial glucose response[342]
Lunch + EVOO17 men and 13 women patients with impaired fasting glucoseRCT crossover designLunch + EVOO reduces glucose, TG, ApoB-48, and DPP4 activity and increases insulin and GLP1. Chol and HDL do not change[303]
Lunch + EVOO12 healthy men and 13 healthy womenRC crossover designLunch + EVOO decreases postprandial glucose and LDL[343]
Lunch + EVOO vs lunch + corn oilHealthy subjects (12 men and 13 women)RCT crossover designLunch + EVOO ameliorates postprandial oxidative stress and endothelial dysfunction being lunch + corn oil ineffective[344]
Lunch + EVOO30 patients with impaired fasting glucoseRC crossover designLunch+EVOO attenuates the increase of oxidative stress and in LPS[345]
Lunch + EVOOSubgroup of the PREDIMED study, 110 women with metabolic syndromeMulticenter, controlled parallel groupMedDiet + EVOO decreases urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine and prostanoids[346]
MedDiet + EVOO vs MedDiet + nuts vs MedDiet with advice to use low fat7477 individuals (57% women) at high CV riskRandomized multicenter PREDIMED study testing the MedDiet in primary CV preventionMedDiet + EVOO and MedDiet + nuts reduce the incidence of major CV events by approximately 30% vs the control diet[347]
MedDiet + EVOO vs MedDiet + nuts vs MedDiet with advice to use low fat2292 (1343 women) patients with high CV risk
2210 (1200 women)
2203 (1323 women)
Post hoc analysis of the PREDIMED studyMedDiet + EVOO reduces the risk of atrial fibrillation[348]
MedDiet + EVOO vs MedDiet + nuts vs MedDiet with advice to use low fat351 men and women with DM2 or CV risk ≥3A subgroup of PREDIMED studyMedDiet + EVOO decreases the BW and changes fat distribution[349]
MedDiet + EVOO vs MedDiet + nuts vs MedDiet with advice to use low fatMen and women (3541 patients) at high CV riskPREDIMED studyThe MedDiet + EVOO reduces DM2 risk among persons with high CV risk[350]
MedDiet + EVOO vs MedDiet + nuts vs MedDiet with advice to use low fat3230 men and women with DM2PREDIMED studyMedDiet + EVOO may delay the introduction of glucose-lowering medications[351]
MedDiet + EVOO vs MedDiet + nuts, low-fat dietOld men and womenPREDIMED studyMedDiet especially if supplemented with EVOO changes the transcriptomic response of genes related to CV risk[352]
MedDiet + EVOO vs MedDiet + nuts, low-fat dietOld men and womenPREDIMED studyBoth diets decrease IL-6, IL-8, MCP-1, and MIP-1β. MedDiet + EVOO decreases IL-1β, IL-5, IL-7, IL-12p70, IL-18, TNF-α, IFNγ, GCSF, GM-CSF, ENA78, E-selectin, and sVCAM-1 vs the MedDiet + nuts group[353]
MedDiet + EVOO vs MedDiet + nuts, low-fat diet160 (74 men and 86 women) with high CV riskPREDIMED study subgroupBoth diets reduce CRP, IL-6, TNF-α, and MCP-1. After 3 years, both reduce CD49d and CD40 expressions in T lymphocytes and monocytes and increase HDL but decrease Chol, LDL, TG, and BP. At 5 y, low-fat diet increases glucose and glycated hemoglobin[354]
MedDiet vs MedDiet + EVOO MedDiet + corn oil12 men and 13 womenRC crossover design EVOO but not corn oil counteracts the upregulation of NOX2 protecting from postprandial oxidative stress[344]
MedDiet rich in OO805 patients (sex not reported) with CHD, who had their last coronary event more than 6 months before enrolment, stratified in diabetes and prediabetesProspective, randomized, single-blind, controlled trial (CORDIOPREV)MedDiet rich in OO improves endothelial function in patients with prediabetes and DM vs low-fat diet[355]
Leaf extract60 prehypertensive menDouble-blind, RC crossover designIt reduces plasma TC, LDL, TAG, HDL, Chol/HDL ratio, IL-8. It does not affect oxLDL, CRP, adiponectin, ICAM-1, VCAM-1, P-selectin, E-selectin, IL-6, IL-10, IL-1β, TNF-α, fasting glucose, insulin, fructosamine or calculated HOMA-IR or QUICKI indices, nitrites. It reduces SBP and DBP[356]
Leaf extract9 male and 9 female healthy volunteersDouble-blind, RC crossover designIt modulates positively vascular functions and IL-8 production[357]
Leaf extract46 participants (sex not reported)Double-blinded RC, placebo-controlled trialIt improves insulin secretion and sensitivity and increases IL-6, IGFBP-1, and IGFBP-2. It does not affect IL-8, TNF-α, CRP, lipid profile, BP, body composition, carotid intima-media thickness, or liver function[358]
Leaf extract152 patients with stage-1 hypertension (85.4% and 87.6% women in OO and captopril groups, respectively)Double-blind RCLeaf extract and captopril reduce SBP and DBP in a similar manner. Only leaf extract reduces TG[359]