Table 2.
Studies examining various interventions with OO consumption and their beneficial outcomes on cardiovascular health.
| Study Design | Compound | Intervention | Outcomes/ Biomarkers |
Results | Reference |
|---|---|---|---|---|---|
| RCT, double-blind, crossover, subsample from EUROLIVE study on 18 healthy men, age: 20–60 years old |
EVOO ROO |
Ingestion of 25 mL/day f OO (366 mg/kg phenolic compounds) for 3 weeks, preceded by 2-week washout periods | Anthropometric and blood pressure measurements, TC, LDL, HDL, TG, glucose, blood pressure-related gene expression analysis | EVOO decreased systolic blood pressure, maintained diastolic blood pressure, and decreased ACE, NR1H2 and IL8RA gene expression | [59] |
| RCT, double blind, parallel on 41 women overweight and obese age: 26–28 years old |
EVOO | 9 weeks, 25 mL/day intake of one of the tested oils, EVOO or soybean oil, associated with energy-restricted normofat diets | Anthropometric, body composition and blood pressure measurements; metabolic biomarkers |
EVOO consumption reduced body fat, diastolic blood pressure, alkaline phosphatase; increased serum creatinine; and tended to reduce IL-1β concentrations | [60] |
| RCT, parallel, multicenter, PREDIMED study on 7403 high CVD risk patients, age: 55–80 years old |
EVOO | 5 years of intervention, 3 groups: MedDiet + EVOO (1 L/week), MedDiet + nuts (210 g/week), low-fat diet |
Heart failure incidence | MedDiet with EVOO and MedDiet with nuts showed no significant effect on lowering heart failure incidence | [73] |
| Prospective, case-cohort, nested in the PREDIMED study on 980 high CVD risk patients |
EVOO | 5 years of intervention, 3 groups: MedDiet + EVOO, MedDiet + nuts, low-fat diet |
Plasma ceramides concentration | MedDiet enriched with EVOO or nuts showed the potential to mitigate the deleterious effects of elevated plasma ceramide concentration on CVD risk | [74] |
| RCT, parallel, multicenter, substudy of PREDIMED on 90 high CVD risk women, age: 60–80 years old |
EVOO | 1 year of intervention, 3 groups: MedDiet + EVOO (52 g/day), MedDiet + nuts (30 g/day), low-fat diet |
Endothelial markers involved in blood pressure control |
MedDiet with EVOO or nuts reduced blood pressure values | [62] |
| RCT, parallel, multicenter, subsample of PREDIMED study on 210 high CVD risk patients, age: 58–73 years old |
VOO | 1 year of intervention, 3 groups: MedDiet + VOO (1 L/week), MedDiet + nuts (210 g/week), low-fat diet |
LDL atherogenic traits: resistance against oxidation, particle size, composition, cytotoxicity |
MedDiet + VOO decreased LDL atherogenicity by increasing LDL resistance against oxidation, LDL particle size and composition (cholesterol-rich), and decreasing LDL oxidative modifications and particles cytotoxicity | [75] |
| RCT, parallel, multicenter, subsample of PREDIMED study on 296 high CVD risk patients, age: 59–72 years old |
VOO | 1 year of intervention, 3 groups: MedDiet + VOO (1 L/week), MedDiet + nuts (210 g/week), low-fat diet |
HDL functionality | MedDiet, especially when enriched with VOO, improved HDL atheroprotective functions; both MedDiet increased cholesterol efflux capacity; MedDiet + VOO decreased cholesteryl ester transfer protein activity and increased HDL ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity; the 3 diets increased the percentage of large HDL particles |
[76] |
| RCT, single-center, placebo study on 60 postmenopausal women, age: 50–61 years old |
EVOO | 1 year of oral supplementation with placebo or EVOO enriched with vitamins D3, K1 and B6 20 mL/day |
Platelet membrane fluidity, Na+/K+-ATPase activity, serum nitric oxide (NO), and peroxynitrite |
EVOO enriched with vitamins decreased platelet membrane anisotropy, NO and peroxynitrite, and increased Na+/K+-ATPase activity | [68] |
| RCT, double-blind, crossover, post hoc analyses from VOHF study on 33 hypercholesterolemics adults, 19 men and 14 women, TC > 200 mg/dL, age: 35–80 years old |
VOO FVOO FVOOT |
The different OO will be sequentially ingested (30 mL/day) during three periods of 3 weeks, preceded by 2-week washout periods | HDL composition, fluidity, oxidation, size and cholesterol efflux capacity | VOO ingestion increased HDL fluidity and apolipoprotein A-I concentration in HDL, and decreased HDL oxidative status, which are main determinants for cholesterol efflux capacity enhancement | [80] |
| Case-cohort design, subcohort of PREDIMED study on 983 high CVD risk patients, age: 61–76 years old |
EVOO | 1 year of intervention, 3 groups: MedDiet + EVOO (50 g/day), MedDiet + nuts (30 g/day), low-fat diet |
Lipid species | Although the MedDiet interventions, supplemented with EVOO or nuts, induced some significant changes in the lipidome, they were not significantly associated with subsequent CVD risk | [77] |
| RCT, double-blind, crossover, subsample from VOHF study on 12 hypercholesterolemic adults, 7 men and 5 women, TC > 200 mg/dL, age: 46–67 years old |
VOO FVOO FVOOT |
The different OO will be sequentially ingested (30 mL/day) during three periods of 3 weeks, preceded by 2-week washout periods | Blood lipids, faecal quantitative changes in microbial populations, short chain fatty acids, cholesterol microbial metabolites, bile acids, and phenolic metabolites |
FVOOT decreased ox-LDL, increased bifidobacteria numbers, and increased protocatechuic acid levels | [81] |
| RCT, double-blind, crossover, VOHF study on 33 hypercholesterolemics adults, 19 men and 14 women, TC > 200 mg/dL, age: 35–80 years old |
VOO FVOO FVOOT |
The different OO were sequentially ingested (25 mL/day) during three periods of 3 weeks, preceded by 2-week washout periods | HDL fatty acids, HDL antioxidant content, HDL monolayer fluidity, HDL cholesterol efflux capacity |
The FVOO and FVOOT increased HDL antioxidant content, but α-tocopherol was only augmented after FVOOT | [82] |
| RCT, prospective on 160 patients with T2D, 118 men and 42 women, age: 40–60 years old |
OO | Diet without or with 1.1 mL of OO + 500 mg of garlic powder for 3 months | Serum cholesterol and serum TG |
Combination of OO with garlic powder significantly normalized the cholesterol and TG levels | [55] |
| RCT double-blind, crossover, NUTRAOLEOUM Study on 51 healthy adults |
VOO OVOO Functional Olive Oil (FOO) |
VOO (124 ppm PC, 86 ppm triterpenes), OVOO (490 ppm PC, 86 ppm triterpenes) and FOO (487 ppm PC and 389 ppm triterpenes) all at (30 mL/day) were sequentially administered over three periods of 3 weeks preceded by 2-week washout periods | Metabolic syndrome and endothelial function biomarkers | VOO, OVOO, and FOO reduced the plasma endothelin-1 levels; no effect of triterpenes was observed. |
[63] |
| RCT, parallel, multicenter, subsample of PREDIMED study on 7447 high CVD risk patients, 4282 women and 3165 men, age: 55–80 years old |
EVOO | 5 years of intervention, 3 groups: MedDiet + EVOO (50 mL/day), MedDiet + nuts (30 g/day), low-fat diet |
CVD incidence | MedDiet supplemented with EVOO or nuts decreased the incidence of major cardiovascular events, including acute myocardial infarction, stroke and death for CVD | [72] |
| RCT, parallel, multicenter, subsample of PREDIMED study on 296 high CVD risk patients |
VOO | 1-year increases in the consumption of VOO (10 g/day), nuts (30 g/day), legumes (25 g/day), whole grains (25 g/day), and fish (25 g/day) | HDL functionality | Increases in the consumption of VOO, nuts, legumes, whole grains, and fish improved HDL functions; VOO increased cholesterol efflux capacity | [83] |
| Prospective, population-based study, ATTICA study on 2020 CVD-free adults, age: 18–89 years old |
OO | 10-year follow up; participants were classified into 3 groups: no use, mixed use, and exclusive use of OO |
Fatal/non-fatal CVD incidence | Exclusive OO use decreased the risk of developing CVD | [52] |
| RCT, double-blind, multiarm parallel study on 86 healthy young adults, 43 men and 43 women, age: 18–30 years old |
OO | 12 weeks of 3 g/day supplementation of OO, eicosapentaenoic acid or docosahexaenoic acid |
Resting hemodynamics and muscle sympathetic nerve activity | OO supplementation reduced resting systolic and diastolic blood pressure and reduced muscle sympathetic nerve activity | [61] |
| RCT, crossover, double-blind study on 7 healthy males, active runners engaged in endurance activities (10–14 h/week), age: 28–36 years old, BMI: 23.1 ± 1.7 Kg/m2 |
EVOO | Three separate effort test sessions were carried out separated by 7-day interval. During each session, participants repeated the same test, but under different acute dietary supplementation in a randomized order: EVOO (25 mL), palm oil (25 mL), and placebo |
Cardiorespiratory coordination and performance | Supplementation with EVOO increased cardiorespiratory coordination during a progressive walking test at moderate intensity, although it did not change performance | [71] |
| Follow-up study on 92,978 adults: 61,181 women and 31,797 men, Free of cancer, heart disease, and stroke |
OO | 24-year follow up; OO intake was categorized into 4 categories: (1) never or <1/month; (2) >0 to ≤4.5 g/day; (3) >4.5 to ≤7 g/day; and (4) >7g/day |
CVD, coronary heart disease and stroke risk; inflammatory and lipid biomarkers | Higher OO intake was associated with lower risk of coronary heart disease and CVD; in a subset of participants, higher OO intake was associated with lower levels of circulating inflammatory biomarkers and a better lipid profile |
[53] |
| RCT, parallel-arm, open label study on 48 patients with at least one classic CVD risk factor (hypertension, dyslipidemia, or diabetes), 44 men and 4 women, age: 51–64 years old |
ROO | Ingestion of 25 mL/day of ROO or CO for 6 weeks |
Plasma lipids, some selected inflammatory markers, lipoprotein-associated phospholipase A2 (Lp-PLA2) levels |
OO consumption significantly decreased IL-6 concentration | [54] |
| RCT, parallel, single-center study on 204 patients with stable coronary artery disease, age: 40–80 years old |
EVOO | 12 weeks, 3 groups: healthy diet, healthy diet + 30 mL/day EVOO, healthy diet + 30 g/day pecans |
TG, TC, LDL, HDL, non-HDL, TC/HDL ratio, LDL/HDL ratio, HDL/TG ratio, atherogenic index |
There were no significant differences in LDL levels after the consumption of a healthy diet supplemented with EVOO or pecans; supplementing the healthy diet with pecan nuts may improve other lipid profile markers |
[57] |
| RCT, double-blind, preliminary study on 30 women with fibromyalgia, age: 44–60 years old |
EVOO ROO |
Ingestion of 50 mL/day of EVOO or ROO for 3 weeks | Thrombosis-related parameters, ESR, inflammatory markers, NO levels, lipid profile and cortisol levels |
Consumption of EVOO decreased significantly red blood cell count, ESR and cortisol levels. Consumption of ROO significantly increased mean platelet volume and cortisol levels, and reduced platelet distribution width, neutrophil-to-lymphocyte ratio, ESR, and fibrinogen. No significant changes in the lipid profile, inflammatory markers and NO levels |
[67] |
| RCT, postprandial, parallel, double-blind, subsample from VOHF study on 20 healthy participants, age: 22–60 years old |
EVOO | Acute intake of 30 mL of the EVOO after 12 h of fasting | Plasma miR related to CVD | All EVOO, regardless of polyphenol content, decreased the levels of let-7e-5p; Low Phenolic Content Extra-Virgin Olive Oil (L-EVOO) and Medium Phenolic Content Extra-Virgin Olive Oil (M-EVOO) increased miR-17-92 cluster |
[70] |
| Cross-sectional analysis of the PREDIMED study on 4330 high CVD risk patients, with an ankle-brachial pressure index (ABI) <1.4 and total energy intakes: 800–4000 Kcal/day for men, 500–3500 Kcal/day for women |
EVOO VOO ROO VOO mixture Olive-pomace oil |
Consumption of any category of OO and olive-pomace oil was assessed through a validated food-frequency questionnaire | ABI | VOO (EVOO and VOO) consumption was associated with a higher mean ABI | [78] |
| Quasi-experimental on 84 healthy men and women, age: 23–85 years old, divided into 2 groups: 28 young (23–45 years) and 56 elderly (65–85 years) |
EVOO | Consumption of 25 mL/day of raw EVOO for 12 weeks | Blood pressure, TC, LDL, HDL, TG, glucose, CEC of HDL, HDL subclasses distribution |
EVOO significantly decreased the CEC of the HDL of elderly healthy subjects (to a level comparable to that of young healthy subjects), and improved distribution of HDL subclasses (increasing large HDL and decreasing small HDL particles) | [56] |
| RCT, parallel and unicentricstudy in 149 patients with stable coronary artery disease, age: 40–80 years old |
EVOO | 12 weeks, 3 groups: healthy diet, healthy diet + 30 mL/day EVOO, healthy diet + 30 g/day pecans |
Plasma fatty acids | There were no significant differences in plasma fatty acids after the consumption of a healthy diet supplemented with EVOO or pecans | [58] |
| RCT, double-blind, crossover study on 20 adults at risk of T2D, 10 men and 10 women, age: 25–75 years old |
EVOO ROO |
50 mL single dose administration of each of 2 treatments (EVOO—189 ppm phenolic compounds or ROO ≤ 20 ppm PC) in random sequence, with a 1-week washout between treatment assignments | Endothelial function and blood pressure |
EVOO acutely improved endothelial function; no significant effects on systolic or diastolic blood pressure were observed |
[64] |
| RCT single-blind, crossover study on 25 T2D patients, 12 men + 13 women, age: 61–77 years-old |
EVOO | One single intake of 40 g of EVOO-enriched chocolate or 40 g of control chocolate spread. After a 10-day washout phase, participants crossed over to take the opposite chocolate | Endothelial function and oxidative stress | EVOO-enriched chocolate is associated with increased endothelial function (increasing the arterial brachial flow-mediated dilation) and reduction of oxidative stress | [65] |
| Exploratory crossover study on 10 patients with T1D and 6 healthy subjects, 13 men and 3 women, age: 20–36 year old |
EVOO | Each participant received 2 types of high glycemic index meal: one enriched with EVOO and one with butter | Endothelial function, glucose and lipids measurements, and gastric emptying assessment |
EVOO, added to a single high glycemic index meal, significantly increased the endothelial function by increasing the arterial brachial flow-mediated dilation | [66] |
| Prospective study on 63 patients with severe obesity, age: 24–40 years old, BMI: 44.1 ± 8.5 kg/m2 |
OO | OO intake was stratified into <1 time/week, 1–3 times/week, ≥4 times/week |
Platelet activation with and without thrombin exposure |
More frequent OO intake reduced thrombin-induced platelet activation | [69] |
| Prospective, randomized, single-blind, controlled trial in 1002 coronary heart disease patients analysis | EVOO | 2 groups following a MedDiet or low-fat diet monitored at baseline and after 5 and 7 years. | IMT-CC, carotid plaque number and height | EVOO-rich MedDiet was linked to reduced atherosclerosis progression and lower carotid plaquemax height and IMT-CC while no changes were observed with the low-fat diet group, evidencing the MedDiet’s advantages as secondary CVD prevention. | [84] |
| Three-arm, randomized, controlled-feeding trial in 90 middle-aged and elderly Chinese women at high cardiovascular risk | OO | 3 groups using n-6 PUFA-rich soybean oil, MUFA-rich olive oil, or MUFA-rich camellia seed oil as cooking oils within traditional Chinese eating habits for 3 months | Body weight, cardiovascular profiles, HDL, and AST | MUFA-rich OO and camellia seed oil were shown to be more beneficial on the cardiometabolic profiles as they had a role in increasing HDL-C and decreasing AST, respectively. | [85] |
| CORDIOPREV randomized controlled trial in 1002 coronary heart disease patients | EVOO | 2 groups followed a MedDiet or a low-fat diet monitored at baseline and after 5 years | Kidney function by determination of serum creatinine-based estimated glomerular filtration rate | The advantages of the MedDiet rich in EVOO as a secondary CVD prevention was supported as it may have a preservation role for kidney function and a reduction in estimated glomerular filtration rate decrease in coronary heart disease patients with T2D. HDL-C had a minimal increase in the OO group and AST was decreased more in camellia seed oil in comparison to the soybean oil. | [86] |
| A crossover, randomized trial in 30 healthy participants | OO | 2 groups consuming isoenergetic ghee or OO for 4 weeks | Fasting plasma apo-B, non-HDL-cholesterol, LDL-cholesterol, total cholesterol:HDL-cholesterol ratio | The diet that included ghee increased the fasting plasma Apo-B and non-HDL cholesterol. Despite the non-significant differences between the two groups on LDL-C, this study emphasizes the recommendation of replacing SFA with unsaturated fats to decrease the risk of CVD. | [87] |
| A randomized trial in 43 hypercholesterolemic adults | OO | 2 groups consuming cottonseed oil or OO diets for 8 weeks | blood lipid responses | The partial outpatient feeding intervention concluded that cottonseed oil was more effective in improving the fasting and postprandial blood lipids and postprandial glycemia in hypercholesterolemic adults. | [88] |
| A case-control study nested in the PREDIMED study; 167 peripheral artery disease cases matched with 250 controls | EVOO | 3 groups: MedDiet with supplementation of tree nuts, MedDiet with EVOO supplementation, or control (low-fat diet) | Plasma amino acids and risk of peripheral artery disease | MedDiet+EVOO group was protected against peripheral artery disease regardless of baseline threonine which can be an early biomarker of future disease incidences in high-risk CVD individuals. | [79] |
| Study performed on 40 chronic kidney disease patients under conservative therapy for the in vivo clinical testing | EVOO rich in phenolic compounds | Participants consumed 40 mL/day of raw EVOO for 9 weeks | Inflammatory parameters, oxidative stress biomarkers, lipid and purine metabolism, atherogenic indices | Inflammatory parameters, carotid intima-media thickness (CIMT), and oxidative stress biomarkers decreased while the lipid and purine metabolism, atherogenic indices, and body compositions were enhanced. | [89] |
(ABI: Ankle-Brachial Pressure Index; ACE: angiotensin I-converting enzyme; Apo B: Apolipoprotein B; AST: Aspartate Aminotransferase; BMI: Body Mass Index; CEC: Cholesterol Efflux Capacity; CIMT: carotid intima-media thickness; CO: Canola Oil; CVD: Cardiovascular Disease; ESR: Erythrocyte Sedimentation Rate; EVOO: Extra-Virgin Olive Oil; FOO: Functional Olive Oil; FVOO: Phenol-Enriched VOO; FVOOT: Phenol-Enriched VOO and Thyme; HDL or HDL-C: High-Density Lipoprotein-Cholesterol; IL: Interleukin; IL8RA: Interleukin 8 receptor alpha; IMT-CC: Intima-Media Thickness of Both Common Carotid Arteries; LDL or LDL-C: Low-Density Lipoprotein-Cholesterol; L-EVOO: Low Phenolic Content Extra-Virgin Olive Oil; Lp-PLA2: Lipoprotein-Associated Phospholipase A2; MedDiet: Mediterranean Diet; M-EVOO: Medium Phenolic Content Extra-Virgin Olive Oil; miR: MicroRNAs; MUFA: Monounsaturated Fatty Acids; NO: Nitric Oxide; NR1H2: nuclear receptor subfamily 1, group H, member 2; OO: Olive Oil; OVOO: Ordinary Virgin Olive Oil; PC: Phenolic Compounds; PUFA: Polyunsaturated Fatty Acids; RCT: Randomized Control Trial; ROO: Refined Olive Oil; SFA: Saturated Fatty Acids; T1D: Type 1 Diabetes; T2D: Type 2 Diabetes; TC: Total Cholesterol; TG: Triacylglycerols; VOHF: VOO and HDL Functionality VOO: Virgin Olive Oil).