Table 1.
Studies examining various interventions with OO consumption and their beneficial outcomes on metabolic outcomes.
| Study Design | Compound | Intervention | Outcomes/ Biomarkers |
Results | Reference |
|---|---|---|---|---|---|
| Clinical trial on 12 healthy subjects (age: 27–31 years old) and 12 patients with metabolic syndrome (age: 32–38 years old), 12 men and 12 women |
High-Polyphenol Extra-Virgin Olive Oil (HP-EVOO) Low-Polyphenol Extra-Virgin Olive Oil (LP-EVOO) |
Acute ingestion of 50 mL of HP-EVOO or LP-EVOO, after 1-week washout period and overnight fasting | Gene and miR expression analysis | In healthy subjects, HP-EVOO improved glycaemia and insulin sensitivity, and modulated the transcription of genes and miR involved in metabolism, inflammation, and cancer, modifying to a less deleterious inflammatory phenotype; In healthy subjects and in patients with metabolic syndrome, LP-EVOO showed weaker effects |
[48] |
| RCT, crossover on 17 overweight women, age: 20–50 years old, BMI: 25–29.9 kg/m2 |
OO | Two 6-week periods, separated by a 2-week washout period, to consume either a usual diet or an OO-rich diet | Omentin and adiponectin | OO-rich diet tended to increase omentin and adiponectin |
[29] |
| Randomized, blind, parallel on 43 subjects with prediabetes, 25 men and 18 women |
EVOO | 12 weeks of isocaloric weight-maintaining diet containing MUFA (OO) or extra fiber or habitual food (control diet) | Hepatic fat, glucose tolerance, insulin action and secretion |
Diet rich in MUFA from OO significantly decreased hepatic fat and improved both hepatic and total insulin sensitivity | [45] |
| Randomized, crossover on 30 patients with impaired fasting glucose, 17 men and 13 women, age: 45–70 years old |
EVOO | Patients were randomized to receive a meal including or not 10 g of EVOO in a crossover design; there was an interval of at least 7 days between the two phases of the study |
Post-prandial glucose, lipid profile, glucose, insulin, GLP-1, DPP4, TG, total cholesterol, HDL, Apo B-48 |
EVOO reduced glucose and DPP4, significantly increased insulin and GLP-1, and significantly decreased TG and Apo B-48; total cholesterol and HDL levels did not significantly change; EVOO improved post-prandial glucose and lipid profile with a mechanism probably related to incretin up-regulation |
[35] |
| Randomized double blind, crossover on 13 healthy young men, BMI: 23–25 kg/m2 age: 22–24 years old |
OO | On 4 occasions, each separated by 3–14 days, ingestion of a control drink (450 mL) or iso-volumetric drinks containing protein/carbohydrate/fat: (1) 14 g/28 g/12.4 g, (2) 70 g/28 g/12.4 g, (3) 70 g/0 g/0 g |
Gastric emptying, glucose, insulin, ghrelin, CCK, GLP-1, total energy intake |
The substitution of whey protein with carbohydrate (dextrose) and fat (OO) resulted in faster gastric emptying, reduced suppression of ghrelin, and less stimulation of CCK and GLP-1; meanwhile, the addition of carbohydrate and fat to whey protein did not further slow gastric emptying, suppress ghrelin, or increase CCK and GLP-1 responses |
[31] |
| Unstratified case-cohort study within the PREDIMED study on 251 patients with T2D and 641 without T2D, age: 60–73 years old |
EVOO | 1 year of intervention, 3 groups: MedDiet + EVOO (4 tablespoons/day/person), MedDiet + nuts (30 g mixed nuts—walnuts, hazelnuts, and almonds), low-fat diet |
Plasma levels of amino acids | MedDiet + EVOO significantly lowered the levels of branched-chain amino acids (BCAAs) | [47] |
| RCT, single blind on 43 patients with NAFLD, 26 men and 17 women, BMI: 29.7 ± 0.58 kg/m2 age: 36–56 years old |
VOO | 12 weeks, 2 groups consuming a hypocaloric diet: (1) enriched with OO, or (2) with normal fat |
ALT, AST, liver steatosis severity |
Diet containing OO significantly decreased weight and ALT and AST levels, but the severity of liver steatosis did not change significantly during the study. | [34] |
| Randomized, double blind, crossover on 100 healthy adults, 47 men and 53 women, mean age: 40 years old, BMI: 18.5–24.9 kg/m2 |
OO | After 2-week run-in period, ingestion of 48 g/day of palm olein or OO during two phases of 5-week intervention period with a 2-week washout period between them | Anthropometric data and lipid profile | Palm olein and OO had no significantly different effect on body fatness or blood lipids | [40] |
| Randomized, single blind, crossover on 13 overweight patients with T2D, 8 men and 5 women, BMI: 30 ± 4.3 kg/m2 age: 47–75 years old |
EVOO | On 3 different days, separated by 2–10 days, in random order, acute intake of either: (a) 200 g carrot, (b) 19 g EVOO + 200 g carrot, or (c) 10.7 g C4 dietary oil + 200 g carrot |
Secretion of gut and pancreatic hormones | Both EVOO and C4-dietary oil resulted in greater secretion of GLP-1 and GIP | [41] |
| RCT, parallel, not blind on 94 healthy subjects, 31 men and 63 women, age: 50–75 years old |
EVOO | 4 weeks consumption of 50 g/day of one of 3 different dietary fats: EVOO, coconut oil or butter | Blood lipid profile, weight, fat distribution, and metabolic markers |
Butter significantly increased LDL, TC/HDL ratio and non-HDL; coconut oil significantly increased HDL; there were no significant differences on weight, fat distribution and metabolic markers among any of the three dietary fats |
[49] |
| RCT, parallel, multicenter, from the PREDIMED study on 7447 high CVD risk patients, >90% overweight or obese, 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 |
Bodyweight and waist circumference |
MedDiet enriched with EVOO or nuts showed small reductions in weight and lesser increases in waist circumference | [25] |
| Randomized, crossover on 67 healthy adults, 33 men and 34 women, BMI: 19.2–22.6 kg/m2 age: 21–25 years old |
EVOO | 18-weeks: first phase was a 2-week run-in period, followed by 3 phases of 4-week experimental period with a 2-week washout period between them; 3 groups of subjects consumed alternately a Chinese diet containing one of the 3 fats: EVOO, palm olein or cocoa butter |
Lipid profile and LDL subfractions |
Palm olein significantly lowered serum TG concentrations than EVOO; All the other lipid indices and LDL subfractions showed no significant differences amongst the three test fats |
[50] |
| RCT, multicenter, parallel-group, subgroup analysis of PREDIMED trial on 100 men and women at high CVD risk, age: 55–80 years old |
EVOO | 3-year follow up, 3 groups: Med Diet + EVOO 60 mL/day, Med Diet + 30 g/day nuts, Low-fat diet (control group) |
Hepatic steatosis | Med Diet + EVOO is associated with a lower prevalence of hepatic steatosis | [32] |
| RCT, crossover on 11 patients with T1D, 5 men and 6 women, age: 32–50 years old | EVOO | Consumption, alternating at 1-week intervals of one of 3 experimental meals, with different amount and quality of fat: 37 g EVOO (high-MU fat), 43 g butter (high-saturated fat), and 8 g (low fat) | Glucose, gastric emptying rate, GLP-1, GIP, glucagon, lipids |
EVOO reduced glucose and significantly increased gastric emptying rate, GLP-1 and TG; GIP and glucagon were not significantly different between EVOO and butter |
[36] |
| RCT, parallel, double-blind on 66 adults with NAFLD, BMI: 25 kg/m2 |
OO | 12 weeks, 2 groups consuming: 20 g/day OO or 20 g/day SFO, both combined with a hypocaloric diet |
Fatty liver grade, liver enzymes, anthropometric data, blood pressure, serum lipid profile, glucose, insulin, malondialdehyde (MDA), TAC, IL-6 |
OO intake lessened fatty liver grade and reduced body-fat percentage but did not affect liver enzymes and cardiometabolic risk factors; OO and SFO reduced weight, waist circumference, blood pressure, and serum aminotransferases |
[33] |
| Randomized, single blind, crossover on 10 patients with T2D, 9 women and 1 man, BMI: 20–30 kg/m2 age: 30–60 years old |
EVOO | EVOO or rice bran oil (15 mL/day) was administered for 4 weeks, followed by a 2-week washout period and a crossover for another 4 weeks | Glycemic control and lipid profiles | EVOO or rice bran oil significantly decreased only the HDL levels | [39] |
| RCT, parallel, double-blind, multicentre, PREDIABOLE study on 176 prediabetic subjects (with IFG and impaired glucose tolerance (IGT)), BMI: 25–39.9 kg/m2 age: 30–80 years old |
OA-enriched OO non-enriched OO |
55 mL/day of OA-enriched OO or non-enriched OO during 25–30 months | New-onset T2D incidence | The intake of OA-enriched OO substantially reduced the risk of developing T2D | [44] |
| RCT, parallel, multicenter, subgroup of PREDIMED study on 3230 patients with T2D, without treatment, 1552 men and 1678 women, age: 61–74 years old |
EVOO | 5 years of intervention, 3 groups: MedDiet + EVOO (1 L/week), MedDiet + nuts (30 g/day), low-fat diet |
Need for glucose-lowering medications and for insulin treatment | MedDiet + EVOO significantly decreased the need for glucose-lowering medications; MedDiet, with EVOO or nuts, did not result in a lower need for insulin treatment |
[46] |
| Experimental in 23 subjects with metabolic syndrome and hepatic steatosis, 15 men and 8 women, age: 49–71 years old |
EVOO | EVOO with high oleocanthal concentration was given (32 g/day) for 2 months | Anthropometric data, metabolic parameters, hepatic steatosis, abdominal fat distribution, and pro- and anti-inflammatory cytokines |
Oleocanthal-enriched EVOO significantly reduced body weight, waist circumference, body mass index, alanine transaminase, hepatic steatosis, pro-inflammatory cytokines (IL-6, IL-17A, TNF-α, IL-1B), while significantly increased anti-inflammatory cytokine (IL-10) | [24] |
| Cross-sectional observational study on 200 healthy adults, age: 20–30 years old |
OO | Participants were divided in 2 groups regarding their OO consumption: low < 12.5 g/day, and high ≥ 12.5 g/day |
BMI and waist circumference | OO consumption was not associated with increasing body mass index and waist circumference |
[26] |
| RCT, parallel, blind on 111 adults with severe obesity, BMI ≥ 35 kg/m2 age: 18–64 years old |
EVOO | 12 weeks of intervention, 3 groups: DieTBra, EVOO (52 mL/day) and DieTBra + EVOO (52 mL/day) |
Body composition and sarcopenia indicators | DieTBra + EVOO significantly reduced body weight and reduced total body fat; DieTBra significantly reduced body weight, and total body fat, and significantly improved walking speed and handgrip strength (sarcopenia indicators); EVOO alone did not improve any of the outcomes |
[27] |
| Exploratory randomized crossover on 20 10 RYGB-operated patients and 10 controls | EVOO | Ingestion during 3 days, on separated occasions and in randomized order, of different triacylglycerol formulations: (1) 20 mL EVOO, (2) 13.8 mL C8-dietary oil, and (3) 10.7 mL tricaprylin |
Enteroendocrine secretions, glucose, lipid, and bile acid metabolism |
EVOO was significantly more effective in stimulating enteroendocrine secretion in RYGB-operated patients and controls, and gut hormone release was greater in RYGB-operated patients |
[30] |
| RCT, crossover on 13 patients with T2D, 6 men and 7 women, age: 53–63 years old, BMI under the overweight or obese class |
EVOO | Participants received a meal with or without EVOO followed by a 1-week washout period, after which they were given the other intervention | Postprandial blood glucose | Meals with EVOO increased the postprandial blood glucose, providing no additional benefit | [37] |
| RCT single blind, crossover on 25 patients with T2D and 20 healthy subjects, 22 men and 23 women, age: 27–77 year old |
EVOO | One single intake of 40 g of oleuropein-enriched chocolate (addition of EVOO to enable final concentration of 4 mg% oleuropein) or 40 g of control chocolate spread. After 10 days washout phase, participants crossed over to take the opposite chocolate | Glucose, insulin |
EVOO, as a source of oleuropein, is associated with a modest increase or no change of glycemia in T2D and healthy subjects, respectively | [42] |
| RCT, double blind in 72 women with polycystic ovarian syndrome, age: 18–45 years old |
OO | 3 groups receiving 25 g/day of OO, CO or SFO for 10 weeks | Lipid profile and fatty liver severity |
OO consumption resulted in no significant reduction in lipid profile; OO and CO significantly decreased fatty liver grade and HOMA-IR |
[23] |
| Short-term, open clinical trial, proof-of-concept study on 41 adults, lean (BMI 18.5–24.9 kg/m2) and obese/overweight (BMI 25–35 kg/m2), age: 25–40 years old |
EVOO | Participants were encouraged to increase their usual OO consumption by replacing their habitual vegetable oil for OO during 4 weeks | Brown adipose tissue | EVOO ingestion leads to increased brown adipose tissue activity by significant increase in leptin, secretin, FGF21 and 12, 13 di-HOME in lean but not in overweight/obese volunteers | [28] |
| RCT, double blind, crossover on 20 healthy normal-weight subjects, 10 men and 10 women, age: 23–25 years old |
EVOO | 2-weeks consumption of 100 g/day chocolate spread enriched with either EVOO or palm oil, followed by 1 week of washout period and another 2 weeks of the opposite treatment | Ceramides concentration, glucose and lipid metabolism, inflammatory markers, appetite regulation |
EVOO-enriched chocolate spread consumption led to decreased circulating harmful sphingolipids, HOMA-IR and plasma insulin; no major significant changes in TC, TG, HDL, inflammatory markers, and appetite regulation were observed between the groups |
[43] |
| RCT, parallel, within the PREDIMED study on 150 subjects free of T2D, BMI: 27–35 kg/m2 |
EVOO | 1 year of intervention, 3 groups: MedDiet + EVOO, MedDiet + nuts, low-fat diet |
Exosomal non-coding RNAs (Ribonucleic acid) (Long Non-Coding RNAs (lncRNAs), messenger RNA (mRNA) and miRs) modulation | MedDiet + nuts and MedDiet + EVOO modulated exosomal RNA content, with the former affecting a higher number of miR | [51] |
| RCT in 40 adults aged 18–64 years with T2D and class II/III obesity | EVOO | 2 groups receiving EVOO or EVOO+DieTBra for 12 weeks | Glycemic parameters, inflammatory markers, BMI, and weight | DieTBra significantly reduced fasting insulin levels and decreased BMI, weight, serum levels of inflammatory cytokines, IL-1α and adiponectin and increased TNF-α showing its role in ameliorating inflammatory profiles and fasting insulin levels. | [38] |
(12, 13 Di-HOME: 12,13-Dihydroxy-9Z-Octadecenoic Acid; ALT: Alanine Aminotransferase; Apo B-48: Apolipoprotein B-48; AST: Aspartate Aminotransferase; BCAAs: Branched-Chain Amino Acids; BMI: Body Mass Index; CCK: Cholecystokinin; CO: Canola Oil; CVD: Cardiovascular Disease; DieTBra: Traditional Brazilian Diet; DPP4: Dipeptidyl-Peptidase-4; EVOO: Extra-Virgin Olive Oil; FGF21: Fibroblast Growth Factor 21; GIP: Glucose-Dependent Insulinotropic Polypeptide; GLP-1: Glucagon-Like Peptide-1; HDL or HDL-C: High-Density Lipoprotein-Cholesterol; HOMA-IR: Homeostatic Model Assessment of Insulin Resistance; HPOO: High Polyphenol Extra-Virgin Olive Oil; IFG: Impaired Fasting Glucose; IGT: Impaired Glucose Tolerance; IL: Interleukin; LDL or LDL-C: Low-Density Lipoprotein-Cholesterol; lncRNAs: Long Non-Coding RNAs; LP-EVOO: Low-Polyphenol Extra-Virgin Olive Oil; MDA: Malondialdehyde; MedDiet: Mediterranean Diet; miR: MicroRNAs; mRNA: messenger RNA; NAFLD: Nonalcoholic Fatty Liver Disease; OA: Oleanolic Acid; OO: Olive Oil; RCT: Randomized Control Trial; RNA: Ribonucleic acid; RYGB: Roux-en-Y Gastric Bypass; SFO: Sunflower Oil; T2D: Type 2 Diabetes; TAC: Total Antioxidant Capacity; TC: Total Cholesterol; TG: Triacylglycerols; TNF-α: Tumor Necrosis Factor Alpha; VOO: Virgin Olive Oil).