Table 1.
Overview of human trials testing the efficacy of dietary interventions on cardiometabolic risk.
| Dietary intervention | Diet characteristics and duration | Follow-up time | Disease/target population | Study design/Number of participants/Sex | Effect | Study outcomes | Reference/Trial title |
|---|---|---|---|---|---|---|---|
| Mediterranean diet | Until follow-up | 4.8 years | High-risk for cardiovascular disease | RCT 7,447 participants 57% women | ↓ | 30% reduced cardiovascular disease risk | (11) |
| 12 weeks Therapeutic lifestyle changes (diet plus exercise) |
- | Metabolic syndrome | Prospective pilot study 25 participants 76% women | ↓ ↑ |
Body weightBody-mass-indexFasting insulinHDL function | (12) | |
| 1-year intervention Enriched with extra-virgin olive oil or nuts |
- | High-risk for cardiovascular disease | RCT 296 participants 51% women | ↑ | HDL atheroprotective functions | (13) PREDIMED | |
| 1-year intervention Enriched with extra-virgin olive oil or nuts |
- | High-risk for cardiovascular disease | RCT 1,139 participants 55% women | ↓ ↑ |
LDL-cholesterolInflammatory biomarkers (VCAM-1, intracellular adhesion molecule, IL-6, TNFα, monocyte chemotactic protein 1)HDL-cholesterol | (14) PREDIMED | |
| 3-month intervention Enriched with extra-virgin olive oil or nuts | - | High-risk for cardiovascular disease | RCT 49 participants 53% women | ↓ | Pro-atherothrombotic genes | (15) PREDIMED | |
| Enriched with extra-virgin olive oil or nuts | 4.1 years | High-risk for cardiovascular disease | RCT 3541 participants 70% women | ↓ | Diabetes risk | (16) PREDIMED | |
| Increased fish consumption (non-fried) | 10 years | Healthy post-menopausal women | Observational study 84,493 women | ↓ | Heart failure risk | (17) WHI-OS | |
| During early adulthood increased fish (non-fried) and long chain omega-3 PUFAs | 25 years | Young adults, free form metabolic syndrome and diabetes | Prospective cohort study 4,356 participants 53% women | ↓ | Metabolic syndrome incidence | (18) CARDIA | |
| Caloric restriction (CR) | 2-year intervention 25% CR |
- | Healthy, non-obese | RCT 220 participants 67% women | ↓↑ | Body weightGeneral health | (19) CALERIE 2 |
| 2-year intervention 25% CR |
- | Healthy, non-obese | RCT 53 participants (analyzed) 68% women |
↓ | 10-year cardiovascular disease risk by 30%Blood pressureBody weightSubcutaneous and visceral fatInsulin resistance (at 12 months of intervention)LDL-cholesterolCholesterolTriglycerides | (20) CALERIE 2 | |
| 6-month intervention 25% CR plus other groups with exercise and varied % of CR | - | Overweight | RCT 48 participants 57% women | ↓ | Body weightFat massLeptin | (21) CALERIE | |
| 2-year intervention 25% CR |
- | Normal weight to moderately overweight | RCT 218 participants 68% women | ↓ ↑ |
Body weightBlood pressureInsulin resistanceInflammatory biomarkers (triiodothyronine, TNFα)TriglyceridesLDL-cholesterolTotal cholesterolEnergy expenditureHDL-cholesterol | (22) CALERIE | |
| 6-month intervention | - | Metabolic syndrome | Observational study 18 men | ↓ ↑ |
Body weightInsulin levelsFasting glucosePro-inflammatory cytokinesLipoprotein composition | (23) | |
| 6-month intervention 25% CR, additional subgroup for 2 days/week |
- | Healthy, obese or overweight, family history of breast cancer in 54% of participants | RCT 107 women | ↓ ↑ |
Body weightBlood pressureFasting insulinInsulin resistanceLeptinC-reactiveProteinLDL-cholesterolTriglyceridesIGF-1 BP | (24) | |
| 16-week intervention Calorie reduction of 700 or 500 kcal/day (latter coupled to physical exercise) |
- | Diabetes mellitus type 2 | RCT 63 participants 51% women | ↓ = |
Body weightEpicardial fatTotal fat massCardiometabolomic profile | (25) | |
| 20-week intervention calorie deficit of ~400 kcal/day | - | Older, heart failure with preserved ejection fraction | RCT 92 participants 80% women | ↑ | Peak oxygen consumption | (26) | |
| CR for 6.5 ± 4.6 years | - | Healthy | Cross-sectional 50 participants 19% women |
↓ ↑ |
Blood pressure C-reactive protein TNFα, TGFβ1Diastolic function | (27) | |
| Intermittent fasting | 2-week intervention ~17 h fasting cycles |
- | Diabetes mellitus type 2 + metformin, obese | Observational study 10 participants 90% women | ↓ ↑ |
Body weightMorning glucose levelPostprandial glucose levelPhysical activity | (28) |
| 8-week intervention 16 h fasting cycles |
- | Healthy men | RCT 34 men | ↓ ↑ |
Fat massIGF-1TestosteroneRespiratory ratioAdiponectin | (29) | |
| Alternate-day fasting | 8-week intervention Allowed for 25% of energy intake on fasting days |
- | Obese | Interventional study 16 participants 75% women | ↓ | Body weightBody fat percentageBlood pressureTotal LDLLDL-cholesterolTriglycerols | (30) |
| 22-day intervention No control group |
- | Non-obese | 16 participants 50% women | ↓ ↑ |
Body weightFasting insulinRespiratory quotientFat oxidation | (31) | |
| 4-week and 6-month intervention | - | Healthy non-obese | Cohort study with integrated pilot RCT 90 participants for long term ADF 58% women57 participants in RCT 60% women | ↓ ↑ |
Cardiovascular disease riskFat-to-lean ratioInflammatory markers (sICAM-1, triiodothyronine) LDL-cholesterolKetones PUFAs |
(32) InterFast | |
| 8-week intervention High-fat (45%) or low-fat (25%) diet on non-fasting days |
- | Obese | RCT 32 women | ↓ | Coronary heart disease riskBody weightFat massLDL-cholesterolTriacylglycerol | (33) | |
| Intermittent fasting vs. caloric restriction | 12-week intervention Continuous CR (5,000–6,500 kJ/day) or intermittent fasting for 2 days/week | - | Overweight/obese and Diabetes mellitus type 2 | RCT 63 participants 52% women | ↓ | Body weight HbA1cComparable results between IF and CR | (34) |
| Alternate-day fasting vs. caloric restriction | 1-year intervention 25% of energy intake allowed on fasting days or 25% CR continuously |
- | Obese | RCT 100 participants 86% women | ↓ ↑ |
Body weightHDL-cholesterol in alternate-day fasting (6 months of intervention) | (35) |
| 3-week intervention 150 or 200% energy intake on non-fasting days or 25% CR continuously |
- | Healthy and lean | RCT 36 participants 58% women | ↓ ↑ |
Body weight (not for 200% energy intake)Body fat (not for 200% energy intake)LDL-cholesterol (only CR)LeptinHDL-cholesterolAdiponectinCR more effectively reduces body weight than alternate-day fasting with 25% reduced energy intake, which confers no additional short-term metabolic or cardiovascular benefits | (36) |
We searched the US clinical trial registry (https://www.clinicaltrials.gov/) and PubMed using terms “Mediterranean diet,” “Caloric restriction,” “Intermittent Fasting,” “Alternate-day fasting,” and “Cardiovascular risk/disease” for completed, pending or ongoing clinical trials testing the effects of dietary regimes on cardiovascular risk factors.
HDL, High-density lipoprotein; IGF-1, Insulin-like growth factor-1; IGF-1 BP, Insulin-like growth factor-1 binding protein; IL-6, Interleukin-6; LDL, Low-density lipoprotein; PUFA, Polyunsaturated fatty acid; RCT, Randomized clinical trial; sICAM-1, Soluble intercellular adhesion molecule-1; TGFβ1, Transforming growth factor β1; TNFα, Tumor necrosis factor α; VCAM-1, Vascular cell adhesion protein-1.
↑ (arrow up) indicates increase or improvement, ↓ (arrow down) indicates decrease or decline, = indicates no change.