Table 2.
Characteristics of included randomized controlled trials related to cardiovascular health.
| No. | Study, Year, Ref. | Country | Population Age | Duration Type of Study |
Intervention | Comparison/Diets | Outcomes |
|---|---|---|---|---|---|---|---|
| 1 | Braam et al., 2004 [71] | The Netherlands | 181 PM women of which 150 completed the study; analysis performed on 108 participants | 3 years, double-blind, parallel, placebo-controlled intervention study | The participants were divided into 3 groups that received a daily supplement:
|
The elastic properties of the common carotid artery were measured (including CC, DC, IMT, E) | After 3 years of supplementation and after adjustment for baseline heart rate, mean arterial pressure, age, weight and smoking: ↓ DC (8.8%, 95% CI: 1.9 to 21.4; p < 0.05) and CC (8.6%, 95% CI: 1.8 to 20.3; p < 0.05) in MDK group vs. placebo; ↑ Pulse pressure (6.3%, 95% CI: 0.7 to 17.1; p < 0.05) and E (13.2%, 95% CI: 5.3 to 35.8; p < 0.01) in MDK group vs. placebo; - no significant differences between the MD group and placebo for all parameters, as well as between the three groups for the change of IMT |
| 2 | Shea et al., 2009 [72] | USA | 388 healthy men and PM women (60–80 y) | 3 years, double-blind study |
|
CAC progression | In a subgroup analysis of the participants who were adherent to supplementation (≥85%, n = 367): ↓ CAC progression in the phylloquinone group vs. control group (p = 0.03); In a subgroup analysis of the participants with preexisting CAC (Agatston score > 10 at baseline): ↓ CAC progression in the phylloquinone group at 6% vs. control group (p = 0.04); ↑ serum MGP in the phylloquinone group and ↓ in the control group (treatment effect: p ≤ 0.03 in all analysis) |
| 3 | Knapen et al., 2015 [73] | The Netherlands | 39 healthy men and 26 PM women, mean age 56 ± 5 y (45–65 y) | 12 weeks |
|
Comparison between the groups at baseline and after 12 weeks | ↑ circulating MK-7 levels (from 0.28 to 1.94 ng/mL) (p = 0.004 vs. standard yogurt) ↓ serum ucOC levels (p = 0.001) and plasma dp-ucMGP levels (p < 0.0001) vs. standard yogurt |
| 4 | Knapen et al., 2016 [74] | The Netherlands | 43 healthy men and 64 PM women, 45–65 y | Intervention period of 42 days followed by a washout period of 2 weeks |
|
The plasma MK-7, dp-ucMGP and ucOC were quantified and compared between the groups at baseline and after 14, 28, and 42 days - plasma MK-7 also determined at days 45, 49, and 56 (during the washout period) |
Plasma MK-7 levels after 42 days: (A) 2.29 ± 0.08 ng/mL; (B) 2.17 ± 0.09 ng/mL; (C) 2.00 ± 0.09 ng/mL (p = 0.047 between the three groups) (mean ± SE) ↑ plasma MK-7 in (A) vs. (C) (p = 0.042) ↓ plasma MK-7 levels to 0.79 ± 0.05 ng/mL after 14 days of the washout period, being still higher compared with that at the start (p < 0.0001) ↓ plasma dp-ucMGP levels after 42 days: overall 445 ± 18 pmol/L (p = 0.005); (A) 485 ± 30 pmol/L; (B) 417 ± 33 pmol/L; (C) 434 ± 31 pmol/L (p = 0.019 between-group comparisons) ↓ ucOC levels after consumption of the yogurt products and the MK-7 capsules (p = 0.012), but w/o significant differences between groups |
| 5 | Vignini et al., 2017 [75] | Italy | 60 healthy white PM women, 50–61 y | 1 year, placebo-controlled trial | Oral supplementation with: (1) VitVOO group: 20 mL/d VOO fortified with D3 (50 μg/100 mL), K1 (0.70 mg/100 mL), and B6 (6.0 mg/100 mL); (2) PlaVOO group: only 20 mL/day VOO as placebo | Comparison between the groups at baseline and after 1 year | After 1 year of supplementation: ↓ NO levels in Vit VOO group vs. PlaVOO (37.20 ± 3.2 vs. 42.59 ± 4.31 nmol/mg protein; p < 0.001) ↓ hROS levels in Vit VOO group vs. PlaVOO (159.24 ± 15.3 vs. 226.23 ± 21.57; p < 0.05) ↑ plasma Na+/K+-ATPase activity in Vit VOO group vs. PlaVOO (0.650 ± 0.073 vs. 0.411 ± 0.043 µmol Pi/mg protein; p < 0.001) ↓ anisotropy in Vit VOO group vs. PlaVOO (0.152 ± 0.015 vs. 0.208 ± 0.025 arbitrary fluorescence numbers, p < 0.001); (0.204 ± 0.011 vs. 0.240 ± 0.014 arbitrary absorbance numbers, p < 0.001) |
| 6 | Rønn et al., 2021 [76] | Denmark | 142 PM women with osteopenia, 63–73 y | 12 months, placebo-controlled trial |
|
Comparison between the groups at baseline and after 3, 6, and 12 months | ↓ ucOC in the MK-7 group (−70.3 (−75.6; −63.8)%) vs. placebo (−7.2 (−15.9; 2.0)%) after 12 months (p < 0.01) ↑ P-adiponectin in the MK-7 group (6.1 ± 20.1%) vs. placebo group (−0.7 ± 15.5%) after 12 months (p = 0.03) HOMA-IR and p-leptin—no changes |
CAC—coronary artery calcification; CC—compliance coefficient; DC—distensibility coefficient; E—the Young’s Modulus; IMT—intima-media thickness; HOMA—IR-Homeostatic Model Assessment for Insulin Resistance; hROS—highly reactive oxygen species; MGP—matrix Gla protein; MK-7—menaquinone-7; NO—nitric oxide; OC—osteocalcin; PM—postmenopausal; ucOC—uncarboxylated osteocalcin; VOO—extra virgin olive oil; ↑—increase; ↓—decrease.