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. 2021 Apr 1;13(4):1165. doi: 10.3390/nu13041165

Table 1.

Studies regarding dietary compounds effects on cholesterol efflux capacity of HDL-C *.

Author, Year Dietary
Compounds
Dose/Time Study Design
n
Main Results on Efflux
Capacity on HDL-C
Hernáez, 2017 [27] TMD enriched with EVOO
TMD enriched with nuts
(walnuts,
hazelnuts, and
almonds)
1 L/week
30 g/d (15 g walnuts,
7.5 g hazelnuts,
7.5 g almonds)
1 year
A randomized controlled trial subsample PREDIMED study
296 subjects
(TMD-EVOO; n = 100 and TMD-Nuts; n = 100,
low-fat control diet;
n = 96).
↑ CEC TMD-EVOO interventions relative to baseline
(0.01 ± 0.007; p = 0.018)
↑ CEC TMD-Nuts interventions relative to baseline
(0.02 ± 0.09; p = 0.013)
Hernáez, 2019 [81] EVOO
Whole grains
10 g/d (one spoonful)
25 g/d
1 year
A randomized controlled trial subsample PREDIMED study
296 older adults’ high cardiovascular risk
(50–80 years)
↑ 0.7 % CEC (0.08–1.2; p = 0.026) with EVOO
↑0.6% CEC (0.1–1.1; p = 0.017) with whole grains.
Fernández-Castillejo, 2017 [83] VOO (80 ppm)
FVOO enriched with its own PC (500 ppm)
FVOOT with its own PC plus thyme (500 ppm)
25 mL/day
3 weeks
Crossover, double-blind, controlled trial from the VOHF
33 hypercholesterolemic
subjects
↑ CEC post-intervention vs. pre-intervention values
(4.1% ± 1.4; p = 0.042).
↑ HDL ApoA-I concentration
(0.6 ± 0.1; p = 0.014).
Independent of VOO type.
CEC was related to concentration in HDL of ApoA-I (p = 0.004).
Farràs, 2017 [84] VOO (80 ppm)
FVOO enriched with its own PC (500 ppm)
FVOOT with its own PC plus thyme (500 ppm)
25 mL/day raw OO
(between meals)
3 weeks
2 weeks wash-out
periods
Randomized, double-blind, crossover, controlled trial from the VOHF
33 hypercholesterolemic
subjects
FVOOT versus FVOO intervention
↑ CEC (1.3% ± 3.9 and 1.2% ± 3.8, respectively; p = 0.019)
FVOOT versus VOO
↓ (−0.03% + 5.4)
FVOOT post-intervention versus baseline.
↑ CEC (29.7% ± 5.6 vs. 28.3% ± 6.7;
p = 0.086)
Tindall, 2019 [87] Walnuts
Vegetable oils
WD
WFMD
ORAD
Randomized, crossover, controlled-feeding study
34 individuals at risk of
cardiovascular disease
(aged 30–65 years)
~ CEC mediated for ABCA1 (p = 0.1) or global efflux in all diets
(WD 3.5% ± 0.2, WFMD 3.5% ± 0.2, ORAD 3.8% ± 0.2; p = 0.1).
↓ global efflux after the WFMD compared with WD and ORAD
(p = 0.01).
Manninen, 2019 [89] Fish
Camelina sativa oil
20 mL of CSO *
4 meals/week of lean Fish
1 g EPA + DHA per day of fatty fish
Control *
* CSO and control allow one fish per week
12 weeks
Randomized controlled trial
79 impaired glucose
metabolism subjects
(40–75 years)
~ CEC of HDL (p = 0.123) had no significant effect after 12 weeks of fatty fish ingestion.
Yang, 2019 [90] Fish
LCMUFA, omega-3 FA, MUFA
12 g saury oil, control oil (sardine + olive oil) Randomized, doble blind, crossover trial
30 healthy normolipidemic subjects
[>18 years, (34.8 ± 12.5)]
8 weeks
↑ 6.2% HDL-C levels,
↑ 8% CEC
Richter, 2017 [88] Soya protein
(isoflavone)
0, 25 and 50 g/day soya protein
8 weeks
Randomized, placebo-controlled, three period crossover study
20 adults with moderately elevated blood pressure
(35–60 years)
~ CEC
No significant effects in CE ex vivo.
↓ 12.7 % ABCA1-specific efflux (p = 0.02) from baseline following supplementation with the control
Change not significant compared with ABCA1 efflux by 50 g/day of soya protein (3.1%; p = 0.4).
Millar, 2018 [92] Grape 60 g/day of freeze-dried grape powder (GRAPE, 195 mg polyphenols)
60 g/day of placebo
powder
(without polyphenols)
4 weeks
3 weeks washout
Randomized, double-blind, crossover placebo-controlled study
20 adults with MS
(aged 32–70 years)
~ CEC after interventions with grape and placebo (15.1% ± 5.0 and 14.4 ± 5.5; respectively).
Grape not affect HDL CEC
compared with placebo
(0.7 ± 4.2; p = 0.47)
Marín-Echeverri, 2018 [93] Agraz (fruit) 200 mL freeze-dried agraz reconstituted/day
Placebo (similar beverage without any polyphenols) 12 weeks
Double-blind crossover study
40 women with MS
~ CEC (0.5% ± 2.9; p = 0.324) after comparing the end of both intervention periods
(placebo versus agraz)
Talbot, 2018
[97]
Cocoa
(theobromine)
20 mL drink (500 mg of theobromine)
20 mL placebo drink per day
4 weeks
Randomized, double-blind, controlled, crossover study
44 overweight and obese
subjects
(aged 45–70 years)
Not affect fasting CEC after theobromine intervention (+0.4% point; −2.81, 3.57; p = 0.81).
~ CEC after theobromine on fasting and postprandial CEC
(97.5% ± 9.2 to 99.1 ± 11.7).
Nicod, 2014 [91] Polyphenols
(red wine, cocoa, or green tea)
50 μM total polyphenols (gallic acid equivalents)
24 h
In vitro study Caco-2 monolayer model No change of cholesterol efflux, via SR-B1 (cholesterol is taken up by SR-B1)
Voloshyna, 2013 [78] Resveratrol 10, 25 μM
4 h (CEC of ApoA-1)
6 h (CEC to HDL)
In vitro study TPH-1 monocytes and macrophages, HAEC, PBMC, HMDM
18 h
ABCA1 message (10 μM) in TPH1 and HAEC vs. control (168.2 ± 13.3; 141.3 ± 15.4%; p < 0.001)
ABCG1 expression in TPH-1
(169.9 ± 15.1%; p < 0.001)
LXRα mRNA (10 μM) in TPH-1 and HAEC vs. control (148.9 ± 13.3% vs. 125.8 ± 10.3%; p < 0.05)
↑ 4.6% CEC to ApoA-1 in TPH-1
(20 μM/mL, 4 h) vs. 3.8% control
(p < 0.05).
↑ 136.2 (±8.5%; p < 0.001) PPARγ expression vs. control
Sun, 2015 [75] Quercetin 0, 25,50, 100, 200 μM
0, 4, 8, 16, 24, 32 h
In vitro study
TPH-1 derived foam cells
200 uM, 32 h
↑ ApoA-I dependent CEC after 200 μM, 32 h vs. without treatment (>30% vs. 10%; p < 0.001)
PPARγ expression and activation (p < 0.001) in 200 μM, 32 h.
Cui, 2017 [76] Quercetin Quercetin
12.5 mg/Kg/d in 0.5% CMCNa
2.5, 5.0, 10.0 μM
8 weeks
In vivo study
Experimental animal model (apoE-deficient mice fed a high-fat diet)
24 mice
CMCNa group (n = 12), quercetin group (n = 12).
↑ 31.8% CEC from macrophages in the quercetin-treated mice vs. controls (p < 0.01)
↑22% HDL in quercetin group
(p < 0.01)
↑ CEC in a concentration-depend manner 5.0 and 10.0 μM (p < 0.01)
Zhong, 2017 [79] Curcumin 10, 20, 40 μM
12 h
In vitro study
Murine macrophage RAW264.7 cell line and monocyte TPH-1 cell line
↑ CEC in macrophage in a dose-dependent manner (10, 20, 40 μM) vs. untreated group (p < 0.05).
ABCA1 and SRB1 expression and protein level (10, 20, 40 μM) vs. control group (p < 0.05).
~ SRB1 expression.

Abbreviations and symbols: TMD, traditional Mediterranean diet; EVOO, extra virgin olive oil; PREDIMED, PREvención con DIeta MEDiterránea; TMD-EVOO, traditional Mediterranean diet enriched with extra virgin olive oil; TMD-Nuts, traditional Mediterranean diet enriched with nuts; CEC, cholesterol efflux capacity; TPH-1, human acute monocyte leukemia cells line; VOO, virgin olive oil; FVOO, functional virgin olive oil; PC, phenolic compounds; FVOOT, functional virgin olive oil plus thyme; VOHF, virgin olive oil and HDL functionality; Fu5 AH, macrophages and rat hepatoma cell; HMDM, human monocyte-derived macrophages; ABCA-1, ATP binding cassette subfamily A member 1; ABCG-1, ATP binding cassette subfamily G member 1; WD, walnut diet; WFMD, walnut fatty acid-matched diet; ORAD, oleic acid replaces ALA diet; CSO, camelia sativa oil; EPA, eicosapentanoic acid; DHA, docosahexaenoic acid; HDL, high-density lipoprotein; MS, metabolic syndrome; ApoA-I, apolipoprotein A-I; HAEC, human aortic endothelial cells; PBMC, human peripheral blood mononuclear cells; LXRα, liver X receptor alfa; PPARγ, peroxisome proliferator-activated receptor; Caco-2; human colon carcinoma cell line; SRB1, scavenger receptor class B type 1; CMCNa, carboxymethyl cellulose sodium; LCMUFA, long-chain monounsaturated fatty acid; MUFA, monounsaturated fatty acid; FA, fatty acid; ALA; alpha-linolenic acid. ~ not significant differences. * In vitro studies were performed independent of the study design for the CEC assessment (different cell lines included). ↓: decreasing; ↑: increasing.