Table 3.

Studies on dietary compounds effects on antioxidant capacity of HDL-C through PON1.

Author, Year	Bioactive Compounds	Dose/Time	Study Design n	Main Results on PON1 Activity/ Expression
Michaličková, 2019 [94]	Polyphenol-enriched tomato Juice	IG: 200 g tomato fruit juice enriched with 1 g of ethanolic extract or whole tomato fruit CG: 200 g tomato fruit juice 4 weeks	Randomized controlled single-blind study 26 subjects (aged 45–60 years) with Stage 1 Hypertension	~ PON1 in both groups No significative changes baseline and 4 weeks after IG and CG [157 U/L (141–541)-172 U/L (157–447); 413 U/L (264–484)-405 U/L (294–514)]; p = 0.769
Lazavi, 2018 [95]	Barberry juice	IG: 200 mL/d of BJ CG: no intervention 8 weeks	Randomized clinical trial 41 diabetic subjects (aged 30–75 years)	↑56.0 mg/dL PON1 concentrations (±68.29; p = 0.015) for IG at the end of the trial.
Millar, 2018 [92]	Grape	60 g/d of freeze-dried grape powder (GRAPE, 195 mg polyphenols) 60 g/d 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)	~ PON1 arylesterase and PON1 lactonase activities after interventions with grape and placebo (84.5 kU/L ± 17.4 and 86.3 kU/L ± 16.2) and (15.8 kU/L ± 3.2 and 15.6 kU/L ± 2.5; respectively) Grape not affect PON1 lactonase activity compared with placebo (0.2 kU/L ± 1.8; p = 0.6).
Tabatabaie, 2020 [98]	Resveratrol	2 capsules (1000 mg) of resveratrol per day 2 capsules of methylcellulose (placebo) per day 8 weeks	Randomized, double-blind controlled trial 71 patients with type 2 diabetes (aged 30–60 years)	↑ PON1 activity after supplementation with resveratrol (15.3 U/L ± 13.9; p < 0.001) and compared with placebo group (p = 0.04) Significantly after adjusting confounding variables (p < 0.001).
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 (aged 25–60 years).	~ PON1 arylesterase and lactonase activities (-0.7 kU/L ± 8.8, p = 0.643; 0.2 kU/L ± 1.6, 0.862) after comparing the end of both intervention periods (placebo versus agraz); respectively.
Hernáez, 2017 [27]	TMD- EVOO TMD- Nuts	1 L/week 1 year	Randomized controlled trial subsample PREDIMED Study 296 subjects (older adults) TMD-EVOO TMD-Nuts Low-fat control diet.	~ PON1 in both groups
Hernáez, 2019 [81]	EVOO Nuts Legumes Fish	1 L/week 30 g per day 25 g per day 25 g per day 2 servings/week each (one) 1 year	Randomized controlled trial PREDIMED Study 296 older adult high cardiovascular risk (aged 50–80 years)	Nuts, legumes and fish ↑ 12.2%, 11.7% and 3.9% PON1 antioxidant activity (0.13–24.2; p < 0.049; 0.44–22.8; p= 0.043; 0.40–7.45; p = 0.030); respectively.
Fernández-Castillejo, 2017 [85]	First Study (acute intake) FVOOT (different concentrations) Second Study (sustained intake) Olive oil PC Thyme PC	30 mL single dose L-FVOO 250 ppm M-FVOO 500 ppm H-FVOO, 750 ppm 25 mL per day FVOO (80 ppm) + OO-PC control FVOO (550 ppm) own PC FVOOT (550 ppm) own PC (50% secoiridoid derivatives) FVOOT plus thyme (50%; flavonoids, PC, and monoterpenes)	Two randomized, crossover-controlled trial 12 healthy subjects and 33 hypercholesterolemic subjects; respectively. Single-dose and 3 weeks	↓ PON1 protein after 2 h of 30 mL of L-FVOO and M-FVOO (5.1–6.4%; p < 0.005) ↑PON1 raw activity at 4 h time point (p < 0.05). ↓ 10.9–12.4% PON1 protein levels after VOO and FVOO (p < 0.05) ↑ 5.1% PON3 protein levels and PON1 catalytic activity (p < 0.05) Pon1 gene expression correlated with PPARγ (r = 0.966; p = 0.034).
Balsan, 2019 [96]	Green tea Yerba mate	1000 mL per day of: GT YM AT (control) 8 weeks	Randomized, controlled, clinical trial 142 overweight or obesity and dyslipidemia (aged 35–60 years)	↑9.7% PON1 serum levels after YM intervention (2625 pg/mL to 2880 pg/mL, change 255 pg/mL; p = 0.005). ~ PON1 serum levels after green tea intervention (2899 pg/mL to 2745 pg/mL, change -154 pg/mL; p = 0.154).

Abbreviations and symbols: IG, intervention group; CG, control group; BJ, barberry juice; MS, metabolic syndrome; FVOOT, functional virgin olive oil; PC, phenolic compounds; L-FVOO, low-functional olive oil; M-FVOO, medium-functional olive oil; H-FVOO, high-functional olive oil; OO-PC, olive oil oleuropein derivatives; PC, phenolic compounds; PON1, paraoxonase 1; PON3, paraoxonase 3; PPARγ, peroxisome proliferator-activated receptor; TMD-EVOO, traditional Mediterranean diet enriched with extra virgin olive oil; TMD-Nuts, traditional Mediterranean diet enriched with nuts; PREDIMED, PREvención con DIeta MEDiterránea Study; DP, dietary pattern; GT, green tea; YM, yerba mate; AT, apple tea. ~ not significant differences. ↓: decreasing; ↑: increasing.