Table 2: Evidence of clinical trials with natural products attenuating oxidative stress and inflammation in patients with CVD, DM, and RA.

NumberType of studyNumber of participantsAge (years)InterventionComparison/controlPeriod of interventionOutcomesYear [references]

Cardiovascular disease (CVD)

1Randomized controlled crossover trial30 (, )Control, apple, spinach, and apple + spinachHealthy control4 weeksAll treatments showed higher flow-mediated dilatation (FMD) () and lower pulse pressure () and apple and spinach resulted in lower systolic blood pressure ()2012 [49]

2Double-blind randomized crossover trialTwo lyophilized apples (40 g), polyphenol-rich and polyphenol-poor, providing, respectively, 1.43 g and 0.21 g polyphenols per dayHypercholesterolemic6 weeksFMD did not differ between the polyphenol-rich and the polyphenol-poor apples, neither did the other cardiovascular disease risk factors (plasma lipids, homocysteine, and antioxidant capacity)2010 [50]

3Open prospective randomized crossover controlled feeding trial40 (, )Raw tomatoes/kg (7.0 g), 3.5 g of tomato sauce/kg, 3.5 g of tomato sauce with refined olive oil/kg, and 0.25 g of sugar solved in water/kg Healthy control12 daysTomato sauce enriched with refined olive oil can regulate lipid profile and soluble inflammatory biomarkers better than raw tomatoes or tomato sauces2016 [51]

4Double-blind controlled randomized trialGenistein from soybeans (54 mg/day); estrogen/progestin therapy (1 mg/day); estrogen/progestin combined with norethisterone acetate (0.5 mg/day)Healthy postmenopausal women1 yearGenistein therapy improved endothelium function similar to estrogen/progestin regimen2003 [52]

5Double-blinded placebo-controlled crossover trial93 (, )25–65Quercetin/day from fruits and vegetable sources (150 mg)Overweight/obese6 weeksReduced SBP and plasma oxidized LDL level with a high-CVD risk phenotype2009 [53]

6Double-blinded randomized placebo-controlled crossover trial35–51Anthocyanins from fruits and vegetable sources (640 mg/day)Prehypertensive4 weeksHDL-C and blood glucose were significantly higher after anthocyanin versus placebo treatment ( and , resp.)2013 [54]

7Randomized double-blind placebo-controlled clinical trial10520–60 One 350 mg whortleberry extract capsule every 8 hoursHyperlipidemic2 monthsLowered total-C (), TG (), and LDL-C () but increased HDL-C levels () compared with the placebo group at the endpoint2014 [55]

8Randomized double-blind placebo-controlled clinical trial50≥18 mg of anthocyanin from Vaccinium arctostaphylos L. fruit extractHyperlipidemic4 weeksSignificantly reduced total-C (), LDL-C (), TG (), and MDA () compared to placebo2014 [56]

9Randomized controlled investigator blinded parallel-group trial, NCT0042149944 (, )56–73Dark chocolate (6.3 g/day) containing 30 mg of polyphenolsStage-1 hypertensive18 weeksReduced mean (SD) SBP by 2.9 (1.6) mmHg () and DBP by 1.9 (1.0) mmHg ()2007 [57]

10Randomized placebo-controlled single-blind crossover trial, NCT0053808345 (, )30–75In phase 1, solid dark chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar. In phase 2, sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa (containing 22 g cocoa powder), or a placeboHealthy control1 weekThe acute ingestion of both solid dark chocolate and liquid cocoa improved endothelial function and lowered blood pressure in overweight adults2008 [58]

Diabetes mellitus (DM)

11Open label randomized clinical trial6035–55Standard metformin therapy with turmeric (2 g) supplementsStandard metformin treatment4 weeksTurmeric administered group significantly () reduced the lipid peroxidation, MDA, inflammatory marker, CRP, HbA1c, and fasting blood glucose levels and enhanced the total antioxidant status2015 [59]

12Randomized double-blind controlled clinical trial7030–70Powdered rhizome of ginger (1600 mg)Wheat flour placebo (1600 mg)12 weeksGinger significantly reduced the fasting plasma glucose, HbA1c, insulin, triglyceride, total cholesterol, CRP, and PGE22014 [60]

13Randomized triple-blind controlled trialCapsule of 350 mg of RES enriched grape extract (GE)350 mg of capsules containing either maltodextrin (placebo) or RES lacking GE12 monthsRES enriched GE downregulated the proinflammatory cytokines expression via involving the inflammation-related miRs in circulating immune cells2013 [61]

14Randomized double-blind controlled trial36 (, )FDS beverage of 2 cups (50 g of FDS is equivalent to 500 g of fresh strawberries)Placebo powder with strawberry flavor6 weeksFDS significantly () decreased the CRP levels and lipid peroxidation (mainly MDA) and increased the total antioxidant status2013 [62]

15Randomized double-blind controlled trial6438–65Ginger supplementationPlacebo8 weeksGinger supplementation significantly reduced the TNF-α, CRP, and IL-6 levels2013 [63]

16Randomized double-blind clinical trial8118–60BSP at 10 g/day () BSP at 5 g/day ()Placebo4 weeksBSP significantly decreased the MDA, OSI, and oxidized low density lipoprotein cholesterol and increased the TAC2011 [64]

17Double-blinded randomized crossover trial32 (, )GSE (600 mg/day)Placebo4 weeksGSE significantly improved the inflammatory markers (mainly CRP), glycemia, and oxidative stress2009 [65]

Rheumatoid arthritis (RA)

18Randomized single-blind pilot study45 (, )Curcumin (500 mg) and diclofenac sodium (50 mg) alone or in combinationDiclofenac sodium (anti-inflammatory drug)8 weeksCurcumin alone proved to be the most effective () and safest to attenuate RA complications2012 [66]

19Randomized double-blind placebo-controlled crossover study20 (, )Quercetin (166 mg/capsule) + vitamin C (133 mg/capsule); α-lipoic acid (300 mg/capsule)Placebo6 weeksNo significant difference was found among the proinflammatory cytokines; however quercetin tended to reduce VAS of RA2009 [67]

20Randomized double-blind placebo-controlled study10555–75Polyphenolic-rich olive extractPlacebo8 weeksSignificant () decrease of plasma homocysteine level (responsible for cardiovascular complications in RA) and notable reduction of CRP were observed2007 [68]

F: female; M: male; RA: rheumatoid arthritis; VAS: visual analogue scale; NR: not reported; CRP: C-reactive protein; RES: resveratrol; GE: grape extract; miRs: microRNAs; FDS: freeze-dried strawberry; MDA: malondialdehyde; GSE: grape seed extract; BSP: broccoli sprouts powder; OSI: oxidative stress index; TAC: total antioxidant capacity; PGE2: prostaglandin E2; HbA1c: glycosylated hemoglobin; CAD: coronary artery disease; LDL-C: low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol; SBP: systolic blood pressure.