Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

Table 2

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

Number	Type of study	Number of participants	Age (years)	Intervention	Comparison/control	Period of intervention	Outcomes	Year [references]
Cardiovascular disease (CVD)
1	Randomized controlled crossover trial	30 (, )		Control, apple, spinach, and apple + spinach	Healthy control	4 weeks	All treatments showed higher flow-mediated dilatation (FMD) () and lower pulse pressure () and apple and spinach resulted in lower systolic blood pressure ()	2012 [49]
2	Double-blind randomized crossover trial			Two lyophilized apples (40 g), polyphenol-rich and polyphenol-poor, providing, respectively, 1.43 g and 0.21 g polyphenols per day	Hypercholesterolemic	6 weeks	FMD 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]
3	Open prospective randomized crossover controlled feeding trial	40 (, )		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 control	12 days	Tomato sauce enriched with refined olive oil can regulate lipid profile and soluble inflammatory biomarkers better than raw tomatoes or tomato sauces	2016 [51]
4	Double-blind controlled randomized trial			Genistein from soybeans (54 mg/day); estrogen/progestin therapy (1 mg/day); estrogen/progestin combined with norethisterone acetate (0.5 mg/day)	Healthy postmenopausal women	1 year	Genistein therapy improved endothelium function similar to estrogen/progestin regimen	2003 [52]
5	Double-blinded placebo-controlled crossover trial	93 (, )	25–65	Quercetin/day from fruits and vegetable sources (150 mg)	Overweight/obese	6 weeks	Reduced SBP and plasma oxidized LDL level with a high-CVD risk phenotype	2009 [53]
6	Double-blinded randomized placebo-controlled crossover trial		35–51	Anthocyanins from fruits and vegetable sources (640 mg/day)	Prehypertensive	4 weeks	HDL-C and blood glucose were significantly higher after anthocyanin versus placebo treatment ( and , resp.)	2013 [54]
7	Randomized double-blind placebo-controlled clinical trial	105	20–60	One 350 mg whortleberry extract capsule every 8 hours	Hyperlipidemic	2 months	Lowered total-C (), TG (), and LDL-C () but increased HDL-C levels () compared with the placebo group at the endpoint	2014 [55]
8	Randomized double-blind placebo-controlled clinical trial	50	≥18	mg of anthocyanin from Vaccinium arctostaphylos L. fruit extract	Hyperlipidemic	4 weeks	Significantly reduced total-C (), LDL-C (), TG (), and MDA () compared to placebo	2014 [56]
9	Randomized controlled investigator blinded parallel-group trial, NCT00421499	44 (, )	56–73	Dark chocolate (6.3 g/day) containing 30 mg of polyphenols	Stage-1 hypertensive	18 weeks	Reduced mean (SD) SBP by 2.9 (1.6) mmHg () and DBP by 1.9 (1.0) mmHg ()	2007 [57]
10	Randomized placebo-controlled single-blind crossover trial, NCT00538083	45 (, )	30–75	In 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 placebo	Healthy control	1 week	The acute ingestion of both solid dark chocolate and liquid cocoa improved endothelial function and lowered blood pressure in overweight adults	2008 [58]
Diabetes mellitus (DM)
11	Open label randomized clinical trial	60	35–55	Standard metformin therapy with turmeric (2 g) supplements	Standard metformin treatment	4 weeks	Turmeric administered group significantly () reduced the lipid peroxidation, MDA, inflammatory marker, CRP, HbA1c, and fasting blood glucose levels and enhanced the total antioxidant status	2015 [59]
12	Randomized double-blind controlled clinical trial	70	30–70	Powdered rhizome of ginger (1600 mg)	Wheat flour placebo (1600 mg)	12 weeks	Ginger significantly reduced the fasting plasma glucose, HbA1c, insulin, triglyceride, total cholesterol, CRP, and PGE2	2014 [60]
13	Randomized triple-blind controlled trial			Capsule of 350 mg of RES enriched grape extract (GE)	350 mg of capsules containing either maltodextrin (placebo) or RES lacking GE	12 months	RES enriched GE downregulated the proinflammatory cytokines expression via involving the inflammation-related miRs in circulating immune cells	2013 [61]
14	Randomized double-blind controlled trial	36 (, )		FDS beverage of 2 cups (50 g of FDS is equivalent to 500 g of fresh strawberries)	Placebo powder with strawberry flavor	6 weeks	FDS significantly () decreased the CRP levels and lipid peroxidation (mainly MDA) and increased the total antioxidant status	2013 [62]
15	Randomized double-blind controlled trial	64	38–65	Ginger supplementation	Placebo	8 weeks	Ginger supplementation significantly reduced the TNF-α, CRP, and IL-6 levels	2013 [63]
16	Randomized double-blind clinical trial	81	18–60	BSP at 10 g/day () BSP at 5 g/day ()	Placebo	4 weeks	BSP significantly decreased the MDA, OSI, and oxidized low density lipoprotein cholesterol and increased the TAC	2011 [64]
17	Double-blinded randomized crossover trial	32 (, )		GSE (600 mg/day)	Placebo	4 weeks	GSE significantly improved the inflammatory markers (mainly CRP), glycemia, and oxidative stress	2009 [65]
Rheumatoid arthritis (RA)
18	Randomized single-blind pilot study	45 (, )		Curcumin (500 mg) and diclofenac sodium (50 mg) alone or in combination	Diclofenac sodium (anti-inflammatory drug)	8 weeks	Curcumin alone proved to be the most effective () and safest to attenuate RA complications	2012 [66]
19	Randomized double-blind placebo-controlled crossover study	20 (, )		Quercetin (166 mg/capsule) + vitamin C (133 mg/capsule); α-lipoic acid (300 mg/capsule)	Placebo	6 weeks	No significant difference was found among the proinflammatory cytokines; however quercetin tended to reduce VAS of RA	2009 [67]
20	Randomized double-blind placebo-controlled study	105	55–75	Polyphenolic-rich olive extract	Placebo	8 weeks	Significant () decrease of plasma homocysteine level (responsible for cardiovascular complications in RA) and notable reduction of CRP were observed	2007 [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.