Effects of Polyphenol-Rich Foods on Lipids and Oxidative Stress Status in Patients with Hyperlipidemia: A Systematic Review of Randomized Controlled Trials

Figures & data

Figure 1 Literature screening process.

Note: Adapted from Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. J Clin Epidemiol. 2021;134:178–189.²⁰

Figure 2 Results of methodological quality evaluationg.

Note: Adapted from Cumpston M, Li T, Page MJ, et al. Upduidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019; 10: ED000142.²⁴

Table 1 Basic Characteristics of the Included Studies

First Author, Publication Year	Country	Related Polyphenol Types	Study Design	Patients	Sample Size (T/C)	Sex (Male/Female) (T/C)	Intervention, Time	Control Condition	Outcomes	Time Points of Measurements	Outcome Details
Beitollah Alipoor,^Citation25 2012	Iran	Lignans	RCT	Patients with HLP	38 (19/19)	Unreported	Follow a daily diet and exercise plan, consuming 40 grams of white sesame seeds every day, 60 days	Follow a daily diet and exercise plan, 60 days	①: a, b, c, d; ②: f, g, h	After 60 days	The levels of TC, LDL-C, and TBARS were reduced, while the activities of GPX and SOD were increased
LeAnne T. Bloedon,^Citation26 2013	America	Lignans	RCT	Hypercholesterolemic men and postmenopausal women	62 (30/32)	T: 16/14C: 15/17	A low-fat, low-cholesterol diet supplemented with 20 grams of flaxseed in the morning and evening, 10 weeks	A low fat, low- cholesterol diet and consuming a bran product similar to flax baking product twice daily, 10 weeks	①: a, b, c, d, e; ②: i	After 5, 10 weeks	After 5 weeks of intervention, TC and LDL-C were significantly reduced, but the effect was not sustained after 10 weeks. There was no significant effect on TG and VLDL-C. HDL-C decreased in men but remained unchanged in women, and there was no significant impact on markers of oxidative stress
Jan Fedacko,^Citation27 2016	India	Flavonoids	RCT	Patients with HLP	60 (29/31)	T: 24/5 C: 25/6	American Heart Association Step 1 Diet + 20.0g of fenugreek seed powder dissolved in 300mL of water, taken before meals three times daily, 12 weeks	American Heart Association Diet + 1.0 g sachet of powdered microcrystalline cellulose dissolved in 300 mL of water, taken three times daily before meals, 12 weeks	①: a, b, c, d	After 4, 8, 12, 24 weeks	The intervention group exhibited significantly reduced concentrations of TC, LDL-C, and TG, while HDL-C levels were significantly elevated
Farzad Shidfar,^Citation28 2009	Iran	Flavonoids	RCT	Postmenopausal women with hypercholesterolemia	42 (21/21)	Female	Consumption of 50 grams of soy protein (roasted soybeans) containing 164 mg of isoflavones per day, 10 weeks	Consumption of 50 grams of whey protein per day, similar in appearance to roasted soybeans, 10 weeks	①: a, b, c, d; ②: j	After 10 weeks	The intervention group significantly decreased LDL-C, TC, LDL-C/ HDL-C, and TG/HDL-C, and significantly increased HDL-C and PON1 activity
Lorenza Conterno,^Citation29 2019	Italy	Polyphenol	RCT	Patients with hypercholesterolemia	62 (34/28)	Unreported	90g single dose of olive puree cookies once a day, 8 weeks	Wheat flour crackers similar in appearance, flavor, and texture, once a day, 8 weeks	①: a, b, c, d; ②: i	After 8 weeks	There were no significant changes in TC, HDL, LDL, and TG, and a trend toward lower Ox LDL in the intervention group, but the effect was not significant
Jurairat Khongrum,^Citation30 2022	Thailand	Polyphenol	RCT	Patients with dyslipidemia	40 (20/20)	Unreported	Polyphenol-rich juice drink (300 mL) once a day, 8 weeks	Placebo drink (300 mL) once a day, 8 weeks	①: a, b, c, d; ②: k, l	After 4, 8 weeks	Significant reduction in LDL-C and TG levels, no significant improvement in TC, HDL-C, reduction in MDA, and enhancement of GSH, and improvement in oxidative stress in the intervention group
Fangfei Zhou,^Citation31 2022	China	Flavonoids	RCT	Hypercholesterolemic men and postmenopausal women	111 (56/55)	T: 8/48 C: 12/43	Consumption of 30 g of sea buckthorn puree after meals, 3 times daily, 12 weeks	Consumption of 30 g placebo after meals 3 times daily, 12 weeks	①: a, b, c, d	After 6, 12 weeks	Sand buckthorn fruit puree had no effect on serum TC, LDL-C and TG levels. However, HDL-C levels were reduced in the first 6 weeks and increased in the second 6 weeks
Rasa Troup,^Citation32 2015	America	Flavonoids	Cross RCT	Patients with hypercholesterolemia	57 (30/27)	32/25	Low-flavonoid diet + 5 cups of black tea daily, 4 weeks	Low-flavonoid diet + 5 cups of black tea-based placebo per day, 4 weeks	①: a, b, c, d	After 7,14,21,28 days	Drinking 5 cups of black tea per day for 4 weeks did not significantly change TC, LDL-C, HDL-C, or TG concentrations
Joel Constans,^Citation33 2014	France	Flavonoid	Cross RCT	Hypercholesterolemic men	25	Male	Break-in period 4 weeks after classic French diet + 200 mL of orange juice 3 times/day (212 mg of hesperidin), 4 weeks	Break-in period 4 weeks classic French diet after + 200mL of control drink 3 times/day, 4 weeks	①: a, b, c, d; ②: f, g	After 8 weeks	Daily intake of orange juice significantly increased antioxidant effects, but had no significant effect on blood lipids
Britt Burton-Freeman,^Citation17 2014	America	Polyphenol	Cross RCT	Overweight HLP patients	24	10/14	Drinking an active strawberry drink (containing 10 grams of freeze-dried fruit), 6 weeks	Drinking placebo (pbo) drinks, 6 weeks	①: a, b, c, d; ②: i	After 12 weeks	Strawberry drinks resulted in significant reductions in postprandial TC, LDL, and TG concentrations, as well as a reduction in OxLDL, with the effect being more pronounced in women
Leailin Huang^Citation18 2021	America	Polyphenol	Cross RCT	Patients with moderate HLP	46	21/25	Two drinks (25 g, equivalent to 250 g of fresh strawberries, spaced at least 6 hours apart) per day, 4 weeks	Drinking energy-matched control powder daily, 4 weeks	①: a, b, c, d	After 4 weeks	Strawberry drink did not affect human measurements of fasting lipids, but had an overall therapeutic effect on vascular function (flow-mediated dilation was significantly increased)
Athanasios Koutsos,^Citation19 2020	England	Anthocyanin	Cross RCT	Mild hypercholesterolemia	43	18/25	Consumption of 2 fresh apples (340 g coreless) per day, 8 weeks	Consumption of 500 mL of control apple juice drink (100 mL concentrate + 400 mL water) per day, 8 weeks	①: a, b, c, d	After 1, 8, 12, 20 weeks	Fresh apples reduced serum TC, LDL cholesterol and TG, but there was no significant difference in HDL compared to the control group.
S Auclair,^Citation16 2010	France	Polyphenol	Cross RCT	Hypercholesterolemic men	30	Male	Consume two bags of freeze-dried apples rich in polyphenols daily, which is equivalent to about two 135g fresh apples, while maintaining a normal diet, 4 weeks	Consume two bags of freeze-dried apples with low polyphenol content daily while maintaining a regular diet, 4 weeks	①: a, b, c, d; ②: m, n	After 4, 8 weeks	The regular consumption of apples rich in polyphenols did not show any significant impact on lipid levels or plasma antioxidant capacity

Notes: ① Blood lipid: a. LDL-C; b. TC; c. HDL-C; d. TG; e. very low density lipoprotein cholesterol, ② oxidative stress index: f. glutathione peroxidase(GPX); g. superoxide dismutase(SOD); h. thiobarbituric acid reactive substances(TBARS); i. oxidized LDL(Ox LDL); j. paraoxonase 1 (PON1); k. malondialdehyde(MDA); l. glutathione(GSH); m. ferric-reducing ability of plasma(FRAP); n. oxygen radical absorbance capacity(ORAC).

Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. J Clin Epidemiol. 2021;134:178–189. doi:10.1016/j.jclinepi.2021.03.001

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Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019;10:ED000142. doi:10.1002/14651858.ED000142

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Bloedon LT, Balikai S, Chittams J, et al. Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. J Am Coll Nutr. 2008;27(1):65‐74. doi:10.1080/07315724.2008.10719676

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Fedacko J, Singh RB, Niaz MA, et al. Fenugreek seeds decrease blood cholesterol and blood glucose as adjunct to diet therapy in patients with hypercholesterolemia. World Heart J. 2016;8(3):239–249.

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Data Sharing Statement

The original data involved in the manuscript can be obtained from the references.