Lignan supplementation may be associated with blood lipids improvement; however, the current evidence from clinical trials is inconsistent. The present study aimed to systematically review and analyze clinical trials assessing the effects of lignan supplementation on blood lipids.
Methods
We searched the databases SCOPUS, PubMed, ISI Web of Science, and Google Scholar until August 10th, 2025. The effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals (CI).
Results
A total of 10 eligible trials (13 effect sizes) with a total sample size of 448 participants were included in this meta-analysis. Lignans used in these trials were secoisolariciresinol diglucoside (SDG), sesamin, sesamolin, and flaxseed-derived lignan. Our analysis showed that lignan supplementation significantly decreased serum total cholesterol (TC) (WMD: −11.01 mg/dL, 95% CI: −18.67, −3.35, P = 0.005) and LDL cholesterol (LDL-c) (WMD: −8.71 mg/dL, 95% CI: −14.49 to −2.94, P = 0.003), with no significant effect on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) levels. Subgroup analyses showed that lignan administration with dosage less than 500 mg/day, intervention periods less than 10 weeks, BMI less than 25 and 25–29 kg/m2 and in hypercholesterolemic subjects was more likely to decrease TC and LDL-c.
Conclusion
Evidence suggests that lignan supplementation is associated with reductions in TC and LDL-c in adults. Therefore, lignan may play a significant role in reducing the risk of dyslipidemia/hyperlipidemia.
CrismaruIPantea StoianABratuOG, et al.Low-density lipoprotein cholesterol lowering treatment: the current approach. Lipids Health Dis2020; 19: 1–10.
2.
BerberichAJHegeleRA. A modern approach to dyslipidemia. Endocr Rev2022; 43: 611–653.
3.
ShahwanMJJairounAAFarajallahA, et al.Prevalence of dyslipidemia and factors affecting lipid profile in patients with type 2 diabetes. Diabetes Metab Syndr Clin Res Rev2019; 13: 2387–2392.
4.
LazarteJHegeleRA. Dyslipidemia management in adults with diabetes. Can J Diabetes2020; 44: 53–60.
5.
VekicJStefanovicAZeljkovicA. Obesity and dyslipidemia: a review of current evidence. Curr Obes Rep2023; 12: 207–222.
6.
MoradinazarMPasdarYNajafiF, et al.Association between dyslipidemia and blood lipids concentration with smoking habits in the Kurdish population of Iran. BMC Public Health2020; 20: 1–10.
7.
OkekunleAPAsowataJOAdedokunB, et al.Secondhand smoke exposure and dyslipidemia among non-smoking adults in the United States. Indoor Air2022; 32: e12914.
8.
KalraSAggarwalSKhandelwalD. Thyroid dysfunction and dysmetabolic syndrome: the need for enhanced thyrovigilance strategies. Int J Endocrinol2021; 2021: 9641846.
9.
SimhaV. Management of hypertriglyceridemia. Br Med J2020; 371: m3109.
10.
ShahPBanerjeeSSinghA, et al.From traditional to modern medicine: the role of herbs and phytoconstituents in pharmaceuticals, nutraceuticals, and cosmetics. Formulating Pharma-, Nutra-, and Cosmeceutical Products from Herbal Substances: Dosage Forms and Delivery Systems2025: 3–73. doi:10.1002/9781119769484.ch1
11.
LiuJDongKDengQ, et al.Regulation of aging-related chronic diseases by dietary polyphenols: an updated over-view. Curr Res Food Sci2025; 11: 101163.
12.
BhuiaMSWilairatanaPChowdhuryR, et al.Anticancer potentials of the lignan magnolin: a systematic review. Molecules2023; 28: 3671.
13.
PourrajabBSohouliMHAmirinejadA, et al.The impact of rice bran oil consumption on the serum lipid profile in adults: a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr2022; 62: 6005–6015.
14.
SohouliMHHaghshenasNHernández-RuizÁ, et al.Consumption of sesame seeds and sesame products has favorable effects on blood glucose levels but not on insulin resistance: a systematic review and meta-analysis of controlled clinical trials. Phytother Res2022; 36: 1126–1134.
15.
RažnáKNôžkováJVargaováA, et al.Biological functions of lignans in plants. Agriculture (Pol'nohospodárstvo)2021; 67: 155–165.
16.
KalinováJPMarešováITřískaJ, et al.Distribution of lignans in Panicum miliaceum, Fagopyrum esculentum, Fagopyrum tataricum, and Amaranthus hypochondriacus. J Food Compos Anal2022; 106: 104283.
17.
Rodríguez-GarcíaCSánchez-QuesadaCToledoE, et al.Naturally lignan-rich foods: a dietary tool for health promotion?Molecules2019; 24: 917.
18.
PetersonJDwyerJAdlercreutzH, et al.Dietary lignans: physiology and potential for cardiovascular disease risk reduction. Nutr Rev2010; 68: 571–603.
19.
ShiYWangJYanH. Therapeutic potential of naturally occurring lignans as anticancer agents. Curr Top Med Chem2022; 22: 1393–1405.
20.
HeinonenSNurmiTLiukkonenK, et al.In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol. J Agric Food Chem2001; 49: 3178–3186.
21.
AdlercreutzH. Lignans and human health. Crit Rev Clin Lab Sci2007; 44: 483–525.
22.
LandeteJMArquésJMedinaM, et al.Bioactivation of phytoestrogens: intestinal bacteria and health. Crit Rev Food Sci Nutr2016; 56: 1826–1843.
23.
KittsDYuanYWijewickremeA, et al.Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol and enterolactone. Mol Cell Biochem1999; 202: 91–100.
24.
LeeBKimKHJungHJ, et al.Matairesinol inhibits angiogenesis via suppression of mitochondrial reactive oxygen species. Biochem Biophys Res Commun2012; 421: 76–80.
25.
van der SchouwYTPijpeALebrunCE, et al.Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women. Arterioscler, Thromb, Vasc Biol2002; 22: 1316–1322.
26.
Kreijkamp-KaspersSKokLBotsML, et al.Dietary phytoestrogens and plasma lipids in Dutch postmenopausal women; a cross-sectional study. Atherosclerosis2005; 178: 95–100.
27.
de KleijnMJvan der SchouwYTWilsonPW, et al.Dietary intake of phytoestrogens is associated with a favorable metabolic cardiovascular risk profile in postmenopausal U.S. Women: the framingham study. J Nutr2002; 132: 276–282.
28.
MokhberMKeshavarzAShidfarF, et al.WITHDRAWN ARTICLE: effect of sesame lignan supplementation on carotid intima-Media thickness, Serum lipid profile, Serum VEGF, VCAM-1, ICAM-1 and vWF levels in cardiovascular disease patients. Int J Endocrinol Metab2020; 19: e82984.
29.
NakamuraYOkumuraHOnoY, et al.Sesame lignans reduce LDL oxidative susceptibility by downregulating the platelet-activating factor acetylhydrolase. Eur Rev Med Pharmacol Sci2020; 24: 2151–2161.
30.
TseTJGuoYShimYY, et al.Availability of bioactive flax lignan from foods and supplements. Crit Rev Food Sci Nutr2023; 63: 9843–9858.
31.
NavarroSLLevyLCurtisKR, et al.Effect of a flaxseed lignan intervention on circulating bile acids in a placebo-controlled randomized, crossover trial. Nutrients2020; 12: 1837.
32.
DuarteSShahMASanches SilvaA. Flaxseed in diet: a comprehensive Look at pros and cons. Molecules2025; 30: 1335.
33.
YangQLaCPrabaharK, et al.The effect of capsaicin, capsinoids, and pepper-based interventions on lipid profiles in overweight or obese individuals: a systematic review and meta-analysis of randomized controlled trials. Diabetes Res Clin Pract2025; 112478.
34.
WangLFengLPrabaharK, et al.The effect of phytosterol supplementation on lipid profile: a critical umbrella review of interventional meta-analyses. Phytother Res2024; 38: 507–519.
35.
XiaWXiangSGamanMA, et al.The effects of phytosterol and phytostanol supplementation on the lipid profile in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Phytother Res2022; 36: 4398–4408.
36.
LiJChenRChenY, et al.The effect of guar gum consumption on the lipid profile in type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr2023; 63: 2886–2895.
37.
MasjediMSPourPMShokoohiniaY, et al.Effects of flaxseed on blood lipids in healthy and dyslipidemic subjects: a systematic review and meta-analysis of randomized controlled trials. Curr Probl Cardiol2022; 47: 100931.
38.
SabetHRAhmadiMAkramiM, et al.Effects of flaxseed supplementation on weight loss, lipid profiles, glucose, and high-sensitivity C-reactive protein in patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials. Clin Cardiol2024; 47: e24211.
39.
HadiAAskarpourMSalamatS, et al.Effect of flaxseed supplementation on lipid profile: an updated systematic review and dose-response meta-analysis of sixty-two randomized controlled trials. Pharmacol Res2020; 152: 104622.
40.
MoherDShamseerLClarkeM, et al.Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev2015; 4: 1.
41.
DerSimonianRLairdN. Meta-analysis in clinical trials. Control Clin Trials1986; 7: 177–188.
42.
HigginsJP. Cochrane handbook for systematic reviews of interventions version 5.0. 1. The Cochrane Collaboration. http://www cochrane-handbook org. 2008.
43.
HozoSPDjulbegovicBHozoI. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol2005; 5: 13.
44.
HigginsJPThompsonSG. Quantifying heterogeneity in a meta-analysis. Stat Med2002; 21: 1539–1558.
45.
GreenhouseJBIyengarS. Sensitivity analysis and diagnostics. In: The handbook of research synthesis and meta-analysis. 2nd ed. 2009, pp.417–433.
46.
DuvalSTweedieR. Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis. Biometrics2000; 56: 455–463.
47.
MohammadshahiMZakerzadehMZakerkishM, et al.Effects of sesamin on the glycemic index, lipid profile, and serum Malondialdehyde level of patients with type II diabetes. 2016.
48.
HelliBMowlaKMohammadshahiM, et al.Effect of sesamin supplementation on cardiovascular risk factors in women with rheumatoid arthritis. J Am Coll Nutr2016; 35: 300–307.
49.
BarreDMizier-BarreKStelmachE, et al.Flaxseed lignan complex administration in older human type 2 diabetics manages central obesity and prothrombosis—an invitation to further investigation into polypharmacy reduction. J Nutr Metab2012; 2012: 585170.
50.
CornishSMChilibeckPDPaus-JennsenL, et al.A randomized controlled trial of the effects of flaxseed lignan complex on metabolic syndrome composite score and bone mineral in older adults. Applied physiology. Nutrition, and Metabolism2009; 34: 89–98.
51.
FukumitsuSAidaKShimizuH, et al.Flaxseed lignan lowers blood cholesterol and decreases liver disease risk factors in moderately hypercholesterolemic men. Nutr Res2010; 30: 441–446.
52.
ZhangWWangXLiuY, et al.Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects. Br J Nutr2008; 99: 1301–1309.
53.
PanASunJChenY, et al.Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial. PloS one2007; 2: e1148.
54.
AlmarioRUKarakasSE. Lignan content of the flaxseed influences its biological effects in healthy men and women. J Am Coll Nutr2013; 32: 194–199.
55.
WuJHHodgsonJMPuddeyIB, et al.Sesame supplementation does not improve cardiovascular disease risk markers in overweight men and women. Nutrition, Metabolism and Cardiovascular Diseases2009; 19: 774–780.
56.
HallundJRavn-HarenGBügelS, et al.A lignan complex isolated from flaxseed does not affect plasma lipid concentrations or antioxidant capacity in healthy postmenopausal women. J Nutr2006; 136: 112–116.
57.
MusazadehVNezamoleslamiSFaghfouriAH, et al.The effect of flaxseed supplementation on anthropometric indices, blood pressure, and lipid profile in diabetic patients: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Syndr Clin Res Rev2025; 19: 103241.
58.
SoleymaniSHabtemariamSRahimiR, et al.The what and who of dietary lignans in human health: special focus on prooxidant and antioxidant effects. Trends Food Sci Technol2020; 106: 382–390.
59.
HuYLiYSampsonL, et al.Lignan intake and risk of coronary heart disease. J Am Coll Cardiol2021; 78: 666–678.
60.
LandeteJM. Plant and mammalian lignans: a review of source, intake, metabolism, intestinal bacteria and health. Food Res Int2012; 46: 410–424.
61.
UrsoniuSSahebkarAAndricaF, et al.Effects of flaxseed supplements on blood pressure: a systematic review and meta-analysis of controlled clinical trial. Clin Nutr2016; 35: 615–625.
62.
AskarpourMKarimiMHadiA, et al.Effect of flaxseed supplementation on markers of inflammation and endothelial function: a systematic review and meta-analysis. Cytokine2020; 126: 154922.
63.
RenG-YChenC-YChenG-C, et al.Effect of flaxseed intervention on inflammatory marker C-reactive protein: a systematic review and meta-analysis of randomized controlled trials. Nutrients2016; 8: 136.
64.
PanAYuDDemark-WahnefriedW, et al.Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr2009; 90: 288–297.
65.
JenkinsDJKendallCWAugustinLS, et al.Effect of wheat bran on glycemic control and risk factors for cardiovascular disease in type 2 diabetes. Diabetes Care2002; 25: 1522–1528.
66.
LucasEAWildRDHammondLJ, et al.Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J Clin Endocrinol Metab2002; 87: 1527–1532.
67.
van der SchouwYTKreijkamp-KaspersSPeetersPH, et al.Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in western women. Circulation2005; 111: 465–471.
68.
MilderIEFeskensEJArtsIC, et al.Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the zutphen elderly study. Am J Clin Nutr2006; 84: 400–405.
69.
KuijstenAArtsICVreeTB, et al.Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside. J Nutr2005; 135: 795–801.
70.
RowlandIRWisemanHSandersTA, et al.Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora. Nutr Cancer2000; 36: 27–32.
71.
PossemiersSBolcaSEeckhautE, et al.Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria: producer phenotyping and relation with intestinal community. FEMS Microbiol Ecol2007; 61: 372–383.
72.
ClavelTHendersonGAlpertC-A, et al.Intestinal bacterial communities that produce active estrogen-like compounds enterodiol and enterolactone in humans. Appl Environ Microbiol2005; 71: 6077–6085.
73.
Bach KnudsenKENørskovNBolvigAK, et al.Dietary polyphenols. Dietary Polyphenols: Their Metabolism and Health Effects2020: 365–406.
74.
PilkingtonLI. Lignans: a chemometric analysis. Molecules2018; 23: 1666.
75.
MilderIEFeskensEJArtsIC, et al.Intake of the plant lignans secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol in Dutch men and women. J Nutr2005; 135: 1202–1207.
76.
Van NiekerkJHendriks TJAGLHavekesL, et al.The lipid-lowering effects of 3-hydroxy-3-methylglutaric acid and bile acid drainage in WHHL rabbits. Clinical Science (London, England: 1979)1984; 67: 439–444.
77.
SunJ-HLiuXCongL-X, et al.Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans in diet-induced hyperlipidemia mice. Lipids Health Dis2017; 16: 1–14.
78.
ParkJBVelasquezMT. Potential effects of lignan-enriched flaxseed powder on bodyweight, visceral fat, lipid profile, and blood pressure in rats. Fitoterapia2012; 83: 941–946.
79.
PrasadK. Suppression of phosphoenolpyruvate carboxykinase gene expression by secoisolariciresinol diglucoside (SDG), a new antidiabetic agent. International Journal of Angiology2002; 11: 107–109.
80.
PrasadK. Antioxidant activity of secoisolariciresinol diglucoside-derived metabolites, secoisolariciresinol, enterodiol, and enterolactone. International Journal of Angiology2000; 9: 220–225.
81.
PrasadK. Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed. Mol Cell Biochem1997; 168: 117–123.
82.
Di PadovaCBosisioECighettiG, et al.3-Hydroxy-3-methylglutaric Acid (HMGA) reduces dietary cholesterol induction of saturated bile in hamster. Life Sci1982; 30: 1907–1914.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
