The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Abstract

Background

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 10^th, 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.

Keywords

lignan SDG TC LDL-c HDL-c TG

Highlights

Lignans are dietary phenolic compounds, produced by various plants, have structural similarities, and require activation by the intestinal microbiome to exert possible health-beneficial effects

whether these phenolic compounds have serum cholesterol-lowering capacity is not well-known. So based on available trials, we analyzed the effects of lignans on adults’ serum lipid profile.

This review and meta-analysis showed that lignan supplementation can significantly decrease serum total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c). In contrast it has no significant effects on high-density lipoprotein cholesterol (HDL-c) and triglycerides (TG) levels.

1. Introduction

Hyperlipidemia refers to imbalances in cholesterol levels in the body, including elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and decreased high-density lipoprotein cholesterol (HDL-c). Maintaining the right balance of cholesterol is crucial for regulating the amounts of HDL and LDL in the body. When the body can't regulate these lipoproteins, imbalances may lead to cardiovascular diseases (CVDs), cancer, and stroke.^1,2 Another common condition is hypertriglyceridemia, which occurs when triglyceride (TG) levels exceed 200 milligrams per deciliter (mg/dL), leading to disorders such as CVDs. Risk factors for lipid profile imbalances include consuming high amounts of trans and saturated fatty acids, low physical activity, genetics, thyroid dysfunction, obesity, smoking, and diabetes.^1,3–8 Medications like statins and other drug classes are used to control lipid profiles, but they come with disadvantages such as myopathy, liver and gastrointestinal adverse effects, and liver toxicity.^1,9 This underlies the growing scientific and public interest in plant-based supplements, which are sought after for their favorable safety profile, accessibility, and potential to mitigate the side effects associated with conventional drugs. The therapeutic potential of these botanicals is largely attributed to their rich content of specific plant bioactive compounds.¹⁰ Among the broad spectrum of plant bioactive compounds, polyphenols hold a prominent place in metabolic research.¹¹

Lignans are a prominent subgroup of dietary polyphenols found in a variety of plant-based foods, including flaxseed, sesame seeds, whole grains, fruits, and vegetables.¹² In support of the lipid-modulating potential of lignan-containing plant compounds, a recent systematic review and meta-analysis of randomized controlled trials¹³ reported that consumption of rice bran oil—an oil rich in lignans and other phenolic compounds—significantly improved serum lipid parameters, including reductions in TC, LDL-c, and TG in adults.¹³ These findings provide indirect evidence that dietary lignans and related phenolic constituents may contribute to favorable lipid profile modulation. Also, the consumption of some of lignan-rich foods, such as flaxseed and sesame seeds, has been associated with beneficial metabolic effects in clinical studies. For instance, a recent meta-analysis reported that sesame consumption has favorable effects on parameters like blood glucose levels.¹⁴

Studies have shown that dietary consumption of lignans decreases the risk of colon cancer, esophageal carcinoma, gastric adenocarcinoma, and CVDs.^12,15–19 Lignan, as a polyphenol, is metabolized by gut microbiota to produce enterolignans, which have estrogenic and anti-inflammatory effects, improving cardiovascular health. These compounds also act as antioxidants, reducing DNA damage and lipid peroxidation, and have been shown to promote insulin sensitivity, reduce aortic stiffness, and improve lipid profiles.^20–28 A study on rabbits has reported that sesame Lignan consumption downregulates plasma platelet-activating factor acetylhydrolase (PAF-AH) activity and decreases LDL-c.c.²⁹ Additionally, flaxseed lignan has been found to lower cholesterol, TG, LDL-c, and lipid peroxidation.³⁰ Laboratory analyses have shown a positive association between entrolactone (a lignan microbial metabolite) and bacterial expression of hydroxysteroid dehydrogenases and bile acid-inducible gene clusters.³¹ Determining the specific role of lignans in studies that have used whole foods is difficult. Interventions using flaxseed, sesame, or other lignan-rich foods contain a blend of other bioactive ingredients such as fiber, protein, and various fatty acids, each capable of independently influencing lipid metabolism.³² Thus, the observed effects cannot be attributed solely to lignans. This confounding factor poses a fundamental barrier to establishing a direct causal relationship between lignans and lipid profile improvement. Conversely, the beneficial effects on lipid levels of other isolated plant bioactive compounds, such as capsaicin, phytosterols, and guar gum, have been successfully demonstrated through focused meta-analyses.^33–36 This highlights the importance and validity of examining specific bioactive agents separately from their whole-food sources to ascertain their intrinsic effects. Given this context, although several meta-analyses^14,37–39 have investigated the effects of flaxseed and sesame seeds on blood lipids and metabolic indices, no meta-analysis or systematic review has specifically evaluated the effect of supplementation with isolated, purified lignans on the lipid profile. Therefore, this meta-analysis seeks to determine how lignan supplementation can influence the serum lipid profiles of adults, highlighting its potential benefits as a polyphenol for overall heart health.

2. Method

This meta-analysis was designed according to the guidelines of the PRISMA⁴⁰ statement. In addition, we registered the study in Prospero with the code CRD 42024520813.

2.1. Search strategy

The databases SCOPUS, PubMed, ISI Web of Science, and Google Scholar (first 100 most relevant results) were searched until August 10^th, 2025, using the following MeSH terms and related keywords: “Lignans” OR “Lignan” OR “enterolignan” OR “enterolactone” OR “enterodiol” OR “medioresinol” OR “secoisolarisiresinol” OR “pinoresinol” OR “lariciresinol” OR “sesamin” OR “sesamol” OR “artigenin” OR “syringaresinol” OR “medioresinol” OR “phytoestrogen”. Details of our search strategy are shown in Supplementary Table 1.^1,2 References of all the articles are included in the meta-analysis, and all related meta-analysis and review articles were hand-searched to find other relevant studies.

2.2. Study selection

Z.E. and Z.S.H. independently screened titles and abstracts to identify potentially relevant studies using predesignate selection criteria. In the case of any disagreement, a third investigator was consulted (B.P.). Articles were selected for analysis based on the following inclusion criteria¹: were RCTs or controlled clinical trials or clinical trials (parallel or crossover design), 2) provided adequate information including 95% confidence interval (CI), standard error (SE) or standard deviation (SD) of data set at the beginning and at the end of the study in both intervention (lignan supplement) and control groups, 3) had an age range of greater than or equal to 18 years, 4) had an intervention duration of at least 2 weeks. The inclusion criteria also included lignans, whether in the form of supplements, extracts, or fortified food products. For fortified food products, studies were only included if the energy, protein, fat, and micronutrient content were the same in both groups (i.e., lignan-fortified bar and placebo bar), and the only difference between the two groups was in the lignan content, allowing for the examination of the net effect of lignans.

Studies with animal, case-control, cross-sectional, or cohort designs, lacking necessary data or ease of data extraction, with an intervention duration of less than two weeks, trials without appropriate controlled design, and unrelated or inaccessible articles were excluded from this meta-analysis. Studies that did not specifically specify the amount and type of lignans were also not included in the review.

2.3. Data extraction

The following data were extracted from each of the qualified articles by two separate authors (Z.E and Z.SH): first author's name, publication year, the study location, the study design, duration of the intervention, sample size and participant population, mean age, sex, mean BMI, and type and dose of intervention and placebo (Table 1).

Table 1.
Characteristics of the randomized clinical trials that were included in the systematic review of the effect of lignan supplementation versus placebo on serum lipid profile in adults.

Author, years Study location Study design Study duration(week) Sample size Sex Study population Mean age (years) BMI(kg/m2) Control Intervention(lignan supplementation)

Mohammadshahi.2016 Iran Parallel 8 44 female & male Type 2 diabetes 51 29.1 200 mg starch capsule 200 mg sesamin capsule

Helli. 2016 Iran Parallel 6 44 female Rheumatoid arthritis 49 32.8 200 mg starch capsule 200 mg sesamin capsule

Almario. 2013 USA Parallel 6 25 female & male Healthy 54 28.8 2 Flaxeed oil Bars (300 mg Lignan/day) 2 Flaxeed oil Bars (820 mg Lignan/day)

Barre. 2012 Canada Crossover 12 16 female & male Type 2 diabetes 66 31.2 4 placebo capsules 4 capsules (600 mg total SDG/day)

Fukumitsu. 2010 ¹ Japan Parallel 12 16 male Moderately hypercholesterolemic 33 24.6 placebo capsules (contained corn starch/ 0 mg SGD) 2 capsules (20 mg SGD/ day)

Fukumitsu. 2010 ² Japan Parallel 12 16 male Moderately hypercholesterolemic 33 24.6 placebo capsules (contained corn starch/ 0 mg SGD) 2 capsules (100 mg SGD/ day)

Cornish. 2009 ¹ Canada Parallel 24 39 male Healthy 63 28.9 3 placebo tablet contained 550 mg of 90% maltodextrin and 10% caramel color 3 tablet (543 mg total SGD/day)

Cornish. 2009 ² Canada Parallel 24 53 female Healthy 61 28.1 3 placebo tablet contained 550 mg of 90% maltodextrin and 10% caramel color 3 tablet (543 mg total SGD/day)

Wu. 2009 Australia Crossover 5 33 female & male Overweight and obese 54 30.8 60 gr placebo bar (complex) 60 gr sesame seeds bar (52 mg sesamin and sesamolin)

Zhang. 2008 ¹ China Parallel 8 35 female & male Hypercholesterolemic 56 26.1 tablet containing 0 mg SDG tablet containing 300 mg SDG

Zhang. 2008 ² China Parallel 8 37 female & male Hypercholesterolemic 54 26.1 tablet containing 0 mg SDG tablet containing 600 mg SDG

Pan. 2007 China Crossover 12 68 female & male Type 2 diabetic patients with mild hypercholesterolemia 63 25.1 3 Capsules containing rice flour 3 Capsules (total 360 mg flaxseed-derived lignin/day)

Hallund. 2006 Denmark Crossover 6 22 female Healthy 61 24.1 58 gr low-fat muffin containing 0 mg SGD 58 gr low-fat muffin containing 500 mg/SGD

Author, years	Study location	Study design	Study duration(week)	Sample size	Sex	Study population	Mean age (years)	BMI(kg/m2)	Control	Intervention(lignan supplementation)
Mohammadshahi.2016	Iran	Parallel	8	44	female & male	Type 2 diabetes	51	29.1	200 mg starch capsule	200 mg sesamin capsule
Helli. 2016	Iran	Parallel	6	44	female	Rheumatoid arthritis	49	32.8	200 mg starch capsule	200 mg sesamin capsule
Almario. 2013	USA	Parallel	6	25	female & male	Healthy	54	28.8	2 Flaxeed oil Bars (300 mg Lignan/day)	2 Flaxeed oil Bars (820 mg Lignan/day)
Barre. 2012	Canada	Crossover	12	16	female & male	Type 2 diabetes	66	31.2	4 placebo capsules	4 capsules (600 mg total SDG/day)
Fukumitsu. 2010 ¹	Japan	Parallel	12	16	male	Moderately hypercholesterolemic	33	24.6	placebo capsules (contained corn starch/ 0 mg SGD)	2 capsules (20 mg SGD/ day)
Fukumitsu. 2010 ²	Japan	Parallel	12	16	male	Moderately hypercholesterolemic	33	24.6	placebo capsules (contained corn starch/ 0 mg SGD)	2 capsules (100 mg SGD/ day)
Cornish. 2009 ¹	Canada	Parallel	24	39	male	Healthy	63	28.9	3 placebo tablet contained 550 mg of 90% maltodextrin and 10% caramel color	3 tablet (543 mg total SGD/day)
Cornish. 2009 ²	Canada	Parallel	24	53	female	Healthy	61	28.1	3 placebo tablet contained 550 mg of 90% maltodextrin and 10% caramel color	3 tablet (543 mg total SGD/day)
Wu. 2009	Australia	Crossover	5	33	female & male	Overweight and obese	54	30.8	60 gr placebo bar (complex)	60 gr sesame seeds bar (52 mg sesamin and sesamolin)
Zhang. 2008 ¹	China	Parallel	8	35	female & male	Hypercholesterolemic	56	26.1	tablet containing 0 mg SDG	tablet containing 300 mg SDG
Zhang. 2008 ²	China	Parallel	8	37	female & male	Hypercholesterolemic	54	26.1	tablet containing 0 mg SDG	tablet containing 600 mg SDG
Pan. 2007	China	Crossover	12	68	female & male	Type 2 diabetic patients with mild hypercholesterolemia	63	25.1	3 Capsules containing rice flour	3 Capsules (total 360 mg flaxseed-derived lignin/day)
Hallund. 2006	Denmark	Crossover	6	22	female	Healthy	61	24.1	58 gr low-fat muffin containing 0 mg SGD	58 gr low-fat muffin containing 500 mg/SGD

SDG; secoisolariciresinol diglucoside, mg; milligram

2.4. Quality assessment

Evaluation of the risk of bias in the included studies was done using the Cochrane Assessment Tool, which has several areas for assessing the risk of bias. These areas consist of the following: adequacy of sequence generation (selection bias), allocation sequence concealment (selection bias), blinding (performance bias), blinding of outcome assessment (detection bias), addressing of dropouts (attrition bias), reporting selective outcomes (reporting bias), and other potential sources of bias. “Low,” “High,” or “Unclear” terms were used to express each area.

2.5. GRADE profile

The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was used as a way to assess the quality of evidence by examining factors such as risk of bias, inconsistency, indirectness, imprecision, publication bias, and effect size.

2.6. Quantitative data synthesis and statistical analysis

The effect of lignan supplementation on the following outcomes was assessed: 1) triglycerides (mg/dL), 2) total cholesterol (mg/dL),³ LDL-c (mg/dL), and⁴ HDL-c (mg/dL). Effect sizes were obtained from weighted mean differences (WMDs) and 95% confidence intervals and the random effects model⁴¹ was used to pool the results. Before inclusion in the analysis, all reported units of outcomes were converted to the milligram/deciliter (mg/dl) to standardize units of measurement. To calculate net changes in each group, the mean and standard deviation of blood lipid levels before and after the intervention were used for both lignan supplementation and control ((value at the end of follow-up in the intervention group - value at beginning in the intervention group) - (value at end of follow-up in the control group - value at beginning in the control group)). The following formula was used to compute SDs of mean differences: square root [(SD pre-treatment) ² +(SD post-treatment) ² - (2 R × SD pre-treatment × SD post-treatment)], where in correlation coefficient (R) was considered to be 0.5.⁴² When SD did not exist and a standard error of the mean (SEM) was provided instead of SD, we converted it to SD by the following formula: SEM × square root (n), in which “n” was the number of subjects in each group. For multi-arm studies, the shared control group was analyzed separately with each intervention group to avoid reweighting of the control group and double-counting.

In the case of medians and ranges or 95% CIs, mean and SD values were calculated by Hozo et al.⁴³ methods. To obtain the heterogeneity between the studies, Cochran's Q test (with significance set at P < 0.1) and the I² test⁴⁴ for estimate the percentage of heterogeneity was used. The sensitivity analysis was performed by the leave-one-out method⁴⁵ (ie, removing a single trial each time and repeating the analysis) to evaluate the impact of each study on the overall effect size. The subgroup analyses were performed to assess the impact of age (greater than or equal to 55 years and less than 55 years), dose of supplementation (greater than or equal to 500 mg/day and less than 500 mg/day), intervention duration (greater than or equal to 10 weeks versus less than 10 weeks), BMI categories (greater than or equal to 27 versus less than 27 for TG) (greater than or equal to 30, 25–29, and less than 25 for TC, LDL-c, and HDL-c), and health status (healthy, type 2 diabetic and hypercholesterolemic) to examine the possible influence of these covariates on net effect size also for identifying the potential source of heterogeneity. Meta-regression was done to explore the association between the effect size and potential moderator variables such as age, dose of supplementation, body mass index, and duration of supplementation. Publication bias was explored by funnel plot, Begg's rank correlation test, and Egger's weighted regression test. The “trim and fill” and “fail-safe N” methods⁴⁶ were employed to evaluate the potential impact of publication bias and to examine the robustness of the pooled results as a sensitivity analysis. All analyses were done by Comprehensive Meta-Analysis (CMA) V3 software (Biostat Inc, United States).

3. Results

3.1. Search results

The PRISMA flow diagram of the search process is depicted in Figure 1. Initially, 1513 records were identified through database searches. After removing duplicates (452), 1061 studies remained. Of these, 1046 records were excluded based on title/abstract screening, leaving 15 for detailed review. Eventually, 5 studies were excluded for insufficient baseline data, letters to the editor, use of lignan in combination with other components (inappropriate for isolated analysis), and absence of numerical reporting. Thus, 10 studies with 13 arms were included in the meta-analyses.

Figure 1.

Flow chart of the study selection process.

3.2. Characteristics of the included studies

The characteristics of the included studies are presented in Table 1. Among the 10 studies, two were conducted in Iran,^47,48 two in Canada,^49,50 one in Japan,⁵¹ two in China,^52,53 one in the USA,⁵⁴ one in Australia,⁵⁵ and one in Denmark.⁵⁶ The sample sizes ranged from 16 to 68 participants. Six studies employed a parallel design,^{47,48,50–52}^,54 while four utilized a crossover design.^49,53,55,56 All four studies that were designed as crossovers had a washout period, which preceded each intervention period.

The duration of treatment varied, with a minimum of 5 weeks and a maximum of 24 weeks. Most studies included both male and female participants, with ages ranging from 33 to 66 years. Specific participant groups included three studies involving healthy individuals,^50,54,56 two with individuals having type 2 diabetes,^47,49 two with hypercholesterolemic individuals,^51,52 and one with type 2 diabetic patients also displaying mild hypercholesterolemia.⁵³ Additionally, one study focused on individuals with rheumatoid arthritis,⁴⁸ and another on overweight and obese individuals.⁵⁵ The BMI of participants ranged from 24.1 to 32.8 kg/m². Regarding interventions, two studies administered sesamin capsules,^47,48 one used flaxseed oil bars,⁵⁴ five used secoisolariciresinol diglucoside (SDG),^49–52^,56 one provided 52 mg of sesamin and sesamolin,⁵⁵ and one administered a total of 360 mg of flaxseed-derived lignan per day.⁵³

3.3. Risk of bias assessment

The results presented in Table 2 show the risk of bias assessment according to the Cochrane Collaboration's guidelines. The overall assessment indicated that the risk of bias was unclear in eight studies, low in one study, and high in another.

Table 2.
Risk of bias assessment according to the cochrane collaboration's risk of bias assessment tool in the systematic review of the effect of lignan supplementation versus placebo on serum lipid profile in adults.

Study, year (reference) Random sequence generation Allocation concealment Blinding of participants and personnel Blinding of outcome assessment Incomplete outcome data Selective reporting Overall assessment of risk of bias

Hallund, 2006 Unclear Unclear Low Unclear Low Low Unclear

Cornish., 2009 Low Low Low Low High High High

Mohammadshahi, 2016 Unclear Unclear Low Unclear Low Low Unclear

Fukumitsu, 2010 Unclear Unclear Low Unclear Unclear Low Unclear

Zhang, 2008 Unclear Unclear Low Unclear Unclear Low Unclear

Pan, 2007 Low Low Low Low Low Low Low

Wu, 2009 Low Unclear Unclear Low Low Low Unclear

Helli, 2016 Low Unclear Low Unclear Low Low Unclear

Almario, 2013 Unclear Unclear Low Unclear Low Low Unclear

Barre, 2012 Unclear Unclear Low Unclear Low Low Unclear

Study, year (reference)	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Overall assessment of risk of bias
Hallund, 2006	Unclear	Unclear	Low	Unclear	Low	Low	Unclear
Cornish., 2009	Low	Low	Low	Low	High	High	High
Mohammadshahi, 2016	Unclear	Unclear	Low	Unclear	Low	Low	Unclear
Fukumitsu, 2010	Unclear	Unclear	Low	Unclear	Unclear	Low	Unclear
Zhang, 2008	Unclear	Unclear	Low	Unclear	Unclear	Low	Unclear
Pan, 2007	Low	Low	Low	Low	Low	Low	Low
Wu, 2009	Low	Unclear	Unclear	Low	Low	Low	Unclear
Helli, 2016	Low	Unclear	Low	Unclear	Low	Low	Unclear
Almario, 2013	Unclear	Unclear	Low	Unclear	Low	Low	Unclear
Barre, 2012	Unclear	Unclear	Low	Unclear	Low	Low	Unclear

3.4. Quality of evidence

GRADE results are presented in Table 4. This analysis showed that the quality of the reviewed articles was high in the case of TC and LDL-c, however, it was moderate in the case of HDL-c and low in the case of TG (Table 4).

3.5. Meta-analysis results

3.5.1 Tg

Ten trials with 13 arms and a sample size of 448 reported TG as the outcome variable. The pooled results from the random-effects model of these studies have demonstrated that lignan consumption may lead to a reduction in TG concentration. Still, it wasn't statistically significant (WMD: −1.60 mg/dL, 95% CI: −11.04 to 7.82, p = 0.738). There was no heterogeneity observed among the studies (I² = 00.00%, p = 0.95) (Figure 2A and Table 3).

Figure 2.

Forest plots of randomized controlled trials investigating the effect of lignan consumption versus placebo on serum lipid profile: A) TG, B) TC, C) LDL-c, and D) HDL-c.

Table 3.

Meta-analysis showing the overall analysis in the systematic review and mata-analysis of the effect of lignan supplementation versus placebo on serum lipid profile in adults.

Outcome	Number of studies (Num. arms)	Meta-analysis		Heterogeneity
Outcome	Number of studies (Num. arms)	WMD (95%CI)	P effect	Q statistic	P-heterogeneity	I² (%)
TG (mg/dL)	10 (13)	−1.60 (−11.04 to 7.82)	0.73	5.12	0.95	00.00
TC (mg/dL)	9 (11)	−11.01 (−18.67 to −3.35)	0.005*	18.94	0.04*	47.21
LDL-c (mg/dL)	9 (11)	−8.71 (−14.49 to −2.94)	0.003*	16.25	0.09*	38.49
HDL-c (mg/dL)	9 (11)	−0.46 (−1.78 to 0.85)	0.487	7.79	0.64	00.00

Abbreviation: WMD; weight mean difference, CI; confidence interval, TG; triglyceride, TC; total cholesterol, LDL-c; low-density lipoprotein cholesterol, HDL-c; high-density lipoprotein cholesterol

* Statistically significant

Table 4.

GRADE analysis of included studies in the meta-analysis of the effect of lignan supplementation versus placebo on serum lipid profile in adults.

	Mean difference(95% CI)	No. of studies	Study design	Risk of Bias	Effect size	GRADE quality
TG (mg/dL)	−1.60 (−11.04 to 7.82)	13	RCT	−2 ≠	0	$- - + +$ Low
TC (mg/dL)	−11.01 (−18.67 to −3.35	11	RCT	−1 ≠	+2 $	$+ + + +$ High
LDL-c (mg/dL)	−8.71 (−14.49 to −2.94)	11	RCT	−1 ≠	+2 $	$+ + + +$ High
HDL-c (mg/dL)	−0.46 (−1.78 to 0.85)	11	RCT	−1 ≠	0	$- + + +$ Moderate

The symbols $+ + - -$ shows the quality of evidence.

Abbreviations: CI; Confidence Interval, GRADE; Grades of Recommendation, Assessment, Development and Evaluation, RCT; Randomized Controlled Trial.

≠ Down-graded two and one level as the risk of bias was considerable

$ Up-graded two level as the effect size was considerable

3.5.2 Tc

Nine trials with 11 arms and a 356 sample size reported TC as the outcome variable. The pooled results from the random-effects model of these studies have demonstrated that lignan consumption is associated with a significant reduction in TC concentration (WMD: −11.01 mg/dL, 95% CI: −18.67 to −3.35, p = 0.005) with moderate heterogeneity (I² = 47.21%, p = 0.04). Age, BMI, duration of intervention, lignan dose, and health status were found as sources of heterogeneity, and the P-heterogeneity between subgroups was significant only for lignan dose

3.5.3 LDL-c

Nine studies with 11 arms involving 356 individuals, assessed the effect of lignan supplementation on LDL-c concentration. The pooled results from the random-effects model of these studies have shown that lignan supplementation may significantly reduce LDL-c levels (WMD: −8.71 mg/dL, 95% CI: −14.49 to −2.94, p = 0.003), with low heterogeneity (I² = 38.49%, p = 0.09). Age, BMI, and intervention duration were identified as sources of heterogeneity. None of them showed significant P-heterogeneity between subgroups

3.5.4 HDL-c

Nine studies with 11 arms, consisting of 356 individuals, evaluated the effect of lignan supplementation on HDL-c concentration. The combined results from the random-effects model of these studies showed that lignan supplementation probably had no significant effect on HDL-c levels (WMD: −0.46 mg/dL, 95% CI: −1.78 to 0.85, p = 0.487). There was no heterogeneity among the studies (I² = 0.00%, p = 0.64)

3.6. Sensitivity analysis

The relatively stable positioning of the pooled estimate in the figures suggests that no single study disproportionately influences the overall finding of the meta-analysis.

3.7. Subgroup analysis

The findings from subgroup analyses are shown in Table 5 and Figures 3A-3E, 4A-4E, 5A-5E, and 6A-6E. When stratified by age (less than 55 and greater than or equal to 55 years old), a significant reduction in TC (WMD: −14.64 mg/dL; 95% CI: −26.33 to −2.96, p = 0.01) (Figure 4A) and LDL-c (WMD: −10.91 mg/dL; 95% CI: −19.26 to −2.57, p = 0.01) (Figure 5A) was observed in trials involving individuals under 55 years of age. In the subgroup with a BMI of 25–29 kg/m², TC showed a significant decrease, with a WMD of −18.84 mg/dL (95% confidence interval: −33.30 to −4.37, p = 0.011). Although a decrease in TC was also noted in individuals with a BMI of less than 25 kg/m², this change was not statistically significant, although it was close to significance (p = 0.06) (Figure 4B). Furthermore, both individuals with a BMI under 25 kg/m² and those with a BMI between 25–29 kg/m² experienced significant reductions in LDL-c. For the BMI under 25 kg/m², the WMD in LDL-c was −9.25 mg/dL (95% CI: −18.25 to −0.24, p = 0.04). In the 25–29 kg/m² group, the reduction in LDL-c was −13.81 mg/dL (95% CI: −23.66 to −3.96, p = 0.006) (Figure 5B). In terms of trial duration (less than 10 weeks and greater than or equal to 10 weeks), trials lasting less than 10 weeks showed a significant reduction in both TC (WMD: −15.15 mg/dL; 95% CI: −27.12 to −3.18, p = 0.01) (Figure 4C) and LDL-c (WMD: −11.13 mg/dL; 95% CI: −19.28 to −2.98, p = 0.00) (Figure 5C). Furthermore, TC (WMD: −7.55 mg/dL; 95% CI: −13.77 to −1.34, p = 0.01) (Figure 4E) and LDL-c (WMD: −7.46 mg/dL; 95% CI: −14.12 to −0.81, p = 0.02) (Figure 5E) decreased in studies where the dosage was less than 500 mg/day. For health status (healthy, type 2 diabetic, and hypercholesterolemic), lignan supplementation significantly reduced TC (WMD: −19.21 mg/dL; 95% CI: −34.06 to −4.35, p = 0.01) (Figure 4D) and LDL-c (WMD: −15.42 mg/dL; 95% CI: −23.11 to −7.72, p < 0.001) (Figure 5D) in trials with hypercholesterolemia patients.

Figure 3.

Forest plots from the meta-analysis of randomized controlled trials investigating the effects of the lignan consumption versus placebo on serum TG levels based on A) age (greater than or equal to 55 and less than 55), B) BMI (greater than or equal to 27 and less than 27), C) duration (greater than or equal to 10 week and less than 10 week), D) health status (healthy, type 2 diabetic, and hypercholesterolemic), and E) lignan dose (greater than or equal to 500 mg and less than 500 mg).

Figure 4.

Forest plots from the meta-analysis of randomized controlled trials investigating the effects of the lignan consumption versus placebo on serum TC levels based on A) age (greater than or equal to 55 and less than 55), B) BMI (greater than or equal to 30, 25-29, and less than 25), C) duration (greater than or equal to 10 week and less than 10 week), D) health status (healthy, type 2 diabetic, and hypercholesterolemic), and E) lignan dose (greater than or equal to 500 mg and less than 500 mg).

Figure 5.

Forest plots from the meta-analysis of randomized controlled trials investigating the effects of the lignan consumption versus placebo on serum LDL-c levels based on A) age (greater than or equal to 55 and less than 55), B) BMI (greater than or equal to 30, 25-29, and less than 25), C) duration (greater than or equal to 10 week and less than 10 week), D) health status (healthy, type 2 diabetic, and hypercholesterolemic), and E) lignan dose (greater than or equal to 500 mg and less than 500 mg).

Figure 6.

Forest plots from the meta-analysis of randomized controlled trials investigating the effects of the lignan consumption versus placebo on serum HDL-c levels based on A) age (greater than or equal to 55 and less than 55), B) BMI (greater than or equal to 30, 25-29, and less than 25), C) duration (greater than or equal to 10 week and less than 10 week), D) health status (healthy, type 2 diabetic, and hypercholesterolemic), and E) lignan dose (greater than or equal to 500 mg and less than 500 mg).

Table 5.

Subgroup analysis of included randomized controlled trials in the systematic review and meta-analysis of the effect of lignan supplementation versus placebo on serum lipid profile in adults.

Group	No. of trials	WMD (95% CI)	P value	I² (%)	P-heterogeneity
TG
Age (years)					0.90
greater than or equal to 55	6	−1.98 mg/dL; −13.38 to 9.40	0.73	00.00	0.67
less than 55	7	−0.77 mg/dL; −17.61 to 16.05	0.92	00.00	0.92
BMI					0.26
less than 27	6	−6.37 mg/dL; −18.94 to 6.19	0.32	00.00	0.90
greater than or equal to 27	7	4.53 mg/dL; −9.74 to 18.81	0.53	00.00	0.89
Duration (week)					0.96
less than 10	7	−1.73 mg/dL; −12.80 to 9.33	0.75	00.00	0.94
greater than or equal to 10	6	−1.27 mg/dL; −19.31 to 16.76	0.89	00.00	0.64
Dose (mg/day)					0.98
greater than or equal to 500	6	−1.53 mg/dL; −13.25 to 10.18	0.79	00.00	0.66
less than 500	7	−1.74 mg/dL; −17.64 to 14.15	0.83	00.00	0.93
Health status					0.91
Healthy	5	−0.09 mg/dL; −10.98 to 10.78	0.98	00.00	0.76
Type 2 diabetic	3	−4.09 mg/dL; −28.27 to 20.09	0.74	00.00	0.37
Hypercholesterolemic	4	−13.68 mg/dL; −51.13 to 23.76	0.47	00.00	0.86
TC
Age (years)					0.23
greater than or equal to 55	4	−5.90 mg/dL; −13.40 to 1.59	0.12	00.00	0.47
less than 55	7	−14.64 mg/dL; −26.33 to −2.96	0.01*	60.02	0.02*
BMI					0.18
less than 25	3	−9.15 mg/dL; −18.88 to 0.57	0.065	0.00	0.48
25-29	5	−18.84 mg/dL; −33.30 to −4.37	0.011*	67.80	0.01*
greater than or equal to 30	3	0.36 mg/dL; −11.62 to 12.35	0.95	0.00	0.42
Duration (week)					0.13
less than 10	7	−15.15 mg/dL; −27.12 to −3.18	0.01*	56.71	0.03*
greater than or equal to 10	4	−5.61 mg/dL; −12.59 to 1.37	0.11	00.00	0.42
Dose (mg/day)					0.08*
greater than or equal to 500	4	−16.89 mg/dL; −39.35 to 5.57	0.14	67.41	0.02*
less than 500	7	−7.55 mg/dL; −13.77 to −1.34	0.01*	12.26	0.33
Health status					0.14
Healthy	3	−2.89 mg/dl; −15.68 to 9.89	0.65	12.19	0.32
Type 2 diabetic	3	−5.02 mg/dl; −14.66 to 4.61	0.30	6.91	0.34
Hypercholesterolemic	4	−19.21 mg/dl; −34.06 to −4.35	0.01*	67.17	0.02*
LDL-c
Age (years)					0.27
greater than or equal to 55	4	−5.80 mg/dL; −13.56 to 1.96	0.14	27.35	0.24
less than 55	7	−10.91 mg/dL; −19.26 to −2.57	0.01*	45.18	0.09*
BMI					0.068
less than 25	3	−9.25 mg/dL; −18.25 to −0.24	0.04*	0.00	0.61
25-29	5	−13.81 mg/dL; −23.66 to −3.96	0.006*	58.68	0.04*
greater than or equal to 30	3	1.29 mg/dL; −7.90 to 10.49	0.78	0.00	0.89
Duration (week)					0.11
less than 10	7	−11.13 mg/dL; −19.28 to −2.98	0.00*	44.58	0.09*
greater than or equal to 10	4	−4.27 mg/dL; −10.70 to 2.15	0.19	00.00	0.41
Dose (mg/day)					0.31
greater than or equal to 500	4	−11.54 mg/dL; −23.71 to 0.61	0.06	43.72	0.14
less than 500	7	−7.46 mg/dL; −14.12 to −0.81	0.02*	39.52	0.12
Health status					0.07*
Healthy	3	−2.24 mg/dl; −12.50 to 8.01	0.66	00.00	0.45
Type 2 diabetic	3	−5.95 mg/dl; −17.58 to 5.67	0.31	53.41	0.11
Hypercholesterolemic	4	−15.42 mg/dl; −23.11 to −7.72	0.00*	16.66	0.30
HDL-c
Age (years)					0.99
greater than or equal to 55	4	−0.46 mg/dl; −2.26 to 1.33	0.61	00.00	0.96
less than 55	7	0.07 mg/dl; −2.47 to 2.33	0.95	20.31	0.27
BMI					0.13
less than 25	3	1.56 mg/dL; −2.69 to 5.83	0.47	0.00	0.69
25-29	5	−1.09 mg/dL; −2.56 to 0.36	0.14	0.00	0.73
greater than or equal to 30	3	3.02 mg/dL; −1.35 to 7.40	0.17	0.00	0.59
Duration (week)					0.39
less than 10	7	−.79 mg/dL; −2.33 to 0.73	0.30	0.41	0.42
greater than or equal to 10	4	0.51 mg/dL; −2.10 to 3.13	0.70	00.00	0.79
Dose (mg/day)					0.10
greater than or equal to 500	4	−2.24 mg/dL; −4.77 to 0.29	0.08	00.00	0.86
less than 500	7	0.19 mg/dL; −1.35 to 1.73	0.80	00.00	0.61
Health status					0.26
Healthy	3	−0.79 mg/dl; −5.75 to 4.15	0.75	00.00	0.63
Type 2 diabetic	3	0.01 mg/dl; −2.78 to 2.85	0.99	00.00	1.00
Hypercholesterolemic	4	−1.03 mg/dl; −2.66 to 0.59	0.21	00.00	0.41

Abbreviation: WMD; weight mean difference, CI; confidence interval, TG; triglyceride, TC; total cholesterol, LDL-c; low-density lipoprotein cholesterol, HDL-c; high-density lipoprotein cholesterol, BMI; body mass index Footnote: In the subgroup rows, the p-values indicate within-subgroup heterogeneity, while the p-values in the rows with variable names represent the total between-subgroup differences. * Statistically significant

3.8. Publication bias

According to Eggers and Begg's test, no publication bias was detected in studies on TG, TC, LDL-c, and HDL-c

3.9. Meta-regression

None of the associations between the factors (age, supplementation dosage, body mass index, and supplementation duration) and the lipid profile components (TG, TC, LDL-c, and HDL-c) are statistically significant, except for the dosage with HDL-c, which is very close to being significant (P-value = 0.05). This shows that, based on this meta-regression analysis, these factors probably do not have a significant effect on the lipid profile in adults when comparing supplementation of lignan versus placebo. Although there is a possibility that HDL-c will be affected by increasing the dose of lignan

4. Discussion

In this meta-analysis, it was found that supplementation with lignan significantly reduced the levels of TC and LDL-C. However, its effect on TG and HDL-C was not statistically significant. Subgroup analysis on TC and LDL-c revealed significant reductions in these lipids in hypercholesterolemic individuals, participants less than 55 years, and BMI less than 25 and 25–29, duration of intervention less than 10 weeks, and lignan supplementation dose less than 500 mg/day.

The meta-analysis studies that have been done recently on the effect of flaxseed on lipid profile have conflicting results with each other as well as with our study. Although these studies^37–39 investigated the effects of flaxseed and the present study investigated the effects of lignan (secondary metabolite found in nuts, seeds, fruits, vegetables, and cereals). A meta-analysis by Hadi et al.³⁹ found that consuming flaxseed (10.0 to 60.0 grams per day) beneficially lowers TC, LDL-c, and TG in humans, though it doesn't affect HDL-c levels. Similarly, Masjedi et al.³⁷ showed that flaxseed improves lipid profiles in dyslipidemic patients, reducing TC, LDL-c, and TG, while HDL-c levels remained unchanged. But, in healthy individuals, flaxseed increased HDL-c, LDL-c, and TG. Also, subgroup analysis showed that flaxseed improved LDL-c levels in healthy overweight individuals with a higher BMI.³⁷ Conversely, the study by Sabet et al.³⁸ reported no significant changes in lipid factors (TC, LDL-c, TG, HDL-c) after flaxseed intake in coronary artery disease patients, but a sensitivity analysis indicated a significant decrease in TG levels.³⁸ And finally, a recent meta-analysis conducted in 2025 by Musazadeh et al. indicated that flaxseed consumption significantly reduced TG levels in individuals with type 2 diabetes but had no significant impact on other serum lipid indices.⁵⁷

Lignans are complex bioactive polyphenolic compounds formed by the coupling of coniferyl alcohol residues. They are grouped into plant lignans and mammalian lignans. Mammalian lignans are produced in the human body dominated by Peptostreptococcus species.⁵⁸ It is well-established that plant lignans can be efficiently processed by human gut microbiota to produce enterolignans (mammalian lignans) which are subsequently absorbed into the human body⁵⁹ and routinely detected in human plasma and urine.⁵⁸ Experimental studies have shown that enterolactone (ENL) and enterodiol (the bioactive forms of mammalian lignans³⁰) may improve cardiovascular health primarily through their estrogenic and anti-inflammatory effects,⁵⁹ and also may provide protection against hyperlipidemia, cancers, and menopausal syndrome.⁶⁰ Although differences exist between “in vivo” and “in vitro” experiments, the discrepancy is often attributed to the low bioavailability of lignans.⁶⁰ Observational studies have shown associations between plant lignan intake and improved cardiovascular disease risk parameters, but findings are not entirely consistent.⁵⁹

Clinical studies have shown inconsistent findings. Some studies have suggested that flaxseed supplementation may have benefits such as lowering blood pressure,⁶¹ reducing inflammatory biomarkers,^62,63 and improving blood lipid profiles,⁶⁴ while a fiber-rich diet containing significant amounts of lignans did not show the same improvements in CVD risk factors among diabetes patients.^59,65 A study⁶⁶ conducted in menopausal subjects did not find a statistically significant relationship between lignan and TG, LDL-c, and HDL-c. However, they did find that flaxseed, which is rich in lignan, improved apolipoprotein (apo) A1 and apo B levels.⁶⁶ Previous cohort studies such as Dutch Prospect-EPIC (European Prospective Study Into Cancer and Nutrition) cohort⁶⁷ and Zutphen Elderly Study⁶⁸ have shown mixed results, with some finding no association between total lignan intake and coronary heart disease (CHD) risk and mortality, while others identified associations for only specific types of lignans, such as matairesinol.^67,68 Some factors may affect the contradiction of the results, including various efficiencies of converting different plant lignans into enterolignan, lack of repeated measurements of diet, varying follow-up periods, and modest sample sizes.⁵⁹ Addressing these limitations, another study⁵⁹ found that lignans, including 4 individual lignans, were associated with a lower risk of CHD, in a possibly non-linear relationship. On the other hand, differences in the gut microbiome can affect the efficiency of enterolignan production from different plant lignans in the same amount.^59,69–72

The most common plant lignans in foods are pinoresinol (Pino), matairesinol (Mat), lariciresinol (Lari), medioresinol (Med), syringaresinol (Syr), sesamin (Ses), secoisolariciresinol (Seco), the glycosylated form of Seco – secoisolariciresinol diglucoside (SDG), and hydroxymatairesinol (hMat),⁷³ are found in most fiber-rich plants, especially seeds, whole grains, fruits, vegetables, wine, tea, and coffee.⁵⁹ The lignan content in foods is usually low, typically not exceeding 2 mg/100 g. An exception to this is sesame seeds and flaxseed, which have lignan contents several times higher than other dietary sources.^58,74 In our study, as well, most of the investigated lignans were flaxseed lignans such as SDG (the major lignan in flaxseed⁷³), and sesamin based on the available studies. SDG has demonstrated efficacy in lowering blood lipids.

SDG is naturally present in flaxseed hull in a bound form with 3-hydroxy-3-methylglutaric acid (HMGA). The natural bound structure of SDG with HMGA (SDG polymer) encompasses bioactive compounds that are beneficial in the prevention of high cholesterol. Upon consumption of the lignan-bound structure, SDG and HMGA are released in the stomach and small intestines. Subsequently, SDG is metabolized into secoisolariciresinol, enterolactone, and enterodiol. These metabolites are distributed throughout the body and accumulate in the liver, kidney, skin, as well as other tissues and organs, leading to a reduction in cholesterol, TG, LDL-c, and lipid peroxidation products.³⁰

Neolignans and flax lignans have been linked to benefits in diabetes and hypercholesterolemia,¹⁷ and several studies have shown that supplementing with lignans can be effective in reducing central obesity, hypertension, dyslipidemia, and platelet aggregation.^75,76 Furthermore, in-vivo studies have demonstrated that supplementation with Schisandra chinensis lignans in mice leads to a significant decrease in the expression of cholesterol metabolism in the liver by reducing sterol regulatory elements (SREBP-2) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR).^77–79 Also, some in-vivo studies have shown that supplementation with lignan can decrease atherosclerosis by activating antioxidant reserves and reducing oxygen radicals.^76,80–82

Our meta-analysis provides several advantages. It is the first comprehensive evaluation of the effects of lignan intake on lipid profiles in adults, considering lignan rather than focusing on flaxseed as previous analyses have done. Second, our search strategy was thorough and inclusive, with no time limitations. Third, the GRADE analysis results for studies concerning TC and LDL-c indicated that these studies were of high quality. This finding supports the conclusions of the current study regarding the probability of effectiveness of lignan supplementation in reducing these two serum indicators. Fourth, sensitivity analysis showed that no single study significantly influenced the overall results, and there was no significant publication bias for the assessed lipids. Fifth, we reviewed an ample number of articles for each lipid. Sixth, the heterogeneity among articles was low for TG and HDL-c, and we identified sources of heterogeneity for TC and LDL-c through subgroup analysis. Seventh, we also conducted a meta-regression to examine the relationship between the effect size and potential moderator variables such as age, supplementation dosage, body mass index, and supplementation duration. However, there are some restrictions to be noted: First, the participants had various primary blood lipid levels, which may have impacted study outcomes. however, we conducted a subgroup analysis based on the health status of the participants. Second, we analyzed both crossover and parallel studies, which differ in methods and biases. Third, it was not possible to perform subgroup analysis on different lignans due to the various number of lignans in each group. Fourth, apart from the 3 studies,^53,55,56 the others did not appear to measure urinary lignans. Therefore, it is suggested that this issue be further investigated to examine compliance rates in future studies. Finally, the findings of this meta-analysis may be impacted by the unclear quality of the studies as assessed by the Cochrane risk of bias assessment, and this lack of detailed methodology raises potential concerns about bias in the results, which should be considered during interpretation. Also, the studies related to TG were assessed to be of low quality based on the GRADE analysis, while those involving HDL-c were rated as moderate quality. This suggests that the lack of observed effects from lignan supplementation on TG and HDL-c requires further high-quality research to confirm these results.

5. Conclusion

Lignan supplementation is associated with reductions in TC and LDL-c in adults. However, no significant effect was observed for TG and HDL-c. Given the observed decrease in TG levels following lignan supplementation, and considering the low quality of the articles that addressed this factor, it is suggested to conduct additional studies of higher quality to more precisely determine the significance of this effect especially in hypercholesterolemic individuals. On the other hand, based on the meta-regression analysis, there was a possibility that HDL-C would be affected by increasing the dose of lignan (p-value = 0.05), so it is also important to further investigate this issue in future studies.

Supplemental Material

sj-jpg-1-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-1-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-2-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-2-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-3-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-3-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-4-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-4-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-5-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-5-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-6-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-6-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-7-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-7-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-8-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-8-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-9-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-9-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-10-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-10-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-11-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-11-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-12-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-12-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-13-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-13-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-14-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-14-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-15-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-15-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-16-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-16-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-17-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-17-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-18-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-18-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-19-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-19-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-20-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-20-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-21-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-21-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-22-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-22-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-23-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-23-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-jpg-24-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-jpg-24-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Supplemental Material

sj-docx-25-mnm-10.1177_1973798X261437685 - Supplemental material for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials

Supplemental material, sj-docx-25-mnm-10.1177_1973798X261437685 for The effect of lignan supplementation on lipid profile in adults: A systematic review and meta-analysis of randomized controlled trials by Zohreh Ebrahimi, Behnaz Pourrajab, Zahra Shojaeian and Mohammad Gholizadeh in Mediterranean Journal of Nutrition and Metabolism

Footnotes

ORCID iD

Behnaz Pourrajab

Authors’ contributions

Z.E. conceived and designed the study's search strategy. Z.E. and Z.SH. selected studies, while Z.SH. extracted data. B.P. evaluated the studies for bias and performed data analysis. M.GH. interpreted the results. Z.E., B.P., and M.GH. drafted the initial manuscript, which was reviewed and approved by B.P. and other authors. B.P. and Z.E. revised the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data-availability

All data generated or analyzed during this study is unequivocally included in this published article.

Supplemental material

Supplemental material for this article is available online.

References

Crismaru

Pantea Stoian

Bratu

, et al. Low-density lipoprotein cholesterol lowering treatment: the current approach. Lipids Health Dis 2020; 19: 1–10.

Berberich

Hegele

. A modern approach to dyslipidemia. Endocr Rev 2022; 43: 611–653.

Shahwan

Jairoun

Farajallah

, et al. Prevalence of dyslipidemia and factors affecting lipid profile in patients with type 2 diabetes. Diabetes Metab Syndr Clin Res Rev 2019; 13: 2387–2392.

Lazarte

Hegele

. Dyslipidemia management in adults with diabetes. Can J Diabetes 2020; 44: 53–60.

Vekic

Stefanovic

Zeljkovic

. Obesity and dyslipidemia: a review of current evidence. Curr Obes Rep 2023; 12: 207–222.

Moradinazar

Pasdar

Najafi

, et al. Association between dyslipidemia and blood lipids concentration with smoking habits in the Kurdish population of Iran. BMC Public Health 2020; 20: 1–10.

Okekunle

Asowata

Adedokun

, et al. Secondhand smoke exposure and dyslipidemia among non-smoking adults in the United States. Indoor Air 2022; 32: e12914.

Kalra

Aggarwal

Khandelwal

. Thyroid dysfunction and dysmetabolic syndrome: the need for enhanced thyrovigilance strategies. Int J Endocrinol 2021; 2021: 9641846.

Simha

. Management of hypertriglyceridemia. Br Med J 2020; 371: m3109.

10.

Shah

Banerjee

Singh

, 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 Systems 2025: 3–73. doi:10.1002/9781119769484.ch1

11.

Liu

Dong

Deng

, et al. Regulation of aging-related chronic diseases by dietary polyphenols: an updated over-view. Curr Res Food Sci 2025; 11: 101163.

12.

Bhuia

Wilairatana

Chowdhury

, et al. Anticancer potentials of the lignan magnolin: a systematic review. Molecules 2023; 28: 3671.

13.

Pourrajab

Sohouli

Amirinejad

, 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 Nutr 2022; 62: 6005–6015.

14.

Sohouli

Haghshenas

Hernández-Ruiz

, 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 Res 2022; 36: 1126–1134.

15.

Ražná

Nôžková

Vargaová

, et al. Biological functions of lignans in plants. Agriculture (Pol'nohospodárstvo) 2021; 67: 155–165.

16.

Kalinová

Marešová

Tříska

, et al. Distribution of lignans in Panicum miliaceum, Fagopyrum esculentum, Fagopyrum tataricum, and Amaranthus hypochondriacus. J Food Compos Anal 2022; 106: 104283.

17.

Rodríguez-García

Sánchez-Quesada

Toledo

, et al.

Naturally lignan-rich foods: a dietary tool for health promotion?

Molecules 2019; 24: 917.

18.

Peterson

Dwyer

Adlercreutz

, et al. Dietary lignans: physiology and potential for cardiovascular disease risk reduction. Nutr Rev 2010; 68: 571–603.

19.

Shi

Wang

Yan

. Therapeutic potential of naturally occurring lignans as anticancer agents. Curr Top Med Chem 2022; 22: 1393–1405.

20.

Heinonen

Nurmi

Liukkonen

, et al. In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol. J Agric Food Chem 2001; 49: 3178–3186.

21.

Adlercreutz

. Lignans and human health. Crit Rev Clin Lab Sci 2007; 44: 483–525.

22.

Landete

Arqués

Medina

, et al. Bioactivation of phytoestrogens: intestinal bacteria and health. Crit Rev Food Sci Nutr 2016; 56: 1826–1843.

23.

Kitts

Yuan

Wijewickreme

, et al. Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol and enterolactone. Mol Cell Biochem 1999; 202: 91–100.

24.

Lee

Kim

Jung

, et al. Matairesinol inhibits angiogenesis via suppression of mitochondrial reactive oxygen species. Biochem Biophys Res Commun 2012; 421: 76–80.

25.

van der Schouw

Pijpe

Lebrun

, et al. Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women. Arterioscler, Thromb, Vasc Biol 2002; 22: 1316–1322.

26.

Kreijkamp-Kaspers

Kok

Bots

, et al. Dietary phytoestrogens and plasma lipids in Dutch postmenopausal women; a cross-sectional study. Atherosclerosis 2005; 178: 95–100.

27.

de Kleijn

van der Schouw

Wilson

, et al. Dietary intake of phytoestrogens is associated with a favorable metabolic cardiovascular risk profile in postmenopausal U.S. Women: the framingham study. J Nutr 2002; 132: 276–282.

28.

Mokhber

Keshavarz

Shidfar

, 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 Metab 2020; 19: e82984.

29.

Nakamura

Okumura

Ono

, et al. Sesame lignans reduce LDL oxidative susceptibility by downregulating the platelet-activating factor acetylhydrolase. Eur Rev Med Pharmacol Sci 2020; 24: 2151–2161.

30.

Tse

Guo

Shim

, et al. Availability of bioactive flax lignan from foods and supplements. Crit Rev Food Sci Nutr 2023; 63: 9843–9858.

31.

Navarro

Levy

Curtis

, et al. Effect of a flaxseed lignan intervention on circulating bile acids in a placebo-controlled randomized, crossover trial. Nutrients 2020; 12: 1837.

32.

Duarte

Shah

Sanches Silva

. Flaxseed in diet: a comprehensive Look at pros and cons. Molecules 2025; 30: 1335.

33.

Yang

Prabahar

, 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 Pract 2025; 112478.

34.

Wang

Feng

Prabahar

, et al. The effect of phytosterol supplementation on lipid profile: a critical umbrella review of interventional meta-analyses. Phytother Res 2024; 38: 507–519.

35.

Xia

Xiang

Gaman

, 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 Res 2022; 36: 4398–4408.

36.

Chen

, 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 Nutr 2023; 63: 2886–2895.

37.

Masjedi

Pour

Shokoohinia

, 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 Cardiol 2022; 47: 100931.

38.

Sabet

Ahmadi

Akrami

, 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 Cardiol 2024; 47: e24211.

39.

Hadi

Askarpour

Salamat

, 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 Res 2020; 152: 104622.

40.

Moher

Shamseer

Clarke

, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4: 1.

41.

DerSimonian

Laird

. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.

42.

Higgins

. Cochrane handbook for systematic reviews of interventions version 5.0. 1. The Cochrane Collaboration. http://www cochrane-handbook org. 2008.

43.

Hozo

Djulbegovic

Hozo

. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13.

44.

Higgins

Thompson

. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539–1558.

45.

Greenhouse

Iyengar

. Sensitivity analysis and diagnostics. In: The handbook of research synthesis and meta-analysis . 2nd ed. 2009, pp.417–433.

46.

Duval

Tweedie

. Trim and fill: a simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000; 56: 455–463.

47.

Mohammadshahi

Zakerzadeh

Zakerkish

, et al. Effects of sesamin on the glycemic index, lipid profile, and serum Malondialdehyde level of patients with type II diabetes. 2016.

48.

Helli

Mowla

Mohammadshahi

, et al. Effect of sesamin supplementation on cardiovascular risk factors in women with rheumatoid arthritis. J Am Coll Nutr 2016; 35: 300–307.

49.

Barre

Mizier-Barre

Stelmach

, 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 Metab 2012; 2012: 585170.

50.

Cornish

Chilibeck

Paus-Jennsen

, 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 Metabolism 2009; 34: 89–98.

51.

Fukumitsu

Aida

Shimizu

, et al. Flaxseed lignan lowers blood cholesterol and decreases liver disease risk factors in moderately hypercholesterolemic men. Nutr Res 2010; 30: 441–446.

52.

Zhang

Wang

Liu

, et al. Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects. Br J Nutr 2008; 99: 1301–1309.

53.

Pan

Sun

Chen

, et al. Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial. PloS one 2007; 2: e1148.

54.

Almario

Karakas

. Lignan content of the flaxseed influences its biological effects in healthy men and women. J Am Coll Nutr 2013; 32: 194–199.

55.

Hodgson

Puddey

, et al. Sesame supplementation does not improve cardiovascular disease risk markers in overweight men and women. Nutrition, Metabolism and Cardiovascular Diseases 2009; 19: 774–780.

56.

Hallund

Ravn-Haren

Bügel

, et al. A lignan complex isolated from flaxseed does not affect plasma lipid concentrations or antioxidant capacity in healthy postmenopausal women. J Nutr 2006; 136: 112–116.

57.

Musazadeh

Nezamoleslami

Faghfouri

, 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 Rev 2025; 19: 103241.

58.

Soleymani

Habtemariam

Rahimi

, et al. The what and who of dietary lignans in human health: special focus on prooxidant and antioxidant effects. Trends Food Sci Technol 2020; 106: 382–390.

59.

Sampson

, et al. Lignan intake and risk of coronary heart disease. J Am Coll Cardiol 2021; 78: 666–678.

60.

Landete

. Plant and mammalian lignans: a review of source, intake, metabolism, intestinal bacteria and health. Food Res Int 2012; 46: 410–424.

61.

Ursoniu

Sahebkar

Andrica

, et al. Effects of flaxseed supplements on blood pressure: a systematic review and meta-analysis of controlled clinical trial. Clin Nutr 2016; 35: 615–625.

62.

Askarpour

Karimi

Hadi

, et al. Effect of flaxseed supplementation on markers of inflammation and endothelial function: a systematic review and meta-analysis. Cytokine 2020; 126: 154922.

63.

Ren

G-Y

Chen

C-Y

Chen

G-C

, et al. Effect of flaxseed intervention on inflammatory marker C-reactive protein: a systematic review and meta-analysis of randomized controlled trials. Nutrients 2016; 8: 136.

64.

Pan

Demark-Wahnefried

, et al. Meta-analysis of the effects of flaxseed interventions on blood lipids. Am J Clin Nutr 2009; 90: 288–297.

65.

Jenkins

Kendall

Augustin

, et al. Effect of wheat bran on glycemic control and risk factors for cardiovascular disease in type 2 diabetes. Diabetes Care 2002; 25: 1522–1528.

66.

Lucas

Wild

Hammond

, et al. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J Clin Endocrinol Metab 2002; 87: 1527–1532.

67.

van der Schouw

Kreijkamp-Kaspers

Peeters

, et al. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in western women. Circulation 2005; 111: 465–471.

68.

Milder

Feskens

Arts

, et al. Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the zutphen elderly study. Am J Clin Nutr 2006; 84: 400–405.

69.

Kuijsten

Arts

Vree

, et al. Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside. J Nutr 2005; 135: 795–801.

70.

Rowland

Wiseman

Sanders

, et al. Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora. Nutr Cancer 2000; 36: 27–32.

71.

Possemiers

Bolca

Eeckhaut

, et al. Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria: producer phenotyping and relation with intestinal community. FEMS Microbiol Ecol 2007; 61: 372–383.

72.

Clavel

Henderson

Alpert

C-A

, et al. Intestinal bacterial communities that produce active estrogen-like compounds enterodiol and enterolactone in humans. Appl Environ Microbiol 2005; 71: 6077–6085.

73.

Bach Knudsen

Nørskov

Bolvig

, et al. Dietary polyphenols. Dietary Polyphenols: Their Metabolism and Health Effects 2020: 365–406.

74.

Pilkington

. Lignans: a chemometric analysis. Molecules 2018; 23: 1666.

75.

Milder

Feskens

Arts

, et al. Intake of the plant lignans secoisolariciresinol, matairesinol, lariciresinol, and pinoresinol in Dutch men and women. J Nutr 2005; 135: 1202–1207.

76.

Van Niekerk

Hendriks T

JAGL

Havekes

, 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.

Sun

J-H

Liu

Cong

L-X

, et al. Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans in diet-induced hyperlipidemia mice. Lipids Health Dis 2017; 16: 1–14.

78.

Park

Velasquez

. Potential effects of lignan-enriched flaxseed powder on bodyweight, visceral fat, lipid profile, and blood pressure in rats. Fitoterapia 2012; 83: 941–946.

79.

Prasad

. Suppression of phosphoenolpyruvate carboxykinase gene expression by secoisolariciresinol diglucoside (SDG), a new antidiabetic agent. International Journal of Angiology 2002; 11: 107–109.

80.

Prasad

. Antioxidant activity of secoisolariciresinol diglucoside-derived metabolites, secoisolariciresinol, enterodiol, and enterolactone. International Journal of Angiology 2000; 9: 220–225.

81.

Prasad

. Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed. Mol Cell Biochem 1997; 168: 117–123.

82.

Di Padova

Bosisio

Cighetti

, et al. 3-Hydroxy-3-methylglutaric Acid (HMGA) reduces dietary cholesterol induction of saturated bile in hamster. Life Sci 1982; 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.

0.11 MB

0.03 MB

0.10 MB

0.11 MB

0.00 MB

0.14 MB

0.12 MB

0.11 MB

0.12 MB

0.11 MB

0.10 MB

0.35 MB

0.34 MB

0.35 MB

0.15 MB

0.12 MB

0.39 MB

0.11 MB

0.10 MB

0.11 MB

0.12 MB

0.14 MB