NICEVIVA
MONOGRAPH SPEC LATEST 2025

Flaxseed Oil

OMEGA FATTY ACIDS · Evidence Monograph

Flaxseed Oil is an evidence-graded omega fatty acids monograph evaluated across 30 peer-reviewed PubMed studies (10 meta-analyses, 2 systematic reviews, and 6 randomized controlled trials, encompassing n = 2,640 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for cell membrane phospholipid integrity, triglyceride modulation, and eicosanoid resolution.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 30 Studies
Meta-Analyses · Reviews 10 Meta · 2 Systematic Reviews
Randomized Trials (RCT) 6 RCTs (8 Double-Blind)
Cumulative Participants n = 2,640
Reported Trial Dosages 3 g/day · 2000mg · 20 g
Trial Duration Range 10 weeks · 12 weeks · 6 weeks
Reading Time ~15 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for cell membrane phospholipid integrity, triglyceride modulation, and eicosanoid resolution (supported by 30 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (3 g/day · 2000mg · 20 g) over a structured 10 weeks evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Purified Small-Fish rTG or Triglyceride-Form EPA/DHA
Choose IFOS/heavy-metal-tested small-pelagic fish or algal oil in individual blister packs to prevent lipid peroxidation.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Absence of fishy reflux and gradual improvement in lipid profile or ocular surface comfort.
Dose Adjustment Signal: Discontinue and consult a physician if easy bruising, epistaxis, or gingival bleeding occurs—especially if taking antiplatelets.
CHRONOBIOLOGY · Optimal Dosing Window PM 19:00
Immediately After a Fat-Containing Meal
Bile acid and pancreatic lipase secretion during meals increases omega-3 fatty acid micellar absorption by up to 3-fold.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
inflammation (PubMed clinical endpoint)
blood pressure (PubMed clinical endpoint)
weight (PubMed clinical endpoint)
brain (PubMed clinical endpoint)
01

What Is Flaxseed Oil & Why Does Form Matter?

Flaxseed Oil is classified under OMEGA FATTY ACIDS and has been investigated across 30 peer-reviewed PubMed publications for its role in cell membrane phospholipid integrity, triglyceride modulation, and eicosanoid resolution.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (3 g/day, 2000mg, 20 g).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Flaxseed Oil frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (6 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Flaxseed Oil acts on pathways governing cell membrane phospholipid integrity, triglyceride modulation, and eicosanoid resolution. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Choose IFOS/heavy-metal-tested small-pelagic fish or algal oil in individual blister packs to prevent lipid peroxidation.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Flaxseed Oil an overall evidence rating of GRADE High (4.0 / 4.0) based on 30 PubMed studies: 10 meta-analyses, 2 systematic reviews, and 6 randomized controlled trials (8 double-blind, n = 2,640 total participants).

Representative peer-reviewed findings include: • PMID:39558500 (2024) — "Supplementation of Olive Oil and Flaxseed Oil on Blood Pressure and Inflammation in Healthy and At-Risk Adults: A Systematic Literature Review and Meta-Analysis." (CONCLUSION: Longer-duration, higher-dose, and larger-scale RCTs are needed to better understand the efficacy of OO and FLO supplementation on BP.) • PMID:38992480 (2024) — "The effects of flaxseed (Linum usitatissimum) supplementation on anthropometric indices: An updated systematic review and meta-analysis of randomized clinical trials." (Therefore, flaxseed can be considered as an adjunctive therapeutic approach in improving obesity.) • PMID:37778442 (2023) — "Effect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials." (Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.)

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

Study (PMID · Year)MD Effect Size & 95% CI DistributionEstimate (95% CI)PMID 39558500-0.47 (-1.76–0.8)PMID 38992480-0.63 (-1–-0.27)PMID 35859037-3.86 (-7.59–-0.13)PMID 33183549-0.22 (-0.43–-0.01)PMID 31115436-0.38 (-1.19–-0.3)PMID 29228348-7.32 (-11.66–-2.97)PMID 38726572-85.78 (-155.24–-16.32)-1.8e+02Null (0)24Metric: MD
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Purified Small-Fish rTG or Triglyceride-Form EPA/DHA. Choose IFOS/heavy-metal-tested small-pelagic fish or algal oil in individual blister packs to prevent lipid peroxidation.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 3 g/day · 2000mg · 20 g · 220 mg over 10 weeks · 12 weeks · 6 weeks · 3 months. Optimal timing window: PM 19:00 · Immediately After a Fat-Containing Meal (Bile acid and pancreatic lipase secretion during meals increases omega-3 fatty acid micellar absorption by up to 3-fold.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Absence of fishy reflux and gradual improvement in lipid profile or ocular surface comfort.

Adjustment & Discontinuation Signals: Discontinue and consult a physician if easy bruising, epistaxis, or gingival bleeding occurs—especially if taking antiplatelets.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Flaxseed Oil, but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 19:00 · Immediately After a Fat-Containing Meal) with a full glass of water.
  • Stay within clinically studied daily dosages (3 g/day · 2000mg · 20 g) and re-evaluate efficacy after 10 weeks.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (30 Studies) · 19 Quantitative Analyses

01
META-ANALYSIS Current hypertension reviews (2024) PMID: 39558500 ↗
Supplementation of Olive Oil and Flaxseed Oil on Blood Pressure and Inflammation in Healthy and At-Risk Adults: A Systematic Literature Review and Meta-Analysis.
Clinical Trial Synthesis 2024 Meta-Analysis published in Current hypertension reviews involving n = 17 participants; statistical significance reported at p = 0.65 (MD -0.47). Key conclusion: CONCLUSION: Longer-duration, higher-dose, and larger-scale RCTs are needed to better understand the efficacy of OO and FLO supplementation on BP.
View Original PubMed Abstract ↓

BACKGROUND: Adding olive oil (OO) and flaxseed oil (FLO) to the diet has been reported to improve endothelial function and reduce inflammation. However, the efficacy of supplementing OO and FLO on blood pressure (BP) in normo-, pre-, and hypertensive stage 1 adults is uncertain. OBJECTIVE: This study aimed to systematically review the literature on OO and FLO supplementation on BP and select inflammatory markers in healthy adults and adults at risk of hypertension. METHODS: Four databases, PubMed, CINHAL, Web of Science, and Medline (Ovid), were searched from inception until October 2023 for randomized control trials (RCTs) comparing OO and FLO supplementation in normotensive or adults at risk of hypertension. The outcomes included were systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) and at least one inflammatory marker, C-reactive protein (CRP), interleukin6 (IL6), or tumor necrosis factor alpha (TNFα). The risk of bias was assessed using version 2 of the Cochrane risk of bias tool for RCTs, publication bias visualization was performed using funnel plots, and meta-analysis was completed to generate average estimates of effects in 2024. RESULTS: Seventeen RCTs, comprising 14 studies on OO and 3 on FLO, met the inclusion criteria. Meta-analysis using a random-effects model reported no significant effect on SBP n=17 mean difference (MD) -0.48; 95% CI: -1.76, 0.80; p=0.65, I2 =0%) and DBP (n=16, MD -0.47; 95% CI: -1.33, 0.39; p=0.65, I2 =0%) or inflammatory markers, CRP (n=8, MD 0.11; 95% CI: -1.18, 0.40; p=0.98, I2 =0%), IL6 (n=3, MD -0.15; 95% CI: -0.57, 0.27; p=0.87, I2 =0%), and TNFα (n=3, MD-0.08; 95% CI: -0.12, -0.03; p=0.98, I2 =0%). CONCLUSION: Longer-duration, higher-dose, and larger-scale RCTs are needed to better understand the efficacy of OO and FLO supplementation on BP. Further insight will better inform dietary supplement use for preventing hypertension.

02
META-ANALYSIS Complementary therapies in medicine (2024) PMID: 38992480 ↗
The effects of flaxseed (Linum usitatissimum) supplementation on anthropometric indices: An updated systematic review and meta-analysis of randomized clinical trials.
Clinical Trial Synthesis 2024 Meta-Analysis published in Complementary therapies in medicine; statistical significance reported at p = 0.001 (MD -0.63). Key conclusion: Therefore, flaxseed can be considered as an adjunctive therapeutic approach in improving obesity.
View Original PubMed Abstract ↓

OBJECTIVE: Flaxseed (Linum usitatissimum) supplementation has shown promise as an anti-obesity agent in various clinical trials, although results have been inconsistent. To provide a more accurate assessment of the impact of flaxseed supplementation on anthropometric indices, a systematic review and meta-analysis was performed. METHODS: We searched several international databases until August 2023, including Scopus, PubMed, Web of Science, Embase, and Cochrane Library. Weighted mean differences (WMDs) were analyzed using a random-effects model. RESULTS: Sixty-four trials comprising 72 treatment arms were included. All studies reported the intervention types (Lignans, Whole flaxseed, and Flaxseed oil) and dosage. However, three studies did testing for purity, and 40 studies reported potency. Also, the risk of contamination with heavy metals was not mentioned in studies. Another limitation was the lack of blind evaluation in the studies. According to three trials included in the systematic review, flaxseed did not affect anthropometric indices. Our meta-analysis revealed significant reductions in body weight (WMD = -0.63 kg; 95 % CI: -1.00, -0.27, P < 0.001; I2 = 76.7 %, P < 0.001), body mass index (BMI) (WMD: -0.24 kg/m2, 95 % CI: -0.36, -0.11, P < 0.001; I2 = 78.5 %, P < 0.001) and waist circumference (WC) (WMD: -1.43 cm, 95 % CI: -2.06, -0.80, P < 0.001; I2 = 81.1 %, P < 0.001) following flaxseed supplementation. Subgroup analyses indicated that interventions lasting 10-20 weeks, and studies involving subjects with higher BMI (>30 kg/m2) showed more significant anti-obesity effects. Based on the GRADE evaluation, body weight, BMI, and WC results were considered as moderate-certainty evidence. CONCLUSION: Our systematic review and meta-analysis suggests that supplementation with flaxseed (Linum usitatissimum) leads to meaningful improvements in body weight, BMI, and WC. Therefore, flaxseed can be considered as an adjunctive therapeutic approach in improving obesity.

03
META-ANALYSIS Advances in nutrition (Bethesda, Md.) (2023) PMID: 37778442 ↗
Effect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Clinical Trial Synthesis 2023 Meta-Analysis published in Advances in nutrition (Bethesda, Md.) involving n = 1,183 participants (SMD -0.45). Key conclusion: Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.
View Original PubMed Abstract ↓

Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia, and hypertension. Alpha-linolenic acid (ALA) is a plant-based essential polyunsaturated fatty acid associated with reduced CVD risks. This systematic review and meta-analysis aimed to investigate the effects of supplementation with ALA compared with the placebo on CVD risk factors in people with obesity or overweight (International Prospective Register of Systematic Reviews Registration No. CRD42023429563). This review included studies with adults using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomly assigned trials with parallel or crossover designs. The Cochrane Collaboration tool was used for assessing the risk of bias (Version 1). PubMed, Web of Science, Embase, and Cochrane library databases were searched from inception to April 2023. Nineteen eligible randomized controlled trials, including 1183 participants, were included in the meta-analysis. Compared with placebo, dietary ALA supplementation significantly reduced C-reactive protein concentration (standardized mean difference [SMD] = -0.38 mg/L; 95% confidence interval [CI]: -0.72, -0.04), tumor necrosis factor-α concentration (SMD = -0.45 pg/mL; 95% CI: -0.73, -0.17), triglyceride in serum (SMD = -4.41 mg/dL; 95% CI: -5.99, -2.82), and systolic blood pressure (SMD = -0.37 mm Hg; 95% CI: -0.66, -0.08); but led to a significant increase in low-density lipoprotein cholesterol concentrations (SMD = 1.32 mg/dL; 95% CI: 0.05, 2.59). ALA supplementation had no significant effect on interleukin-6, diastolic blood pressure, total cholesterol, or high-density lipoprotein cholesterol (all P ≥ 0.05). Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.

04
META-ANALYSIS Nutritional neuroscience (2024) PMID: 37589276 ↗
A systematic review and meta-analysis of the omega-3 fatty acids effects on brain-derived neurotrophic factor (BDNF).
Clinical Trial Synthesis 2024 Meta-Analysis published in Nutritional neuroscience involving n = 587 participants; statistical significance reported at p = 0.001 (SMD 0.72). Key conclusion: Therefore, omega-3 FAs should be prioritized as agents for increasing BDNF in interventions.
View Original PubMed Abstract ↓

BACKGROUND: Omega-3 fatty acids (omega-3 FAs) have attracted the attention of researchers because of their influence on circulatory levels of brain-derived neurotrophic factor (BDNF). Our objective was to review systematically and Meta-analyze randomized controlled trials (RCTs) to assess the effects of omega-3 FAs supplementation on serum BDNF concentration. METHODS: Scopus, PubMed, Web of Science, and Cochrane Library were systematically searched until April 2023. The Cochrane risk of bias assessment tool was utilized to evaluate the quality of the studies. A random-effects model was employed to estimate the overall effect size of BDNF levels, using the Standard Mean Difference (SMD) and a 95% confidence interval (CI). The heterogeneity among the studies was assessed using chi-squared and I2 statistics. RESULTS: A total of 12 studies involving 587 subjects were included. The supplementation of PUFA was found to be associated with a significant increase in serum levels of BNDF in the group receiving the supplements, as compared to the placebo group (SMD: 0.72 pg/mL, 95% CI: 0.28, 1.15; P < 0.001) (I2 = 84.39%, P < 0.001). Sub-group analyses revealed similar findings in trials with fewer than 10 weeks, which utilized both animal (fish oil) and herbal (flaxseed) forms of omega-3 supplements with a high daily dosage of 2000mg. CONCLUSION: The present systematic review and meta-analysis indicate the efficacy of omega-3 FAs in increasing the serum concentration of BDNF. Therefore, omega-3 FAs should be prioritized as agents for increasing BDNF in interventions.

05
META-ANALYSIS Phytotherapy research (2022) PMID: 35859037 ↗
The effect of flaxseed oil consumtion on blood pressure among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized clinical trials.
Clinical Trial Synthesis 2022 Meta-Analysis published in Phytotherapy research; statistical significance reported at p = 0.04 (MD -3.86). Key conclusion: However, the overall effect illustrated no significant change in diastolic (WMD: -1.71 mmHg, 95% CI: -3.67 to 0.26, p = .09) BP (DBP) in the intervention group compared with the control group.
View Original PubMed Abstract ↓

We systematically reviewed randomized clinical trials (RCTs) to elucidate the overall effects of flaxseed oil consumption on blood pressure (BP) in patients with metabolic syndrome and related disorders. PubMed, Scopus, Cochrane Library, and ISI Web of Science databases were systematically searched until March 31, 2020, to find RCTs that examined the effect of flaxseed oil consumption on BP. Weighed mean difference (WMD) was pooled using a random-effects model. Standard methods were used for the assessment of heterogeneity, sensitivity analysis, and publication bias. Meta-analysis of five trials (6 arms) showed significant reductions in systolic (WMD: -3.86 mmHg, 95% CI: -7.59 to -0.13, p = .04) BP (SBP) after flaxseed oil consumption. However, the overall effect illustrated no significant change in diastolic (WMD: -1.71 mmHg, 95% CI: -3.67 to 0.26, p = .09) BP (DBP) in the intervention group compared with the control group. Our findings revealed that flaxseed oil consumption has favorable effects on SBP in patients with metabolic syndrome and related disorders. However, further investigations are needed to provide more reliable evidence. © 2022 John Wiley & Sons Ltd.

06
META-ANALYSIS Clinical nutrition ESPEN (2020) PMID: 33183549 ↗
Effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.
Clinical Trial Synthesis 2020 Meta-Analysis published in Clinical nutrition ESPEN (MD -0.22). Key conclusion: This suggests that flaxseed oil supplementation may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders.
View Original PubMed Abstract ↓

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to analyze the effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome (MetS) and related disorders. METHODS: Databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central library were searched until January 31th, 2019. RESULTS: 14 effect sizes from 12 studies were identified eligible to be included in current meta-analysis. Flaxseed supplementation resulted in a significant reduction in interleukin 6 (IL-6) (WMD: -0.22; 95% CI: -0.43, -0.01) and malondialdehyde (MDA) (WMD: -0.17; 95% CI: -0.31, -0.03) and a significant increase in total antioxidant capacity (TAC) levels (WMD: 137.25; 95% CI: 68.04, 206.47). Flaxseed oil supplementation did not affect other biomarkers of inflammation and oxidative stress. CONCLUSIONS: Overall, this meta-analysis demonstrated flaxseed oil supplementation decreased IL-6 and MDA levels, and increased TAC, but did not affect other biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. This suggests that flaxseed oil supplementation may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders.

07
CLINICAL STUDY The Cochrane database of systematic reviews (2020) PMID: 32677037 ↗
Nutritional interventions for treating foot ulcers in people with diabetes.
Clinical Trial Synthesis 2020 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews involving n = 629 participants. Key conclusion: Nutritional interventions may improve wound healing of foot ulcers in people with diabetes.
View Original PubMed Abstract ↓

BACKGROUND: Foot ulcers in people with diabetes are non-healing, or poorly healing, partial, or full-thickness wounds below the ankle. These ulcers are common, expensive to manage and cause significant morbidity and mortality. The presence of a wound has an impact on nutritional status because of the metabolic cost of repairing tissue damage, in addition to the nutrient losses via wound fluid. Nutritional interventions may improve wound healing of foot ulcers in people with diabetes. OBJECTIVES: To evaluate the effects of nutritional interventions on the healing of foot ulcers in people with diabetes. SEARCH METHODS: In March 2020 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated the effect of nutritional interventions on the healing of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS: Two review authors, working independently, assessed included RCTs for their risk of bias and rated the certainty of evidence using GRADE methodology, using pre-determined inclusion and quality criteria. MAIN RESULTS: We identified nine RCTs (629 participants). Studies explored oral nutritional interventions as follows: a protein (20 g protein per 200 mL bottle), 1 kcal/mL ready-to-drink, nutritional supplement with added vitamins, minerals and trace elements; arginine, glutamine and β-hydroxy-β-methylbutyrate supplement; 220 mg zinc sulphate supplements; 250 mg magnesium oxide supplements; 1000 mg/day omega-3 fatty acid from flaxseed oil; 150,000 IU of vitamin D, versus 300,000 IU of vitamin D; 250 mg magnesium oxide plus 400 IU vitamin E and 50,000 IU vitamin D supplements. The comparator in eight studies was placebo, and in one study a different dos

08
META-ANALYSIS Advances in nutrition (Bethesda, Md.) (2019) PMID: 31115436 ↗
Effects of Flaxseed Interventions on Circulating Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Clinical Trial Synthesis 2019 Meta-Analysis published in Advances in nutrition (Bethesda, Md.); statistical significance reported at p = 0.001 (MD -0.38). Key conclusion: According to this meta-analysis, flaxseed significantly reduced circulating concentrations of hs-CRP and TNFα, but did not affect IL6 and CRP.
View Original PubMed Abstract ↓

Comment in Adv Nutr. 2020 Sep 1;11(5):1400-1401. doi: 10.1093/advances/nmaa046. Adv Nutr. 2020 Sep 1;11(5):1399-1400. doi: 10.1093/advances/nmaa045. Adv Nutr. 2022 Feb 1;13(1):352-354. doi: 10.1093/advances/nmab146. There have been various clinical studies on the effect of flaxseed-derived products on circulating inflammatory biomarkers, but the findings from these are contradictory. The aim of the present study was to clarify any association. A comprehensive literature search was conducted from inception to May 2018. From the eligible trials, 32 articles describing studies conducted on adults aged 18-70 y were selected for the meta-analysis. Meta-analyses using the random-effects model were performed to investigate the data and results showed significant effects of flaxseed intake on circulating high-sensitivity CRP (hs-CRP) [weighted mean difference (WMD) = -0.75; 95% CI: -1.19, -0.30; P < 0.001] and TNFα (WMD = -0.38; 95% CI: -0.75,-0.01; P = 0.04). However, no significant changes were found in IL6 concentration (WMD = -0.24; 95% CI: -0.70, 0.21; P = 0.28) and C-reactive protein (CRP) (WMD = -0.34; 95% CI:-0.89, 0.20; P = 0.22). Moreover, by eliminating 1 of the studies from the sensitivity analysis, changes in IL6 concentration were significant (WMD = -0.44; 95% CI: -0.81, -0.08). The changes in inflammatory biomarkers were dependent on study design (parallel or crossover), supplement type (flaxseed, flaxseed oil, or lignan), study quality (high or low), and participants' age and BMI. According to this meta-analysis, flaxseed significantly reduced circulating concentrations of hs-CRP and TNFα, but did not affect IL6 and CRP. Further research is needed to examine the effect of different doses and long-term benefits of flaxseed and its derivatives on inflammatory factors.

09
META-ANALYSIS Nutrition reviews (2018) PMID: 29228348 ↗
Flaxseed supplementation on glucose control and insulin sensitivity: a systematic review and meta-analysis of 25 randomized, placebo-controlled trials.
Clinical Trial Synthesis 2018 Meta-Analysis published in Nutrition reviews; statistical significance reported at p = 0.015 (MD -7.32). Key conclusion: CONCLUSIONS: Whole flaxseed, but not flaxseed oil and lignan extract, has significant effects on improving glycemic control.
View Original PubMed Abstract ↓

CONTEXT: The results of human clinical trials investigating the effects of flaxseed on glucose control and insulin sensitivity are inconsistent. OBJECTIVE: The present study aimed to systematically review and analyze randomized controlled trials assessing the effects of flaxseed consumption on glycemic control. DATA SOURCES: PubMed, Medline via Ovid, SCOPUS, EMBASE, and ISI Web of Sciences databases were searched up to November 2016. STUDY SELECTION: Clinical trials in which flaxseed or its products were administered as an intervention were included. DATA EXTRACTION: The outcomes were fasting blood glucose, insulin concentration, insulin resistance (HOMA-IR), insulin sensitivity (QUIKI), and hemoglobin A1c (HbA1c). RESULTS: A total of 25 randomized clinical trials (30 treatment arms) were included. Meta-analysis suggested a significant association between flaxseed supplementation and a reduction in blood glucose (weighted mean difference [WMD], -2.94 mg/dL; 95%CI, -5.31 to - 0.56; P = 0.015), insulin levels (WMD, -7.32 pmol/L; 95%CI, -11.66 to -2.97; P = 0.001), and HOMA-IR index (WMD, -0.49; 95%CI,: -0.78 to - 0.20; P = 0.001) and an increase in QUIKI index (WMD, 0.019; 95%CI, 0.008-0.031; P = 0.001). No significant effect on HbA1c (WMD, -0.045%; 95%CI, -0.16 to - 0.07; P = 0.468) was found. In subgroup analysis, a significant reduction in blood glucose, insulin, and HOMA-IR and a significant increase in QUIKI were found only in studies using whole flaxseed but not flaxseed oil and lignan extract. Furthermore, a significant reduction was observed in insulin levels and insulin sensitivity indexes only in the subset of trials lasting ≥12 weeks. CONCLUSIONS: Whole flaxseed, but not flaxseed oil and lignan extract, has significant effects on improving glycemic control. Further studies are needed to determine the benefits of flaxseed on glycemic parameters. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: [email protected].

10
META-ANALYSIS The American journal of clinical nutrition (2009) PMID: 19515737 ↗
Meta-analysis of the effects of flaxseed interventions on blood lipids.
Clinical Trial Synthesis 2009 Meta-Analysis published in The American journal of clinical nutrition. Key conclusion: CONCLUSIONS: Flaxseed significantly reduced circulating total and LDL-cholesterol concentrations, but the changes were dependent on the type of intervention, sex, and initial lipid profiles of the subjects.
View Original PubMed Abstract ↓

BACKGROUND: Several clinical trials have investigated the effects of flaxseed and flaxseed-derived products (flaxseed oil or lignans) on blood lipids; however, the findings have been inconsistent. OBJECTIVE: We aimed to identify and quantify the effectiveness of flaxseed and its derivatives on blood lipid profiles. DESIGN: A comprehensive literature search was performed on the basis of English reports of randomized controlled trials of flaxseed or its derivatives on lipid profiles in adults, which were published from January 1990 to October 2008. Attempts also were made to access unpublished data. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted. RESULTS: Twenty-eight studies were included. Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L (95% CI: -0.20, 0.00 mmol/L) and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), respectively; significant reductions were observed with whole flaxseed (-0.21 and -0.16 mmol/L, respectively) and lignan (-0.28 and -0.16 mmol/L, respectively) supplements but not with flaxseed oil. The cholesterol-lowering effects were more apparent in females (particularly postmenopausal women), individuals with high initial cholesterol concentrations, and studies with higher Jadad scores. No significant changes were found in the concentrations of HDL cholesterol and triglycerides. CONCLUSIONS: Flaxseed significantly reduced circulating total and LDL-cholesterol concentrations, but the changes were dependent on the type of intervention, sex, and initial lipid profiles of the subjects. Further studies are needed to determine the efficiency of flaxseed on lipid profiles in men and premenopausal women and to explore its potential benefits on other cardiometabolic risk factors and prevention of cardiovascular disease.

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