Comparisons of the effects of different flaxseed products consumption on lipid profiles, inflammatory cytokines and anthropometric indices in patients with dyslipidemia related diseases: systematic review and a dose–response meta-analysis of randomized controlled trials
Authors: Yang Chao , Xia Hui , Wan Min , Lu Yifei , Xu Dengfeng , Yang Xian , Yang Ligang , Sun Guiju 
Published: October 2021

Abstract
Background
Flaxseed is widely used as a functional food for its rich sources of linolenic acid, lignans and dietary fibers in the world. This systematic review and dose–response meta-analysis on randomized controlled trials (RCTs) is first to evaluate effects of different flaxseed products (whole flaxseed, oil and lignans) on lipid profiles, inflammatory and anthropometric parameters in patients with dyslipidemia related diseases.

Methods
Literature search was performed in PubMed, Embase, Cochrane Central, Scopus, and Web of Science from the inception dates to January, 2020. Weighted mean differences with the 95% confidence interval (CI) were pooled using fix or random-effects models.

Results
Thirty-one RCTs involving 1,698 participants were included. The present meta-analysis revealed that flaxseed consumption had an overall beneficial effect on serum TC, LDL-C, TG, apo B and IL-6 in patients with dyslipidemia related diseases, but not on apo A, HDL-C, hs-CRP, CRP and anthropometric indices. However, different flaxseed products showed obviously different effects. Whole flaxseed supplementation significantly reduced TC (− 11.85 mg/dl, 95% CI − 20.12 to − 3.57, P = 0.005), LDL-C (− 10.51 mg/dl, 95% CI − 14.96 to − 6.06, P < 0.001), TG (− 19.77 mg/dl, 95% CI − 33.61 to − 5.94, P = 0.005), apolipoprotein B (− 5.73 mg/dl, 95% CI − 7.53 to − 3.93, P < 0.001), TC/HDL-C (− 0.10, 95% CI − 0.19 to − 0.003, P = 0.044) and weight (− 0.40 kg, 95% CI − 0.76 to − 0.05, P = 0.027); Lignans supplementation significantly reduced TC (− 17.86 mg/dl, P = 0.004), LDL-C (− 15.47 mg/dl, P < 0.001) and TC/HDL-C (− 0.45, P = 0.04). Although flaxseed oil supplementation had no such lowering-effect on lipid, meta-analysis revealed its lowering-effect on IL-6 (− 0.35 pg/ml, P = 0.033) and hs-CRP (− 1.54 mg/l, P = 0.004). Subgroup analysis revealed that whole flaxseed decreased TC, LDL-C and TG levels irrespective of country and the intervention time prescribed, but was more pronounced when the dose of whole flaxseed was ≤ 30 g/day (TC: WMD − 13.61 mg/mL; LDL-C: WMD − 10.52 mg/mL; TG: WMD − 23.52 mg/mL), rather not a dose > 30 g/day. Moreover, a linear relationship between dose of whole flaxseed and absolute changes in C-reactive protein (P = 0.036) and a nonlinear relationship between with IL-6 (P < 0.001) were detected.

Conclusions
Flaxseed intervention suggested the positive effects on lipid profiles, inflammatory cytokines and anthropometric indices in patients with dyslipidemia related diseases. Of these, whole flaxseed and lignans play an important role in reducing blood lipid, while flaxseed oil mainly plays in anti-inflammatory. Lipid- and weight-lowering was significant when whole flaxseed was consumed at doses < 30 mg/d, for lipid status with mixed dyslipidemia and patients with BMI > 25.

Graphic abstract