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.
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Key Points
This meta-analyses conducted an updated systematic review and dose–response meta-analysis of randomized controlled trials (1) to summarize the pooled effects of flaxseed intervention on patients with dyslipidemia related diseases to detect the most immediate effect not only on lipid profiles, inflammatory cytokines but also anthropometric indices, (2) to distinguish the functions of different types of flaxseed product i.e., oil, lignan and whole flaxseed, and (3) to explore the dose–response relationship between whole flaxseed and flaxseed oil with the above indexes.
The present systematic review and 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. Moreover, different flaxseed products (whole flaxseed, flaxseed oil and flaxseed lignan) had obviously different effects. Meta-analysis revealed a significant reduction on TC, LDL-C, TG, apo B, TC/HDL-C and weight loss in patients allocated to whole flaxseed; flaxseed lignan had a significant lowering effect on TC, LDL-C and TC/HDL-C; however, flaxseed oil showed a significant reduction on IL-6 and hs-CRP.
Different bioactive components are present in different flaxseed-derived products and this meta-analysis revealed flaxseed oil had little protective effect compared with whole flaxseed or lignans. Whole flaxseed is a combination of multiple nutrients including not only α-linolenic acid (ALA), but also phytoestrogen, and lignans, together with high-quality protein and soluble fiber which could result in synergistic interactions. Flaxseed SDG has antioxidant, anti-inflammatory, and potent angiogenic and antiapoptotic properties, which plays a role in antiatherosclerosis.
Subgroup analysis revealed that whole flaxseed had significant effects on the net reductions in TC, LDL-C, TG and apo B in patients with dyslipidemia and with abnormal weight. One of the plausible explanations for the findings is that patients with dyslipidemia were more sensitive to lipid-lowering products than healthy adults. Moreover, apo (B)-lowering effects of whole flaxseed intervention were shown in present meta-analysis. Apolipoprotein B is an essential part of the very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), which facilitates their binding to receptors. Flaxseed is the richest plant source of SDG, which is one of the three major groups of phytoestrogens. No significant effects of flaxseed or its derivatives on HDL cholesterol were found.
The present meta-analysis indicated that flaxseed supplementation significantly decreased IL-6, rather not CRP, hs-CRP and TNF-α. This meta-analysis was conducted in a specific population with dyslipidemia related diseases. This meta-analysis found whole flaxseed consumption had a significant reduction on net change for weight (WMD = − 0.40 kg; P = 0.027; I2 = 0.0%) compared to control group. Although we did not find its significant reduction on BMI value (P = 0.719), however, subgroup result suggested its significant net change in participants with dyslipidemia (n = 6, WMD = − 0.31, P = 0.007). These results suggest that flaxseed has a beneficial effect on anthropometric indices. Whole flaxseed rather than flaxseed-oil seems effective in weight and BMI reduction which is attributed to the fact that the flaxseed can control the energy intake and increase satiety by containing 28% fibers. These findings also could explain by the subsequent increase in circulating ALA after flaxseed supplementation. The anti-obesity effects of eicosapentaenoic acid and docosahexaenoic acid have been shown in previous studies
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. Additionally, a linear association between whole flaxseed consumption and absolute changes in C-reactive protein and a nonlinear relationship between with IL-6 was observed.