A comprehensive review of the health benefits of flaxseed oil in relation to its chemical composition and comparison with other omega-3-rich oils

**Background:** Flaxseed oil, derived from *Linum usitatissimum*, is a rich plant source of polyunsaturated omega-3 fatty acids, particularly α-linolenic acid (ALA), which constitutes over 70% of its fatty acid content. It also contains linoleic acid, tocopherols, phytosterols, polyphenols, and lignans. These components contribute to a wide range of biological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, and anti-osteoporotic effects. This review aims to summarize the health benefits of flaxseed oil in relation to its chemical composition, drawing on evidence from cell-based assays, animal studies, and clinical trials.

**Methods:** The authors conducted a comprehensive literature review using Web of Science, PubMed, and Scopus databases. Search terms included 'flaxseed oil' combined with targeted biological effects such as antioxidant, anti-inflammatory, antimicrobial, anticancer, antiulcer, anti-osteoporotic, cardioprotective, neuroprotective, and metabolic syndrome. Inclusion criteria focused on studies demonstrating a defined role of flaxseed oil in health benefits. Exclusion criteria included preprints, conference proceedings, abstracts-only papers, and non-English publications. After screening titles and abstracts, relevant original research underwent full-text review, and reference lists of key papers were examined, resulting in 112 cited papers.

**Key Results:** The review presents findings across multiple health domains: - **Cardiovascular and metabolic effects:** Supplementation with flaxseed oil increased EPA in erythrocyte membranes by 133% (P<0.05) and DPA by 120% (P<0.01), while DHA remained unchanged. In a clinical study of 57 men with atherogenic lipoprotein phenotype, flaxseed oil reduced total plasma cholesterol by 12.3% (P=0.001), compared to 7.6% (P=0.014) for sunflower oil and 7.3% (P=0.033) for fish oil. Another trial in 59 dyslipidemic men showed significant decreases in systolic and diastolic blood pressure (P=0.016 and P=0.011, respectively) with 8 g/day flaxseed oil for 12 weeks. - **Bone health:** In ovariectomized rats, 10% flaxseed oil for 4 weeks significantly decreased alkaline phosphatase (ALP) from 300±49.1 to 166.80±17.9 and tartrate-resistant acid phosphatase (TRAP) from 0.80±0.08 to 0.37±0.08. A high-fat diet with 10% flaxseed oil improved trabecular bone markers but did not significantly affect cortical bone. - **Anticancer activity:** Flaxseed oil reduced growth of B16-BL6 melanoma cells by ~50% at 0.3% (v/v) and completely at 0.9% (v/v). In MCF-7 breast cancer cells, 0.3% oil reduced growth by 75%. In ovariectomized mice, flaxseed oil (40 g/kg diet) decreased tumor size by 33% (P<0.05) and cell proliferation by 38% (P<0.05), and increased apoptosis by 110% (P<0.001). Combined with low-dose trastuzumab (2.5 mg/kg), flaxseed oil (8%) led to 84% tumor regression compared to 187% growth in controls. - **Antimicrobial activity:** Flaxseed oil showed comparable antibacterial activity to cefoperazone against *Staphylococcus aureus* (inhibition zones 17.83 mm vs. 17.33 mm) and *Streptococcus agalactiae* (19.66 mm vs. 18.33 mm), and superior activity against *Enterococcus faecalis*, *Micrococcus luteus*, and *Candida albicans*. - **Antioxidant activity:** Daily consumption of 3 ml/kg flaxseed oil for 3 weeks in diabetic rats significantly reduced thiobarbituric acid reactive substances, glutathione, and catalase levels in liver, kidney, and heart by 2.4-, 1.7-, and 1.6-fold, respectively. In vitro, the polar fraction of oil from 160°C-roasted seeds showed DPPH, ABTS, FRAP, and ORAC values of 125, 199, and 122 μmol TE/100 g. - **Neuroprotective and antidepressant effects:** In a rat model of postpartum depression, oral flaxseed oil (270 mg/kg/day) for 2 weeks improved anxiety and depressive symptoms. - **Other effects:** Flaxseed oil (5 ml/kg) significantly reduced ethanol-induced gastric ulcer number and length (P<0.001) compared to corn oil. In Sjögren's syndrome patients, 1-2 g/day flaxseed oil capsules reduced ocular surface inflammation.

**Clinical Implications:** The review highlights flaxseed oil's potential as a nutraceutical for preventing and managing cardiovascular disease, osteoporosis, cancer, infections, and inflammatory conditions. Its hypocholesterolemic, antihypertensive, and anti-inflammatory effects support dietary recommendations for omega-3 intake. The synergistic effects with drugs like trastuzumab and doxorubicin suggest potential for reducing chemotherapy doses. However, the authors note that more controlled clinical trials are needed to confirm efficacy, especially for neuroprotective and anti-osteoporotic effects, and to elucidate mechanisms of action. The review also emphasizes the need for standardized extraction methods to optimize bioactive compound content.