Safety and tolerability of prescription omega-3 fatty acids: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are widely recommended for health promotion. Over the last decade, prescription omega-3 fatty acid products (RxOME3FAs) have been approved for medical indications. Nonetheless, there is no comprehensive analysis of safety and tolerability of RxOME3FAs so far. METHODS: A systematic review of randomized controlled trials (RCTs) was carried out based on searches in six electronic databases. The studies involving marketed RxOME3FA products were included, and adverse-effect data were extracted for meta-analysis. Subgroup analysis and meta-regression were conducted to explore the sources of potential heterogeneity. RESULTS: Among the 21 included RCTs (total 24,460 participants; 12,750 from RxOME3FA treatment cohort and 11,710 from control cohort), there was no definite evidence of any RxOME3FA-emerging serious adverse event. Compared with the control group, RxOME3FAs were associated with more treatment-related dysgeusia (fishy taste; p = 0.011) and skin abnormalities (eruption, itching, exanthema, or eczema; p < 0.001). Besides, RxOME3FAs had mild adverse effects upon some non-lipid laboratory measurements [elevated fasting blood sugar (p = 0.005); elevated alanine transaminase (p = 0.022); elevated blood urea nitrogen (p = 0.047); decreased hemoglobin (p = 0.002); decreased hematocrit (p = 0.009)]. Subgroup analysis revealed that EPA/DHA combination products were associated with more treatment-related gastrointestinal adverse events [eructation (belching; p = 0.010); nausea (p = 0.044)] and low-density lipoprotein cholesterol elevation (p = 0.009; difference in means = 4.106mg/dL). CONCLUSION: RxOME3FAs are generally safe and well tolerated but not free of adverse effects. Post-marketing surveillance and observational studies are still necessary to identify long-term adverse effects and to confirm the safety and tolerability profiles of RxOME3FAs.

Effects of Davallia formosana Hayata Water and Alcohol Extracts on Osteoblastic MC3T3-E1 Cells.

The Taiwanese native fern Davallia formosana Hayata (DFH) is used to treat bone diseases in classical Chinese medicine. We analyzed MC3T3E1 osteoblasts treated with different concentrations of water and ethanol extracts (10, 25, and 50 [both], and 100 µg/mL [DFE only]) using cell viability, expression of osteoblast differentiation markers [bone morphogenetic protein 2 (BMP-2), collagen 1 (CoL-1), alkaline phosphatase (ALP), and Runt-related transcription factor 2 (Runx 2)], and mineralization. These were significantly increased by DFW or DFE after 24-h incubation compared with the untreated controls. Compared with other treatments, DFW 50 and DFE 100 µg/mL significantly increased MC3T3E1 cell survival. DFW 25 and 50 µg/mL increased bone BMP-2, CoL-1, ALP, and Runx2 protein expression, ALP activity, and mineralization more than DFE did. Repeated chromatographic separation of DFW yielded compound (-)-epicatechin-3-O-d-allipyranoside (ECAP), which was characterized using 1 H and 13 C nuclear magnetic resonance spectroscopy. (-)-Epicatechin-3-O-d-allipyranoside (0.01 µg/mL) significantly increased cell survival (118.9%) and mineralization (218.7%) compared with that of the control treatment. We inferred that ECAP could mediate the main activity of DFW in bone formation, likely through BMP-2-induced Runx2 transcription, which increased bone cell differentiation factors ALP and CoL-1 and promoted mineralization. (-)-Epicatechin-3-O-d-allipyranoside could be an anti-osteoporotic agent. Copyright © 2017 John Wiley & Sons, Ltd.