18 research outputs found
Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature
ackground: Omega-3 (n-3) fatty acid supplementation is becoming increasingly popular. However given its
antithrombotic properties the potential for severe adverse events (SAE) such as bleeding has safety implications,
particularly in an older adult population. A systematic review of randomized control trials (RCT) was conducted to
explore the potential for SAE and non-severe adverse events (non-SAE) associated with n-3 supplementation in
older adults.
Methods: A comprehensive search strategy using Medline and a variety of other electronic sources was conducted.
Studies investigating the oral administration of n-3 fish oil containing eicosapentaenoic acid (EPA), docosahexaenoic
acid (DHA) or both against a placebo were sourced. The primary outcome of interest included reported SAE
associated with n-3 supplementation. Chi-square analyses were conducted on the pooled aggregate of AEs.
Results: Of the 398 citations initially retrieved, a total of 10 studies involving 994 older adults aged ≥60 years were
included in the review. Daily fish oil doses ranged from 0.03 g to 1.86 g EPA and/or DHA with study durations
ranging from 6 to 52 weeks. No SAE were reported and there were no significant differences in the total AE rate
between groups (n-3 intervention group: 53/540; 9.8%; placebo group: 28/454; 6.2%; p= 0.07). Non-SAE relating to
gastrointestinal (GI) disturbances were the most commonly reported however there was no significant increase in
the proportion of GI disturbances reported in participants randomized to the n-3 intervention (n-3 intervention
group: 42/540 (7.8%); placebo group: 24/454 (5.3%); p= 0.18).
Conclusions: The potential for AEs appear mild-moderate at worst and are unlikely to be of clinical significance. The
use of n-3 fatty acids and the potential for SAE should however be further researched to investigate whether this
evidence is consistent at higher doses and in other populations. These results also highlight that well-documented data
outlining the potential for SAE following n-3 supplementation are limited nor adequately reported to draw definitive
conclusions concerning the safety associated with n-3 supplementation. A more rigorous and systematic approach for
monitoring and recording AE data in clinical settings that involve n-3 supplementation is required.The authors would like to acknowledge funding
provided for the ongoing ATLANTIC randomized controlled trial supported
by the National Health and Medical Research Council (NHMRC), Australia
DHA Metabolism: Targeting the Brain and Lipoxygenation
International audienc
Double lipoxygenation of polyunsaturated fatty acids of nutritional interest
International audienceDouble lipoxygenation of polyunsaturated fatty acids having at least three methylene-interrupted double bonds can be made by two lipoxygenases, e.g. 5 and 12-LOX, or 15-LOX only, followed by reduction of the hydroperoxide products through the glutathione peroxidase action. Several biological activities have been reported for such a double 15-LOX product of docosahexaenoic acid, called protectin DX to differentiate it from protectin D1, a stereo and geometric isomer described for its potent anti-inflammatory potential. The geometric characteristic of the double lipoxygenase products is the conjugated triene E,Z,E (trans,cis,trans), which appears crucial in their biological activities. A focus is also done on single lipoxygenation of mono-hydroxylated products first made by aspirin-treated cyclooxygenase-2. The resulting (R,S)-diOH, E,Z,E conjugated trienes, instead of the (S,S)-diOH isomer in case of double lipoxygenation, seem to be even more active for some biological effects, making biologically relevant the single lipoxygenation in aspirin-treated situations
Glutathione peroxidase 4 is reversibly induced by HCV to control lipid peroxidation and to increase virion infectivity
International audienceOBJECTIVE: Inflammation and oxidative stress drive disease progression in chronic hepatitis C (CHC) towards hepatocellular carcinoma. HCV is known to increase intracellular levels of reactive oxygen species (ROS), but how it eliminates ROS is less well known. The role of the ROS scavenger glutathione peroxidase 4 (GPx4), induced by HCV, in the viral life cycle was analysed. DESIGN: The study was performed using a replicative in vitro HCV infection model and liver biopsies derived from two different CHC patient cohorts. RESULTS: A screen for HCV-induced peroxide scavengers identified GPx4 as a host factor required for HCV infection. The physiological role of GPx4 is the elimination of lipid peroxides from membranes or lipoproteins. GPx4-silencing reduced the specific infectivity of HCV by up to 10-fold. Loss of infectivity correlated with 70% reduced fusogenic activity of virions in liposome fusion assays. NS5A was identified as the protein that mediates GPx4 induction in a phosphatidylinositol-3-kinase-dependent manner. Levels of GPx4 mRNA were found increased in vitro and in CHC compared with control liver biopsies. Upon successful viral eradication, GPx4 transcript levels returned to baseline in vitro and also in the liver of patients. CONCLUSIONS: HCV induces oxidative stress but controls it tightly by inducing ROS scavengers. Among these, GPx4 plays an essential role in the HCV life cycle. Modulating oxidative stress in CHC by specifically targeting GPx4 may lower specific infectivity of virions and prevent hepatocarcinogenesis, especially in patients who remain difficult to be treated in the new era of interferon-free regimens
Full characterization of PDX, a neuroprotectin/protectin D1 isomer, which inhibits blood platelet aggregation.
International audienceOur study aimed to establish the complete structure of the main dihydroxy conjugated triene issued from the lipoxygenation (soybean enzyme) of docosahexaenoic acid, named PDX, an isomer of protectin/neuroprotectin D1 (PD1/NPD1) described by Bazan and Serhan. NMR approaches and other chemical characterization (e.g. GC-MS, HPLC and LC-MS/MS) indicated that PDX is 10(S),17(S)-dihydroxy-docosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid. The use of (18)O(2) and mass spectrometry showed that PDX is a double lipoxygenation product. Its structure differs from PD1, with E,Z,E geometry (PDX) instead of E,E,Z (PD1) and S configuration at carbon 10 instead of R. PDX inhibits human blood platelet aggregation at sub-micromolar concentrations