These properties are strongly linked to the physiological impact of fibre on digestion and gut function, including, for instance, effects on nutrient bioaccessibility and rate of gastric emptying/GI transit, inhibition of the flow and mixing efficiency of digesta, changes in the rate and extent of macronutrient digestion/absorption, and prebiotic effects on gut microflora. The role of fibre in physically encapsulating/entrapping nutrients in particular has been identified as a major mechanism by which structurally intact plant tissues tend to be digested at a slower rate and to a lesser extent, thereby attenuating the postprandial rise in glycaemia and/or lipaemia( 6 – 8 ). These physiological changes are considered to be of benefit in the dietary treatment and risk reduction of cardiometabolic diseases such as type 2 diabetes and CVD and may also have a positive impact on obesity management( 9 , 10 ).
Notably, our meta‐analysis highlights an increase in bleeding risk only in patients receiving high‐dose purified EPA (icosapent ethyl). Moreover, we postulate a possible association between EPA dose and increased bleeding risk. An EPA dose‐dependent bleeding risk would be plausible, in line with the biochemical interactions between omega‐3 and omega 6 PUFAs. Nevertheless, it is important to highlight that icosapent ethyl has no DHA component as active product and the purity of icosapent ethyl may also enhance pleotropic effects on platelet activation. EPA can increase the release of nitric oxide, which is a potent inhibitor of platelet aggregation and could potentially exacerbate the bleeding risk when using icosapent ethyl.38 Although DHA can also increase nitric oxide release, its effect on endothelial function was not similar to EPA.38 Moreover, its ability to inhibit oxidation of Apo‐B‐containing particles was less sustained than that of EPA.38
NSAIDs for primary prevention: NSAIDs are recommended for primary prevention of cardiovascular disease, especially for those aged 50-59 years. However, caution is needed due to the increased risk of gastrointestinal bleeding, and further studies are required to determine the risk and benefit balance in this population [46].
The limited evidence from intervention studies indicates that the combined supplementation with B vitamins and omega-3 PUFAs may be promising and more effective at reducing plasma Hcy, TG, and LDL-C than each supplementation alone. However, there is no solid evidence that the joint supplementation of these two can offer a synergistic effect on preventing CVD and decreasing the relevant morbidity and/or mortality in susceptible populations. Due to the methodological challenges and heterogeneity in study design of the existing trials, it is difficult to draw any definitive conclusions based on the current literature. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.
