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CPD ACTIVITY 75 Figure 2. Commonly available plant sterol-containing supplements for cholesterol and plant sterol-enriched foods. Brand Active Ingredients Suggested Dose Blackmores Cholesterol Health Vegetable oil phytoserol esters (plant sterols) 1g (1000mg) Beta-carotene 1.5mg 1 BD Now Foods Beta-Sitosterol Plant Sterols Campesterol and Stigmasterol Equivalent: 1000mg 2 BD Sanitarium Weet-Bix Cholesterol Lowering Enriched with 2g of plant sterols 2 daily Flora Pro Activ Dairy Margarine 2g plant sterols per serving (10g 1 serve daily cholesterol and provided an assessment of its impact on the markers non-HDL cholesterol and apolipoprotein B (apoB).6 A total of 28 trials were analysed with 1,924 participants. The average daily intake of psyllium was 10.2g. The study found that psyllium had a significant effect on LDL cholesterol, with a mean difference of –0.33 mmol/lt. This effect was shown irrespective of the baseline cholesterol status of patients. Pooled analysis of 27 studies (including 28 comparisons; n = 1899) showed a significant effect of psyllium on non-HDL cholesterol with a mean difference of –0.39 mmol/lt. This result was also shown to be irrespective of the baseline cholesterol of the patients. Pooled effects of nine studies (n = 895) showed a significant effect of psyllium on apoB of –0.05g/lt. The authors concluded that psyllium fibre effectively improves conventional and alternative lipids markers, theoretically delaying the process of atherosclerosis- associated CVD risk in those with or without hypercholesterolaemia, although none of these trials examined CVD risk as dedicated end points. Studies investigating purified fibre intake and drug interactions are limited and their results are varied. Concomitant fibre intake appears to consistently impact on the absorption of lithium. However, the studies performed had extremely modest sample sizes. The impact of fibre on other drugs with narrow therapeutic windows, such as digoxin, has also been studied, with varied impacts. A study was conducted that examined the steady-state concentrations of digoxin in 30 elderly patients who received the drug for four weeks, alone or with fibre (wheat bran or psyllium husk). The addition of wheat bran lowered digoxin plasma levels (at two weeks but not at four weeks), but as concentrations remained within the therapeutic range, this was not deemed to be clinically significant. In this study, the psyllium husk group experienced no impact.7 Careful monitoring of patients commenced on strict fibre supplementation may be deemed appropriate if they are also taking lithium or digoxin. Omega-3 supplementation Omega-3 fatty acids are a heterogeneous group of fatty acids with a double bond between the third and fourth carbon atoms from the methyl end. They are classified as polyunsaturated fatty acids (PUFAs). Fish oils contain high, but variable, levels of omega-3 long chain polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)8. Increased consumption of omega-3 fats is widely promoted globally because of a common belief that it will protect against heart disease or positively impact cholesterol. The Omega-3 index (red blood cell omega-3 concentration) is itself now a biomarker for CVD. It’s important to establish a clear distinction between the evidence for omega-3 fatty acid (FA) supplementation on serum lipids (cholesterol and triglycerides) and evidence for benefits of FA supplementation on cardiovascular outcomes.8,9 Significant research has been conducted in this area and comprehensive reviews for examination exist. In a 2009 meta-analysis by Eslick et al10, 47 studies with 16,511 participants were examined. The supplements used were a combination of EPA/DHA. The authors concluded that fish oil supplements significantly decreased plasma TG levels by about 14 per cent without resulting in clinically significant changes in total LDL-C or HDL-C levels after about one month of treatment. This effect of fish oil on plasma TG levels was seen in a previous meta-analysis. It’is important to note that the reduction in plasma TG levels was directly related to baseline plasma TG levels (ie, the higher the baseline TG level the greater the reduction in TGs with fish oil). Additionally, the higher the dose of EPA/DHA, the greater the reduction in plasma TGs, with clinically significant reductions occurring with about 3.25g EPA/DHA daily. The daily consumption of fish oil in a typical Western diet does not exceed 130mg daily, and TG lowering effects are not evident at this level.10 An increased level of circulating TG is an independent risk factor for the onset of CVD.1 The triglyceride lowering ability of fish oil supplementation is evident only at ‘pharmacological doses’ in excess of at least 3g daily, and EPA and DHA appear to be equally potent in lowering plasma TG. The mechanism behind the hypotriglyceridaemic effect of EPA/DHA supplementation is multifactorial, but it’s thought to be largely due to the alibility of fish oil to reduce VLDL-TG production. This reduces the rate of FA incorporation into VLDL.9 EPA/DHA has been implicated in reduced non-esterified fatty acid (NEFA) delivery to the liver, suppressed adipose tissue inflammation, enhanced hepatic and skeletal muscle β-oxidation that contributes to reduced free fatty acid delivery to the liver, and enhanced TG clearance.9 Research into the impact of omega-3 supplementation on CV outcomes including myocardial infarction, coronary heart disease (CHD) related death, total CHD, total stroke, CVD related death, total CVD and major vascular events has demonstrated varied results. Several large long-term and large-scale studies assessing these outcomes with omega-3 supplementation have recently been published, ASCEND11, VITAL12 and REDUCE-IT.13 Importantly, these studies have been incorporated in a 2020 Cochrane review on the topic.14 The ASCEND study looked at 15,480 patients with any type of diabetes, but TO PAGE 76 RETAIL PHARMACY • AUG 2020