Beyond blood lipids: phytosterols, statins and omega-3 polyunsaturated fatty acid therapy for hyperlipidemia

Abstract Phytosterols and omega-3 fatty acids are natural compounds with potential cardiovascular benefits. Phytosterols inhibit cholesterol absorption, thereby reducing total-and LDL cholesterol. A number of clinical trials have established that the consumption of 1.5-2.0 g/day of phytosterols can result in a 10-15% reduction in LDL cholesterol in as short as a 3-week period in hyperlipidemic populations. Added benefits of phytosterol consumption have been demonstrated in people who are already on lipid-lowering medications (statin drugs). On the other hand, omega-3 fatty acid supplementation has been associated with significant hypotriglyceridemic effects with concurrent modifications of other risk factors associated with cardiovascular disease, including platelet function and pro-inflammatory mediators. Recent studies have provided evidence that the combination of phytosterols and omega-3 fatty acids may reduce cardiovascular risk in a complementary and synergistic way. This article reviews the health benefits of phytosterols and omega-3 fatty acids, alone or in combination with statins, for the treatment/management of hyperlipidemia, with particular emphasis on the mechanisms involved

Anti-inflammatory and cardioprotective effects of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic individuals

Background: Risk factors of cardiovascular disease such as lipid aberrations, hypertension, abdominal adiposity and elevations in systemic inflammation, are prominent aetiologies in hyperlipidemia. Supplementation with n-3 PUFA is associated with a reduction in cardiovascular events through its hypotriglyceridemic, anti-aggregatory and anti-inflammatory properties. Plant sterols have potent hypocholesterolemic properties, although their effect on the inflammatory cascade is uncertain. This study investigated the effect of combined supplementation with n-3 PUFA and plant sterols on cardiovascular risk factors, blood pressure, body composition, markers of systemic inflammation and overall risk, in hyperlipidemic individuals. Methods: The study was a 3-week randomised, double-blind, placebo-controlled, 2 × 2 factorial design, in four parallel groups. Sixty hyperlipidemic participants were randomised to recieve either sunola oil or 1.4 g/d n-3 PUFA capsules with or without 2 g plant sterols per day. Results: The combination of n-3 PUFA and plant sterols reduced several inflammatory markers. High sensitivity C-reactive protein (hs-CRP) was reduced by 39% (P = 0.009), tumor necrosis factor-α (TNF-α) by 10% (P = 0.02), interleukin-6 (IL-6) by 10.7% (P = 0.009), leukotriene B₄ (LTB₄) by 29.5% (P = 0.01) and adiponectin was increased by 29.5% (P = 0.05). Overall cardiovascular risk was reduced by 22.6% (P = 0.006) in the combination group. Conclusion: We have demonstrated, for the first time that dietary intervention with n-3 PUFA and plant sterols reduces systemic inflammation in hyperlipidemic individuals. Furthermore, our results suggest that reducing inflammation provides a potential mechanism by which the combination of n-3 PUFA and plant sterols are cardioprotective

Combined supplementation with EPA-rich fish oil and phytosterols improve plasma lipid profile and C-Reactive Protein (CRP) in individuals with hyperlipidemia

The treatment of hyperlipidemia, particularly reducing LDL-cholesterol and triglyceride concentration, is established as an efficacious means of reducing both morbidity and mortality from CVD. Dietary supplementation with phytosterols is known to reduce LDL-cholesterol, whilst omega-3 PUFA are hypotriglyceridemic and have immuno-modulatory properties. The objective of this study was to examine the effect of combined supplementation with EPA-rich fish oil and phytosterols on cardiovascular risk factors in individuals with combined hyperlipidemia. Fifty-eight healthy hyperlipidemic adults, were randomly assigned to consume 3 x 1 g EPA-rich (550 mg 20:5n-3 and 120 mg 22:6n-3) fish oil capsules daily or 3 x 1 g placebo (sunola oil) capsules daily, either alone or in combination with 25 g phytosterolenriched spread (2 g phytosterols) daily for 3 weeks. Blood pressure, plasma lipid profile, plasma fatty acids and inflammatory status were analysed. Phytosterol supplementation significantly reduced total-cholesterol and LDL-cholesterol (-8.0 % and -7.5 %, P < 0.01), whilst fish oil supplementation significantly improved triglycerides and HDL-cholesterol (-8.5%, P < 0.05; +6.5 %, P < 0.01). Total-cholesterol, LDL-cholesterol, triglycerides and HDL-cholesterol were significantly improved (-9.5 %, P < 0.01; -7.5 %, P < 0.01; -22.2 %, P < 0.01; +7.1 %, P < 0.01) following the combined dietary supplementation. CRP concentration was reduced by 11 % (P = 0.02) in the combination group. In conclusion, the combined supplementation of EPA-rich fish oil capsules and a phytosterol-enriched spread provide cardiovascular health benefits, by way of optimising plasma lipid profile and improving inflammatory status in individuals with combined hyperlipidemia

Exploring cyanobacterial genomes for natural product biosynthesis pathways

Cyanobacteria produce a vast array of natural products, some of which are toxic to human health, while others possess potential pharmaceutical activities. Genome mining enables the identification and characterisation of natural product gene clusters; however, the current number of cyanobacterial genomes remains low compared to other phyla. There has been a recent effort to rectify this issue by increasing the number of sequenced cyanobacterial genomes. This has enabled the identification of biosynthetic gene clusters for structurally diverse metabolites, including non-ribosomal peptides, polyketides, ribosomal peptides, UV-absorbing compounds, alkaloids, terpenes and fatty acids. While some of the identified biosynthetic gene clusters correlate with known metabolites, genome mining also highlights the number and diversity of clusters for which the product is unknown (referred to as orphan gene clusters). A number of bioinformatic tools have recently been developed in order to predict the products of orphan gene clusters; however, in some cases the complexity of the cyanobacterial pathways makes the prediction problematic. This can be overcome by the use of mass spectrometry-guided natural product genome mining, or heterologous expression. Application of these techniques to cyanobacterial natural product gene clusters will be explored

Advances in genomics, transcriptomics and proteomics of toxin-producing cyanobacteria

A common misconception persists that the genomes of toxic and non-toxic cyanobacterial strains are largely conserved with the exception of the presence/absence of the genes responsible for toxin production. Implementation of –omics era technologies has challenged this paradigm, with comparative analyses providing increased insight into the differences between strains of the same species. Implementation of genomic, transcriptomic and proteomic approaches has revealed distinct profiles between toxin-producing and non-toxic strains. Further, metagenomics and metaproteomics highlight the genomic potential and functional state of toxic bloom events over time. In this review, we highlight how these technologies have shaped our understanding of the complex relationship between these molecules, their producers and the environment at large within which they persist

Assessment and Treatment of Hepatitis C Virus Infection Among People Who Inject Drugs in the Opioid Substitution Setting: ETHOS Study

Vertical rainfall profile retrieval based on reflectivity data collected by spaceborne rain radars can be improved through the techniques that exploit an estimation of the sea surface Normalised Radar Cross Section (NRCS) as an additional information. However, errors that can currently be made in predicting the sea surface NRCS may significantly affect their performance. Therefore, in this paper we first address the problem to evaluate the NCRS of the sea surface perturbed by rain, when observed at nadir. For this purpose, the dominant effect of ring waves generated by rainfall is considered. The joint effect of wind is also considered. The proposed model is based on the Full Wave Model (FWM) theory. Some comparisons are made with an alternative, less flexible model based on the Integral Equation Model (IEM) theory, and partial comparisons are also made with experimental data, which authorize to consider the proposed model well grounded and exploitable for application. then, we show that the model can be usefully exploited to improve rainfall rate vertical profile retrieval over the sea surface, inthe case of nadir looking, single frequency radars

The effect of social functioning and living arrangement on treatment intent, specialist assessment and treatment uptake for hepatitis C virus infection among people who inject drugs: the ETHOS study

Background: The objective was to assess social functioning and its association with treatment intent, specialist assessment and treatment uptake for hepatitis C virus (HCV) infection among people with a history of injecting drug use. Methods: ETHOS is a prospective observational cohort evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from nine community health centres and opioid substitution treatment clinics (NSW, Australia). Social functioning was assessed using a short form of the Opioid Treatment Index social functioning scale. Those classified in the highest quartile (score >6) were considered having lower social functioning. Analyses were performed using logistic regression. Results: Among 415 participants (mean age 41 years, 71% male), 24% were considered having lower social functioning, 70% had early HCV treatment intent (intention to be treated in the next 12 months), 53% were assessed by a specialist and 27% initiated treatment. Lower social functioning was independently associated with unemployment, unstable housing, recent injecting drug use and moderate to extremely severe symptoms of depression, anxiety and stress. Lower social functioning was independently associated with reduced early HCV treatment intent (aOR 0.51, 95% CI 0.30-0.84) and lower specialist assessment (aOR 0.48, 95% CI 0.29-0.79), but not HCV treatment uptake (aOR 0.76, 95% CI 0.40-1.43). Living with someone was independently associated with HCV treatment uptake (with someone and children: aOR 2.28, 95% CI 1.01-5.14; with someone and no children: aOR 2.36, 95% CI 1.30-4.31), but not early HCV treatment intent or specialist assessment. Conclusions: This study highlights the need for the development and implementation of strategies targeting people who inject drugs with lower social functioning to enhance HCV treatment intent and specialist assessment. Further, strategies to enhance social support may play a role in increasing HCV treatment uptake.This work was supported by the National Health and Medical Research Council (NHMRC, 568985) and New South Wales Health. The Centre for Social Research in Health is supported by a grant from the Australian Government Department of Health and Ageing. This publication was funded by the Australian Government Department of Health and Ageing. GD and PH are supported through NHMRC Practitioner Fellowships. JG is supported through a NHMRC Career Development Fellowship

Depression, Anxiety, and Stress among People with Chronic Hepatitis C Virus Infection and a History of Injecting Drug Use in New South Wales, Australia

Objective: The aims of this study were to assess symptoms of depression, anxiety, and stress and associated sociodemographic factors among people living with chronic hepatitis C virus (HCV) infection with a history of injecting drug use and to assess the association between symptoms of depression, anxiety, or stress and HCV treatment intent, specialist assessment, or treatment uptake. Methods: The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings was an observational cohort study evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from 9 community health centers and opioid substitution therapy (OST) clinics (New South Wales, Australia). Symptoms were assessed using the Depression Anxiety Stress Scales (DASS-21). Analyses were performed using logistic regression. Results: Among 415 participants (mean age 41 years, 71% male), 47%, 52%, and 36% demonstrated moderate to extremely severe symptoms of depression, anxiety, and stress, respectively. In adjusted analyses, depression symptoms were associated with recent injecting drug use [adjusted odds ratio (aOR) 1.63, 95% confidence interval (CI) 1.07-2.49), whereas stress symptoms were associated with unemployment (aOR 2.99, 95% CI 1.09-8.15) and not living with a spouse or other relatives/friends (aOR 1.55, 95% CI 1.01-2.39). Symptoms of depression, anxiety, or stress or having a history of treated mental illness were not independently associated with HCV treatment intent, specialist assessment, or treatment uptake. Conclusions: Findings suggest a need for improved interventions and care regarding mental health among people living with chronic HCV with a history of injecting drug use, but suggest that symptoms of depression, anxiety, and stress should not be immediate contraindications to HCV assessment and treatment