Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP).

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Integrated Care for Atrial Fibrillation Management: The Role of the Pharmacist.

Within Europe and the Asia-Pacific, the Atrial Fibrillation Better Care (ABC) pathway is the gold standard integrated care strategy for atrial fibrillation management. Atrial fibrillation diagnosis should be confirmed and characterized (CC) prior to implementation of ABC pathway components: 1) "A"- Anticoagulation/Avoid stroke; 2) "B"- Better symptom management; and 3) "C"- Cardiovascular and other comorbidity optimization. Pharmacists have the potential to expedite integrated care for atrial fibrillation across the health care continuum: hospital, community pharmacy, and general practice. This review summarizes the available evidence base for pharmacist-led implementation of the "CC to ABC" model.

Red yeast rice for dyslipidaemias and cardiovascular risk reduction: A position paper of the International Lipid Expert Panel.

The risk of atherosclerotic cardiovascular disease (ASCVD) is strongly related to lifetime exposure to low-density lipoprotein (LDL)-cholesterol in longitudinal studies. Lipid-lowering therapy (using statins, ezetimibe and PCSK9 inhibitors) substantially ameliorates the risk and is associated with long-term reduction in cardiovascular (CV) events. The robust evidence supporting these therapies supports their continued (and expanding) role in risk reduction. In addition to these 'conventional' therapeutics, while waiting for other innovative therapies, growing evidence supports the use of a range of 'nutraceuticals' (constituents of food prepared as pharmaceutical formulations) including preparations of red yeast rice (RYR), the product of yeast (Monascus purpureus) grown on rice, which is a constituent of food and is used in traditional Chinese medicine. The major active ingredient, monacolin K, is chemically identical to lovastatin. RYR preparations have been demonstrated to be safe and effective in reducing LDL-C, and CV events. However, surprisingly, RYR has received relatively little attention in international guidelines - and conventional drugs with the strongest evidence for event reduction should always be preferred in clinical practice. Nevertheless, the absence of recommendations relating to RYR may preclude the use of a product which may have clinical utility in particular groups of patients (who may anyway self-prescribe this product), what in the consequence might help to reduce population CV risk. This Position Paper of the International Lipid Expert Panel (ILEP) will use the best available evidence to give advice on the use of red-yeast rice in clinical practice.

Nutraceuticals for the Control of Dyslipidaemias in Clinical Practice.

Dyslipidaemias result in the deposition of cholesterol and lipids in the walls of blood vessels, chronic inflammation and the formation of atherosclerotic plaques, which impede blood flow and (when they rupture) result in acute ischaemic episodes. Whilst recent years have seen enormous success in the reduction of cardiovascular risk using conventional pharmaceuticals, there is increasing interest amongst patients and practitioners in the use of nutraceuticals to combat dyslipidaemias and inflammation in cardiovascular disease. Nutraceutical is a portmanteau term: 'ceutical' indicate pharmaceutical-grade preparations, and 'nutra' indicates that the products contain nutrients from food. Until relatively recently, little high-quality evidence relating to the safety and efficacy of nutraceuticals has been available to prescribers and policymakers. However, as a result of recent randomised-controlled trials, cohort studies and meta-analyses, this situation is changing, and nutraceuticals are now recommended in several mainstream guidelines relating to dyslipidaemias and atherosclerosis. This article will summarise recent clinical-practice guidance relating to the use of nutraceuticals in this context and the evidence which underlies them. Particular attention is given to position papers and recommendations from the International Lipid Expert Panel (ILEP), which has produced several practical and helpful recommendations in this field.

Impact of nutraceuticals on markers of systemic inflammation: Potential relevance to cardiovascular diseases - A position paper from the International Lipid Expert Panel (ILEP).

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties.

Potential Benefits of Phytochemicals for Abdominal Aortic Aneurysm.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are a leading cause of death in older adults due to aortic rupture. There are currently no effective medical therapies for AAA, with surgery being the only acceptable treatment. There is frequently an extended period between AAA diagnosis and treatment by corrective surgery, during which an effective drug therapy could prevent or delay the need for AAA repair. OBJECTIVE: This review aimed to critically summarize prior research investigating the potential benefits of phytochemicals in preventing or treating AAA. METHODS: In vitro, in vivo, and human studies examining the effect of phytochemicals in AAA models and patients were critically summarised. RESULTS: Some preliminary data support the further investigation of curcumin, radix astragali, grape seed polyphenols, resveratrol, Ginkgo biloba extract (EGb 761), Ginsenoide Rb1, Dan Hong, Epigallocatechin-3-gallate, Baicalein, Fucoidan, Quercetin, and Salvianolic acid as potential treatments for AAA. CONCLUSION: Experimental in vivo and in vitro studies suggest the potential benefits of a number of medicinal herbs and phytochemicals in preventing or reducing the progression of AAA. In order to assess whether these findings can be translated into proven treatments, adequately designed double-blind randomized clinical trials will be required.

Natural compounds as anti-atherogenic agents: Clinical evidence for improved cardiovascular outcomes.

Atherosclerosis, a chronic progressive inflammatory condition characterized by the formation of lipid-laden lesions in arterial walls, is associated with substantial morbidity (including ischaemic stroke and myocardial infarction) and mortality. Risk factors for atherosclerosis are well understood and can be ameliorated by evidence-based and guideline-directed pharmaceutical agents (e.g. the reduction of circulating concentrations of low-density lipoprotein cholesterol by statins). Additionally, many natural products (usually food derivatives) and 'nutraceuticals' (pharmaceutical formulations prepared from components of foods) have been shown to have favourable effects on risk factors for atherosclerotic cardiovascular disease. This literature review summarises the evidence for anti-atherogenic natural compounds. The article focuses on agents which are discussed in international guidelines and are supported by extensive high-quality randomized-controlled trial (RCT) data. We focus on micronutrients (compounds present in food in small quantities) and nutraceuticals, in particular, phytosterols, polyunsaturated ω-3 fatty acids and red-yeast rice. We conclude that the 'nutraceutical approach' (identify the active ingredients in natural products; produce high-quality products according to Good Manufacturing Practice guidelines; evaluate them in long-term outcomes trials) is the mechanism by which the domains of natural product research and evidence-based medicine can move closer together.

The Role of Nutraceuticals in the Optimization of Lipid-Lowering Therapy in High-Risk Patients with Dyslipidaemia.

PURPOSE OF REVIEW: We aimed to summarize recent guidelines, position papers, and high-quality clinical research relating the use of nutraceuticals in the management of individuals at high risk of atherosclerotic cardiovascular disease. RECENT FINDINGS: It is essential that individuals at high risk of cardiovascular disease receive guideline-directed evidence-based therapies to reduce their risk of morbidity and mortality from cardiovascular events. Compared with conventional therapeutics, nutraceuticals have undergone relatively little investigation in randomized controlled trials. Thus, recommendations for nutraceuticals in international guidelines are rare, and nutraceuticals should not be used preferentially in place of statins. Nevertheless, recent position papers from the International Lipid Expert Panel and clinical evidence from studies of triglyceride reduction by polyunsaturated fatty acid administration demonstrate that nutraceuticals do have an important role in optimizing therapy in individuals at high risk of cardiovascular disease. Roles for nutraceuticals include as follows: (1) managing residual risk associated with lipids other than low-density lipoprotein cholesterol (LDL-C); (2) managing non-lipid-mediated residual risk; (3) optimizing LDL-C treatment in statin intolerance; (4) optimizing LCL-C treatment when add-on therapies for statins are not available; (5) as adjuncts to lifestyle for individuals at high lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The strength of evidence for each of these applications is variable. In addition to guideline-directed therapeutics, nutraceuticals may have roles in optimizing preventative therapy and targeting residual risk in individuals at high risk of ASCVD. Application of Good Manufacturing Practice and randomized controlled trials when producing and evaluating nutraceuticals will expand the armoury of evidence-based agents for the prevention of ASCVD.

Association of types of dietary fats and all-cause and cause-specific mortality: A prospective cohort study and meta-analysis of prospective studies with 1,164,029 participants.

BACKGROUND: Associations between dietary fats and mortality are unclear. METHODS: We evaluated the relationship between quartiles of total fat, mono-unsaturated (MUFA), polyunsaturated (PUFA) and saturated fatty acid (SFA) consumption, and all-cause, coronary heart disease (CHD), stroke, and type 2 diabetes (T2D)-associated mortality in 24,144 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999-2010. We added our results to a meta-analysis based on searches until November 2018. RESULTS: In fully adjusted Cox-proportional hazard models in our prospective study, there was an inverse association between total fat (HR: 0.90, 95% confidence interval 0.82, 0.99, Q4 vs Q1) and PUFA (0.81, 0.78-0.84) consumption and all-cause mortality, whereas SFA were associated with the increased mortality (1.08, 1.04-1.11). In the meta-analysis of 29 prospective cohorts (n = 1,164,029) we found a significant inverse association between total fat (0.89, 0.82-0.97), MUFA (0.94, 0.89-0.99) and PUFA (0.89, 0.84-0.94) consumption and all-cause mortality. No association was observed between total fat and CVD (0.93, 0.80-1.08) or CHD mortality (1.03 0.99-1.09). A significant association between SFA intake and CHD mortality (1.10, 1.01-1.21) was observed. Neither MUFA nor PUFA were associated with CVD or CHD mortality. Inverse associations were observed between MUFA (0.80, 0.67-0.96) and PUFA (0.84, 0.80-0.90) intakes and stroke mortality. CONCLUSIONS: We showed differential associations of total fat, MUFA and PUFA with all-cause mortality, but not CVD or CHD mortalities. SFA was associated with higher all-cause mortality in NHANES and with CHD mortality in our meta-analysis. The type of fat intake appears to be associated with important health outcomes.