Lowering Blood LDL-cholesterol Research Articles

Gut ribotoxic stress responses facilitate dyslipidemia via metabolic reprogramming: an environmental health prediction.

Rationale: The gut and its accessory organ, the liver, are crucial determinants of metabolic homeostasis via the regulation of circulating lipids for cardiovascular health. In response to environmental insults, cells undergo diverse adaptation or pathophysiological processes via stress-responsive eukaryotic initiation factor 2 alpha (eIF2α) kinase signaling and subsequent cellular reprogramming. We noted that patients with inflammatory gut distress display enhanced levels of ribosomal stress-responsive eIF2α kinase, which is notably associated with lipid metabolic process genes. Based on an assumption that eukaryotic ribosomes are a promising stress-responsive module for molecular reprogramming, chemical ribosome-inactivating stressors (RIS) were assessed for their involvement in enterohepatic lipid regulation. Methods: Experimental assessment was based on prediction using the clinical transcriptome and single-cell RNA-sequencing analysis of inflammatory bowel diseases and obesity. The prediction was verified using RIS exposure models of mice, gut organoids, and intestinal cells. The lipidomic profiling was performed to address RIS-induced intracellular fat alterations. Biochemical processes of the mechanisms were evaluated using RT-PCR, western blot analysis, luciferase reporter assays, and confocal microscopy of genetically ablated or chemically inhibited mice, organoids, and cells. Results: Chemical RIS including deoxynivalenol promoted enterohepatic lipid sequestration while lowering blood LDL cholesterol in normal and diet-induced obese mice. Although ribosomal stress caused extensive alterations in cellular lipids and metabolic genes, the cholesterol import-associated pathway was notably modulated. In particular, ribosomal stress enhanced gut levels of the low-density lipoprotein receptor (LDLR) via both transcriptional and post-transcriptional regulation. Subsequently, LDLR facilitated enterohepatic cholesterol accumulation, leading to dyslipidemia in response to ribosomal stress. Moreover, genetic features of stress-responsive LDLR modulators were consistently proven in the inflammation- and obesity-associated gut model. Conclusion: The elucidated ribosome-linked gut lipid regulation provides predictive insights into stress-responsive metabolic rewiring in chronic human diseases as an environmental health prediction.

Snacking on whole almonds for 6 weeks improves endothelial function and lowers LDL cholesterol but does not affect liver fat and other cardiometabolic risk factors in healthy adults: the ATTIS study, a randomized controlled trial

BackgroundThere is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations, but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined.ObjectivesWe aimed to investigate whether isoenergetic substitution of whole almonds for control snacks with the macronutrient profile of average snack intakes, had any impact on markers of cardiometabolic health in adults aged 30–70 y at above-average risk of cardiovascular disease (CVD).MethodsThe study was a 6-wk randomized controlled, parallel-arm trial. Following a 2-wk run-in period consuming control snacks (mini-muffins), participants consumed either whole roasted almonds (n = 51) or control snacks (n = 56), providing 20% of daily estimated energy requirements. Endothelial function (flow-mediated dilation), liver fat (MRI/magnetic resonance spectroscopy), and secondary outcomes as markers of cardiometabolic disease risk were assessed at baseline and end point.ResultsAlmonds, compared with control, increased endothelium-dependent vasodilation (mean difference 4.1%-units of measurement; 95% CI: 2.2, 5.9), but there were no differences in liver fat between groups. Plasma LDL cholesterol concentrations decreased in the almond group relative to control (mean difference −0.25 mmol/L; 95% CI: −0.45, −0.04), but there were no group differences in triglycerides, HDL cholesterol, glucose, insulin, insulin resistance, leptin, adiponectin, resistin, liver function enzymes, fetuin-A, body composition, pancreatic fat, intramyocellular lipids, fecal SCFAs, blood pressure, or 24-h heart rate variability. However, the long-phase heart rate variability parameter, very-low-frequency power, was increased during nighttime following the almond treatment compared with control (mean difference 337 ms2; 95% CI: 12, 661), indicating greater parasympathetic regulation.ConclusionsWhole almonds consumed as snacks markedly improve endothelial function, in addition to lowering LDL cholesterol, in adults with above-average risk of CVD.This trial was registered at clinicaltrials.gov as NCT02907684.

Rapid UHPLC-MS metabolite profiling and phenotypic assays reveal genotypic impacts of nitrogen supplementation in oats

IntroductionOats (Avena sativa L.) are a whole grain cereal recognised for their health benefits and which are cultivated largely in temperate regions providing both a source of food for humans and animals, as well as being used in cosmetics and as a potential treatment for a number of diseases. Oats are known as being a cereal source high in dietary fibre (e.g. β-glucans), as well as being high in antioxidants, minerals and vitamins. Recently, oats have been gaining increased global attention due to their large number of beneficial health effects. Consumption of oats has been proven to lower blood LDL cholesterol levels and blood pressure, thus reducing the risk of heart disease, as well as reducing blood-sugar and insulin levels.ObjectivesOats are seen as a low input cereal. Current agricultural guidelines on nitrogen application are believed to be suboptimal and only consider the effect of nitrogen on grain yield. It is important to understand the role of both variety and of crop management in determining nutritional quality of oats. In this study the response of yield, grain quality and grain metabolites to increasing nitrogen application to levels greater than current guidelines were investigated.MethodsFour winter oat varieties (Mascani, Tardis, Balado and Gerald) were grown in a replicated nitrogen response trial consisting of a no added nitrogen control and four added nitrogen treatments between 50 and 200 kg N ha−1 in a randomised split-plot design. Grain yield, milling quality traits, β-glucan, total protein and oil content were assessed. The de-hulled oats (groats) were also subjected to a rapid Ultra High Performance Liquid Chromatography—Mass Spectrometry (UHPLC-MS) metabolomic screening approach.ResultsApplication of nitrogen had a significant effect on grain yield but there was no significant difference between the response of the four varieties. Grain quality traits however displayed significant differences both between varieties and nitrogen application level. β-glucan content significantly increased with nitrogen application. The UHPLC-MS approach has provided a rapid, sub 15 min per sample, metabolite profiling method that is repeatable and appropriate for the screening of large numbers of cereal samples. The method captured a wide range of compounds, inclusive of primary metabolites such as the amino acids, organic acids, vitamins and lipids, as well as a number of key secondary metabolites, including the avenanthramides, caffeic acid, and sinapic acid and its derivatives and was able to identify distinct metabolic phenotypes for the varieties studied. Amino acid metabolism was massively upregulated by nitrogen supplementation as were total protein levels, whilst the levels of organic acids were decreased, likely due to them acting as a carbon skeleton source. Several TCA cycle intermediates were also impacted, potentially indicating increased TCA cycle turn over, thus providing the plant with a source of energy and reductant power to aid elevated nitrogen assimilation. Elevated nitrogen availability was also directed towards the increased production of nitrogen containing phospholipids. A number of both positive and negative impacts on the metabolism of phenolic compounds that have influence upon the health beneficial value of oats and their products were also observed.ConclusionsAlthough the developed method has broad applicability as a rapid screening method or a rapid metabolite profiling method and in this study has provided valuable metabolic insights, it still must be considered that much greater confidence in metabolite identification, as well as quantitative precision, will be gained by the application of higher resolution chromatography methods, although at a large expense to sample throughput. Follow up studies will apply higher resolution GC (gas chromatography) and LC (reversed phase and HILIC) approaches, oats will be also analysed from across multiple growth locations and growth seasons, effectively providing a cross validation for the results obtained within this preliminary study. It will also be fascinating to perform more controlled experiments with sampling of green tissues, as well as oat grains, throughout the plants and grains development, to reveal greater insight of carbon and nitrogen metabolism balance, as well as resource partitioning into lipid and secondary metabolism.

Statement for Appropriate Clinical Use of PCSK9 Inhibitors.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein that promotes the degradation of LDL receptors. Evolocumab (Repatha®), a recombinant human IgG2 antibody, and alirocumab (Praluent ®), a recombinant human IgG1 antibody, are new types of drug that lower blood LDL cholesterol (LDL-C) by inhibiting PCSK9 and increasing the number of LDL receptors on the surface of hepatocytes. In combination with statins, PCSK9 inhibitors achieve a very strong LDL-C lowering effect making them a powerful option for patients with insufficient LDL-C management with existing drugs. However, the drugs are expensive. Therefore, from the viewpoints of medical and medical economics, it is an urgent issue to identify the types of patients who really need them and would be benefitted greatly from their use. In this regard, the Japan Atherosclerosis Society would like to express its views in accordance with the JAS Guidelines for the Diagnosis and Prevention of Atherosclerotic Cardiovascular Diseases 20171).

Scientific Opinion on the modification of the authorisation of a health claim related to plant sterol esters and lowering blood LDL‐cholesterol; high blood LDL‐cholesterol is a risk factor in the development of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006, following a request in accordance with Article 19 of Regulation (EC) No 1924/2006

Following an application from SANOFI-AVENTIS FRANCE, submitted pursuant to Article 19 of Regulation (EC) No 1924/2006 via the Competent Authority of France, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the modification of the authorisation of a health claim related to plant sterol esters and lowering blood LDL-cholesterol (high blood LDL-cholesterol is a risk factor in the development of (coronary) heart disease), pursuant to Article 14 of Regulation (EC) No 1924/2006. The applicant requested an extension of the conditions of use to powder supplements to be diluted in water at a dose of 2 g per day, which would lower blood LDL-cholesterol concentrations by “5.4-8.1 %” after six weeks of daily consumption. Plant sterol esters are sufficiently characterised. Lowering blood LDL-cholesterol concentrations is a beneficial physiological effect and elevated blood LDL-cholesterol concentration is a risk factor for coronary heart disease. The target population is subjects who need and want to lower their blood cholesterol. In weighing the evidence, the Panel took into account that only one human intervention study showed a reduction in blood LDL-cholesterol concentrations after six weeks of consuming 2 g/day of plant sterol esters in powder, the large uncertainty surrounding the estimates of this effect, and that the results of that study have not been replicated in other studies. The Panel reiterates its previous conclusion that, while plant sterols added to foods such as margarine-type spreads, mayonnaise, salad dressings, and dairy products have been shown consistently to lower blood LDL-cholesterol concentrations in a large number of studies, the effective dose of plant sterols (as powder diluted in water) needed to achieve a given magnitude of effect in a given timeframe cannot be established with the data provided.

Effects of Carnosine Supplementation on Carnosine Concentrations in Muscles and Blood Biochemical Indices of Rats

This study evaluated the effects of carnosine supplementation on carnosine concentration in muscles and blood biochem-ical indices of rats. Thirty-two eight-week-old Sprague-Dawley male rats were randomly divided into a control group(CON) as well as three carnosine-treated groups. The carnosine-treated groups included groups fed diets composed of0.01% carnosine (LC), 0.1% carnosine (MC), and 1.0% carnosine (HC). Body weight gain, food intake, feed efficacy rate,protein efficacy rate, and organ weights were not significantly different among the groups. In all groups, the mean carnosinelevels in gastrocnemius muscles were higher than the mean carnosine levels in soleus muscles. Carnosine concentrations insoleus muscles and gastrocnemius muscles were significantly higher in the HC group compared to all other groups ( p<0.05).Serum triglyceride and LDL-cholesterol concentrations in all of the carnosine-supplemented groups were significantlylower than those of the control group (p<0.05), while HDL-cholesterol levels were significantly higher than those of thecontrol group (p<0.05). Aspartate aminotransferase levels in rats supplemented with carnosine were significantly higherthan those of the control group. In conclusion, diets supplemented with high levels of carnosine can increase carnosine con-centrations in skeletal muscles, which might contribute to increased exercise capacity. Furthermore, these findings suggestthat high levels of dietary carnosine improve the lipid profile of rats by lowering blood LDL-cholesterol and increasingHDL-cholesterol levels. Key words: carnosine, muscle carnosine, lipid profile, rats

Scientific Opinion on the substantiation of a health claim related to 3 g/day plant stanols as plant stanol esters and lowering blood LDL-cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006

Following an application from Raisio Nutrition Ltd, submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Finland, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to 3 g/day plant stanols as plant stanol esters per day and lowering blood LDL-cholesterol by 12 % and reduced risk of (coronary) heart disease. The applicant has further requested that the minimum duration to obtain the effect be stated to be one to two weeks, and that the claims be authorised for an extended range of foods, including yellow fat spreads, dairy products, cheese, rye bread, oatmeal, fermented soy milk based products (drinkable and spoonable yoghurt-type products), and oat based milk drinks. The applicant provided an unpublished meta-analysis with 18 randomised, controlled human studies on the LDL-lowering efficacy of plant stanol esters at intakes between 2.7 to 3.3 g per day plant stanols. On the basis of the data presented, the Panel concludes that plant stanol esters at a daily intake of 3 g plant stanols (range 2.7 g to 3.3 g) in matrices approved by Regulation (EC) No 376/2010 (yellow fat spreads, dairy products, mayonnaise and salad dressings) lowers LDL-cholesterol by 11.4 % (95% CI: 9.8 – 13.0), that the minimum duration required to achieve the maximum effect of plant stanol esters on LDL-cholesterol lowering is two to three weeks, and that while plant stanol esters added to foods such as margarine-type spreads, mayonnaise, salad dressings, and dairy products such as milk, yoghurts including low-fat yoghurts, and cheese have been shown consistently to lower blood LDL-cholesterol levels, the size of the cholesterol-lowering effect of plant stanols added to other food formats is less well established.

Scientific Opinion on the substantiation of a health claim related to 3 g/day plant sterols/stanols and lowering blood LDL-cholesterol and reduced risk of (coronary) heart disease pursuant to Article 19 of Regulation (EC) No 1924/2006

Following an application from Unilever PLC and Unilever NV, submitted pursuant to Article 19 of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of an application to modify the conditions of use of an authorised Article 14 claim related to 1.5 – 3.0 g plant sterols/stanols per day and lowering blood LDL-cholesterol by 7 – 12 % and reduced risk of (coronary) heart disease. The applicant has further requested that the minimum duration to obtain the effect be one to two weeks. The applicant provided a published systematic review and meta-analysis that evaluated the comparative efficacy of plant sterols and plant stanols for lowering blood LDL-cholesterol in healthy and hypercholesterolaemic subjects and an unpublished meta-analysis on 27 randomised controlled human studies on the LDL-lowering efficacy at a dose range between 2.6 and 3.4 g per day. On the basis of the data presented, the Panel concludes that plant sterols and stanol esters at daily intakes ranging from 1.5 to 3.0 g plant sterols/stanols in matrices approved by Regulation (EC) No 376/2010 (yellow fat spreads, dairy products, mayonnaise and salad dressings) have a similar efficacy on blood LDL-cholesterol lowering, that plant sterols and stanol esters at a daily intake of 3 g (range 2.6 g to 3.4 g) plant sterols/stanols in matrices approved by Regulation (EC) No 376/2010 lower LDL-cholesterol by 11.3 % (95 % CI: 10.0 – 12.5), and that the minimum duration required to achieve the maximum effect of plant sterols and stanols on LDL-cholesterol lowering is two to three weeks.

Acides grasoméga-6et maladies cardiovasculaires

Omega-6 polyunsaturated fatty acids (n-6 PUFA) are well known for their critical role in many physiological functions and reduce risks of cardiovascular disease (CVD). However, some argue that excessive consumption of n-6 PUFA may lead to adverse effects on health and therefore recommend reducing dietary n-6 PUFA intake or fixing an upper limit. Epidemiological studies show that n-6 PUFA dietary intake significantly lowers blood LDL-cholesterol levels. In addition, n-6 PUFA intake lower several cardiovascular risk factors such as blood pressure, inflammatory markers, haemostatic parameters and obesity. Data from prospective cohort and interventional studies converge towards a specific protective role of dietary n-6 PUFA intake, in particular linoleic acid, against CVD. In regards to studies examined in this narrative review, recommendation for n-6 PUFA intake above 5%, and ideally about 10% of total energy appears justified for the prevention of ischemic heart disease.

Scientific Opinion on the substantiation of a health claim related to oat beta glucan and lowering blood cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006

Following an application from CreaNutrition AG submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to oat beta glucan and lowering of blood LDL and total cholesterol. Oat beta-glucan is sufficiently characterised. Lowering blood LDL-cholesterol concentrations is a beneficial physiological effect by decreasing the risk of coronary heart disease. The applicant identified a total of 22 references, which included three meta-analyses and 19 randomised controlled trials, as being pertinent to the health claim. In weighing the evidence, the Panel took into account that most of the trials investigating the effects of oat beta-glucan at doses of at least 3 g/d have shown a statistically significant decrease in LDL-cholesterol concentrations, and that there was strong evidence supporting the biological plausibility of the effect. The Panel concludes that a cause and effect relationship has been established between the consumption of oat beta-glucan and lowering of blood LDL-cholesterol concentrations. The following wording reflects the scientific evidence: “Oat beta-glucan has been shown to lower/reduce blood cholesterol. Blood cholesterol lowering may reduce the risk of (coronary) heart disease”. The Panel considers that, in order to bear the claim, foods should provide at least 3 g of oat beta-glucan per day. This amount can reasonably be consumed as part of a balanced diet. The target population is adults who want to lower their blood cholesterol concentrations.

N-6 Fatty acids and cardiovascular health: a review of the evidence for dietary intake recommendations

n-6 PUFA are well known for their critical role in many physiological functions and seem to reduce risks of CHD. However, some argue that excessive consumption of n-6 PUFA may lead to adverse effects on health and therefore recommend reducing dietary n-6 PUFA intake or fixing an upper limit. In this context, the present work aimed to review evidence on the link between n-6 PUFA and risks of CVD. Epidemiological studies show that n-6 PUFA dietary intake significantly lowers blood LDL-cholesterol levels. In addition, n-6 PUFA intake does not increase several CVD risk factors such as blood pressure, inflammatory markers, haemostatic parameters and obesity. Data from prospective cohort and interventional studies converge towards a specific protective role of dietary n-6 PUFA intake, in particular linoleic acid, against CVD. n-6 PUFA benefits are even increased when SFA intake is also reduced. In regards to studies examined in this narrative review, recommendation for n-6 PUFA intake above 5 %, and ideally about 10 %, of total energy appears justified.

Caracterização físico-química de creme vegetal enriquecido com ésteres de fitosteróis

Atualmente, esteróis e estanóis têm sido adicionados a margarinas especiais, comercialmente disponíveis como alimentos funcionais, com o intuito de reduzir os níveis de colesterol. Como parte de uma dieta saudável, é cientificamente comprovado que esse tipo de produto reduz o colesterol LDL em aproximadamente 10-15%. A literatura disponível sobre os efeitos dos fitosteróis/fitostanóis na redução do colesterol no organismo, bem como a forma como estes componentes são metabolizados, é muito vasta. Porém, informações sobre as propriedades físicas e químicas destas substâncias e os efeitos de sua aplicação em alimentos, do ponto de vista tecnológico, dificilmente são encontradas. Este trabalho tem como objetivo caracterizar um creme vegetal enriquecido com fitosteróis e comparar suas propriedades físicas com as de margarinas comuns disponíveis comercialmente. As composições em ácidos graxos e em esteróis foram determinadas por cromatografia gasosa. Foram, também, analisados ponto de amolecimento, textura, composição química e estrutura cristalina. O creme vegetal enriquecido é composto de 49,3% de umidade, 49,6% de lipídios e 1,1% de sólidos. O b-sitosterol é o esterol mais abundante, constituindo 36,1% do total de esteróis. O ácido linoléico (C18:2 n-6) corresponde a 45,3% do total de ácidos graxos e é o que está presente em maior quantidade. Em geral, as propriedades de textura da base gordurosa e do creme vegetal apresentaram correlação linear significativa. Embora um pouco mais duro que as margarinas cremosas comerciais, o creme vegetal com fitosteróis apresenta plasticidade satisfatória na faixa de temperatura entre a de refrigeração e a ambiente e maior resistência à temperatura do que as margarinas cremosas. Em geral, os ésteres de fitosteróis apresentaram comportamento de fusão e cristalização diferentes dos óleos e gorduras comestíveis.