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Parkinson's disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress., This work was supported by the Horizon 2020 Framework Programme (grant number 634821, PROPAG-AGEING).

Background Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits. Methods Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity. Results Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08–1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed. Conclusions This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk.

This article summarizes the results of studies on the exposure of the Finnish Sami people to radioactive fallout and the estimations of the related cancer risk. We also discuss the lifestyle, genetic origin and diet of this population. The Sami people are an indigenous people who live in the northern part of Scandinavia and Finland. The review is based on the available scientific literature of Finnish Sami. The traditional Sami diet, high in animal products, persists in Sami groups still involved in reindeer-herding, but others have adopted the typical diet of western cultures. Studies have consistently shown an overall reduced cancer risk among the Finnish Sami people, except for stomach cancer among the Skolt Sami. Common cancers among the Finnish main population, such as prostate, breast and skin cancer are especially rare among the Finnish Sami. The incidence of cancer among the Finnish Sami are mostly similar to those of the Swedish and Norwegian Sami. To conclude, we observed no effect of radioactive pollution on cancer incidence. The lifestyles and environments of the Sami are changing, and their cancer mortality rate today is similar to that of the majority of the Finnish and western population.

Dietary modifications including plant stanol ester consumption are recommended measures to control serum and low-density lipoprotein (LDL)-cholesterol concentrations, but obesity can affect their responses. We investigated whether body mass index (BMI) affects serum cholesterol levels during plant stanol (mainly sitostanol) ester consumption. This ad hoc analysis was based on earlier results of a cross-over, randomized controlled trial of postmenopausal women consuming rapeseed oil-based margarine without or with plant stanol ester (3 g plant stanols/day) for seven weeks. We classified the subjects as normal-weight (BMI ≤ 25 kg/m2, n = 9, mean 22.6 kg/m2) or overweight/obese (BMI > 25 kg/m2, n = 11, mean 28.4 kg/m2), and recalculated the results, focusing on cholesterol absorption, cholesterol synthesis, and fecal steroid outputs. Serum cholesterol levels were similar in the groups during the control diet. Plant stanol ester reduced serum cholesterol by 0.63 ± 0.19 mmol/L (11%) in normal-weight and by 0.75 ± 0.13 mmol/L (12%) in overweight/obese subjects (p < 0.05 for both), and cholesterol absorption was reduced in both groups. However, relative and dietary cholesterol absorption were more effectively reduced in normal-weight subjects. In conclusion, overweight/obesity did not interfere with the serum cholesterol response to plant stanol ester consumption despite substantial differences in cholesterol metabolism between the groups.

Atherosclerotic cardiovascular diseases (ASCVDs) cause every fifth death worldwide. However, it is possible to prevent the progression of ASCVDs by reducing circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Recent large meta-analyses demonstrated that by reducing the dietary intake of saturated fat and cholesterol, it is possible to reduce the risk of ASCVD events. Plant stanols, as fatty-acid esters, were developed as a dietary adjunct to reduce LDL-C levels as part of a heart-healthy diet. They reduce cholesterol absorption so that less cholesterol is transported to the liver, and the expression of LDL receptors is upregulated. Ultimately, LDL-C concentrations are reduced on average by 9-12% by consuming 2-3 g of plant stanol esters per day. In this review, we discuss recent information regarding the prevention of ASCVDs with a focus on dietary means. We also present new estimates on the effect of plant stanol ester consumption on LDL-C levels and the risk of ASCVD events. Plant stanol esters as part of a heart-healthy diet plausibly offer a means to reduce the risk of ASCVD events at a population level. This approach is not only appropriate for subjects with a high risk of ASCVD, but also for subjects at an apparently lower risk to prevent subclinical atherosclerosis. Non

Although alpha-linolenic acid (ALA) and endurance exercise training independently attenuate hyperlipidaemia-related cardiovascular derangements, there is a paucity of information pertaining to their mechanisms of action and efficacy when combined as a preventative therapeutic approach. Therefore, we used obese Zucker rats to investigate the independent and combined effects of these interventions on cardiovascular disease. Specifically, animals were randomly assigned to one of the following groups: control diet-sedentary, ALA supplemented-sedentary, control diet-exercise trained or ALA supplemented-exercise trained. Following a 4week intervention, although the independent and combined effects of ALA and exercise reduced (P

19 páginas, 4 figuras, 2 tablas; material suplementario con 3 figuras. 2 tablas de material suplementario en: http://dx.doi.org/10.18632/aging.103992, The research of new biomarkers for Parkinson's disease is essential for accurate and precocious diagnosis, as well as for the discovery of new potential disease mechanisms and drug targets. The main objective of this work was to identify metabolic changes that might serve as biomarkers for the diagnosis of this neurodegenerative disorder. For this, we profiled the plasma metabolome from mice with neurotoxin-induced Parkinson's disease as well as from patients with familial or sporadic Parkinson's disease. By using mass spectrometry technology, we analyzed the complete metabolome from healthy volunteers compared to patients with idiopathic or familial (carrying the G2019S or R1441G mutations in the LRRK2 gene) Parkinson's disease, as well as, from mice treated with 6-hydroxydopamine to induce Parkinson disease. Both human and murine Parkinson was accompanied by an increase in plasma levels of unconjugated bile acids (cholic acid, deoxycholic acid and lithocholic acid) and purine base intermediary metabolites, in particular hypoxanthine. The comprehensive metabolomic analysis of plasma from Parkinsonian patients underscores the importance of bile acids and purine metabolism in the pathophysiology of this disease. Therefore, plasma measurements of certain metabolites related to these pathways might contribute to the diagnosis of Parkinson's Disease., This research was supported by “Instituto de Salud Carlos III”, “Fondo de Investigaciones Sanitarias” (PI15/0034), “CIBERNED” (CB06/05/0041 and 2015/03), “MINECO” (SAF2014-52940-R and SAF2017-85199-P) and partially supported by “European Regional Development Fund (ERDF)” from the European Union. SMSY-D was supported by “Isabel Gemio Foundation”. JMB-SP and MN-S were funded by “Ramon y Cajal Program” (RYC-2018-025099-I) and (RYC-2016-20883), respectively. GM-C was supported by “ONCE Foundation”. EU-C is supported by an FPU predoctoral fellowship (FPU16/00684) from “Ministerio de Educación, Cultura y Deporte”. JMF received research support from the “Instituto de Salud Carlos III”; “Fondo de Investigaciones Sanitarias” (PI15/0034) and CIBERNED (CB06/05/0041 and 2015/03). AP-C was supported by MINECO (SAF2014-52940-R and SAF2017-85199- P). JR-M and MZ were supported by Institute de Salud Carlos III, Fondo de Investigaciones Sanitarias (PI19/01653), CIBERNED and PPMI Initiative. JP-T received funding from CIBERNED (CB06/05/1123 and 2015/03). This work was also partially supported by “Fondo Europeo de Desarrollo Regional” (FEDER) from the European Union. GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Le Cancer du Sein, Parlons-en!”; Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085), Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology (ANR-18-IDEX-0001); the RHU Torino Lumière; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and the SIRIC Cancer Research and Personalized Medicine (CARPEM).

Low-density lipoprotein (LDL) cholesterol lowering efficacy of a new type of chewable plant stanol ester food supplement was evaluated in a randomized, double-blind, controlled four-week intervention. The participants (LDL cholesterol > 3 mmol/L) consumed four supplements daily with meals either with (n = 50) or without (n = 53) plant stanol esters. Plant stanol ester supplement (2 g/d plant stanols) lowered LDL cholesterol by 7.6%, serum cholesterol by 4.9%, and non-high density lipoprotein (HDL) cholesterol by 6.6% compared with controls (P

This review covers the current knowledge about plant stanol esters as a dietary treatment option for heterozygous familial hypercholesterolemia (he-FH) children. The current estimation of the prevalence of he-FH is about one out of 200-250 persons. In this autosomal dominant disease, the concentration of plasma low-density lipoprotein cholesterol (LDL-C) is strongly elevated since birth. Quantitative coronary angiography among he-FH patients has revealed that stenosing atherosclerotic plaques start to develop in he-FH males in their twenties and in he-FH females in their thirties, and that the magnitude of the plaque burden predicts future coronary events. The cumulative exposure of coronary arteries to the lifelong LDL-C elevation can be estimated by calculating the LDL-C burden (LDL-C level x years), and it can also be used to demonstrate the usefulness of dietary stanol ester treatment. Thus, when compared with untreated he-FH patients, the LDL-C burden of using statin from the age of 10 is 15% less, and if he-FH patients starts to use dietary stanol from six years onwards and a combination of statin and dietary stanol from 10 years onwards, the LDL-C burden is 21% less compared to non-treated he-FH patients. We consider dietary stanol treatment of he-FH children as a part of the LDL-C-lowering treatment package as safe and cost-effective, and particularly applicable for the family-centered care of the entire he-FH families.

OBJECTIVES: The aim of our study was to investigate vascular effects of oxysterols and oxyphytosterols on reactive oxygen species (ROS), endothelial progenitor cells, endothelial function and atherogenesis. METHODS: Male apoE-/-mice were treated with cholesterol, sitosterol, 7-ss-OH-cholesterol, 7-ss-OH-sitosterol, or cyclodextrin by daily intraperitoneal application. The respective concentrations in the plasma and in the arterial wall were determined by gas chromatography-flame ionization or mass spectrometry. ROS production was assessed by electron-spin resonance spectroscopy in the aorta, endothelial function of aortic rings and atherosclerosis in the aortic sinus was quantitated after 4 weeks. RESULTS: Compared to vehicle, there was no difference in plasma cholesterol levels and arterial wall concentrations after i.p. application of cholesterol. 7-ss-OH-cholesterol concentrations were increased in the plasma (33.7 +/- 31.5 vs. 574.57.2 +/- 244.92 ng/ml) but not in the arterial wall (60.1 +/- 60.1 vs. 59.3 +/- 18.2 ng/mg). Sitosterol (3.39 +/- 0.96 vs. 8.16 +/- 4.11 mg/dL; 0.08 +/- 0.04 vs. 0.16 +/- 0.07 mug/mg, respectively) and 7-ss-OH-sitosterol concentrations (405.1 +/- 151.8 vs. 7497 +/- 3223 ng/ml; 0.24 +/- 0.13 vs. 16.82 +/- 11.58 ng/mg, respectively) increased in the plasma and in the aorta. The i.p-application of the non-oxidized cholesterol or sitosterol did not induce an increase of plasma oxysterols or oxyphytosterols concentrations. Oxidative stress in the aorta was increased in 7-ss-OH-sitosterol treated mice, but not in mice treated with cholesterol, sitosterol, or 7-ss-OH-cholesterol. Moreover, cholesterol, sitosterol, 7-ss-OH-cholesterol, and 7-ss-OH-sitosterol did not affect endothelial-dependent vasodilation, or early atherosclerosis. CONCLUSION: Increased oxyphytosterol concentrations in plasma and arterial wall were associated with increased ROS production in aortic tissue, but did not affect endothelial progenitor cells, endothelial function, or early atherosclerosis.

Context: Cheese may affect lipids and lipoproteins differently than other high-fat dairy foods. Objective: The present systematic review and meta-analysis was performed to evaluate randomized controlled trials that examined the effect of cheese consumption compared with another food product on blood lipids and lipoproteins. Data Sources: A systematic literature search of the MEDLINE, Embase, Scopus, CAB Abstracts, the Cochrane Controlled Trials Register, and the clinicaltrials.gov website was performed. Study Selection: A total of 12 randomized controlled trials (RCTs) were identified that examined the effect of cheese consumption on blood lipids and lipoproteins in healthy adults. Data Extraction : A meta-analysis of 5 RCTs that compared the effects of hard cheese and butter, both of which had a similar ratio of polyunsaturated fatty acids to saturated fatty acids (P/S ratio), was performed. Data Synthesis: Compared with butter intake, cheese intake (weighted mean difference: 145.0 g/d) reduced low-density lipoprotein cholesterol (LDL-C) by 6.5% (−0.22 mmol/l; 95%CI: −0.29 to −0.14) and high-density lipoprotein cholesterol (HDL-C) by 3.9% (−0.05 mmol/l; 95%CI: −0.09 to −0.02) but had no effect on triglycerides. Compared with intake of tofu or fat-modified cheese, cheese intake increased total cholesterol or LDL-C, as was expected on the basis of the P/S ratio of the diets. There was insufficient data to compare intake of cheese with intake of other foods. Conclusion: Despite the similar P/S ratios of hard cheese and butter, consumption of hard cheese lowers LDL-C and HDL-C when compared with consumption of butter. Whether these findings can be attributed to calcium, specific types of saturated fatty acids, or the food matrix of cheese warrants further research.

Physiological adaptations resulting in the development of the metabolic syndrome in man occur over a time span of several decades. This combined with the prohibitive financial cost and ethical concerns to measure key metabolic parameters repeatedly in subjects for the major part of their life span makes that comprehensive longitudinal human data sets are virtually nonexistent. While experimental mice are often used, little is known whether this species is in fact an adequate model to better understand the mechanisms that drive the metabolic syndrome in man. We took up the challenge to study the response of male apoE*3‐Leiden.CETP mice (with a humanized lipid profile) to a high‐fat high‐cholesterol diet for 6 months. Study parameters include body weight, food intake, plasma and liver lipids, hepatic transcriptome, VLDL – triglyceride production and importantly the use of stable isotopes to measure hepatic de novo lipogenesis, gluconeogenesis, and biliary/fecal sterol secretion to assess metabolic fluxes. The key observations include (1) high inter‐individual variation; (2) a largely unaffected hepatic transcriptome at 2, 3, and 6 months; (3) a biphasic response curve of the main metabolic features over time; and (4) maximum insulin resistance preceding dyslipidemia. The biphasic response in plasma triglyceride and total cholesterol appears to mimic that of men in cross‐sectional studies. Combined, these observations suggest that studies such as these can help to delineate the causes of metabolic derangements in patients suffering from metabolic syndrome.

Although α-linolenic acid (ALA) and endurance exercise training independently attenuate hyperlipidaemia-related cardiovascular derangements, there is a paucity of information pertaining to their mechanisms of action and efficacy when combined as a preventative therapeutic approach. Therefore, we used obese Zucker rats to investigate the independent and combined effects of these interventions on cardiovascular disease. Specifically, animals were randomly assigned to one of the following groups: control diet-sedentary, ALA supplemented-sedentary, control diet-exercise trained or ALA supplemented-exercise trained. Following a 4 week intervention, although the independent and combined effects of ALA and exercise reduced (P < 0.05) the serum free/esterified cholesterol ratio, only the ALA supplemented-exercise trained animals displayed a reduction in the content of both serum free and esterified cholesterol. Moreover, although ALA and endurance training individually increased cardiac output, stroke volume and end-diastolic volume, as well as reduced left ventricle fibrosis, mean blood pressure and total peripheral resistance, these responses were all greater following the combined intervention (ALA supplemented-exercise trained). These effects occurred independent of changes in oxidative phosphorylation proteins, markers of oxidative stress or endogenous anti-oxidant capacity. We propose that the beneficial effects of a combined intervention occur as a result of divergent mechanisms of action elicited by ALA and endurance exercise because only exercise training increased the capillary content in the left ventricle and skeletal muscle, and tended to decrease protein carbonylation in the left ventricle (P = 0.06). Taken together, our data indicate that combining ALA and endurance exercise provides additional improvements in cardiovascular disease risk reduction compared to singular interventions in the obese Zucker rat.

BACKGROUND: Lipids and lipoproteins are recognized as the most important modifiable risk factors for cardiovascular disease. Although reference values for the major lipoproteins, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides, have been collected in numerous studies and cohorts, complete contemporary percentile-based reference values are underreported.OBJECTIVE: We set out to provide such reference lipid data using a large contemporary population based cohort study.STUDY DESIGN AND SETTING: Lifelines is a cross-sectional population-based Dutch cohort study. We analyzed 133,540 adult fasting participants without cardiovascular disease and without lipid-lowering drug use. Lipid levels were directly measured and selected percentiles of all lipid parameters were calculated. Friedewald LDL-C estimation was calculated as well.RESULTS: From 20 till 49 years of age, men were found to exhibit a steep 64% increase of LDL-C (median +54 mg/dL), while triglyceride levels increased almost two-fold. In women, LDL-C levels did not change from 18 till 35 years, followed by a steep 42% increase till 59 years (median +42 mg/dL). In contrast to men, triglycerides were stable in ageing women. Overall, Friedewald LDL-C levels are lower compared with the direct measurement, especially with increasing triglyceride levels.CONCLUSIONS: This observational study highlights striking gender-and age-related differences in plasma lipid profiles. The given reference ranges of plasma lipids can assist in early identification of individuals with hypocholesterolemia and hypercholesterolemia, especially familial hypercholesterolemia. These reference ranges are available for physicians and patients at www.my-cholesterol.care/.

Some observational studies raised concern that statins may cause memory impairment, leading to a US Food and Drug Administration warning. Similar questions were raised regarding proprotein convertase subtilisin/kexin-type 9 inhibitors (PCSK9i) and neurocognitive function. No prospectively designed study has evaluated the relationship between long-term PCSK9i use and cognition changes. Patients with prior cardiovascular disease treated with maximally tolerated statin enrolled in FOURIER (the randomized, double-blind, placebo-controlled cardiovascular outcome study of the PCSK9i evolocumab) could participate in this prospective assessment of cognitive function (EBBINGHAUS). Key additional exclusion criteria for EBBINGHAUS were dementia, cognitive impairment, or other significant mental or neurological disorder. Cognitive testing was performed using the Cambridge Neuropsychological Test Automated Battery, a tablet-based tool assessing executive function, working memory, memory function, and psychomotor speed at baseline, weeks 24 and 48, every 48 weeks thereafter, and study end. The primary endpoint was spatial working memory strategy index of executive function (SWMSI). The primary hypothesis was that evolocumab would be noninferior to placebo in the mean change from baseline over time in SWMSI. Fifteen hundred cognitively normal patients completing the assessments provided approximately 97% power to demonstrate that the upper 95% confidence interval for the treatment difference in mean change from baseline in SWMSI over time is

Background/Objectives:Viscous fibers typically reduce total cholesterol (TC) by 3-7% in humans. The cholesterol-lowering properties of the viscous fiber pectin may depend on its physico-chemical properties (viscosity, molecular weight (MW) and degree of esterification (DE)), but these are not typically described in publications, nor required by European Food Safety Authority (EFSA) with respect to its generic pectin cholesterol-lowering claim.Subjects/Methods:Here, different sources and types of well-characterized pectin were evaluated in humans. Cross-over studies were completed in mildly hyper-cholesterolemic persons receiving either 15 g/day pectin or cellulose with food for 4 weeks.Results:Relative low-density lipoprotein (LDL) cholesterol (LDL-C) lowering was as follows: citrus pectin DE-70=apple pectin DE-70 (7-10% reduction versus control)>apple pectin DE-35=citrus pectin DE-35>OPF (orange pulp fiber) DE-70 and low-MW pectin DE-70>citrus DE-0. In a subsequent 3-week trial with 6 g/day pectin, citrus DE-70 and high MW pectin DE-70 reduced LDL-C 6-7% versus control (without changes in TC). In both studies, high DE and high MW were important for cholesterol lowering. Source may also be important as citrus and apple DE-70 pectin were more effective than OPF DE-70 pectin. Pectin did not affect inflammatory markers high-sensitivity C-reactive protein (hsCRP) nor plasma homocysteine.Conclusions:Pectin source and type (DE and MW) affect cholesterol lowering. The EFSA pectin cholesterol-lowering claim should require a minimum level of characterization, including DE and MW.European Journal of Clinical Nutrition advance online publication, 21 December 2011; doi:10.1038/ejcn.2011.208.

About 30 years ago, the first Dutch unifactorial guidelines on hypertension and hypercholesterolaemia were developed. These guidelines have been revised several times, often after publication of landmark studies on new generations of drugs. In 1978, cut-off points for pharmacological treatment of hypertension were based on diastolic blood pressure values =115 mmHg, and in 2000 they were lowered to >100 mmHg. From 1997 onwards, cut-off points for systolic blood pressure values >180 mmHg were introduced, which became leading. In 1987, cut-offs for hypercholesterolaemia of =8 mmol/l were set and from 2006 pharmacological treatment was based on a total/HDL cholesterol ratio >8. Around 2000, treatment decisions for hypertension and/or hypercholesterolaemia were no longer based on high levels of individual risk factors, but on a multifactorial approach based on total risk of cardiovascular diseases (CVD), determined by a risk function. In the 2006 multidisciplinary guideline on cardiovascular risk management, the Framingham risk tables were replaced by European SCORE risk charts. A cut-off point of 10% CVD mortality was set in the Netherlands. In 2011, this cut-off point changed to 20% fatal plus nonfatal CVD risk. Nowadays, ‘the lower the risk factors, the lower the absolute risk’ is the leading paradigm in CVD prevention.

This study investigates the effect of various dietary saturated fatty acid (SFA) profiles on plasma lipid parameters and tissue fatty acid composition in rats. The experiment was designed to monitor polyunsaturated fatty acids (PUFA) levels, while examining different amounts and types of SFA. Four isocaloric diets were prepared, containing 10-11 mol% of fatty acids (FA) as linoleic acid (LNA) and 2.5 mol% as α-linolenic acid (ALA), leading to an identical and well-balanced LNA/ALA ratio. The initial rapeseed oil/corn oil mixture providing ALA and LNA was enriched with olive oil to prepare the olive oil diet. The butterfat diet was supplemented with butterfat, containing short-chain SFA (C4:0-C10:0, 17 mol% of FA), lauric acid (C12:0, 3.2 mol%), myristic acid (C14:0, 10.5 mol%) and palmitic acid (C16:0, 14.5 mol%). The saturates diet was supplemented with trilaurin, trimyristin and tripalmitin to obtain the same level of lauric, myristic and palmitic acids as the butterfat diet, without the short-chain SFA. The trimyristin diet was enriched with trimyristin only. The results showed that the butterfat diet contributed to specific effects, compared to the olive oil diet and the saturates and trimyristin diets: a decrease in plasma total, LDL- and HDL-cholesterol, higher tissue storage of ALA and LNA, and a higher level of (n-3) highly unsaturated fatty acids in some tissues. This study supports the hypothesis that in diets with identical well-balanced LNA/ALA ratios, short chain SFA may decrease circulating cholesterol and increase tissue polyunsaturated fatty acid content in the rat.

BACKGROUND: Farmers from Crete as first studied within the framework of the Seven Countries Study, were historically known for holding the title of the 'gold standard' of health status globally and had a very low prevalence of both cardiovascular disease (CVD) and cancer. Taking the above into account we evaluated the changes in CVD risk factors among farmers in Crete, Greece and compared our findings with data from the 1960s. DESIGN: Cross-sectional. METHODS: Five hundred and two farmers (18-79 years old) from the Valley of Messara in Crete were randomly selected and examined in 2005. Complete clinical, biochemical, dietetic, anthropometrical and lifestyle CVD risk factors were assessed, matched and compared with published data from the 1960s. RESULTS: In comparison with 45 years ago, present day male farmers from Crete were found to have a 30% higher BMI (29.8 vs. 22.9 kg/m, P

Dietary fat may play a role in the aetiology of many chronic diseases. Milk and milk-derived foods contribute substantially to dietary fat, but have a fat composition that is not optimal for human health. We measured the fat composition of milk samples in 1918 Dutch Holstein Friesian cows in their first lactation and estimated genetic parameters for fatty acids. Substantial genetic variation in milk-fat composition was found: heritabilities were high for short- and medium-chain fatty acids (C4:0¿C16:0) and moderate for long-chain fatty acids (saturated and unsaturated C18). We genotyped 1762 cows for the DGAT1 K232A polymorphism, which is known to affect milk-fat percentage, to study the effect of the polymorphism on milk-fat composition. We found that the DGAT1 K232A polymorphism has a clear influence on milk-fat composition. The DGAT1 allele that encodes lysine (K) at position 232 (232K) is associated with more saturated fat; a larger fraction of C16:0; and smaller fractions of C14:0, unsaturated C18 and conjugated linoleic acid (P

Background Age, sex, and blood pressure could modify the associations of total cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular mortality. This meta-analysis combined prospective studies of vascular mortality that recorded both blood pressure and total cholesterol at baseline, to determine the joint relevance of these two risk factors. Methods Information was obtained from 61 prospective observational studies, mostly in western Europe or North America, consisting of almost 900000 adults without previous disease and with baseline measurements of total cholesterol and blood pressure. During nearly 12 million person years at risk between the ages of 40 and 89 years, there were more than 55000 vascular deaths (34000 ischaemic heart disease [IHD], 12000 stroke, 10000 other). Information about HDL cholesterol was available for 150000 participants, among whom there were 5000 vascular deaths (3000 IHD, 1000 stroke, 1000 other). Reported associations are with usual cholesterol levels (ie, corrected for the regression dilution bias). Findings 1 mmol/L lower total cholesterol was associated with about a half (hazard ratio 0 . 44 [95% CI 0.42-0.48]), a third (0.66 [0.65-0.68]), and a sixth (0.83 [0.81-0.85]) lower IHD mortality in both sexes at ages 40-49, 50-69, and 70-89 years, respectively, throughout the main range of cholesterol in most developed countries, with no apparent threshold. The proportional risk reduction decreased with increasing blood pressure, since the absolute effects of cholesterol and blood pressure were approximately additive. Of various simple indices involving HDL cholesterol, the ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40% more informative than non-HDL cholesterol and more than twice as informative as total cholesterol). Total cholesterol was weakly positively related to ischaemic and total stroke mortality in early middle age (40-59 years), but this finding could be largely or wholly accounted for by the association of cholesterol with blood pressure. Moreover, a positive relation was seen only in middle age and only in those with below-average blood pressure; at older ages (70-89 years) and, particularly, for those with systolic blood pressure over about 145 mm Hg, total cholesterol was negatively related to haemorrhagic and total stroke mortality. The results for other vascular mortality were intermediate between those for IHD and stroke. Interpretation Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels. The absence of an independent positive association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained, and invites further research. Nevertheless, there is conclusive evidence from randomised trials that statins substantially reduce not only coronary event rates but also total stroke rates in patients with a wide range of ages and blood pressures.

Cafestol, a diterpene present in unfiltered coffee brews such as Scandinavian boiled, Turkish, and cafetiere coffee, is the most potent cholesterol-elevating compound-knownin the human diet. Several genes involved in cholesterol homeostasis have previously been shown to be targets of cafestol, including cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid biosynthesis. We have examined the mechanism by which cafestol elevates serum lipid levels. Changes in several lipid parameters were observed in cafestol-treated APOE3Leiden mice, including a significant increase in serum triglyceride levels. Microarray analysis of these mice identified alterations in hepatic expression of genes involved in lipid metabolism and detoxification, many of which are regulated by the nuclear hormone receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR). Further studies demonstrate that cafestol is an agonist ligand for FXR and PXR, and that cafestol down-regulates expression of the bile acid homeostatic genes CYP7A1, sterol 12 alpha-hydroxylase, and Na+-taurocholate cotransporting polypeptide in the liver of wild-type but not FXR null mice. Cafestol did not affect genes known to be upregulated by FXR in the liver of wild-type mice, but did increase expression of the positive FXR-target genes intestinal bile acid-binding protein and fibroblast growth factor 15 (FGF15) in the intestine. Because FGF15 has recently been shown to function in an enterohepatic regulatory pathway to repress liver expression of bile acid homeostatic genes, its direct induction in the gut may account for indirect effects of cafestol on liver gene expression. PXR-dependent gene regulation of cytochrome P450 3A11 and other targets by cafestol was also only seen in the intestine. Using a double FXR/PXR knockout mouse model, we found that both receptors contribute to the cafestol-dependent induction of intestinal FGF15 gene expression. In conclusion, cafestol acts as an agonist ligand for both FXR and PXR, and this may contribute to its impact on cholesterol homeostasis.

Background: Disturbances in lipid metabolism have been linked to suicidal behaviour, but little is known about the association between suicide risk and abnormal glucose metabolism in depression. Hyperglycaemia and hyperinsulinaemia may increase the risk of depression and also the risk for suicide, we therefore studied associations between suicidal behaviour and disturbances in glucose metabolism in depressive patients who had been referred to depression nurse case managers. Methods: Patients aged 35 years and older (N = 448, mean age 51 years) who were experiencing a new depressive episode, who were referred to depression nurse case managers in 2008-2009 and who scored = 10 on the Beck Depression Inventory were enrolled in this study. The study was conducted in municipalities within the Central Finland Hospital District (catchment area of 274 000 inhabitants) as part of the Finnish Depression and Metabolic Syndrome in Adults study. The patients' psychiatric diagnoses and suicidal behaviour were confirmed by the Mini-International Neuropsychiatric Interview. Blood samples, for glucose and lipid determinations, were drawn from participants after 12 h of fasting, which was followed by a 2-hour oral glucose tolerance test (OGTT) when blood was drawn at 0 and 2 h. Insulin resistance was measured by the Quantitative Insulin Sensitivity Check Index (QUICKI) method.' Results: Suicidal ideation (49 %) and previous suicide attempts (16 %) were common in patients with major depressive disorder or dysthymia. Patients with depression and suicidal behaviour had higher blood glucose concentrations at baseline and at 2 hours in the OGTT. Glucose levels associated positively with the prevalence of suicidal behaviour, and the linearity was significant at baseline (p for linearity: 0.012, adjusted for age and sex) and for 2-hour OGTT glucose (p for linearity: 0.004, adjusted for age and sex). QUICKI levels associated with suicidal behavior (p for linearity across tertiles of QUICKI: 0.026). Total and LDL cholesterol and triglyceride levels were also higher in those patients with suicidal behaviour. Multivariate analysis revealed that blood glucose levels, BDI scores and antidepressive medications associated with suicidal behaviour. Conclusion: Insulin resistance and disturbances in glucose and lipid metabolism may be more common in middle-aged depressive patients with suicidal behaviour.

The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95 % CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0·97 (95 % CI 0·94, 1·00; dose–response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0·86 (95 % CI 0·69, 1·09; dose–response per 1 mmol/l increment, six studies), with high heterogeneity (I2= 67 and 47 %, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose–response HR 0·94 (95 % CI 0·89, 0·99), seven studies, I2= 78 %; highest v. lowest HR 0·82 (95 % CI 0·66, 1·02), nine studies, I2= 81 %) and HDL-C (dose–response HR 0·81 (95 % CI 0·65, 1·02), five studies, I2= 30 %; highest v. lowest HR 0·82 (95 % CI 0·69, 0·98), five studies, I2= 0 %). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.

The response of plasma lipids to dietary cholesterol and fat varies among individuals. Variations in genes involved in cholesterol metabolism can be important in these interindividual differences. The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7alpha-hydroxylase (CYP7A1). We investigated the effect of the A278-C promoter polymorphism in the CYP7A1 gene on responses of plasma lipids to an increased intake in dietary cholesterol (742 +/- 114 mg/d), cafestol (57 +/- 6 mg/d), saturated fat [change of 8-9 energy percent/d (en%/d)] and trans fat (change of 10-11 en%/d) in 496 normolipidemic subjects. These responses were measured in 26 previously published dietary trials. After adjustment for the apolipoprotein E genotype effect, AA-subjects consuming a cholesterol-rich diet had a smaller increase in plasma HDL cholesterol than CC-subjects (0.00 +/- 0.02 vs. 0.17 +/- 0.04 mmol/L; P < 0.001). Upon intake of cafestol, AA-subjects had a smaller increase in plasma total cholesterol than CC-subjects (0.69 +/- 0.10 vs. 1.01 +/- 0.10 mmol/L; P = 0.028). No effects of the polymorphism were found in the saturated and trans fat interventions. In conclusion, the CYP7A1 polymorphism has a small but significant effect on the increase in plasma HDL cholesterol and plasma total cholesterol after an increased intake of dietary cholesterol and cafestol, respectively.

Serum lipids and lipoprotein concentrations have been associated with dominance aggression in humans. The aim of this study was to investigate the link between serum lipids, including cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) to HDL-C ratio and dominance aggression in dogs. Levels of serum TC, triglyceride and HDL-C were significantly lower in dogs with dominance aggression compared with non-aggressive dogs (P < 0.001). These results suggest that a relationship exists between serum lipid profile and dominance aggression in dogs, and hypocholesterolaemia exists in dogs with dominance aggression.

OBJECTIVES This study was undertaken to project the population-wide effect of full implementation of the Adult Treatment Panel (ATP) II guidelines of the National Cholesterol Education Program (NCEP). BACKGROUND The ATP II has proposed guidelines for cholesterol reduction, but the long-term epidemiologic influence of its components has not been fully examined. METHODS We used a calibrated, validated simulation of the U.S. population, aged 35 to 84 years to estimate the potential for the NCEP guidelines, under varying assumptions, to reduce coronary heart disease morbidity and mortality and overall mortality from the years 2000 to 2020. RESULTS Primary prevention would yield only about half of the benefits of secondary prevention despite requiring nearly twice as many person-years of treatment. The projected increase in quality-adjusted years of life per year of treatment for secondary prevention was 3- to 12-fold higher than for primary prevention. To yield population-wide epidemiologic benefits equivalent to NCEP recommendations for secondary prevention, primary prevention would require a nearly sixfold increase in the number of persons treated compared with NCEP recommendations. All benefits of universal success of the NCEP primary prevention "screen and treat" guidelines could be achieved by a 11 mg/dl (8%) population-wide reduction in low-density lipoprotein cholesterol levels among persons without preexisting coronary heart disease. CONCLUSIONS The NCEP guidelines for targeted primary prevention can be a useful component of a rational public health strategy, but only as a complement to the more appealing strategies of secondary prevention and "across-the-board" programs to lower all cholesterol levels. (J Am Coil Cardiol 1999;34:768-76) (C) 1999 by the American College of Cardiology.

The effect of the apolipoprotein (apo) E genotype on the lipoprotein response to a 1 year low cholesterol diet (200 mg cholesterol per day) was evaluated in 36 patients with Type 1 diabetes mellitus with albuminuria between 10 and 200 mu g min(-1). Apo E genotype was characterized by polymerase chain reaction and restriction isotyping. In 11 IDDM patients with at least one epsilon 4 allele (apo E4 group), baseline serum total and low density lipoprotein (LDL) cholesterol were higher (p

Lipid-lowering therapy now has undoubtedly proven to be an effective therapeutic modality to retard the progression of coronary atherosclerosis, An additional approach for prevention of the progression of atherosclerosis is calcium channel blocker (CCB) treatment. Evidence indicating that CCBs inhibit atherosclerosis is less unequivocal than the clear evidence for lipid-lowering therapy, Many investigations support the view that a number of key processes in atherosclerosis may be influenced by CCBs. From the "negative" and "positive" studies with CCBs performed in animals and humans we must conclude that apparently some, but not all, types or stages of the atherosclerotic process are inhibited by CCBs, To assess whether lipid-lowering therapy and CCB treatment may have an additive or synergistic beneficial effect on human atherosclerosis, which is conceivable because their antiatherosclerotic properties differ, data fi om the angiographic Lipid-lowering trial REGRESS (pravastatin vs. placebo) were reviewed. In REGRESS, patients in the pravastatin group had significantly less progression if cotreated with CCBs as compared with those with no CCB cotreatment, whereas in the placebo (no pravastatin) group no effect of CCB treatment was observed, With respect to angiographic new lesion formation, in the pravastatin group there were 50% less patients with new angiographic lesions if cotreated with CCBs as compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, again, no significant effect of CCB treatment was observed. No beneficial effects of CCB treatment on clinical events mere observed during the a-year study follow-up. In view of the correlation between angiographic progression and subsequent clinical events as demonstrated in several large trials, it is not unrealistic to also anticipate in this population, a beneficial effect on clinical events with longer follow-up. Although the REGRESS trial was not designed to evaluate combination therapy, the results suggest that addition of CCBs to HMG-CoA reductase inhibitor therapy (pravastatin) acts synergistically in retarding the progression of established coronary atherosclerosis, These results appear to warrant prospective randomized trials to determine in a more definitive manner the merits of this combination in the prevention of progression of coronary atherosclerosis. Currently a number of studies in these fields are being designed or are already underway.

Background: Dyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers. Methods: We conducted a case-cohort study on participants recruited to four Italian EPIC centers (Turin, Varese, Naples, and Ragusa; 34,148 subjects). A random subcohort of 850 subjects was obtained and 286 colorectal cancer cases were diagnosed. Triglycerides, total and HDL cholesterol were determined in plasma samples obtained at baseline and stored at -196 degrees C; LDL cholesterol was calculated. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox regression models using the Prentice method. Results: The highest tertiles of total (HR 1.66, 95% CI 1.12-2.45) and LDL cholesterol (HR 1.87, 95% CI 1.27-2.76) were associated with increased colorectal cancer risk compared to lowest tertiles. Risks were greater for men than women, and for postmenopausal than premenopausal women. Highest tertiles of total and LDL cholesterol were also significantly associated with increased risks of colon cancer, distal colon cancer, and rectal cancer, but not proximal colon cancer. Conclusions: Our findings suggest that high levels of total and LDL cholesterol increase colorectal cancer risk, particularly in men and postmenopausal women. However additional studies are needed to clarify the role of plasma lipids in these cancers, particularly in view of the conflicting findings of previous studies. (C) 2014 Elsevier Ltd. All rights reserved.

Patients with coronary artery disease are advised to augment their dietary linoleic acid intakes at the expense of saturated fatty acids. We investigated whether the dietary linoleic acid intake of 57 patients with coronary artery disease (47 males, 10 females; ages 61 +/- 10 years) in Curacao is higher as compared with 77 controls (51 males, 26 females; ages 56 +/- 7 years). For this, we measured plasma cholesterol ester fatty acids, which reflect the dietary fatty acid composition of the preceding weeks. Patients with coronary artery disease and controls had minor differences in cholesterol ester fatty acids. Their cholesterol ester linoleic acid content suggests that the dietary polyunsaturated/saturated fatty acid ratio is far below 1. Comparison with data reported for The Netherlands, Greenland and Crete showed that the dietary fatty acid composition in Curacao is typically Western with a high intake of saturated fatty acids, a low intake of monounsaturated fatty acids and the consumption of linoleic acid as the predominant polyunsaturated fatty acid. Intake of long chain polyunsaturated fatty acids from fatty fish is low. Reduction of dietary saturated fatty acids, augmentation of fish consumption, and an increase of the alpha-linolenic/linoleic acid ratio are likely to be of benefit to both primary and secondary prevention from coronary artery disease in Curacao.

Patients with diabetes mellitus (DM), type 1 and type 2, have an increased risk of coronary heart disease as a result of accelerated atherosclerosis. Dyslipidemia, often found in these patients, plays an important role in this process. This study investigates the efficacy and safety of lipid-lowering therapy with pravastatin, a 3-HMG-Coenzym A reductase inhibitor in hypercholesterolemic type-1 and type-2 diabetic patients. Of 49 patients (22 type-1 DM and 27 type-2 DM), 24 patients were treated with pravastatin, 20 mg/day, and 25 patients with placebo. After 24 weeks, total cholesterol (TC) was decreased by 22.2%, low-density lipoprotein (LDL) cholesterol by 25.8% and triglycerides (TG) by 13.6%. Pravastatin treatment did not induce a significant change in high-density (HDL) cholesterol levels. No differences in effects of pravastatin treatment on serum lipids and lipoproteins were found with respect to the diabetes type. No serious side effects occurred and pravastatin treatment did not cause any deterioration in glycemia control. The data suggest that pravastatin is effective and safe in the treatment of dyslipidemia in both type-1 and type-2 diabetic patients.

Background For decades in Finland, intensive population strategies and preventive activities have been used to lower the risk of atherosclerotic coronary heart disease (CHD). Lifestyle changes, with the emphasis on diet, play an important role in preventive strategies. The aim of this study was to evaluate arterial stiffness and endothelial function in asymptomatic free-living adults and to relate the results to CHD risk factors and lifestyle habits with the emphasis on diet. Methods Ninety-four asymptomatic participants were recruited by advertisements in four large companies and two research institutes employing mainly office workers. Arterial stiffness was assessed as the cardio-ankle vascular index in large arteries, and endothelial function as the reactive hyperemia index with peripheral arterial tonometry. The systematic Cardiovascular Risk Estimation (SCORE) was calculated. Results The data was collected in the spring of 2011. Anthropometric, dietary, and lipid data was available from 92 participants, blood pressure from 85 and vascular measurements from 86–88 subjects (38% males; 62% females; mean age of all 51). The majority (72%) had an elevated low density lipoprotein (LDL) cholesterol concentration and over half were overweight or obese. SCORE stated that 49% of the participants had a moderate risk of cardiovascular disease. When compared to general recommendations, half of the participants had too high intake of total fat and in 66% the consumption of saturated fat was too high. In contrast, the intake of carbohydrates was too low in 90% of the participants and for fiber 73% were below recommendations. There was evidence of borderline or increased arterial stiffness in 72% of the participants and endothelial function was impaired in 8%. Arterial stiffness was associated with LDL cholesterol concentration (p = 0.024), dietary cholesterol intake (p = 0.029), and SCORE (p

Objective: Single nucleotide polymorphisms (SNPs) in genes involved in fatty acid metabolism (FADS1 FADS2 gene cluster) are associated with plasma lipid levels. We aimed to investigate whether these associations are already present early in life and compare the relative contribution of FADS SNPs vs traditional (non-genetic) factors as determinants of plasma lipid levels.Methods: Information on infants' plasma total cholesterol levels, genotypes of five FADS SNPs (rs174545, rs174546, rs174556, rs174561, and rs3834458), anthropometric data, maternal characteristics, and breastfeeding history was available for 521 2-year-old children from the KOALA Birth Cohort Study. For 295 of these 521 children, plasma HDLc and non-HDLc levels were also known. Multivariable linear regression analysis was used to study the associations of genetic and nongenetic determinants with cholesterol levels.Results: All FADS SNPs were significantly associated with total cholesterol levels. Heterozygous and homozygous for the minor allele children had about 4% and 8% lower total cholesterol levels than major allele homozygotes. In addition, homozygous for the minor allele children had about 7% lower HDLc levels. This difference reached significance for the SNPs rs174546 and rs3834458. The associations went in the same direction for non-HDLc, but statistical significance was not reached. The percentage of total variance of total cholesterol levels explained by FADS SNPs was relatively low (lower than 3%) but of the same order as that explained by gender and the non-genetic determinants together.Conclusions: FADS SNPs are associated with plasma total cholesterol and HDLc levels in preschool children. This brings a new piece of evidence to explain how blood lipid levels may track from childhood to adulthood. Moreover, the finding that these SNPs explain a similar amount of variance in total cholesterol levels as the non-genetic determinants studied reveals the potential importance of investigating the effects of genetic variations in early life.

This article discusses various aspects of cholesterol-lowering therapy using the HMG-CoA reductase inhibitor simvastatin in the light of the large Scandinavian Simvastatin Survival Study (4S). In 4S, patients with proven coronary heart disease (CHD) and plasma total cholesterol >5.5 mmol/L (212 mg/dl) despite dietary measures received statin therapy or placebo for greater than or equal to 5 years. A significant mortality reduction was accomplished in those receiving the statin. Moreover, a significant decrease of nonfatal myocardial infarction and requirement for coronary bypass surgery or angioplasty was demonstrated, which will contribute to the cost-effectiveness of this well tolerated therapy. Plaque stabilisation and improvement of endothelial function are thought to be mediators of this therapeutic success. Responsible drug prescription in the post-4S era may result in the recognition and treatment of more patients with CHD. This is likely to be more beneficial than exhaustive efforts to completely achieve the goals of the most strict guidelines in the individual patient. In patients who carry the highest absolute risk for a recurrent event, aggressive drug therapy may be most justified. Reluctance to initiate lipid lowering drug therapy in patients with proven CHD should now be disputed.

We have studied the effects of dietary corn and olive oil versus coconut fat on bile formation and fluidity of hepatic plasma membranes in rats. After 4 weeks of feeding the purified diets containing 9% (w/w) of the test fats, there was no difference in plasma cholesterol concentration between the dietary groups. The amount of free and esterified cholesterol in the liver was significantly higher in rats fed either corn oil or olive oil as compared with coconut fat. In the rats fed olive oil, but not in those fed corn oil this was associated with lower rates of biliary phospholipid excretion. Bile flow was not differently influenced by the three dietary fats. Hepatic plasma membranes of the rats fed corn or olive oil contained more cholesterol and less phospholipids than those on coconut fat, which was, however, not accompanied by changes in fluidity of the membranes. These results indicate that in rats the type of dietary fat can induce considerable changes in hepatic cholesterol metabolism without affecting plasma cholesterol concentrations, and without consistent effects on biliary cholesterol secretion.

The aim of the study was to determine the effects of dietary probiotic supplementation with B. subtilis spores (strain DSM 17299) on the growth performance and carcass traits in broiler chickens and to analyse the influence on the caecal microflora. A total of 364 one day-old male broiler chicks were randomly divided into 2 equal groups (not supplemented controls and birds receiving dietary addition of B. subtilis spores (8x10(5) cfu/kg of food) for 6 weeks). Body weights, body weight gains, food intake and food efficiency were weekly evaluated and the carcass parameters (hot carcass weight and yield) and the caecal microflora composition were determined at the end of the experiment. The probiotic supplementation has significantly increased the final weight gain (P < 0.05) and the hot carcass weight (P < 0.01), reduced the food intake calculated for 6 weeks (P < 0.001) and improved the food conversion ratios since the 4th week with supplementation (p < 0.001). In parallel, in the treated birds, the caecal population of bacilli was markedly enhanced (P < 0.01) whereas those of enterococci (P < 0.001) and coliforms (P < 0.05) were significantly lowered. The Enterobacteriaceae counts were also weakly depressed but not significantly and the numeration of lactobacilli has also tended to slightly increase. These results show that the dietary inclusion of B. subtilis spores improve the weight growth and the food efficiency in broilers probably through the selection of beneficial bacteria to the detriment of pathogen germs in the caecal microflora. Charoen Pokphand Group (Bangkok, Thailand)

Background: Adult cholesterol concentrations might be influenced by early-life factors, such as breastfeeding and birth weight, referred to as "early programming". How such early factors exert their influence over the life course is still poorly understood. Evidence from studies in children and adolescents is scarce and conflicting. We investigated the influence of 6 different perinatal risk factors on childhood total and HDL cholesterol concentrations and total-to-HDL cholesterol ratio measured at 8 years of age, and additionally we studied the role of the child's current Body Mass Index (BMI).Methods: Anthropometric measures and blood plasma samples were collected during a medical examination in 751 8-year-old children participating in the prospective Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study. Linear and logistic regression were performed to estimate associations of total and HDL cholesterol concentrations with breastfeeding, birth weight, infant weight gain, maternal overweight before pregnancy, gestational diabetes and maternal smoking during pregnancy, taking into account the child's current BMI.Results: Linear regressions showed an association between total-to-HDL cholesterol ratio and maternal pre-pregnancy overweight (beta = 0.15, Confidence Interval 95% (CI): 0.02, 0.28), rapid infant weight gain (beta = 0.13, 95% CI: 0.01, 0.26), and maternal smoking during pregnancy (beta = 0.14, 95% CI: 0.00, 0.29). These associations were partly mediated by the child's BMI.Conclusion: Total-to-HDL cholesterol ratio in 8-year-old children was positively associated with maternal pre-pregnancy overweight, maternal smoking during pregnancy and rapid infant weight gain.

It has been hypothesized that blood lipid levels might be associated with prostate cancer risk. The aim of the present study was to evaluate the association between serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and prostate cancer risk in a cohort study among 2842 Dutch men. By the end of follow-up, 64 incident cases of prostate cancer were identified. Serum total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were evaluated as potential risk factors for prostate cancer using multivariable Cox proportional hazards regression models. These analyses were restricted to men who never used cholesterol-lowering drugs (2118 men, 43 cases). Higher total and higher LDL cholesterol were significantly associated with an increased risk of prostate cancer (hazards ratios (HR) and 95% confidence interval (CI) per mmol l(-1) were 1.39 (95% CI 1.03-1.88) and 1.42 (95% CI 1.00-2.02), respectively). Similar results were observed for aggressive prostate cancer, whereas for non-aggressive prostate cancer a significant association with HDL cholesterol was found (HR 4.28, 95% CI 1.17-15.67). The results of this study suggest that blood lipid levels may influence risk of prostate cancer. However, the exact roles of different cholesterol fractions on prostate cancer aggressiveness should be further evaluated. Prostate Cancer and Prostatic Diseases (2011) 14, 340-345; doi:10.1038/pcan.2011.30; published online 5 July 2011

Primary or idiopathic Parkinson's disease (PD) is the second most common late-onset neurodegenerative disease, characterized by several clinical features, such as resting tremor, rigidity, akinesia, depression and sleep disturbances. These symptoms are in most cases related to protein aggregation leading to a marked depletion of dopaminergic neurons in substantia nigra pars compacta of the basal ganglia and by a subsequent malfunction of the nigro-striatal circuitry. Only few risk factors for idiopathic PD have been identified, including both genetic and environmental components. However, some chemical compounds can induce secondary parkinsonism that promote PDlike symptoms, such as antipsychotic drugs, certain calcium channel blockers or anti-epileptic drugs. Despite increasing knowledge on genetic risk factors, the pathophysiology of PD has not been unraveled. Hitherto, mitochondrial dysfunction, oxidative stress and inflammation are suspected to initiate PD associated loss of dopaminergic neurons. [...]

A recent meta-analysis of prospective cohort studies has not found an association between dietary saturated fat intake and CHD incidence. This funnelled the discussion about the importance of the recommendation to lower the intake of saturated fat for the prevention of CHD. At the same time a document of the European Food Safety Authority has suggested that specific quantitative recommendations are not needed for individual fatty acids but that more general statements can suffice. In this review, we discuss methodological aspects of the absence of association between SFA intake and CHD incidence in prospective cohort studies. We also summarise the results of the controlled dietary experiments on blood lipids and on CHD incidence in which saturated fat was replaced by either cis-unsaturated fat or carbohydrates. Finally, we propose a nutritionally adequate diet with an optimal fatty acid composition for the prevention of CHD in the context of dietary patterns. Such diets are characterised by a low intake of saturated fat, and as low as possible intake of trans-fat and fulfil the requirements for the intake of n-6 and n-3 fatty acids. No recommendation is needed for the intake of cis-MUFA.

Background: Prospective cohort studies on biological risk factors of completed suicide are scarce. We aimed to test which biological risk factors independently identify subjects at increased risk of suicidal death. Methods: In the prospective cohort of the Seven Countries Study, 5,321 middle-aged men from Finland, Serbia, Italy, and Greece were included. Completed suicide (ICD-8 codes E950-959) was assessed during 40 years of follow-up. Biological cardiovascular risk factors (including forced vital capacity [FVC] and height) were tested for their role as predictors in multivariable Cox models stratified by country. Results: There were 4518 deaths during follow-up, with 64 from suicide (1.4%). In univariable models, only FVC and height were strongly inversely related with suicide. Socio-economic status and being unmarried were potential confounders. In multivariable models taking these confounders into account, both a low FVC (0.30 for top vs. lowest quartile: 95% CI: 0.12-0.76: P=0.006 for trend) and a low FVC/height ratio (0.37 for top vs. lowest quartile; 95% CI: 0.17-0.82; P=0.004 for trend) were strongly inversely related with completed suicide. Limitations: Information oil proximal causes, such as prior Suicidal ideation, emotional distress and depression, was lacking at baseline. Conclusions: Poor respiratory function in middle-aged men was an independent risk factor for completed suicide. (C) 2009 Elsevier B.V. All rights reserved.

Objective: To assess cardiovascular risk factors over time in patients who received chemotherapy for disseminated testicular cancer and were apparently cured. . Design: Cohort study. . Setting: Referral center. . Patients: Fifty-seven consecutive patients (median age, 28 years; range, 16 to 43 years) who received cisplatin-containing chemotherapy between 1978 and 1985. . Measurements: Serum cholesterol and high-density lipoprotein (HDL) levels, body mass index (BMI), blood pressure, kidney function, and hormonal status were monitored during follow-up after chemotherapy (median follow-up, 88 months; range, 56 to 143 months). The BMI and cholesterol values obtained 4 to 6 years after chemotherapy were compared with values from a sample of healthy, age-matched Dutch men; the cholesterol level was also compared with that of 31 patients treated with orchidectomy for stage I disease. . Results: The mean cholesterol level in patients at the start of chemotherapy was 3.96 +/- 0.98 mmol/L [153 +/- 38 mg/dL], increasing 4 to 6 years later to 6.12 +/- 1.20 mmol/L [237 +/- 46 mg/dL] (P 3.4 mmol/L [130 mg/dL]), with a mean level of 4.47 +/- 1.05 mmol/L [173 +/- 41 mg/dL]. Compared with a sample of healthy Dutch men, the chemotherapy group had an elevated cholesterol level (P