Cholesterol lowering efficacy of plant stanol ester in a new type of product matrix, a chewable dietary supplement

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 <0.003). HDL cholesterol or serum triacylglycerol concentrations were unchanged. The taste of the supplement was considered good/very good by 68% of the responders, and convenience to consume it was considered easy/very easy by 78% of the responders. No side effects were reported. In conclusion, this new type of small-volume chewable plant stanol ester supplement lowered LDL cholesterol concentration in hypercholesterolemic subjects providing a convenient dietary tool to regulate circulating cholesterol levels. (C) 2017 Elsevier Ltd. All rights reserved.Peer reviewe

Serum non-cholesterol sterols and cholesterol metabolism in childhood and adolescence

Background and aims: The profile of cholesterol metabolism, i.e., high absorption vs. high synthesis, may have a role in the development of atherosclerosis, the early lesions of which can be present already in childhood. Since there is no information on cholesterol metabolism in children from birth to adolescence, we evaluated cholesterol metabolism in 0-15 year-old children and adolescents without dyslipidemia. Methods: The study population consisted of 96 children (39 girls, 57 boys) divided into age groups Results: Serum non-cholesterol sterol ratios to cholesterol did not differ between gender. Cholesterol precursors squalene, cholestenol, and desmosterol were higher in the Conclusions: Serum non-cholesterol sterols had different individual profiles by age in childhood and adolescence. From 1 to 10 years of age, cholesterol absorption prevailed cholesterol synthesis. This novel finding emphasizes the importance of dietary aspects related to cardiovascular risk even from early childhood.Peer reviewe

Relation of cholesterol metabolism to pediatric gallstone disease : a retrospective controlled study

Background: Cholesterol metabolism may be involved in pediatric gallstone disease. We aimed to reveal cholesterol metabolites and phytosterols and their relation to stone composition of sterols in children having black pigment and cholesterol stones. Methods: We performed retrospective controlled clinical study, in which we examined parameters of cholesterol metabolism and liver function values in serum (n = 28) and gallstones (n = 46) of consecutively cholecystectomized children. Serum values of age-, body mass index-and sex-matched children (n = 82) and adult gallstones (n = 187) served as controls. Results: Surrogate markers of cholesterol synthesis in serum (squalene/cholesterol, cholestenol/cholesterol and lathosterol/cholesterol) were 26-52 % higher in both stone subclasses compared to controls (p controls > cholesterol stone group (p <0.05 for all). In black pigment stone group, stone cholestanol/cholesterol was associated with serum bile acids (r = 0.620, p = 0.018). In cholesterol stone group, surrogate markers of cholesterol synthesis in serum (e.g., lathosterol/cholesterol) inversely reflected those of absorption (r-range -0.633--0.706, p-range 0.036-0.015). In cholesterol stone group, serum and stone lathosterol/cholesterol and cholestanol/cholesterol were positively interrelated (r-range 0.727-0.847, p <0.05 for both). Conclusions: Gallstone subclasses shared enhanced cholesterol synthesis. Cholesterol stone children were low cholesterol absorbers with intact homeostasis of cholesterol metabolism. Black pigment stone group was characterized by deteriorated cholesterol metabolism, and accumulation of cholestanol, campesterol and sitosterol in serum and stones suggesting their participation in pathogenesis.Peer reviewe

Total fecal IgA levels increase and natural IgM antibodies decrease after gastric bypass surgery

Obesity is associated with low-grade inflammation and increased systemic oxidative stress. Roux-en-Y gastric bypass (RYGB) surgery is known to ameliorate the obesity-induced metabolic dysfunctions. We aimed to study the levels of natural antibodies in feces, before and 6 months after RYGB surgery in obese individuals with and without type 2 diabetes (T2D). Sixteen individuals with T2D and 14 non-diabetic (ND) individuals were operated. Total IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts (MAA adducts), Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44) and phosphocholine (PCho) were measured using chemiluminescence immunoassay. Total fecal IgA was elevated, while total IgM and IgG were not affected by the surgery. Fecal natural IgM specific to oxLDL decreased significantly in both T2D and ND individuals, while fecal IgM to Rgp44 and PCho decreased significantly in T2D individuals. A decrease in IgG to MAA-LDL, Rgp44 and PCho was detected. RYGB surgery increases the levels of total fecal IgA and decreases fecal natural IgG and IgM antibodies specific to oxLDL. Natural antibodies and IgA are important in maintaining the normal gut homeostasis and first-line defense against microbes, and their production is markedly altered with RYGB surgery.Peer reviewe

Serum noncholesterol sterols in Alzheimer's disease : the Helsinki Businessmen Study

Cerebral cholesterol metabolism is perturbed in late-onset Alzheimer's disease (AD), but whether also the extracerebral cholesterol metabolism is perturbed is not known. Thus, we studied whole-body cholesterol synthesis and absorption with serum noncholesterol sterols in men without AD (n = 114) or with (n = 18) "pure" AD (no concomitant atherosclerotic cardiovascular disease) in a long-term cohort (the Helsinki Businessmen Study) of home-dwelling older men without lipid-lowering drugs and on their habitual home diet. Serum lipids did not differ between AD and controls, but age was higher (78 +/- 1 vs 74 +/- 0.3 years, mean f standard error, P <0.001), age-adjusted plasma glucose concentration was lower (4.8 +/- 0.3 vs 5.7 +/- 0.1 mmol/L, P= 0.011), and APOE epsilon 4 allele and frailty were more frequent in AD than in controls. Of the age and frailty-adjusted serum noncholesterol sterols desmosterol and lathosterol ratios to cholesterol reflecting cholesterol synthesis were lower in AD than in controls (eg, lathosterol 114 +/- 12 vs 137 +/- 5 10(2) mu mol/mmol cholesterol, P= 0.004). Cholestanol ratio to cholesterol was higher in AD than in controls suggesting increased cholesterol absorption. lathosterol/sitosteroll ratio reflecting cholesterol metabolism was lower in AD than in controls (0.95 +/- 0.28 vs 1.52 +/- 0.11 10(2) mu mol/mmol cholesterol, P = 0.027). In AD, plasma glucose correlated negatively with cholesterol synthesis, whereas in controls the correlation was positive. In conclusion, extracerebral cholesterol metabolism was altered in AD. This finding along with the low plasma glucose concentration and its paradoxical interaction with cholesterol synthesis opens new perspectives in the regulation of cholesterol metabolism and glucose homeostasis in AD.Peer reviewe

Genetic polymorphism of sterol transporters in children with future gallstones

Background & aims: Gallstone disease is related to hypersecretion of cholesterol in bile, and low serum phytosterol levels. We examined how genetic polymorphisms of sterol transporters affect childhood cholesterol metabolism trait predicting adult gallstone disease. Patients and methods: In retrospective controlled study, we determined D19H polymorphism of ABCG8 gene, genetic variation at Niemann-Pick C1-like 1 (NPC1L1) gene locus (rs41279633, rs17655652, rs2072183, rs217434 and rs2073548), and serum cholesterol, noncholesterol sterols and lipids in children affected by gallstones decades later (n = 66) and controls (n = 126). Results: In childhood, phytosterols were lower (9.7%-23.4%) in carriers of risk allele 19H compared to 19D homozygotes. Lowest campesterol/cholesterol tertile consisted of 1.9-times more future gallstone subjects, and 3.7-times more 19H carriers than highest one. Campesterol/cholesterol-ratio was highest in 19D homozygote controls, but similar to 11% lower in gallstone 19D homozygotes and similar to 25% lower among gallstone and control carriers of 19H. Gallstone subjects with alleles CC of rs41279633 and TT of rs217434 of NPC1L1 had similar to 18% lower campesterol/cholesterol-ratio compared to mutation carriers. Conclusions: Risk trait of cholesterol metabolism (low phytosterols) in childhood favouring cholesterol gallstone disease later in adulthood is influenced by risk variant 19H of ABCG8 and obviously also other factors. NPC1L1 variants have minor influence on noncholesterol sterols. (c) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Diet and cardiovascular health in asymptomatic normo- and mildly-to-moderately hypercholesterolemic participants - baseline data from the BLOOD FLOW intervention study

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Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy

Aims. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). Methods. Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). Results. PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME ( = 0.001), and 76.1 (48.2) for NoDR ( = 0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., = 0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, &gt; 0.001). Conclusions. IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR

Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy

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Validity of fatty liver disease indices in the presence of alcohol consumption

Background & aims Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease frequently coexist. While several blood-based indices exist for the detection of NAFLD, few studies have examined how alcohol use possibly impacts their diagnostic performance. We analysed the effects of alcohol use on the performance of indices for detecting fatty liver disease (FLD). Methods We included participants from the Cardiovascular Risk in Young Finns Study (Finnish sample) and KORA study (German sample) who underwent abdominal ultrasound or magnetic resonance imaging, respectively, for detection of FLD and had serum analyses available for calculation of Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), Lipid Accumulation Product (LAP), and Dallas Steatosis Index (DSI). Alcohol use was estimated by questionnaires as mean daily consumption and binge drinking (Finnish sample only). Predictive performance for FLD was assessed according to alcohol consumption. Results The study included 1426 (Finnish sample) and 385 (German sample) individuals, of which 234 (16%) and 168 (44%) had FLD by imaging. When alcohol consumption was 50 g/day). AUROCs decreased to 0.74-0.80 in the highest binge-drinking category (>2 times/week). Alcohol use correlated with FLI and LAP (r-range 0.09-0.16, p-rangePeer reviewe