Current Diagnosis and Management of Abetalipoproteinemia.

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.

2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults.

The 2021 guidelines primary panel selected clinically relevant questions and produced updated recommendations, on the basis of important new findings that have emerged since the 2016 guidelines. In patients with clinical atherosclerosis, abdominal aortic aneurysm, most patients with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy continues to be recommended. We have introduced the concept of lipid/lipoprotein treatment thresholds for intensifying lipid-lowering therapy with nonstatin agents, and have identified the secondary prevention patients who have been shown to derive the largest benefit from intensification of therapy with these agents. For all other patients, we emphasize risk assessment linked to lipid/lipoprotein evaluation to optimize clinical decision-making. Lipoprotein(a) measurement is now recommended once in a patient's lifetime, as part of initial lipid screening to assess cardiovascular risk. For any patient with triglycerides ˃ 1.5 mmol/L, either non-high-density lipoprotein cholesterol or apolipoprotein B are the preferred lipid parameter for screening, rather than low-density lipoprotein cholesterol. We provide updated recommendations regarding the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy. There are new recommendations on the preventative care of women with hypertensive disorders of pregnancy. Health behaviour modification, including regular exercise and a heart-healthy diet, remain the cornerstone of cardiovascular disease prevention. These guidelines are intended to provide a platform for meaningful conversation and shared-decision making between patient and care provider, so that individual decisions can be made for risk screening, assessment, and treatment.

The effects of KaiXinSan on depression and its association with lipid profiles: A randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Traditional Chinese medicine (TCM) KaiXinSan (KXS) has been used to treat depressed patients for a long time, but its potential underlying mechanisms have not been fully understood. HYPOTHESIS: KXS could mitigate symptoms of patients with atypical depression at least partly via regulating lipid equilibrium. METHODS: Patients meeting DSM-IV criteria for mild or moderate depression were assigned into placebo (N = 68) or KXS 3.2 g/day (N = 66) groups in a randomized, double-blinded, placebo-controlled, parallel clinical trial to investigate the anti-depressive efficacy of KXS and its association with serum lipid profile. RESULTS: The HAMD score and SDS score at 8 weeks were significantly improved in KXS-treated patients the N-BACK accuracy rate was also increased after 8 weeks of KXS treatment compared with baseline. These results indicated that KXS not only improved the specific symptoms of depression, but also had a beneficial effect on cognitive function related working memory. More importantly, KXS treatment improved patients' lipid profile by reducing the ratios of LDL/HDL and ApoB/ApoA1 (p < 0.05), as well as ApoC3 level. Moreover, subgroup analysis found that HAMD score was significantly higher in patients with high lipid profile than in those with normal lipid profile, and lipid improvement after 8 weeks of KXS treatment was more obvious in depressed patients with high lipid profile than with normal lipid profile. CONCLUSION: KXS could mitigate symptoms of patients with minor and modest depression at least partly via regulating lipid equilibrium. Its might shed light that KXS may likely contributes to depressed patients with other cardio-metabolic diseases.

D4F prophylaxis enables redox and energy homeostasis while preventing inflammation during hypoxia exposure.

Apo-A1 is correlated with conditions like hyperlipidemia, cardiovascular diseases, high altitude pulmonary edema and etc. where hypoxia constitutes an important facet.Hypoxia causes oxidative stress, vaso-destructive and inflammatory outcomes.Apo-A1 is reported to have vasoprotective, anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, effects of Apo-A1 augmentation during hypoxia exposure are unknown.In this study, we investigated the effects of exogenously supplementing Apo-A1-mimetic peptide on SD rats during hypoxia exposure. For easing the processes of delivery, absorption and bio-availability, Apo-A1 mimetic peptide D4F was used. The rats were given 10 mg/kg BW dose (i.p.) of D4F for 7 days and then exposed to hypoxia. D4F was observed to attenuate both oxidative stress and inflammation during hypoxic exposure. D4F improved energy homeostasis during hypoxic exposure. D4F did not affect HIF-1a levels during hypoxia but increased MnSOD levels while decreasing CRP and Apo-B levels. D4F showed promise as a prophylactic against hypoxia exposure.

Consumption of Goat Cheese Naturally Rich in Omega-3 and Conjugated Linoleic Acid Improves the Cardiovascular and Inflammatory Biomarkers of Overweight and Obese Subjects: A Randomized Controlled Trial.

This study examines the value of a goat cheese naturally enriched in polyunsaturated fatty acids (PUFA) (n-3 PUFA and conjugated linolenic acid (CLA)) as means of improving cardiovascular and inflammatory health. Sixty-eight overweight and obese subjects (BMI ≥ 27 and <40 kg/m2), with at least two risk factors for cardiovascular disease (CVD) in a lipid panel blood tests, participated in a randomized, placebo-controlled, double-blind, parallel designed study. The subjects consumed for 12 weeks: (1) 60 g/d control goat cheese and (2) 60 g/d goat cheese naturally enriched in n-3 PUFA and CLA. Diet and physical activity were assessed. Anthropometric and dual-energy X-ray absorptiometry (DXA) tests were performed. Blood samples were collected at the beginning and at the end of the study period. Changes in health status, lifestyle and dietary habits, and daily compliance were recorded. The consumption of a PUFA-enriched goat cheese significantly increased plasma high-density lipoprotein (HDL)-cholesterol, as well as in apolipoprotein B, and it significantly decreased high-sensitivity C-reactive protein concentrations compared to the control goat cheese (p < 0.05). The significant improvement of the plasma lipid profile and inflammatory status of people with risk for CVD due to the consumption of PUFA-enriched cheese suggests a potential role of this dairy product as an alternative to develop high nutritional value food in a balanced diet comprising regular exercise.

Ameliorating Effects of Four-Week Fiber-Multivitamin Combination Treatment on Low-Density Lipoprotein Cholesterol, Total Cholesterol, and Apolipoprotein B Profiles in Hypercholesterolemic Participants.

Hyperlipidemia is one of the leading causes of death and requires lipid-lowering treatment to reduce morbidity and mortality. Effective and safe alternative and adjunctive therapies could be beneficial for patients with hyperlipidemia. To assess the effect of a fiber-multivitamin combination product on the lipid parameters low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), triglyceride (TG), and apolipoprotein B (Apo B) in patients with hypercholesterolemia, we conducted a double-blind, randomized, parallel-group study. Forty-one out of 50 randomized hypercholesterolemic participants recruited between August 2016 and March 2018 completed the trial. The participants were assigned to receive either test product (treatment group, n = 20) or placebo (placebo group, n = 21) for 4 weeks following a 6-week dietary intervention (based on education from a dietitian) run-in period. The primary outcome was LDL-c levels and the secondary outcomes were HDL-c, TC, TG, and Apo B levels. All of the outcomes were measured at baseline and week 4 after the completion of run-in period. Participants in both groups had similar LDL-c levels (142 ± 15.7 vs. 143 ± 19.3 mg/dL). After 4 weeks of exposure to test product, participants in the treatment group demonstrated a 17.25 ± 22.26 reduction in LDL-c (p < .05 vs. placebo). This improvement in LDL-c was accompanied by amelioration in TC and Apo B levels, without any detrimental effects on HDL and TG concentration. Results of the present study suggest that fiber-vitamin combination has potential to be used as an adjunct therapy for the management of hypercholesterolemia.

Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials.

AIMS: The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these potential effects vary by different lipid-lowering strategies. METHODS: A total of 29 randomized controlled trials were selected using PubMed, Cochrane Library and EMBASE through 2018. We selected trials of therapies which ultimately clear apolipoprotein B particles by upregulating low-density lipoprotein receptor (LDL-R) expression (statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bile acid sequestrants) or therapies which reduce apolipoprotein B independent of LDL-R (cholesteryl ester transfer protein inhibitor, fibrates, niacin, omega-3 fatty acids) with sample size of ≥1000 patients and follow-up of ≥1 year. The meta-regression and meta-analyses were constructed using a random effects model. RESULTS: In 332,912 patients, meta-regression analyses showed relative risks of 0.95 for all-cause mortality (95% confidence interval 0.92-0.99) and 0.93 (0.88-0.98) for cardiovascular mortality for every 10 mg/dL decrease in apolipoprotein B by all interventions combined. Reduction in all-cause mortality was limited to statins (0.92 (0.86-0.98)). For MACE, the relative risk per 10 mg/dL reduction in apolipoprotein B was 0.93 (0.90-0.97) for all therapies combined, with both statin (0.88 (0.83-0.93)) and non-statin therapies (0.96 (0.94-0.99)). which clear apolipoprotein B by upregulating LDL-R showing significant reductions; whereas interventions which lower apolipoprotein B independent of LDL-R did not demonstrate this effect (1.02 (0.81-1.30)). CONCLUSION: While both statin and established non-statin therapies (PCSK9 inhibitor and ezetimibe) reduced cardiovascular risk per decrease in apolipoprotein B, interventions which reduce apolipoprotein B independently of LDL-R were not associated with cardiovascular benefit.

Complementary low-density lipoprotein-cholesterol lowering and pharmacokinetics of adding bempedoic acid (ETC-1002) to high-dose atorvastatin background therapy in hypercholesterolemic patients: A randomized placebo-controlled trial.

BACKGROUND: Bempedoic acid is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia. OBJECTIVE: The aim of the study was to assess the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of bempedoic acid added to stable high-intensity atorvastatin background therapy and multiple-dose plasma pharmacokinetics of atorvastatin alone and combined with steady-state bempedoic acid. METHODS: This was a phase 2 study in patients with hypercholesterolemia (NCT02659397). Patients received once-daily open-label atorvastatin 80 mg for 4 weeks then were randomized 2:1 at baseline to receive double-blind bempedoic acid 180 mg (n = 45) or placebo (n = 23) plus open-label atorvastatin 80 mg for 4 weeks. Efficacy was assessed 4 weeks after randomization. Atorvastatin and metabolites' steady-state levels were analyzed before first dosing with bempedoic acid and after 2 weeks of treatment. RESULTS: The 4-week stabilization phase with 80 mg atorvastatin resulted in approximately 40% lowering of LDL-C values from screening. The placebo-adjusted least squares mean lowering of LDL-C from baseline to Day 29 with bempedoic acid was 22% (P = .003). Placebo-adjusted reductions from baseline with bempedoic acid also were significant for total cholesterol (-10%; P = .014), non-high-density lipoprotein cholesterol (-13%; P = .015), apolipoprotein B (-15%; P = .004), and high-sensitivity C-reactive protein (-44%; P = .002). Point estimates of bempedoic acid effects on steady-state atorvastatin and ortho-hydroxy atorvastatin area under the curve were <30% and not clinically meaningful. CONCLUSIONS: Bempedoic acid 180 mg added to stable high-dose atorvastatin therapy effectively lowers LDL-C in patients with hypercholesterolemia without causing clinically important increases in atorvastatin exposure.

Cynanchum wilfordii Etanolic Extract Controls Blood Cholesterol: A Double-blind, Randomized, Placebo-Controlled, Parallel Trial.

We evaluated the effects of Cynanchum wilfordii (CW) ethanolic extract on blood cholesterol levels in adults with high low-density lipoprotein cholesterol (LDL-C) levels. In a double-blind, randomized, placebo-controlled, parallel trial, 84 subjects were recruited. Participants were randomly divided into two groups with a low-dose (300 mg/d) or high-dose (600 mg/d) of CW. Levels of very low-density lipoprotein (p = 0.022) and triglycerides (p = 0.022) were significantly lower in the low-dose CW group than in the placebo group after 8 weeks. In a subgroup of participants with LDL-C≥ 150 mg/dL (n = 33), there was a significant decrease in total cholesterol (low-dose, p = 0.012; high-dose, p = 0.021), apolipoprotein B (low-dose, p = 0.022; high-dose, p = 0.016), and cholesteryl ester transfer protein (low-dose, p = 0.037; high-dose, p = 0.016) after 8 weeks of CW. The correlation between changes in total cholesterol and baseline LDL-C levels was significant in the groups that received both doses of CW (low-dose, p = 0.010; high-dose, p = 0.015). These results show that the CW ethanolic extract can regulate blood cholesterol in subjects with LDL-C≥ 150 mg/dL.

A randomized, double blind, placebo controlled, multicenter clinical trial to assess the efficacy and safety of Emblica officinalis extract in patients with dyslipidemia.

BACKGROUND: Dyslipidemia is one of the most frequently implicated risk factors for development of atherosclerosis. This study evaluated the efficacy of amla (Emblica officinalis) extract (composed of polyphenols, triterpenoids, oils etc. as found in the fresh wild amla fruit) in patients with dyslipidemia. METHODS: A total of 98 dyslipidemic patients were enrolled and divided into amla and placebo groups. Amla extract (500 mg) or a matching placebo capsule was administered twice daily for 12 weeks to the respective group of patients. The patients were followed up for 12 weeks and efficacy of study medication was assessed by analyzing lipid profile. Other parameters evaluated were apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1), Coenzyme Q10 (CoQ10), high-sensitive C-reactive protein (hsCRP), fasting blood sugar (FBS), homocysteine and thyroid stimulating hormone (TSH). RESULTS: In 12 weeks, the major lipids such as total cholesterol (TC) (p = 0.0003), triglyceride (TG) (p = 0.0003), low density lipoprotein cholesterol (LDL-C) (p = 0.0064) and very low density lipoprotein cholesterol (VLDL-C) (p = 0.0001) were significantly lower in amla group as compared to placebo group. Additionally, a 39% reduction in atherogenic index of the plasma (AIP) (p = 0.0177) was also noted in amla group. The ratio of Apo B to Apo A1 was reduced more (p = 0.0866) in the amla group as compared to the placebo. There was no significant change in CoQ10 level of amla (p = 0.2942) or placebo groups (p = 0.6744). Although there was a general trend of FBS reduction, the numbers of participants who may be classified as pre-diabetes and diabetes groups (FBS > 100 mg/dl) in the amla group were only 8. These results show that the amla extract used in the study is potentially a hypoglycaemic as well. However, this needs reconfirmation in a larger study. CONCLUSIONS: The Amla extract has shown significant potential in reducing TC and TG levels as well as lipid ratios, AIP and apoB/apo A-I in dyslipidemic persons and thus has scope to treat general as well as diabetic dyslipidemia. A single agent to reduce cholesterol as well as TG is rare. Cholesterol reduction is achieved without concomitant reduction of Co Q10, in contrast to what is observed with statins. TRIAL REGISTRATION: Registered with Clinical Trials Registry- India at www.ctri.nic.in (Registration number: CTRI/2015/04/005682 ) on 8 April 2015 (retrospectively registered).

Mango phenolics increase the serum apolipoprotein A1/B ratio in rats fed high cholesterol and sodium cholate diets.

BACKGROUND: Serum lipoproteins are in dynamic equilibrium, partially controlled by the apolipoprotein A1 to apolipoprotein B ratio (APOA1/APOB). Freeze-dried mango pulp (FDM) is a rich source of phenolic compounds (MP) and dietary fiber (MF), although their effects on lipoprotein metabolism have not yet been studied. RESULTS: Thirty male Wistar rats were fed with four different isocaloric diets (3.4 kcal g-1 ) for 12 weeks: control diet, high cholesterol (8 g kg-1 ) + sodium cholate (2 g kg-1 ) diet either alone or supplemented with MF (60 g kg-1 ), MP (1 g kg-1 ) or FDM (50 g kg-1 ). MP and FDM reduced food intake, whereas MF and MP tended to increase serum APOA1/APOB ratio, independently of their hepatic gene expression. This suggests that lipoprotein metabolism was favorably altered by mango bioactives, MP also mitigated the non-alcoholic steatohepatitis that resulted from the intake of this diet. CONCLUSION: We propose that phenolics are the most bioactive components of mango pulp, acting as anti-atherogenic and hepatoprotective agents, with a mechanism of action tentatively based on changes to the main protein components of lipoproteins. © 2018 Society of Chemical Industry.

Safety and efficacy of Melissa officinalis (lemon balm) on ApoA-I, Apo B, lipid ratio and ICAM-1 in type 2 diabetes patients: A randomized, double-blinded clinical trial.

BACKGROUND: The purpose of this study was to investigate the safety and effects of Melissa officinalis, a good source of bioactive components, on apolipoprotein (Apo)B, Apo A-I, and their ratio, lipids ratios and intercellular adhesion molecule-1(ICAM-1) in patients with type 2 diabetes. METHODS: For the present randomized, double-blinded, placebo-controlled clinical trial, 70 type 2 diabetic patients aged 20-65 years old were randomly assigned to receive hydroalcoholic extract of M. officinalis (HEMO) (700 mg/d) or placebo twice-daily for 12 weeks. RESULTS: There were significant differences in serum Apo A-I, TC/ HDL-c and LDL-c/ HDL-c between the two groups at the end of the study (p < 0.05), but we did not show significant differences in the values for Apo B, Apo B/Apo A-I, TG/HDL-c, ICAM-1 and liver enzymes include AST, ALT, and ALP between the study groups. Although both groups showed a significant reduction in ICAM-1, AST and, ALP (p < 0.05), no significant differences in ICAM-1, AST and, ALP were observed. At end, in M. officinalis group, there was a significant increase in Apo A-I (p = 0.003) and significant reduction in TG/HDL-c (p = 0.05) compared with initial values, as well as in placebo group, there was a significant rising in Apo B/Apo A-I (p = 0.02) and significant reduction in Apo A-I (p = 0.001) compared with baseline values. CONCLUSIONS: M. officinalis is safe and effective in improvement of Apo A-I, Apo B/Apo A-I, and lipids ratios as key factors promoting cardiovascular disease (CVD) in type II diabetic patients.

Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B: a systematic review and meta-analysis of randomized controlled trials.

Background: Studies have identified viscous dietary fiber as potentially attenuating cholesterol, including psyllium, which reduces LDL cholesterol and thus may complement cardiovascular disease (CVD) treatment. Objectives: The aims of this study were to update evidence on the effect of psyllium on LDL cholesterol and to provide an assessment of its impact on alternate markers: non-HDL cholesterol and apolipoprotein B (apoB). Design: Medline, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials were searched through 3 October 2017. Independent reviewers extracted relevant data and assessed risk of bias. We included randomized controlled trials with a duration of ≥3 wk that assessed the effect of psyllium on blood lipids in individuals with or without hypercholesterolemia. Data were pooled by using the generic inverse variance method with random-effects models and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by Cochran's Q statistic and quantified by the I2 statistic. Overall quality of the evidence was assessed by using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Results: We included 28 trials in our analysis (n = 1924). Supplementation of a median dose of ∼10.2 g psyllium significantly reduced LDL cholesterol (MD = -0.33 mmol/L; 95% CI: -0.38, -0.27 mmol/L; P < 0.00001), non-HDL cholesterol (MD = -0.39 mmol/L; 95% CI: -0.50, -0.27 mmol/L; P < 0.00001), and apoB (MD = -0.05 g/L; 95% CI: -0.08, -0.03 g/L; P < 0.0001). Effect estimates for LDL cholesterol and non-HDL cholesterol were graded as moderate quality on the basis of downgrades for inconsistency and graded as high quality for apoB. Conclusion: Psyllium fiber effectively improves conventional and alternative lipids markers, potentially delaying the process of atherosclerosis-associated CVD risk in those with or without hypercholesterolemia. This trial is registered at www.clinicaltrials.gov as NCT03346733.

A comparison of the effects of low- and high-dose atorvastatin on lipoprotein metabolism and inflammatory cytokines in type 2 diabetes: Results from the Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA) randomized trial.

BACKGROUND: Statin therapy is recommended in type 2 diabetes (T2DM) although views on treatment intensity and therapeutic targets remain divided. OBJECTIVES: Our objectives were to compare the effects of high-intensity and moderate-intensity atorvastatin treatment on lipoprotein metabolism and inflammatory markers and how frequently treatment goals are met in high-risk T2DM patients. METHODS: Patients with T2DM and albuminuria (urinary albumin:creatinine ratio >5 mg/mmol, total cholesterol <7 mmol/L, proteinuria <2 g/d, creatinine <200 µmol/L) were randomized to receive atorvastatin 10 mg (n = 59) or 80 mg (n = 60) daily. Baseline and 1-year follow-up data are reported. RESULTS: Patients were at high cardiovascular disease risk (observed combined mortality and nonfatal cardiovascular disease annual event rate 4.8%). The non-high-density lipoprotein cholesterol (HDL-C) goal of <2.6 mmol/L was achieved in 72% of participants receiving high-dose atorvastatin, but only in 40% on low-dose atorvastatin (P < .005). The proportion achieving apolipoprotein B (apoB) <0.8 g/L on high-dose and low-dose atorvastatin was 82% and 70%, respectively (NS). Total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, non-HDL-C, oxidized LDL, apoB, glyc-apoB, apolipoprotein E, and lipoprotein-associated phospholipase A2 decreased significantly, more so in participants on high-dose atorvastatin. Adiponectin increased and serum amyloid A decreased without dose dependency. Neither dose produced significant changes in HDL-C, cholesterol efflux, high-sensitivity C-reactive protein, glycated hemoglobin, serum paraoxonase-1, lecithin:cholesterol acyltransferase, or cholesteryl ester transfer protein. CONCLUSIONS: High-dose atorvastatin is more effective in achieving non-HDL-C therapeutic goals and in modifying LDL-related parameters. Recommended apoB treatment targets may require revision. Despite the increase in adiponectin and the decrease in serum amyloid A, HDL showed no change in functionality.

A 25-Hydroxycholecalciferol-Fortified Dairy Drink Is More Effective at Raising a Marker of Postprandial Vitamin D Status than Cholecalciferol in Men with Suboptimal Vitamin D Status.

Background: One strategy for improving population vitamin D status is consumption of fortified foods. However, the effects of dairy products fortified with different vitamin D isoforms on postprandial vitamin D status and metabolic outcomes have not been addressed.Objective: We investigated whether consumption of dairy drinks fortified with either 25-hydroxycholecalciferol [25(OH)D3] or cholecalciferol (vitamin D3) had differential effects on 24-h circulating plasma 25(OH)D3 concentration (a marker of vitamin D status) and cardiometabolic risk markers.Methods: A randomized, controlled, 3-way crossover, double-blind, postprandial study was conducted in 17 men with suboptimal vitamin D status [mean ± SEM age: 49 ± 3 y; body mass index (in kg/m2): 26.4 ± 0.6; and plasma 25(OH)D3 concentration: 31.7 ± 3.4 nmol/L]. They were randomly assigned to consume 3 different test meals (4.54 MJ, 51 g fat, 125 g carbohydrate, and 23 g protein), which contained either a nonfortified dairy drink (control), 20 µg 25(OH)D3-fortified (+HyD3) dairy drink, or 20 µg vitamin D3-fortified (+D3) dairy drink with toasted bread and jam on different occasions, separated by a 2-wk washout. Plasma 25(OH)D3 concentrations and cardiometabolic risk markers, including vascular stiffness, serum lipids, and inflammatory markers, were measured frequently within 8 h postprandially and 24 h after the dairy drink was consumed.Results: Plasma 25(OH)D3 concentrations (the primary outcome) were significantly higher after the +HyD3 dairy drink was consumed compared with +D3 and control (P = 0.019), which was reflected in the 1.5-fold and 1.8-fold greater incremental area under the curve for the 0-8 h response, respectively. The change in plasma 25(OH)D3 concentrations from baseline to 24 h for the +HyD3 dairy drink was also 0.9-fold higher than the +D3 dairy drink and 4.4-fold higher than the control (P < 0.0001), which were not significantly different from each other.Conclusion: The dairy drink fortified with 25(OH)D3 was more effective at raising plasma 25(OH)D3 concentrations postprandially than was the dairy drink fortified with vitamin D3 in men with suboptimal vitamin D status. This trial was registered at clinicaltrials.gov as NCT02535910.

Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their mechanisms of action on apolipoprotein B-containing lipoproteins in humans: a review.

BACKGROUND: Epidemiological and genetic studies suggest that elevated triglyceride (TG)-rich lipoprotein levels in the circulation increase the risk of cardiovascular disease. Prescription formulations of omega-3 fatty acids (OM3FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma TG levels and are approved for the treatment of patients with severe hypertriglyceridemia. Many preclinical studies have investigated the TG-lowering mechanisms of action of OM3FAs, but less is known from clinical studies. METHODS: We conducted a review, using systematic methodology, of studies in humans assessing the mechanisms of action of EPA and DHA on apolipoprotein B-containing lipoproteins, including TG-rich lipoproteins and low-density lipoproteins (LDLs). A systematic search of PubMed retrieved 55 articles, of which 30 were used in the review; 35 additional arrticles were also included. RESULTS: In humans, dietary DHA is retroconverted to EPA, while production of DHA from EPA is not observed. Dietary DHA is preferentially esterified into TGs, while EPA is more evenly esterified into TGs, cholesterol esters and phospholipids. The preferential esterification of DHA into TGs likely explains the higher turnover of DHA than EPA in plasma. The main effects of both EPA and DHA are decreased fasting and postprandial serum TG levels, through reduction of hepatic very-low-density lipoprotein (VLDL)-TG production. The exact mechanism for reduced VLDL production is not clear but does not include retention of lipids in the liver; rather, increased hepatic fatty acid oxidation is likely. The postprandial reduction in TG levels is caused by increased lipoprotein lipase activity and reduced serum VLDL-TG concentrations, resulting in enhanced chylomicron clearance. Overall, no clear differences between the effects of EPA and DHA on TG levels, or on turnover of TG-rich lipoproteins, have been observed. Effects on LDL are complex and may be influenced by genetics, such as APOE genotype. CONCLUSIONS: EPA and DHA diminish fasting circulating TG levels via reduced production of VLDL. The mechanism of reduced VLDL production does not involve hepatic retention of lipids. Lowered postprandial TG levels are also explained by increased chylomicron clearance. Little is known about the specific cellular and biochemical mechanisms underlying the TG-lowering effects of EPA and DHA in humans.

The Impact of Supplementation with Folic Acid on Homocysteine Concentration and Selected Lipoprotein Parameters in Patients with Primary Hypertension.

The aim of the study was the assessment of the impact of supplementation with folic acid on the concentration of homocysteine, total cholesterol (TC), HDL- and LDL-cholesterol, triglycerides (TG), apoprotein AI (apoAI) and apoprotein B (apoB) in patients suffering from primary hypertension. The examined group comprised 42 patients suffering from primary hypertension. All examined patients underwent laboratory tests as follows: concentration of homocysteine, folic acid, TC, LDL-cholesterol, HDL-cholesterol, TG, apoAI and apoB. All patients were orally administered with 15 mg of folic acid per day for 45 d. After this period, all laboratory tests were repeated. Homocysteine concentration was measured by the FPIA method, concentrations of apoAI and apoB were measured by the nephelometric method, and other parameters with routine methods. After administration of 15 mg of folic acid to patients with primary hypertension, a considerable decrease in the concentration of homocysteine was observed in parallel with a substantive growth of HDL-cholesterol, as well as apoprotein AI concentrations and a reduction of the apoprotein B concentration. Results of statistical analysis indicated a significant correlation between the decline in homocysteine concentration and the increase in HDL-cholesterol concentration, as well as between the increase of folic acid concentration and the increase in apoAI concentration in patients following the intake of folic acid. The drop in homocysteine concentration through the supplementation with folic acid can cause quantitative changes in the lipid and lipoprotein parameters which, in consequence, may lead to the mitigation of risk concerning the development of atherosclerosis.

Lipid Biomarkers for Risk Assessment in Acute Coronary Syndromes.

PURPOSE OF REVIEW: The objective of this review was to summarize evidence gathered for the prognostic value of routine and novel blood lipids and lipoproteins measured in patients with acute coronary syndromes (ACS). RECENT FINDINGS: Data supports clear association with risk and actionable value for non-high-density lipoprotein (Non-HDL) cholesterol and plasma ceramides in a setting of ACS. The prognostic value and clinical actionability of apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] in ACS have not been thoroughly tested, while the data for omega-3 fatty acids and oxidized low-density lipoprotein (Ox-LDL) are either untested or more varied. Measuring basic lipids, which should include Non-HDL cholesterol, at the time of presentation for ACS is guideline mandated. Plasma ceramides also provide useful information to guide both treatment decisions and follow-up. Additional studies targeting ACS patients are necessary for apoB, Lp(a), omega-3 fatty acids, and Ox-LDL.

Impact of Wheatgrass (Triticum aestivum L.) Supplementation on Atherogenic Lipoproteins and Menopausal Symptoms in Hyperlipidemic South Asian Women - A Randomized Controlled Study.

OBJECTIVE: The purpose of this study was to evaluate the effect of wheatgrass (Triticum aestivum L.) on atherogenic lipoproteins, inflammation, and menopausal symptoms. METHODS: Fifty-nine hyperlipidemic women were randomized into control (n = 30) and intervention groups (n = 29). Intervention group was administered 3.5 g of freeze-dried wheatgrass powder in encapsulated form daily for 10 weeks, while the control group received no intervention. RESULTS: The intervention group experienced a reduction of 5.4% in total cholesterol (TC), 4.4% in low-density lipoprotein cholesterol, and 9.5% in triacylglycerols (TAG); however, high-density lipoprotein (HDL) also reduced by 6% following 10 weeks of intervention. Compared with the control group, the baseline-adjusted post-intervention levels of TC, TAG, and Apolipoprotein B (Apo B) were significantly lower in the experimental group compared with the control group (p = 0.043, 0.045, and 0.016, respectively). Prevalence of menopausal symptoms saw nonsignificant reductions: vasomotor, 42%; somatic, 33%; and psychological, 50%, while urogenital symptoms remained unaltered. CONCLUSIONS: Wheatgrass supplementation at a dose of 3.5 g per day for a period of 10 weeks results in significant reductions in Apo B fraction, TC, and TAG without significantly reducing the HDL cholesterol.

Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil.

BACKGROUND: Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels. OBJECTIVES: The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women. SUBJECTS/METHODS: As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation. RESULTS: Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL1+2-C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6 versus 0.7 mg/dl, respectively, P=0.016). CONCLUSIONS: CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.