Reduction In Total Cholesterol Research Articles

Vitamin D supplementation improves foot ulcers among diabetic patients: Pooled analysis of randomized controlled trials

Serum vitamin D level is associated with the development of diabetic foot ulcer (DFU), and it is intriguing to determine if the vitamin supplementation could reverse the diabetic complication. The aim of this study was to investigate the efficacy of vitamin D supplementation in DFU management through qualitative and quantitative systematic review. A systematic search was conducted to screen the records identified in PubMed, Scopus, Embase, Scillit, Sci-Finder, LILACS, EuropePMC, medRxiv, bioRvix, Google Scholar, Semantic Scholar, and Garuda databases as of 10 March 2023. Studies investigating the efficacy of a single dose supplementation of vitamin D in DFU management were included. Quality of the included studies was appraised by Cochrane ‘Risk of Bias’ 2.0. Random-effects-based pooled analysis using Cohen’s d was performed on the wound healing progress as the primary outcome. A sensitivity test with leave-one-out method and meta-regression were also conducted to analyze the effect of heterogenous data. Five studies with a total of 245 patients (123 versus 122 for experimental and control groups, respectively) were finally included in the qualitative and quantitative analysis. The pooled estimate suggested that administering vitamin D to DFU patients could reduce the wound area or depth significantly as compared to control group (p<0.001; Cohen’s d: 2.72; 95% CI: 1.02 to 4.42). The value remained positive throughout the leave-one-out analysis. Vitamin D supplementation significantly contributed to the increased level of serum vitamin D (p=0.026, Cohen’s d: -0.719; 95% CI: -1.35 to -0.09). Elevation of high-density lipoprotein was observed in pooled estimate with p=0.016 and Cohen’d: 1.34 (95% CI: 0.25 to 2.44). Qualitatively, significant reduction of HbA1C, total cholesterol, and C-reactive protein were reported in at least two trials. Significantly improved quantitative insulin sensitivity check index (QUICKI) and decreased malondialdehyde, fructosamine, and fasting blood glucose were reported in at least one trial each. There were conflicting results on the change of low-density lipoprotein level. This study highlights that vitamin D supplementation promotes wound healing process among DFU patients; however, it is too premature to draw solid conclusions as the efficacy could be affected by multiple factors. Therefore, clinical trials from various demographics and ethnicities by using a high- versus low-dose model are needed.

Effects of high calorie dietary nutrition and exercise on energy metabolism parameters in obese Wistar albino rats

Purpose: With the increasing prevalence of metabolic disorders, studies on energy metabolism have advanced, leading to the recent identification of new members in energy metabolism. This study aims to demonstrate the effects of a high-calorie diet and exercise on the newly identified peptides asprosin, irisin, nesfatin-1, and preptin, whose effects on metabolism are still under investigation, and to provide information for future research.
 Materials and Methods: In this study, 24 rats were divided into four groups: control, exercise, high-calorie diet, and high-calorie diet with exercise. Serum levels of asprosin, irisin, preptin, nesfatin-1, and insulin were measured using the ELISA method. Additionally, serum levels of glucose, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined by the colorimetric method.
 Results: Compared to the control group, there were significant increases in body mass index, glucose, asprosin, TG, TC, and LDL-C levels. Serum HDL-C levels were notably lower in the experimental group compared to the control group. In the exercise group, irisin and nesfatin-1 levels significantly increased, accompanied by reductions in LDL-C, TG, TC, glucose, and preptin levels.
 Conclusion: A high-calorie diet was associated with an unfavorable lipid profile, while exercise-induced alterations in the secretion of peptides derived from adipose tissue and/or regulating energy metabolism. Although physical activity emerges as a crucial factor in peptide secretion and maintaining biochemical balance, further research is imperative to comprehensively understand the underlying mechanisms.

Perilla seed oil as an adjunctive treatment with statins improves lipid profiles in elderly patients: a post hoc data analysis

Background: Dyslipidemia is characterized by abnormal lipid concentrations in the bloodstream, heightening the risk of atherosclerosis. While statins are primarily prescribed to treat dyslipidemia, not all patients benefit from them for various reasons, such as intolerance, myopathy, and hepatotoxicity. Perilla frutescens (L.) Britton, traditionally grown in East Asia, has been used for various therapeutic purposes. The seed oil of this plant is prosperous in omega-3 polyunsaturated fatty acids. Previous research found the efficacy of perilla (P. frutescens) seed oil in reducing cholesterol in patients with dementia. Our study aimed to determine if the lipid-lowering effects of P. frutescens seed oil occur on their own or alongside statin treatments by conducting a retrospective analysis of existing data to assess its efficacy in improving lipid profiles among the elderly.Objective: This study aimed to understand if P. frutescens seed oil inherently possesses lipid-lowering properties or if these effects are amplified when combined with statins.Methods: A retrospective post hoc analysis was performed on 182 geriatric patients previously involved in a dementia study. These patients were categorized into four groups: those administered both P. frutescens seed oil and a statin (G1), only P. frutescens seed oil (G2), only a statin (G3), and neither (G4). The outcomes evaluated post-intervention included lipid profiles, liver and renal functions, complete blood count, and neutrophils to lymphocytes and platelets (N/LP) ratio.Results: Patients in G1 exhibited the most pronounced reductions in total cholesterol and LDL-C levels, suggesting a potential synergistic effect when P. frutescens seed oil is combined with statins. Liver enzyme levels remained stable across all groups, suggesting the hepatic safety of P. frutescens seed oil even when co-administered with statins.Conclusion: P. frutescens seed oil, particularly when used alongside statins, exhibits the potential to improve lipid profiles and may also offer liver protection. However, extended studies are necessary to understand its therapeutic significance in cardiovascular disease management fully.Keywords: Perilla frutescens,omega-3,statins, lipid profile, elderly, hepatoprotection, functional food, bioactive compound

Phytochemical profiling, toxicity studies, wound healing, analgesic and anti-inflammatory activities of Musa paradisiaca L. Musaceae (Plantain) stem extract in rats

Ethnopharmacological relevanceThe stem of Musa paradisiaca (plantain) has found application in traditional medicine for the treatment of diabetes, inflammation, ulcers and wound injuries. Aim of the studyThis study investigated the phytochemical composition, toxicity profile, wound healing, anti-inflammatory and analgesic effects of aqueous Musa paradisiaca stem extract (AMPSE) in rats. MethodsPhytochemical analysis of methanol-MPSE was performed by gas chromatography-mass spectrometry (GC-MS). Acute toxicity testing was carried out through oral administration of a single dose of AMPSE up to 5 g/kg. Four separate groups of rats were used for the subacute toxicity testing (n = 6). Group 1 served as a normal control and did not receive AMPSE, groups 2–4 received AMPSE daily by gavage for 28 days. In the experiments with excision and incision wounds, the rats were treated with 10 w/w AMPS extract. The anti-inflammatory and analgesic effects of AMPSE were assessed using egg albumin-induced paw oedema and acetic acid-induced writhing methods, respectively. For the subacute, anti-inflammatory and analgesic studies, AMPSE was administered to the experimental rats at doses of 300, 600 and 900 mg/kg body weight. ResultsBioactive compounds identified include β-sitisterol, n-hexadecanoic acid, octadecanoic acid, diethyl sulfate, p-hydroxynorephedrine, phenylephrine, nor-pseudoephedrine, metaraminol, pseudoephedrine and vanillic acid. No signs of toxicity and no deaths were observed in all the groups. For the groups treated with AMPSE for 28 days, a significant reduction in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, sodium, chloride, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were observed while high density lipoprotein cholesterol, glutathione and superoxide dismutase increased compared to control (p < 0.05). In wound healing experiments, AMPSE showed greater percent wound contraction and wound resistance fracture compared to the povidone-iodine (PI) treated and control groups. Treatment with 900 mg/kg AMPSE resulted in significant (p < 0.05) anti-inflammatory and analgesic effects compared to the control. ConclusionThis study shows that AMPSE is not toxic but contains biologically active compounds with hepatoprotective, anti-inflammatory, lipid-lowering and wound-healing effects. Treatment of rats with AMPSE has shown that AMPSE has anti-inflammatory, analgesic, hepatoprotective, lipid-lowering and wound-healing effects, supporting its therapeutic use in ethnomedicine.

Immature carob pods extract and its fractions prevent lipid metabolism disorders and lipoprotein-rich plasma oxidation in mice: A phytochemical and pharmacological study

Ethnopharmacological relevance: In Morocco carob fruits are used traditionally to treat hypercholesterolemia, diabetes and related diseases. Aims: This study was designed to evaluate the hypolipidemic activity of Ceratonia siliqua green pods extract and its fractions in Triton WR-1339 and high fat/cholesterol diet (HFCD) induced hyperlipidemia mice, as well as their ability to prevent lipoproteins oxidation in vitro. Materials and methods: High performance liquid chromatography (HPLC) analysis was used to determine the phenolic composition of the immature carob pods extract (HWCE). Antioxidant activities were evaluated using the DPPH radical scavenging test as well as MDA measurement in oxidized lipoprotein rich plasma. Plasma lipids, glucose and biliary total cholesterol, as well as lipids level in liver and feces, were analyzed. The acute oral toxicity was performed in mice single dosed with the HWCE at 2000 and 5000 mg/kg body weight. Results: HPLC analysis shows that gallic acid is the main phenolic compound in the HWCE. The acute oral toxicity assessment revealed that the HWCE is not toxic (LD50 is greater than 5000 mg/kg body weight). In the acute hypolipidemic study, mice treated with the HWCE and its fractions exhibited a significant (P < 0.001) reduction in plasma total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels. Importantly, immature carob aqueous extract was more effective in lowering mice hypercholesterolemia than its fractions. Indeed, mice fed the HFCD for 12 weeks showed a significant raise in plasma TC, TG and LDL-C, as well as in hepatic and fecal TC and TG levels. The HWCE at 100 and 200 mg/kg body weight significantly (P < 0.001) reversed the plasmatic levels of these lipid parameters, increased plasma HDL-C level, reduced hepatic lipids accumulation, but increased cholesterol level in the bile and fecal lipids excretion. The HWCE decreased also the atherogenic index, the LDL-C/HDL-C ratio and plasma glucose level after 12 weeks’ experiment. On the other hand, the HWCE was more effective in preventing mice lipoprotein-rich plasma oxidation than its fractions, with a concentration-dependent manner. Conclusion: C. siliqua green fruits extract could be effective in preventing atherosclerosis and related cardiovascular complications through the inhibition of lipoprotein oxidation and cholesterol clearance.

The analysis of serum lipids profile in Guillain-Barre syndrome.

Guillain-Barre syndrome (GBS) is an immune-mediated inflammatory peripheral neuropathy. This study aimed to conduct a systematic analysis of the serum lipids profile in GBS. We measured the serum lipids profile in 85 GBS patients and compared it with that of 85 healthy controls matched for age and sex. Additionally, we analyzed the correlation between lipids and the severity, subtypes, precursor infections, clinical outcomes, clinical symptoms, immunotherapy, and other laboratory markers of GBS. Compared to the healthy controls, GBS exhibited significantly elevated levels of Apolipoprotein B (APOB), Apolipoprotein C2 (APOC2), Apolipoprotein C3 (APOC3), Apolipoprotein E (APOE), triglycerides (TG), and residual cholesterol (RC). Conversely, Apolipoprotein A1 (APOA1), Apolipoprotein A2 (APOA2), and high-density lipoprotein (HDL) were substantially lower in GBS. Severe GBS displayed noticeably higher levels of APOC3 and total cholesterol (TC) compared to those with mild disease. Regarding different clinical outcomes, readmitted GBS demonstrated higher RC expression than those who were not readmitted. Moreover, GBS who tested positive for neuro-virus antibody IGG in cerebrospinal fluid (CSF) exhibited heightened expression of APOC3 in comparison to those who tested negative. GBS with cranial nerve damage showed significantly reduced expression of HDL and APOA1 than those without such damage. Additionally, GBS experiencing limb pain demonstrated markedly decreased HDL expression. Patients showed a significant reduction in TC after intravenous immunoglobulin therapy. We observed a significant positive correlation between lipids and inflammatory markers, including TNF-α, IL-1β, erythrocyte sedimentation rate (ESR), white blood cells, monocytes, and neutrophils in GBS. Notably, APOA1 exhibited a negative correlation with ESR. Furthermore, our findings suggest a potential association between lipids and the immune status of GBS. The research demonstrated a strong connection between lipids and the severity, subtypes, clinical outcomes, precursor infections, clinical symptoms, immunotherapy, inflammation, and immune status of GBS. This implies that a low-fat diet or the use of lipid-lowering medications may potentially serve as an approach for managing GBS, offering a fresh viewpoint for clinical treatment of this condition.

Hepatoprotective Effect of Lactiplantibacillus plantarum DSR330 in Mice with High Fat Diet-Induced Nonalcoholic Fatty Liver Disease.

Lactiplantibacillus plantarum DSR330 (DSR330) has been examined for its antimicrobials production and probiotics. In this study, the hepatoprotective effects of DSR330 were examined against non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-fed C57BL/6 mouse model. To induce the development of fatty liver, a HFD was administered for five weeks, and then silymarin (positive control) or DSR330 (108 or 109 CFU/day) was administered along with the HFD for seven weeks. DSR330 significantly decreased body weight and altered serum and hepatic lipid profiles, including a reduction in triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels compared to those in the HFD group. DSR330 significantly alleviated HFD-related hepatic injury by inducing morphological changes and reducing the levels of biomarkers, including AST, ALT, and ALP. Additionally, DSR330 alleviated the expression of SREBP-1c, ACC1, FAS, ACO, PPARα, and CPT-1 in liver cells. Insulin and leptin levels were decreased by DSR330 compared to those observed in the HFD group. However, adiponectin levels were increased, similar to those observed in the ND group. These results demonstrate that L. plantarum DSR330 inhibited HFD-induced hepatic steatosis in mice with NAFLD by modulating various signaling pathways. Hence, the use of probiotics can lead to hepatoprotective effects.

Role of Eruca sativa L. seeds in boosting the reproductive performance of male Japanese quails (Coturnix c. japonica).

Herein we attempt to shed light on the potential improving effect of Eruca sativa seeds (ESS) on the reproductive aspects of male Japanese quails. To accomplish this objective, two groups of quails were supplemented with ESS powder at doses of 5 and 10 g/kg feed from 7 days to 140 days of age, in addition to the control group, which did not receive treatment. Forty males were reared singly in cages to evaluate sperm characters and 32 males were raised with 64 females to evaluate fertility and sperm penetrability. Sixty-six phytochemical compounds were found according to gas chromatography-mass spectrometry analysis of ESS. The most plentiful ones are 13-docosenoic acid methyl ester, 9-octadecenoic acid methyl ester, and linoleic acid methyl ester. Both 5 g/kg and 10 g/kg doses of ESS showed similar effectiveness in enhancing various reproductive parameters, including gonadal index, sperm characteristics, fertility, libido, and cloacal gland attributes. However, some aspects like sperm concentration and testosterone levels exhibited a dose-dependent response. There is no significant change in mortality rate of supplemented groups compared to the control one. ESS also caused a reduction in feed intake and an enhancement in feed conversion ratio without affecting final body weight and body weight gain. This suggests potential nutritional benefits beyond reproductive health. The low-dose-fed group showed a significant reduction in total cholesterol and malondialdehyde compared to the high-dose-fed and unfed groups. The higher dose notably increased total antioxidant capacity compared to the lower dose and control group. Despite the positive effects on male reproductive parameters, there wasn't a significant impact on hatchability percentage, indicating that while male fertility improved, it might not have directly affected the viability of the eggs. Overall, the study suggests that ESS could be a safe and promising addition to the diet of male Japanese quails to enhance their reproductive capabilities without adverse effects. The findings could have implications for poultry farming by potentially improving breeding efficiency and health outcomes in quails.

Effect of camel milk on lipid profile among patients with diabetes: a systematic review, meta-analysis, and meta-regression of randomized controlled trials

The effects of camel milk (CM) intake on lipid profile among patients with diabetes remain controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to calculate the effect size of CM intake on blood lipids among patients with type 1 (T1D) and type 2 (T2D) diabetes. We searched nine databases from inception until December 31, 2022, to identify relevant RCTs. Effect sizes for total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) were calculated and expressed using mean differences (MD) and confidence intervals (CI). Of 4,054 retrieved articles, 10 RCTs (a total of 347 participants aged 8–70 years, 60.5% male) were eligible for inclusion. The pooled results from a random-effects model showed statistically significant decreases in TC (MD − 21.69, 95% CI: 41.05, − 2.33; p = 0.03; I2=99%), TG (MD − 19.79, 95% CI: −36.16, − 3.42; p=0.02, I2=99%), and LDL (MD −11.92, CI: −20.57, −3.26; p = 0.007, I2=88%), and a significant increase in HDL (MD 10.37, 95% CI, 1.90, 18.84; p=0.02, I2=95%) in patients with diabetes supplemented with CM compared with usual care alone. Subgroup analysis revealed that only long-term interventions (> 6 months) elicited a significant reduction in TC levels and TG levels. Consumption of fresh CM by patients with diabetes resulted in significant reductions in TC, TG, and LDL levels, while showing a significant increase in HDL levels. Patients with T1D elicited a more beneficial effect in lowering TC, LDL, and TG levels and in increasing HDL levels than their corresponding partners with T2D. In conclusion, long-term consumption of CM for patients with diabetes, especially those with T1D, could be a useful adjuvant therapy to improve lipid profile alongside prescribed medications. However, the high heterogeneity in the included studies suggests that more RCTs with larger sample sizes and longer intervention durations are required to improve the robustness of the available evidence.

Dietary supplementation with a mixture of Dunaliella salina and Spirulina enhances broiler performance by improving growth, immunity, digestive enzymes and gut microbiota

The aim of this study is to evaluate the effect of Dunaliella salina and Spirulina (D + S) mixture on performance, carcass yield, kidney and liver markers, lipid profile, and immune responses of fattening chicks. Two hundred broiler chicks at 7 days old were distributed into 5 experimental groups, 5 replicates each with 8 chicks each. Group 1 was fed on only basal diet; group 2 was fed with basal diet and 0.50 g/kg (D + S); group 3 was fed with basal diet and 1.00 g/kg (D + S); group 4 was fed with basal diet and 1.50 g/kg (D + S); and group 5 was fed with basal diet supplemented with 2.00 g/kg (D + S). The additive mixture (D + S) consisted of (1 D. salina: 1 Spirulina). The experiment lasted for 6 wk. The results demonstrated significantly improved better live body weight, body weight gain, and feed conversion ratio (P<0.01) for groups that received (D + S) at levels of 1.0 and 1.5 g/kg diet compared to other groups at 6 wk of age. There was no significant influence of different levels of dietary feed additives on feed intake or carcass traits. The lipid profile was improved through a reduction of total cholesterol and low-density lipoprotein (LDL) values and increasing high-density lipoprotein (HDL) values, as well as the immune response, which was improved through increasing values of complement 3, immunoglobulin M (IgM), and immunoglobulin G (IgG) in the birds treated with (D + S) compared to the control group. The inclusion of all levels of (D + S)/kg decreased triglyceride, while total protein, albumen, and globulin values (P<0.05 or P<0.01) were higher compared to other groups. The inclusion of the different levels of (D + S)/kg improved liver function, whereas aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were lower than in other groups (P<0.001). The lowest values of creatinine, urea, and uric acid were noted in birds fed a diet supplemented with 1.50 g (D + S)/kg. Antioxidant levels were improved through increasing values of catalase (CAT) and reduced glutathione (GSH) enzymes in the treated birds with (D + S) compared with the control chicks. Furthermore, digestive enzymes and microbial content were improved in broiler checks fed on diet supplemented with (D + S) compared to the control group. In conclusion, supplementing broiler chicks with a dietary D. salina and Spirulina combination increased their productive performance, immunity, kidney and liver function, lipid profile, and digestive enzymes.

Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: the TANGO randomized controlled trial

BackgroundWeight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. ObjectivesTo examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. MethodsIn a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. ResultsIn the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. ConclusionMild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. Trial registration numberThis trial was registered at the clinicaltrials.gov as NCT05259475.

Hypolipidemic, Hypoglycemic, and Ameliorative Effects of Boiled Parsley (Petroselinum crispum) and Mallow (Corchorus olitorius) Leaf Extracts in High-Fat Diet-Fed Rats.

Obesity is a major health concern associated with serious conditions such as type 2 diabetes and cardiovascular diseases. This study investigated the potential anti-obesity effects of heat-treated parsley and mallow extracts (PE and ME, respectively) in high-fat diet (HFD)-fed rats. The selected herbs underwent three heat treatments (boiling, blanching, and microwaving), and the most effective treatment was orally administered to the HFD rats for eight weeks. All three treatments effectively increased the total phenolic content (TPC) and antioxidant capacity of the herbs, with boiling treatment exhibiting the most significant increase. Boiled herbs demonstrated approximately 29% higher TPC and an impressive 348% increase in antioxidant activity compared to the other treatments. Oral administration of the boiled herb extracts to the HFD rats resulted in significant reductions in body weight, total cholesterol, triglycerides, and LDL cholesterol levels, while elevating the HDL cholesterol levels compared to the positive control rats. Additionally, the boiled herb extracts exhibited antioxidant, hepatoprotective, and nephroprotective effects. Notably, PE displayed more significant anti-obesity properties compared to ME, potentially due to higher TPC and antioxidant activity observed in PE compared to ME. In conclusion, this study highlights the potential positive effects of boiled parsley against obesity and recommends boiling treatment as the preferred method when heat treatment is required for herbs.

Safety and efficacy of bempedoic acid: a systematic review and meta-analysis of randomised controlled trials

Background and aimsBempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia.MethodsPubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867).ResultsStudy search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79–0.95), myocardial infarction (OR 0.76, 95% CI 0.64–0.88) and unstable angina (OR 0.69, 95% CI 0.54–0.88) compared to control, over a median follow up of 87 (15–162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]–22.42,95% CI − 24.02% to − 20.82%), total cholesterol (− 16.50%,95% − 19.21% to − 13.79%), Apo-B lipoprotein (− 19.55%, − 22.68% to − 16.42%) and high-sensitivity CRP (− 27.83%, − 31.71% to − 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27–1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy.ConclusionsThe improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.

Distinct Microbial Taxa Are Associated with LDL-Cholesterol Reduction after 12 Weeks of Lactobacillus plantarum Intake in Mild Hypercholesterolemia: Results of a Randomized Controlled Study.

Probiotic microbes such as Lactobacillus may reduce serum total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol. The objective of this study was to assess the effect of Lactobacillus plantarum strains CECT7527, CECT7528, and CECT7529 (LP) on the serum lipids, cardiovascular parameters, and fecal gut microbiota composition in patients with mild hypercholesterolemia. A randomized, double-blinded, placebo-controlled clinical trial with 86 healthy adult participants with untreated elevated LDL cholesterol ≥ 160mg/dl was conducted. Participants were randomly allocated to either placebo or LP (1.2 × 109CFU/d) for 12weeks. LDL, HDL, TC, and triglycerides (TG), cardiovascular parameters (blood pressure, arterial stiffness), and fecal gut microbiota composition (16S rRNA gene sequencing) were assessed at baseline and after 12weeks. Both groups were comparable regarding age, sex, and LDL-C at baseline. LDL-C decreased (mean decrease - 6.6mg/dl ± - 14.0mg/dl, Ptime*group = 0.006) in the LP group but not in the placebo group. No effects were observed on HDL, TG, or cardiovascular parameters or overall gut microbiota composition. Responders to LP intervention (> 5% LDL-C reduction) were characterized by higher BMI, pronounced TC reduction, higher abundance of fecal Roseburia, and lower abundance of Oscillibacter. In conclusion, 12weeks of L. plantarum intake moderately reduced LDL-C and TC as compared to placebo. LDL-C-lowering efficacy of L. plantarum strains may potentially be dependent on individual difference in the gut microbiota. Trial registration: DRKS00020384, dated 07/01/2020.

1986. Switching to DOR/3TC/TDF Improves Renal Function and Decreases Lipid Levels in People Living With HIV: a Real-Life Multicentric Study

Abstract Background Pivotal studies on Doravirine (DOR) showed its high tolerability and effectiveness, even on resistant strains. Therefore, DOR and its single tablet combination treatment DOR/lamivudine (3TC)/tenofovir disoproxil fumarate (TDF) has been referred to as a cardiovascular-safe drug. However, data from real-life studies on safety and efficacy of DOR are lacking. Methods Retrospective multicenter cohort study, including 6 Italian HIV centers, evaluated adult treatment-experienced People Living With HIV (PLWH) who switched to DOR/3TC/TDF from June 2020 to June 2022. PLWH with known resistance mutations to DOR were excluded. Clinical and laboratory data were collected at the time of the switch and after 48 weeks. Results A total of 98 PLWH were switched to a DOR/3TC/TDF regimen, 75 (76.5%) male, with a median age of 52.41 years (IQR 42.95-58.79). The main reason for switching to DOR/FTC/TDF regimens was proactive switch (33.3%). No differences were found between the two timepoints on plasma viral load (pVL) (p = 0.345), lymphocytes T CD4+ (CD4+) percentage (p = 0.994) and count (p = 0.611), and CD4+/lymphocytes T CD8+ (CD8+) ratio (p = 0.899), confirming the effectiveness of the drug combination. We also found a significant reduction in total (p &amp;lt; 0.001) and LDL (p = 0.025) cholesterol and triglycerides (p = 0.002). Importantly, we found that the estimated glomerular filtration rate (eGFR) calculated with CKD-EPI formula significantly improved despite the presence of TDF (p = 0.028). Adverse events (AEs) were reported in 2 PLWHs and were characterized by the onset of a nodular rash in both arms and legs after 2 weeks of therapy in one PLWH, and by the onset of a progressive paresthesia in both extremities of arms after one week of treatment in the other PLWH. In both cases the treatment with DOR/3TC/TDF was interrupted. Conclusion The present real-life study showed that DOR/3TC/TDF significantly reduced lipid levels, surprisingly improving estimated renal function. The virological efficacy of DOR/3TC/TDF along with its immunological, metabolic and safety profile are key elements for a proactive management of the cardiovascular risk. Disclosures All Authors: No reported disclosures

Spirulina Supplementation with High-Intensity Interval Training Decreases Adipokines Levels and Cardiovascular Risk Factors in Men with Obesity

Adiposity, a state characterized by excessive accumulation of body fat, is closely linked to metabolic complications and the secretion of specific adipokines. This study explores the potential of exercise and Spirulina supplementation to mitigate these complications and modulate adipokine release associated with obesity. The primary objective of this investigation was to examine the impact of a 12-week regimen of high-intensity training combined with Spirulina supplementation on adipokine concentrations and lipid profiles in male individuals with obesity (N = 44). The participants were randomly distributed into four groups, each consisting of 11 participants: a control group (CG), a supplement group (SG), a training group (TG), and a training plus supplement group (TSG). The intervention comprised a 12-week treatment involving Spirulina supplementation (6 g capsule daily), a 12-week high-intensity interval training (HIIT) protocol with three sessions per week, or a combined approach. Following the interventions, metabolic parameters, anthropometric measurements, cardiorespiratory indices, and circulating adipokines [CRP, Sema3C, TNF-α, IL-6, MCP1, IL-8] were assessed within 48 h of the before and final training session. Statistical analyses revealed significant differences across all measures among the groups (p &lt; 0.05). Notably, post hoc analyses indicated substantial disparities between the CG and the three interventional groups regarding body weight (p &lt; 0.05). The combined training and supplementation approach led to noteworthy reductions in low-density lipoprotein (LDL), total cholesterol (TC), and triglyceride (TGL) levels (all p &lt; 0.0001), coupled with an elevation in high-density lipoprotein–cholesterol (HDL-C) levels (p = 0.0001). Furthermore, adipokine levels significantly declined in the three intervention groups relative to the CG (p &lt; 0.05). The findings from this 12-week study demonstrate that Spirulina supplementation in conjunction with high-intensity interval training reduced adipokine levels, improved body weight and BMI, and enhanced lipid profiles. This investigation underscores the potential of Spirulina supplementation and high-intensity interval training as a synergistic strategy to ameliorate obesity-related complications and enhance overall cardiometabolic well-being in obese males.

Efficacy and Safety of Statin Treatment in Children with Familial Hypercholesterolemia: Outcomes of 20 Years of Experience

Background: The objective of this retrospective cohort study was to present the experience of 20-year-long comprehensive care of pediatric patients with familial hypercholesterolemia (FH) in a single academic center. Methods and Results: The study included 84 children aged 1–18 years with FH. For the whole study group, 535 medical visits were recorded. The mean follow-up period was 33.6 months. Molecular testing performed in 55 children (65%) provided genetic confirmation of the diagnosis in 36 children (43%). Twenty-seven children (32%) were treated pharmacologically with statins. Follow-up during the treatment averaged 29 months. Treatment with statins was associated with a mean reduction in total cholesterol and LDL-cholesterol levels of 24 and 33% from the baseline. Symptoms of statin intolerance occurred incidentally and did not require amendment in the treatment protocol. Significantly higher values of body weight, height, and BMI were found only among girls older than 10 years who were treated with statins. Conclusions: These data confirm a high efficacy and a good safety profile of statin treatment in children with FH, demonstrating no harm to physical development. However, there is a need for further cause-and-effect research regarding associations between long-term treatment with low-cholesterol, low-fat diets, statin therapy, and excessive weight gain.

RBD5044 - a novel anti-ApoC3 GalNAc-siRNA drug resulted in sustained and profound reduction of triglycerides in mice and Rhesus monkeys

Abstract Introduction Hypertriglyceridemia leads to endothelial dysfunction and contributes to the onset and progression of atherosclerosis as well as an increased risk of acute pancreatitis. Inhibition of Apolipoprotein-CIII (APOC3) via the RNA interference mechanism is supposed to reduce plasma Triglycerides (TG) levels with durable and high efficacy. RBD5044, which targets APOC3 mRNA in the liver, is a chemically-modified double-stranded small interfering RNA (siRNA) conjugated with N-acetylgalactosamine (Ribo-GalSTAR). Purpose To investigate the preclinical efficacy and safety profile of RBD5044. Methods Rhesus monkeys with spontaneously developed hypertriglyceridemia were given a single subcutaneous (sc) injection of RBD5044. Humanized APOC3 transgenic mice were treated with a single dose or repeated doses (once every two weeks for three doses, Q2W×3) of RBD5044. Plasma was collected to quantify APOC3 and lipid biomarkers to evaluate preclinical efficacy of RBD5044. SD rats and cynomolgus monkeys were used to evaluate the preclinical toxicology for subcutaneously injected RBD5044, including single-dose toxicity studies and 4-week repeat-dose pivotal toxicology studies. Results In the rhesus monkeys with spontaneous hypertriglyceridemia, the maximum level of inhibition reached 61.2 % in APOC3 and resulted in a TG reduction by 53.3%. The levels of both APOC3 and TG were recovered to baseline till Day 85 after a single dose of 3 mg/kg RBD5044. In humanized APOC3 transgenic mice, RBD5044 achieved an average maximum inhibition level of over 90% for APOC3 and around 90% for TG after both single and repeated doses. The APOC3 and TG levels were recovered on Day 63 after a single dose of 3 mg/kg. On Day 63 after the last repeated dose at 3 mg/kg, the inhibition level remained at 41.6% for APOC3 and 49.4% for TG, hence did not recover to baseline within the study period. RBD5044 also showed reductions in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and elevations in high-density lipoprotein cholesterol (HDL-C) levels. Toxicology studies showed there is a sufficient therapeutic margin that supports the clinical development of RBD5044 with NOAEL of 40 mg/kg in rats and 300 mg/kg in monkeys. Conclusions RBD5044 shows high efficacy, long duration and a good safety profile in preclinical studies. The Phase I trial of RBD5044 injection in healthy volunteers has been initiated in Australia.Figure 1Figure 2

Abstract 13950: Real-World Effectiveness and Safety of Evinacumab in Pediatric and Adult Patients With Homozygous Familial Hypercholesterolemia: A Multi-Site US Perspective

Introduction: Homozygous familial hypercholesterolemia (HoFH) is an autosomal co-dominant disorder characterized by extreme elevations in LDL-C and early onset ASCVD. Unfortunately, patients with HoFH generally experience poor LDL-C lowering with standard lipid-lowering therapy and rarely achieve LDL-C goals. Evinacumab is a monoclonal antibody administered by monthly IV infusion that binds angiopoietin-like 3 and when added to standard lipid-lowering therapies lowers LDL-C by ~50% in clinical trials involving patients with HoFH. Real-world effectiveness and safety of evinacumab is unknown. Methods: We performed retrospective chart review to assess effectiveness and safety of evinacumab in patients with HoFH in clinical practice at six US academic medical centers. The primary efficacy endpoint was the percent change in LDL-C from baseline to first follow-up and to most recent follow-up after evinacumab initiation. Secondary efficacy endpoints were percent change in non-HDL-C, triglycerides, total cholesterol, HDL-C, and achievement of an LDL-C &lt;70 mg/dL. Adverse events were recorded. Results: Twenty-four patients (mean age 38 yrs; range 5-75) with HoFH were followed for a median of 63 weeks. Fifty percent were female, 66.7% had ASCVD, 87.5% were on a statin, 83.3% on ezetimibe, 66.7% on a PCSK9i, 24% on lomitapide, and 33.3% were undergoing lipoprotein apheresis. Significant reductions in LDL-C, non-HDL-C, total cholesterol, triglycerides, and HDL-C were observed both at first follow-up (4 weeks) and most recent follow-up (63 weeks) (p &lt; 0.001 for all) (Table). Significantly more patients achieved LDL-C &lt;70 mg/dL after evinacumab was added. No serious adverse events occurred and evinacumab was generally well-tolerated. Conclusions: Across six US academic medical centers, evinacumab was generally well-tolerated by patients with HoFH and lowered LDL-C by ~50%, consistent with results from clinical trials.

Abstract 14088: Impact of Social Determinants of Health on Blood Pressure and Cholesterol Control in a Smartphone-Based Cardiovascular Risk Self-Management Program

Background: Social determinants of health (SDOH) are environmental factors that have an impact on one's health, outcome, and quality of life. SDOH like language, income, healthcare access, race/ethnicity, and neighborhood characteristics can manifest in inequalities in cardiovascular disease (CVD) and its risk factor burden, resulting in inequitable CVD related morbidity and mortality. Limited data are available on effects of SDOH on CVD risk factor control among users of digital health technology. Aim: To study the impact of SDOH like primary language, household income, access to healthcare and urban/rural residential type on blood pressure (BP) and total cholesterol (TC) control in participants of a smartphone-based cardiovascular risk self-management program with AI-based digital coaching. Methods: Participants’ data were matched with Agency for Healthcare Research and Quality’s 2020 SDOH database by ZIP code. Changes in systolic BP (SBP), diastolic BP (DBP) and TC were evaluated from baseline to 6 months follow up. The SDOH variables- primary language, median household income, distance to healthcare facility and urban/rural residential type - were used to predict changes in BP and TC via regression models adjusted for age, gender, and baseline BP/TC. Results: In 27,553 participants (age 55 ± 0.1 y, 48.5% women), overall reduction in BP and TC were observed (p&lt;0.001). Of those with baseline stage 2 hypertension, 80.5% reduced SBP at follow up, and 82.9% of those with baseline high TC (≥240 mg/dL) reduced TC at follow up. Median household income was associated with change in SBP (β -1.6E-5, p &lt; 0.001) and DBP (β -4.8E-6, p &lt; 0.001), but not TC. This association was not clinically significant as each $62,535 increase in the median household income was associated with an additional 1 mm Hg in BP reduction. No difference in BP or TC change was found based on primary language, distance to healthcare facility, and urban/rural residential type (p &gt; 0.05). Conclusion: In a smartphone-based cardiovascular risk self-management program, the majority (&gt;80%) of high-risk participants reduce BP and TC across various SDOH factors. These results highlight the potential use of this technology to bridge health inequity gaps in prevention and control of CVD risk.