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Nutrients Jun 2024Bile acids help facilitate intestinal lipid absorption and have endocrine activity in glucose, lipid and bone metabolism. Obesity and exercise influence bile acid...
Bile acids help facilitate intestinal lipid absorption and have endocrine activity in glucose, lipid and bone metabolism. Obesity and exercise influence bile acid metabolism and have opposite effects in bone. This study investigates if regular exercise helps mitigate the adverse effects of obesity on bone, potentially by reversing alterations in bile acid metabolism. Four-month-old female Sprague Dawley rats either received a high-fat diet (HFD) or a chow-based standard diet (lean controls). During the 10-month study period, half of the animals performed 30 min of running at moderate speed on five consecutive days followed by two days of rest. The other half was kept inactive (inactive controls). At the study's end, bone quality was assessed by microcomputed tomography and biomechanical testing. Bile acids were measured in serum and stool. HFD feeding was related to reduced trabecular (-33%, = 1.14 × 10) and cortical (-21%, = 2.9 × 10) bone mass and lowered femoral stiffness (12-41%, = 0.005). Furthermore, the HFD decreased total bile acids in serum (-37%, = 1.0 × 10) but increased bile acids in stool (+2-fold, = 7.3 × 10). These quantitative effects were accompanied by changes in the relative abundance of individual bile acids. The concentration of serum bile acids correlated positively with all cortical bone parameters (r = 0.593-0.708), whilst stool levels showed inverse correlations at the cortical (r = -0.651--0.805) and trabecular level (r = -0.656--0.750). Exercise improved some trabecular and cortical bone quality parameters (+11-31%, = 0.043 to 0.001) in lean controls but failed to revert the bone loss related to the HFD. Similarly, changes in bile acid metabolism were not mitigated by exercise. Prolonged HFD consumption induced quantitative and qualitative alterations in bile acid metabolism, accompanied by bone loss. Tight correlations between bile acids and structural indices of bone quality support further functional analyses on the potential role of bile acids in bone metabolism. Regular moderate exercise improved trabecular and cortical bone quality in lean controls but failed in mitigating the effects related to the HFD in bone and bile acid metabolism.
Topics: Animals; Bile Acids and Salts; Female; Rats, Sprague-Dawley; Diet, High-Fat; Physical Conditioning, Animal; Rats; Bone and Bones; Bone Density; X-Ray Microtomography; Feces; Obesity
PubMed: 38892677
DOI: 10.3390/nu16111744 -
Nutrients May 2024(1) Background: The effect of garlic on glucose and lipid metabolism in humans remains controversial. The aim of this study was to investigate the effects of garlic on... (Meta-Analysis)
Meta-Analysis Review
(1) Background: The effect of garlic on glucose and lipid metabolism in humans remains controversial. The aim of this study was to investigate the effects of garlic on blood lipid levels and glucose levels in humans through a systematic review and meta-analysis. (2) Methods: We extensively searched four databases, including PubMed, Web of Science, Embase, and the Cochrane Library, up to February 2024. To assess the collective impact of garlic and its supplements on fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), an analysis was conducted using a random effects model. Subgroup analyses were performed when < 50%. (3) Result: We found that the garlic intervention was effective in controlling FBG (mean difference = -7.01; 95% CI: -8.53, -5.49, < 0.001), HbA1c (mean deviation = -0.66; 95% CI: -0.76, -0.55, < 0.001, = 62.9%), TC (mean difference = -14.17; 95% CI: -19.31, -9.03, < 0.001), and LDL-C (mean difference = -8.20; 95% CI: -15.58, -0.81, = 0.03); moreover, it also increased the level of HDL-C in humans (mean difference = 2.06; 95% CI: 1.54, 2.59; < 0.001). Nonetheless, the intervention involving garlic did not yield a substantial impact on triglyceride (TG) levels. (4) Conclusion: The intervention of garlic is beneficial to control blood glucose and blood lipids in humans.
Topics: Garlic; Humans; Blood Glucose; Randomized Controlled Trials as Topic; Lipids; Glycated Hemoglobin; Dietary Supplements; Triglycerides; Female; Male; Cholesterol, HDL; Middle Aged; Adult
PubMed: 38892625
DOI: 10.3390/nu16111692 -
Nutrients May 2024Vitamin D is a crucial micronutrient, critical to human health, and influences many physiological processes. Oral and skin-derived vitamin D is hydroxylated to form... (Review)
Review
Vitamin D is a crucial micronutrient, critical to human health, and influences many physiological processes. Oral and skin-derived vitamin D is hydroxylated to form calcifediol (25(OH)D) in the liver, then to 1,25(OH)D (calcitriol) in the kidney. Alongside the parathyroid hormone, calcitriol regulates neuro-musculoskeletal activities by tightly controlling blood-ionized calcium concentrations through intestinal calcium absorption, renal tubular reabsorption, and skeletal mineralization. Beyond its classical roles, evidence underscores the impact of vitamin D on the prevention and reduction of the severity of diverse conditions such as cardiovascular and metabolic diseases, autoimmune disorders, infection, and cancer. Peripheral target cells, like immune cells, obtain vitamin D and 25(OH)D through concentration-dependent diffusion from the circulation. Calcitriol is synthesized intracellularly in these cells from these precursors, which is crucial for their protective physiological actions. Its deficiency exacerbates inflammation, oxidative stress, and increased susceptibility to metabolic disorders and infections; deficiency also causes premature deaths. Thus, maintaining optimal serum levels above 40 ng/mL is vital for health and disease prevention. However, achieving it requires several times more than the government's recommended vitamin D doses. Despite extensive published research, recommended daily intake and therapeutic serum 25(OH)D concentrations have lagged and are outdated, preventing people from benefiting. Evidence suggests that maintaining the 25(OH)D concentrations above 40 ng/mL with a range of 40-80 ng/mL in the population is optimal for disease prevention and reducing morbidities and mortality without adverse effects. The recommendation for individuals is to maintain serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) for optimal clinical outcomes. Insights from metabolomics, transcriptomics, and epigenetics offer promise for better clinical outcomes from vitamin D sufficiency. Given its broader positive impact on human health with minimal cost and little adverse effects, proactively integrating vitamin D assessment and supplementation into clinical practice promises significant benefits, including reduced healthcare costs. This review synthesized recent novel findings related to the physiology of vitamin D that have significant implications for disease prevention.
Topics: Humans; Vitamin D; Vitamin D Deficiency; Dietary Supplements; Cardiovascular Diseases
PubMed: 38892599
DOI: 10.3390/nu16111666 -
Nutrients May 2024We previously demonstrated that diet supplementation with seaweed () prevented AD-related pathology in a mouse model of Alzheimer's Disease (AD). Here, we tested a...
We previously demonstrated that diet supplementation with seaweed () prevented AD-related pathology in a mouse model of Alzheimer's Disease (AD). Here, we tested a lipid extract of seaweed () and a supercritical fluid (SCF) extract of that is free of excess inorganic arsenic. Diet supplementation with extract prevented cognitive deterioration in APPswePS1ΔE9 mice. Similar trends were observed for the SCF extract. The cerebral amyloid-β plaque load remained unaffected. However, IHC analysis revealed that both extracts lowered glial markers in the brains of APPswePS1ΔE9 mice. While cerebellar cholesterol concentrations remained unaffected, both extracts increased desmosterol, an endogenous LXR agonist with anti-inflammatory properties. Both extracts increased cholesterol efflux, and particularly, extract decreased the production of pro-inflammatory cytokines in LPS-stimulated THP-1-derived macrophages. Additionally, our findings suggest a reduction of AD-associated phosphorylated tau and promotion of early oligodendrocyte differentiation by . RNA sequencing on the hippocampus of one-week-treated APPswePS1ΔE9 mice revealed effects of on, amongst others, acetylcholine and synaptogenesis signaling pathways. In conclusion, extracts of and show potential to reduce AD-related pathology in APPswePS1ΔE9 mice. Increasing desmosterol concentrations may contribute to these effects by dampening neuroinflammation.
Topics: Animals; Alzheimer Disease; Disease Models, Animal; Dietary Supplements; Seaweed; Mice; Hippocampus; Plant Extracts; Mice, Transgenic; Sargassum; Humans; Plaque, Amyloid; Cholesterol; Male; Amyloid beta-Protein Precursor; tau Proteins
PubMed: 38892548
DOI: 10.3390/nu16111614 -
Nutrients May 2024Recent studies hypothesized that vitamin D supplementation and subsequent higher 25(OH)D serum levels could protect against respiratory infections in children. This...
Recent studies hypothesized that vitamin D supplementation and subsequent higher 25(OH)D serum levels could protect against respiratory infections in children. This cross-sectional study, conducted from May 2022 to December 2023 in Timisoara, Romania, aimed to evaluate the potential influence of vitamin D supplementation on the incidence of respiratory infections among preschool-age children. This study examined 215 children over 18 months who were split into a group of patients with recurrent respiratory infections ( = 141) and another group of patients with only one respiratory tract infection in the past 12 months ( = 74). Patients were evaluated based on their serum vitamin D levels 25(OH)D, demographic characteristics, and health outcomes. The study identified that preschool-age children with recurrent infections had significantly lower mean vitamin D concentrations (24.5 ng/mL) compared to the control group (29.7 ng/mL, < 0.001). Additionally, a higher proportion of vitamin D deficiency was observed among children with recurrent infections in the past 12 months. Notably, vitamin D supplementation above 600 IU/week significantly reduced the likelihood of respiratory infections, evidenced by an odds ratio of 0.523 ( < 0.001), indicating that preschool-age children receiving a dose of vitamin D higher than 600 IU/week were about half as likely to experience respiratory infections compared to those who did not. Furthermore, no significant associations were found between sun exposure, daily sunscreen use, and the incidence of respiratory infections. Conclusively, this study underscores the potential role of vitamin D in helping the immune system against respiratory infections in preschool-age children. The observed protective effect of vitamin D supplementation suggests a potential public health strategy to mitigate the incidence of respiratory infections in preschool children on top of the already known benefits.
Topics: Humans; Respiratory Tract Infections; Child, Preschool; Vitamin D; Cross-Sectional Studies; Male; Female; Vitamin D Deficiency; Dietary Supplements; Incidence; Romania; Infant; Recurrence
PubMed: 38892528
DOI: 10.3390/nu16111595 -
Nutrients May 2024The aim of this study was to assess whether dietary supplementation with a nutraceutical blend comprising extracts of bergamot and artichoke-both standardized in their... (Randomized Controlled Trial)
Randomized Controlled Trial
A Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Effect of a Dietary Supplement Containing Dry Artichoke and Bergamot Extracts on Metabolic and Vascular Risk Factors in Individuals with Suboptimal Cholesterol Levels.
The aim of this study was to assess whether dietary supplementation with a nutraceutical blend comprising extracts of bergamot and artichoke-both standardized in their characteristic polyphenolic fractions-could positively affect serum lipid concentration and insulin sensitivity, high-sensitivity C-reactive protein (hs-CRP), and indexes of non-alcoholic fatty liver disease (NAFLD) in 90 healthy individuals with suboptimal cholesterol levels. Participants were randomly allocated to treatment with a pill of either active treatment or placebo. After 6 weeks, the active-treated group experienced significant improvements in levels of triglycerides (TG), apolipoprotein B-100 (Apo B-100), and apolipoprotein AI (Apo AI) versus baseline. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (Non-HDL-C), and hs-CRP also significantly decreased in the active-treated group compared to both baseline and placebo. At the 12-week follow-up, individuals allocated to the combined nutraceutical experienced a significant improvement in TC, LDL-C, Non-HDL-C, TG, Apo B-100, Apo AI, glucose, alanine transaminase (ALT), gamma-glutamyl transferase (gGT), hs-CRP, several indexes of NAFLD, and brachial pulse volume (PV) in comparison with baseline. Improvements in TC, LDL-C, Non-HDL-C, TG, fatty liver index (FLI), hs-CRP, and endothelial reactivity were also detected compared to placebo ( < 0.05 for all). Overall, these findings support the use of the tested dietary supplement containing dry extracts of bergamot and artichoke as a safe and effective approach for the prevention and management of a broad spectrum of cardiometabolic disorders.
Topics: Humans; Cynara scolymus; Dietary Supplements; Male; Female; Double-Blind Method; Plant Extracts; Middle Aged; Adult; Non-alcoholic Fatty Liver Disease; Cholesterol; C-Reactive Protein; Insulin Resistance; Triglycerides
PubMed: 38892519
DOI: 10.3390/nu16111587 -
Nutrients May 2024The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D formulations (softgels) in healthy adults, at single daily doses of... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D 1000 IU (STD1000), (2) micellar Vitamin D 1000 IU (LMD1000), (3) standard Vitamin D 2500 IU (STD2500), and (4) micellar Vitamin D 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5-60): 992 ± 260 vs. 177 ± 140 nmol day/L; < 0.05, suggesting up to 6 times higher Vitamin D absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D concentrations than the STD1000 group (iAUC(30-60): 680 ± 190 vs. 104 ± 91 nmol day/L; < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D (LipoMicel), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.
Topics: Humans; Pilot Projects; Cholecalciferol; Male; Female; Double-Blind Method; Adult; Dietary Supplements; Micelles; Biological Availability; Administration, Oral; Middle Aged; Young Adult; Calcifediol; Vitamin D
PubMed: 38892507
DOI: 10.3390/nu16111573 -
Nutrients May 2024Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized...
Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5'-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40-75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo ( < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, < 0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, < 0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.
Topics: Humans; Middle Aged; Homocysteine; Female; Male; Dietary Supplements; Methylenetetrahydrofolate Reductase (NADPH2); Double-Blind Method; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Cholesterol, LDL; Aged; Vitamin B 12; Pyridoxal Phosphate; Adult; Ferredoxin-NADP Reductase; Tetrahydrofolates; Polymorphism, Genetic; Vitamin B Complex
PubMed: 38892484
DOI: 10.3390/nu16111550 -
International Journal of Molecular... May 2024The diterpene cafestol represents the most potent cholesterol-elevating compound known in the human diet, being responsible for more than 80% of the effect of coffee on...
The diterpene cafestol represents the most potent cholesterol-elevating compound known in the human diet, being responsible for more than 80% of the effect of coffee on serum lipids, with a mechanism still not fully clarified. In the present study, the interaction of cafestol and 16--methylcafestol with the stabilized ligand-binding domain (LBD) of the Farnesoid X Receptor was evaluated by fluorescence and circular dichroism. Fluorescence quenching was observed with both cafestol and 16--methylcafestol due to an interaction occurring in the close environment of the tryptophan W454 residue of the protein, as confirmed by docking and molecular dynamics. A conformational change of the protein was also observed by circular dichroism, particularly for cafestol. These results provide evidence at the molecular level of the interactions of FXR with the coffee diterpenes, confirming that cafestol can act as an agonist of FXR, causing an enhancement of the cholesterol level in blood serum.
Topics: Diterpenes; Receptors, Cytoplasmic and Nuclear; Cholesterol; Humans; Coffee; Molecular Docking Simulation; Protein Binding; Molecular Dynamics Simulation; Circular Dichroism
PubMed: 38892285
DOI: 10.3390/ijms25116096 -
International Journal of Molecular... May 2024Anxiety is a common comorbidity of obesity, resulting from prescribing long-term caloric restriction diets (CRDs); patients with a reduced food intake lose weight but...
Anxiety is a common comorbidity of obesity, resulting from prescribing long-term caloric restriction diets (CRDs); patients with a reduced food intake lose weight but present anxious behaviors, poor treatment adherence, and weight regain in the subsequent 5 years. Intermittent fasting (IF) restricts feeding time to 8 h during the activity phase, reducing patients' weight even with no caloric restriction; it is unknown whether an IF regime with ad libitum feeding avoids stress and anxiety development. We compared the corticosterone blood concentration between male Wistar rats fed ad libitum or calorie-restricted with all-day or IF food access after 4 weeks, along with their anxiety parameters when performing the elevated plus maze (EPM). As the amygdalar thyrotropin-releasing hormone (TRH) is believed to have anxiolytic properties, we evaluated its expression changes in association with anxiety levels. The groups formed were the following: a control which was offered food ad libitum (C-adlib) or 30% of C-adlib's energy requirements (C-CRD) all day, and IF groups provided food ad libitum (IF-adlib) or 30% of C-adlib's requirements (IF-CRD) with access from 9:00 to 17:00 h. On day 28, the rats performed the EPM and, after 30 min, were decapitated to analyze their amygdalar TRH mRNA expression by in situ hybridization and corticosterone serum levels. Interestingly, circadian feeding synchronization reduced the body weight, food intake, and animal anxiety levels in both IF groups, with ad libitum (IF-adlib) or restricted (IF-CRD) food access. The anxiety levels of the experimental groups resulted to be negatively associated with TRH expression, which supported its anxiolytic role. Therefore, the low anxiety levels induced by synchronizing feeding with the activity phase would help patients who are dieting to improve their diet therapy adherence.
Topics: Animals; Anxiety; Rats; Male; Amygdala; Thyrotropin-Releasing Hormone; Rats, Wistar; Caloric Restriction; Circadian Rhythm; Corticosterone; Down-Regulation; Feeding Behavior; Fasting; Eating; Body Weight
PubMed: 38892044
DOI: 10.3390/ijms25115857