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Cellular and Molecular Neurobiology Aug 2023Parkinson's disease (PD) is one of the most common degenerative brain disorders caused by the loss of dopaminergic neurons in the substantia nigra (SN). Lewy bodies and... (Review)
Review
Parkinson's disease (PD) is one of the most common degenerative brain disorders caused by the loss of dopaminergic neurons in the substantia nigra (SN). Lewy bodies and -synuclein accumulation in the SN are hallmarks of the neuropathology of PD. Due to lifestyle changes and prolonged L-dopa administration, patients with PD frequently have vitamin deficiencies, especially folate, vitamin B6, and vitamin B12. These disorders augment circulating levels of Homocysteine with the development of hyperhomocysteinemia, which may contribute to the pathogenesis of PD. Therefore, this review aimed to ascertain if hyperhomocysteinemia may play a part in oxidative and inflammatory signaling pathways that contribute to PD development. Hyperhomocysteinemia is implicated in the pathogenesis of neurodegenerative disorders, including PD. Hyperhomocysteinemia triggers the development and progression of PD by different mechanisms, including oxidative stress, mitochondrial dysfunction, apoptosis, and endothelial dysfunction. Particularly, the progression of PD is linked with high inflammatory changes and systemic inflammatory disorders. Hyperhomocysteinemia induces immune activation and oxidative stress. In turn, activated immune response promotes the development and progression of hyperhomocysteinemia. Therefore, hyperhomocysteinemia-induced immunoinflammatory disorders and abnormal immune response may aggravate abnormal immunoinflammatory in PD, leading to more progression of PD severity. Also, inflammatory signaling pathways like nuclear factor kappa B (NF-κB) and nod-like receptor pyrin 3 (NLRP3) inflammasome and other signaling pathways are intricate in the pathogenesis of PD. In conclusion, hyperhomocysteinemia is involved in the development and progression of PD neuropathology either directly via induction degeneration of dopaminergic neurons or indirectly via activation of inflammatory signaling pathways.
Topics: Humans; Parkinson Disease; Hyperhomocysteinemia; Levodopa; Substantia Nigra; Neurodegenerative Diseases; Dopaminergic Neurons
PubMed: 37074484
DOI: 10.1007/s10571-023-01350-8 -
Diabetology & Metabolic Syndrome Oct 2023The available evidence regarding the association of antioxidants, minerals, and vitamins with the risk of metabolic syndrome (MetS) traits is currently limited and...
BACKGROUND
The available evidence regarding the association of antioxidants, minerals, and vitamins with the risk of metabolic syndrome (MetS) traits is currently limited and inconsistent. Therefore, the purpose of this Mendelian randomization (MR) study was to investigate the potential causal relationship between genetically predicted antioxidants, minerals, and vitamins, and MetS.
METHODS
In this study, we utilized genetic variation as instrumental variable (IV) to capture exposure data related to commonly consumed dietary nutrients, including antioxidants (β-carotene, lycopene, and uric acid), minerals (copper, calcium, iron, magnesium, phosphorus, zinc, and selenium), and vitamins (folate, vitamin A, B6, B12, C, D, E, and K1). The outcomes of interest, namely MetS (n = 291,107), waist circumference (n = 462,166), hypertension (n = 463,010), fasting blood glucose (FBG) (n = 281,416), triglycerides (n = 441,016), and high-density lipoprotein cholesterol (HDL-C) (n = 403,943), were assessed using pooled data obtained from the most comprehensive genome-wide association study (GWAS) available. Finally, we applied the inverse variance weighting method as the result and conducted a sensitivity analysis for further validation.
RESULTS
Genetically predicted higher iron (OR = 1.070, 95% CI 1.037-1.105, P = 2.91E-05) and magnesium levels (OR = 1.130, 95% CI 1.058-1.208, P = 2.80E-04) were positively associated with increased risk of MetS. For each component of MetS, higher level of genetically predicted selenium (OR = 0.971, 95% CI 0.957-0.986, P = 1.09E-04) was negatively correlated with HDL-C levels, while vitamin K1 (OR = 1.023, 95% CI 1.012-1.033, P = 2.90E-05) was positively correlated with HDL-C levels. Moreover, genetically predicted vitamin D (OR = 0.985, 95% CI 0.978-0.992, P = 5.51E-5) had a protective effect on FBG levels. Genetically predicted iron level (OR = 1.043, 95% CI 1.022-1.064, P = 4.33E-05) had a risk effect on TG level.
CONCLUSIONS
Our study provides evidence that genetically predicted some specific, but not all, antioxidants, minerals, and vitamins may be causally related to the development of MetS traits.
PubMed: 37817280
DOI: 10.1186/s13098-023-01174-y -
Nutrients Jul 2023Micronutrition in pregnancy is critical to impact not only fetal growth and development but also long-term physical and psychiatric health outcomes. (Clinical Trial)
Clinical Trial
BACKGROUND
Micronutrition in pregnancy is critical to impact not only fetal growth and development but also long-term physical and psychiatric health outcomes.
OBJECTIVE
Estimate micronutrient intake from food and dietary supplements in a diverse cohort of pregnant women and compare intake to the Dietary Reference Intakes (DRIs).
DESIGN
Secondary analysis of women enrolled in a multi-site clinical trial of docosahexaenoic acid (DHA) supplementation who provided their dietary intake using the diet history questionnaire-II ( = 843) or multiple 24 h recalls ( = 178) at baseline and their intake of nutritional supplements at baseline through 30 days postpartum.
PARTICIPANTS/SETTING
1021 participants from the parent trial who had reliable data for dietary intake, supplement intake, or both.
MAIN OUTCOME MEASURES
Micronutrient intake from dietary and supplement sources and percentage of intakes meeting the DRIs for pregnancy.
STATISTICAL ANALYSES PERFORMED
Percent of participants whose intake was below the estimated average requirement (EAR) or adequate intake (AI) and above the tolerable upper limit (UL).
RESULTS
Dietary intakes of choline, folate, iron, vitamin D, zinc, vitamin E, magnesium, and potassium, were below the AI or EAR for 30-91% of the participants; thiamin and vitamin B6 were also below the AI or EAR for non-Hispanic/Latina women. Supplement intake improved the intake for most; however, 80% of the group remained below the AI for choline and 52.5% for potassium while 30% remained below the EAR for magnesium. Folate and iron intakes were above the UL for 80% and 19%, respectively.
CONCLUSIONS
Dietary supplements, despite their variability, allowed the majority of this cohort of pregnant women to achieve adequate intakes for most micronutrients. Choline, magnesium, and potassium were exceptions. Of interest, folate intake was above the tolerable UL for the majority and iron for 16.8% of the participants. Clinicians have the opportunity to address the most common nutrient deficits and limits with advice on food sources that provide choline, magnesium, and potassium and to ensure folate is not overabundant. More research is needed to determine if these findings are similar in a cross-sectional population.
Topics: Female; Humans; Pregnancy; Choline; Cross-Sectional Studies; Diet; Dietary Supplements; Folic Acid; Iron; Magnesium; Micronutrients; Nutritional Requirements; Potassium; Pregnant Women; Trace Elements
PubMed: 37513643
DOI: 10.3390/nu15143228 -
Nature Communications Nov 2023Mucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear....
Mucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear. Here we report that MAIT cells that recognize their prototypical ligand, the vitamin B2 intermediate 5-OP-RU presented by MR1, reside in human and mouse kidneys. Single cell RNAseq analysis reveals several intrarenal MAIT subsets, and one, carrying the genetic fingerprint of tissue-resident MAIT17 cells, is activated and expanded in a murine model of crescentic glomerulonephritis (cGN). An equivalent subset is also present in kidney biopsies of patients with anti-neutrophil cytoplasmatic antibody (ANCA)-associated cGN. MAIT cell-deficient MR1 mice show aggravated disease, whereas B6-MAIT mice, harboring higher MAIT cell numbers, are protected from cGN. The expanded MAIT17 cells express anti-inflammatory mediators known to suppress cGN, such as CTLA-4, PD-1, and TGF-β. Interactome analysis predicts CXCR6 - CXCL16-mediated cross-talk with renal mononuclear phagocytes, known to drive cGN progression. In line, we find that cGN is aggravated upon CXCL16 blockade. Finally, we present an optimized 5-OP-RU synthesis method which we apply to attenuating cGN in mice. In summary, we propose that CXCR6 MAIT cells might play a protective role in cGN, implicating them as a potential target for anti-inflammatory therapies.
Topics: Humans; Animals; Mice; Mucosal-Associated Invariant T Cells; Myeloid Cells; Kidney Diseases; Anti-Inflammatory Agents; Histocompatibility Antigens Class I
PubMed: 37968302
DOI: 10.1038/s41467-023-43269-0 -
Environment International Dec 2023Vitamin D deficiency (<20 ng/mL circulating levels) is a worldwide public health concern and pregnant women are especially vulnerable, affecting the health of the...
INTRODUCTION
Vitamin D deficiency (<20 ng/mL circulating levels) is a worldwide public health concern and pregnant women are especially vulnerable, affecting the health of the mother and the fetus. This study aims to evaluate the sociodemographic, lifestyle, and environmental determinants associated with circulating vitamin D levels in Spanish pregnant women.
METHODS
We used data from the Spanish INMA ("Infancia y Medio Ambiente") prospective birth cohort study from the regions of Gipuzkoa, Sabadell, and Valencia. 25-hydroxyvitamin D (25(OH)D) was measured in plasma collected in the first trimester of pregnancy. Information on 108 determinants was gathered: 13 sociodemographic, 48 lifestyle including diet, smoking and physical activity, and 47 environmental variables, representing the urban and the chemical exposome. Association of the determinants with maternal 25(OH)D levels was estimated in single- and multiple-exposure models. Machine learning techniques were used to predict 25(OH)D levels below sufficiency (30 ng/mL).
RESULTS
The prevalence of < 30 ng/mL 25(OH)D levels was 51 %. In the single-exposure analysis, older age, higher socioeconomic status, taking vitamin D, B12 and other sup*plementation, and higher humidity, atmospheric pressure and UV rays were associated with higher levels of 25(OH)D (IQR increase of age: 1.2 [95 % CI: 0.6, 1.8] ng/mL 25(OH)D). In the multiple-exposures model, most of these associations remained and others were revealed. Higher body mass index, PM and high deprivation area were associated with lower 25(OH)D levels (i.e., Quartile 4 of PM vs Q1: -3.6 [95 % CI: -5.6, -1.5] ng/mL of 25(OH)D). History of allergy and asthma, being multiparous, intake of vegetable fat, vitamin B6, alcohol consumption and molybdenum were associated with higher levels. The machine learning classification model confirmed some of these associations.
CONCLUSIONS
This comprehensive study shows that younger age, higher body mass index, higher deprived areas, higher air pollution and lower UV rays and humidity are associated with lower 25(OH)D levels.
Topics: Female; Humans; Pregnancy; Infant; Vitamin D; Pregnant Women; Cohort Studies; Prospective Studies; Spain; Vitamins; Vitamin D Deficiency; Parity; Life Style; Particulate Matter
PubMed: 37984291
DOI: 10.1016/j.envint.2023.108293 -
Scientific Reports Jan 2024Evidence from epidemiological literature on the association of circulating micronutrients with risk of nonalcoholic fatty liver disease (NAFLD) is inconsistent. We aimed...
Evidence from epidemiological literature on the association of circulating micronutrients with risk of nonalcoholic fatty liver disease (NAFLD) is inconsistent. We aimed to elucidate the causal relationships using Mendelian randomization (MR). Single-nucleotide polymorphisms associated with 14 circulating micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, B12, C, D, K1 and zinc) were employed as instrumental variables. Summary level data for NAFLD were obtained from a genome-wide association study (GWAS) meta-analysis of 8434 cases and 770,180 controls (discovery stage) and another two datasets including 1483 NAFLD cases and 17,781 controls (replication stage 1) and 2134 NAFLD cases and 33,433 controls (replication stage 2). Inverse variance-weighted method (IVW) was used as primary analysis, supplemented with a series of sensitivity analysis. Genetically predicted higher β‑carotene levels were suggestively associated with reduced NAFLD risk [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66-0.99; P = 0.047], whereas the association did not survive the false discovery rates (FDR) correction (P = 0.164). Genetically predicted circulating iron (OR 1.16, 95% CI 1.05-1.29; P = 0.006, P = 0.028), selenium (OR 1.11, 95% CI 1.03-1.20; P = 0.005, P = 0.028) and vitamin B12 (OR 1.08, 95% CI 1.03-1.13; P = 0.002, P = 0.028) were significantly associated with increased risk of NAFLD. Moreover, the findings were consistent in individual datasets (P > 0.05) and confirmed in sensitivity analysis. Our study provided evidence that circulating iron, selenium and vitamin B12 might be causally linked to the risk of NAFLD, which deserves further exploration of the potential biological mechanism.
Topics: Humans; beta Carotene; Genome-Wide Association Study; Iron; Mendelian Randomization Analysis; Micronutrients; Non-alcoholic Fatty Liver Disease; Selenium; Vitamin B 12
PubMed: 38212362
DOI: 10.1038/s41598-024-51609-3 -
Frontiers in Cardiovascular Medicine 2023Only a few studies that investigated dietary intakes of folate, vitamin B6, and vitamin B12 in relation to cariovascular disease (CVD). This study aimed to assess the...
BACKGROUND
Only a few studies that investigated dietary intakes of folate, vitamin B6, and vitamin B12 in relation to cariovascular disease (CVD). This study aimed to assess the association of dietary folate, vitamin B6, and vitamin B12 with CVD in the United States population.
METHODS
A cross-sectional analysis of 65,322 adults aged ≥ 20 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999-2018. Before 2003, dietary intake data were assessed using a 24-hour dietary call, and two 24-hour dietary calls were used during 2003 and 2018. Odds ratios and 95% confidence intervals (CIs) for CVD associated with dietary folate, vitamin B6, and vitamin B12 were estimated using multivariate logistic regression models.
RESULTS
Dietary vitamin B6 intake were inversely associated with the odds of CVD. In males, the multivariable OR for the highest vs. lowest quartiles of vitamin B6 was 0.77 (95%: 0.61-0.97, = 0.013) for the odds of CVD. In females, the adjusted OR for the highest quartile of vitamin B6 compared with the lowest quartile was 0.73 (95%CI: 0.56-0.95, = 0.038) for the odds of CVD. No significant association was observed between dietary folate and vitamin B12 intakes and the odds of CVD.
CONCLUSIONS
Our findings indicate that higher intake of dietary vitamin B6 may be associated with lower prevalence of CVD, suggesting that dietary vitamin B6 has major public health implications in the prevention of CVD in the United States population.
PubMed: 38034370
DOI: 10.3389/fcvm.2023.1237103 -
Nutrients Dec 2023The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a... (Review)
Review
The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a strong relationship between the recommended daily dose of selected B vitamins and a functional immune system. Regarding specific B vitamins: (1) Riboflavin is necessary for the optimization of reactive oxygen species (ROS) in the fight against bacterial infections caused by and . (2) Niacin administered within normal doses to obese rats can change the phenotype of skeletal fibers, and thereby affect muscle metabolism. This metabolic phenotype induced by niacin treatment is also confirmed by stimulation of the expression of genes involved in the metabolism of free fatty acids (FFAs) and oxidative phosphorylation at this level. (3) Vitamin B5 effects depend primarily on the dose, thus large doses can cause diarrhea or functional disorders of the digestive tract whereas normal levels are effective in wound healing, liver detoxification, and joint health support. (4) High vitamin B6 concentrations (>2000 mg per day) have been shown to exert a significant negative impact on the dorsal root ganglia. Whereas, at doses of approximately 70 ng/mL, sensory symptoms were reported in 80% of cases. (5) Chronic increases in vitamin B12 have been associated with the increased incidence of solid cancers. Additionally, glucuronolactone, whose effects are not well known, represents a controversial compound. (6) Supplementing with D-glucarates, such as glucuronolactone, may help the body's natural defense system function better to inhibit different tumor promoters and carcinogens and their consequences. Cumulatively, the present review aims to evaluate the relationship between the selected B vitamins group, glucuronolactone, and the immune system and their associations to bioavailability, doses, and efficiency.
Topics: Animals; Rats; Vitamin B Complex; Niacin; Biological Availability; Glucuronates; Vitamin A; Vitamin K; Carcinogens
PubMed: 38201854
DOI: 10.3390/nu16010024 -
ACR Open Rheumatology Oct 2023Hypophosphatasia (HPP) is a rare disease characterized by incomplete or defective bone mineralization due to a mutation in the alkaline phosphatase (ALP) gene causing...
OBJECTIVE
Hypophosphatasia (HPP) is a rare disease characterized by incomplete or defective bone mineralization due to a mutation in the alkaline phosphatase (ALP) gene causing low levels of ALP. Disease presentation is heterogeneous and can present as a chronic pain syndrome like fibromyalgia (FM). Our objective was to determine if there are any potential patients with HPP in the group of patients who were diagnosed with FM. Antiresorptive therapy use can trigger atypical femur fractures in patients with HPP.
METHODS
We performed a retrospective chart review of all patients 18 years or older at a single academic center who were diagnosed with FM and had either a low or a normal ALP level. The following characteristics were reviewed: biological sex; age; history of fractures; diagnosis of osteoporosis, osteopenia, osteoarthritis, and chondrocalcinosis; genetic testing; vitamin B6 level testing; and medications.
RESULTS
Six hundred eleven patients with FM were identified. Two hundred had at least one low ALP level, and 57 had at least three consecutively low measurements of ALP, 44% of which had a history of fractures. No patients had vitamin B6 levels checked. None of the patients had previous genetic testing for HPP or underwent testing for zinc or magnesium levels.
CONCLUSION
The percentage of patients with FM who were found to have consistently low ALP levels was 9.3%. None had vitamin B6 level or genetic testing, suggesting that the diagnosis was not suspected. It is important to diagnose HPP given the availability of enzyme replacement therapy to prevent complications from HPP such as fractures. Our data support screening for this condition as a part of the initial workup of FM.
PubMed: 37661663
DOI: 10.1002/acr2.11591 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2023Optimal maternal vitamin status during pregnancy and lactation is essential to support maternal and infant health. For instance, vitamin D is involved in infant bone... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Optimal maternal vitamin status during pregnancy and lactation is essential to support maternal and infant health. For instance, vitamin D is involved in infant bone development, and B-vitamins are involved in various metabolic processes, including energy production. Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on human milk (HM) concentrations of vitamin D and B-vitamins. In addition, we aimed to characterise longitudinal changes in milk concentrations of these vitamins.
METHODS
Both control and intervention supplements contained calcium, iodine, iron, β-carotene, and folic acid, while the intervention also contained zinc, vitamins B, B, B, and D, probiotics, and myo-inositol. HM samples were collected across 4 time points from 1 week to 3 months post-delivery from 158 mothers in Singapore, and 7 time points from 1 week to 12 months from 180 mothers in New Zealand. HM vitamin D was quantified using supercritical fluid chromatography and B-vitamins with mass spectrometry. Potential intervention effects on HM vitamins D, B, B, and B, as well as other B-vitamin (B and B) concentrations were assessed using linear mixed models with a repeated measures design.
RESULTS
Over the first 3 months of lactation, HM 25-hydroxyvitamin D concentrations were 20% (95% CI 8%, 33%, P = 0.001) higher in the intervention group, with more marked effects in New Zealand. There were no observed intervention effects on HM concentrations of vitamins B, B, B, B, and B. In New Zealand mothers, longitudinally, vitamin D concentrations gradually increased from early lactation up to 12 months, while vitamins B and B peaked at 6 weeks, B at 3 weeks, and B and B at 3 months.
CONCLUSIONS
Maternal supplementation during preconception and pregnancy increased HM vitamin D, but not B-vitamin concentrations in lactation. Further studies are required to examine the discrete benefits of vitamin D supplementation starting preconception vs during pregnancy, and to further characterise the effects of supplementation on later offspring health outcomes.
CLINICAL TRIAL REGISTRATION
Registered at ClinicalTrials.gov on the 16 July 2015 (identifier NCT02509988); Universal Trial Number U1111-1171-8056. This study was academic-led by the EpiGen Global Research Consortium.
Topics: Pregnancy; Infant; Female; Humans; Vitamins; Vitamin D; Milk, Human; Dietary Supplements; Cholecalciferol; Lactation; Vitamin A; Double-Blind Method
PubMed: 38411017
DOI: 10.1016/j.clnu.2023.09.009