Functionalized solid lipid nanoparticles combining docetaxel and erlotinib synergize the anticancer efficacy against triple-negative breast cancer.

The goal of the study was to fabricate folic acid functionalized docetaxel (DOC)/erlotinib (ERL)-loaded solid lipid nanoparticles (SLNs) to synergistically increase the anticancer activity against triple-negative breast cancer. DOC/ERL-SLNs were prepared by the high shear homogenization - ultrasound dispersion method (0.1 % w/v for DOC, and 0.3 %w/v for ERL) and optimized using Plackett Burman Design (PBD) followed by Box Behnken Design (BBD). The optimized SLNs demonstrated particle size < 200 nm, PDI < 0.35, and negative zeta potential with entrapment and loading efficiency of ∼80 and ∼4 %, respectively. The SLNs and folic acid functionalized SLNs (FA-SLNs) showed sustained release for both drugs, followed by Higuchi and Korsemeyer-Peppas drug release models, respectively. Further, the in vitro pH-stat lipolysis model demonstrated an approximately 3-fold increase in the bioaccessibility of drugs from SLNs compared to suspension. The TEM images revealed the spherical morphology of the SLNs. DOC/ERL loaded SLNs showed dose- and time-dependent cytotoxicity and exhibited a synergism at a molar ratio of 1:3 in TNBC with a combination index of 0.35 and 0.37, respectively. FA-DOC/ERL-SLNs showed enhanced anticancer activity as evidenced by MMP and ROS assay and further inhibited the colony-forming ability and the migration capacity of TNBC cells. Conclusively, the study has shown that SLNs are encouraging systems to improve the pharmaceutical attributes of poorly bioavailable drugs.

Folic acid and autism: updated evidences.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that impairs communication, socialization, and behavior. The association of ASD with folic acid has been investigated due to the importance of this vitamin for neurological health. This study is an update of the publication 'Folic acid and autism: What do we know?' and aims to systematically review studies examining the relationship between folic acid and ASD. The search resulted in 2,389 studies on folic acid and ASD, which were selected by two reviewers based on their titles and abstracts. Studies meeting the inclusion criteria were fully read. The 52 included studies involved 10,429 individuals diagnosed with ASD and assessed the intake of vitamin B6, folic acid, and vitamin B12; serum levels of these vitamins, homocysteine, and methionine; therapeutic interventions using folic acid; and the association between maternal exposure to this vitamin and the risk of ASD. The evidence of insufficient folic acid intake in most individuals with ASD remains consistent in this update. No association was found between maternal exposure to folic acid and the risk of ASD in their children. Despite observed improvements in communication, socialization, and behavior in individuals with ASD following folic acid interventions, it is crucial to consider the individuality and complexity of ASD. Given the relevance of the topic, there remains a need for more high-quality research and clinical trials characterized by rigorous methodological designs.

Effects of folic acid supplementation on cognitive function and inflammation in elderly patients with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials.

OBJECT: The aim was to assess the effect of folic acid supplementation on cognitive function and inflammatory cytokines in elderly patients with mild cognitive impairment. METHODS: From its inception until February 2024, four databases including Web of Science were searched. Two researchers independently screened the literature, assessed the quality, extracted data, and conducted a meta-analysis using RevMan. RESULTS: The systematic review included seven studies (with a total of 1102 participants, mean age 65-80 years), seven of which were appropriate for meta-analysis. Although a small number of studies found relatively large heterogeneity, the majority of studies showed significant benefit from folic acid supplementation, including the FSIQ (823 individuals, standardized mean difference [SMD] = 8.36, 95 % confidence interval [CI] = 0.79 - 1.08), Arithmetic (823 individuals, SMD = 0.17, 95 % CI = -0.03-0.31), Information, SMD = 1.73, 95 % CI 0.41-3.05), Digit Span (823 individuals, SMD = 0.17, 95 % CI = -0.03 - 0.31), Block Design (823 individuals, SMD = 0.26, 95 % CI 0.03-0.49), Picture Completion (823 individuals, SMD = 0.27, 95 % CI = -0.15 - 0.69) and Picture Arrangement (823 individuals, SMD = -0.12, 95 % CI = -0.26 - 0.01). Finally, folic acid supplementation had a significant effect on the reduction of most inflammatory cytokines, blood biomarkers of Alzheimer's disease, and Hcy. CONCLUSIONS: Folic acid supplementation seems to have a positive impact on cognitive function in older adults with mild cognitive impairment, but further evidence of its effectiveness in improving inflammatory cytokines is needed from high-quality studies.

National and regional population attributable fractions for anemia risk factors (iron, folate, and vitamin B12) in Belize: potential impact of fortification.

Objective: To estimate the national and regional population attributable fraction (PAF) and potential number of preventable anemia cases for three nutritional risk factors (iron, red blood cell folate [RBCF], and vitamin B12 deficiencies) among women of childbearing age in Belize. Methods: A national probability-based household and micronutrient survey capturing sociodemographic and health information was conducted among 937 nonpregnant Belizean women aged 15-49 years. Blood samples were collected to determine hemoglobin, ferritin, alpha-1-glycoprotein (AGP), RBCF, and vitamin B12 status. All analyses used sample weights and design variables to reflect a complex sample survey. Logistic regression was used to determine adjusted prevalence risk (aPR) ratios, which were then used to estimate national and regional PAF for anemia. Results: The overall prevalence of anemia (hemoglobin <12 g/dL) was 21.2% (95% CI [18.7, 25.3]). The prevalence of anemia was significantly greater among women with iron deficiency (59.5%, 95% CI [48.7, 69.5]) compared to women without iron deficiency (15.2%, 95% CI [12.2, 18.3]; aPR 3.9, 95% CI [2.9, 5.1]). The three nutritional deficiencies examined contributed to 34.6% (95% CI [22.1, 47.1]) of the anemia cases. If all these nutritional deficiencies could be eliminated, then an estimated 5 953 (95% CI [3 807, 8 114]) anemia cases could be prevented. Conclusions: This study suggests that among women of child-bearing age in Belize, anemia cases might be reduced by a third if three modifiable nutritional risk factors (iron, RBCF, and vitamin B12 deficiencies) could be eliminated. Fortification is one potential strategy to improve nutritional status and reduce the burden of anemia in this population.

Nanopore sequencing demonstrates the roles of spermatozoal DNA N6-methyladenine in mediating transgenerational lipid metabolism disorder induced by excessive folate consumpton.

Increased consumption of folic acid is prevalent due to its beneficial effects, but growing evidence emphasizes the side effects pointing to excessive dietary folate intake. The effects of excessive paternal folic acid consumption on offspring and its transgenerational inheritance mechanism have not been elucidated. We hypothesize that excessive folic acid consumption will alter sperm DNA N6-methyladenine (6mA) and 5-methylcytosine (5mC) methylation and heritably influence offspring metabolic homeostasis. Here, we fed roosters either folic acid-control or folic acid-excess diet throughout life. Paternal chronic folic acid excessive supplementation increased hepatic lipogenesis and lipid accumulation but reduced lipolysis both in the roosters and their offspring, which was further confirmed to be induced by one-carbon metabolism inhibition and gene expression alteration associated with the Peroxisome proliferator-activated receptor pathway. Based on the spermatozoal genome-wide DNA methylome identified by Nanopore sequencing, multi-omics association analysis of spermatozoal and hepatic DNA methylome, transcriptome, and metabolome suggested that differential spermatozoal DNA 6mA and 5mC methylation could be involved in regulating lipid metabolism-related gene expression in offspring chickens. This model suggests that sperm DNA N6-methyladenine and 5-methylcytosine methylation were involved in epigenetic transmission and that paternal dietary excess folic acid leads to hepatic lipid accumulation in offspring.

Folic acid and S-adenosylmethionine reverse Homocysteine-induced Alzheimer's disease-like pathological changes in rat hippocampus by modulating PS1 and PP2A methylation levels.

BACKGROUND: Abnormally elevated homocysteine (Hcy) is recognized as a biomarker and risk factor for Alzheimer's disease (AD). However, the underlying mechanisms by which Hcy affects AD are still unclear. OBJECTIVES: This study aimed to elucidate the effects and mechanisms by which Hcy affects AD-like pathological changes in the hippocampus through in vivo and in vitro experiments, and to investigate whether folic acid (FA) and S-adenosylmethionine (SAM) supplementation could improve neurodegenerative injuries. METHODS: In vitro experiments hippocampal neurons of rat were treated with Hcy, FA or SAM for 24 h; while the hyperhomocysteinemia (HHcy) in Wistar rats was established by intraperitoneal injection of Hcy, and FA was added to feed. The expression of ß-amyloid (Aß), phosphorylated tau protein, presenilin 1 (PS1) at the protein level and the activity of protein phosphatase 2A (PP2A) were detected, the immunopositive cells for Aß and phosphorylated tau protein in the rat hippocampus were also evaluated by immunohistochemical staining. RESULTS: FA and SAM significantly repressed Hcy-induced AD-like pathological changes in the hippocampus, including the increased tau protein phosphorylation at Ser214, Ser396 and the expression of Aß42. In addition, Hcy-induced PS1 expression increased at the protein level and PP2A activity decreased, while FA and SAM were able to retard that. CONCLUSIONS: The increase in PS1 expression and decrease in PP2A activity may be the mechanisms underlying the Hcy-induced AD-like pathology. FA and SAM significantly repressed the Hcy-induced neurodegenerative injury by modulating PS1 and PP2A methylation levels.

Vitamins B9 and B12 in children with attention deficit hyperactivity disorder (ADHD).

Background: Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder that begins before age 12. Given the role of B group vitamins in cell metabolism, synthesis of nucleotides, and neurotransmitters, the present study systematically investigated the plasma levels of vitamins B9 and B12 in children with ADHD. Methods: We searched electronic databases including Web of Science, MEDLINE, EMBASE, Scopus, Iran MEDEX, Cochran database, and SID from conception to June 2023. Full-text case-control or cross-sectional studies were included in this study. Participants in the case group were children with ADHD aged 6-12 years. Review Manager Software (RevMan 5.4) was used for statistical analyses. Standardized mean differences (SMD) with 95% CIs were used to determine the differences between the two groups. Results: Six studies were included in the present meta-analysis. They included 982 children, of whom, 204 were girls and 744 were boys. The mean age of the children was 8.86±2.03 years. The level of vitamin B9 was significantly different between children with and without ADHD [SMD -0.80, 95% CI (-1.55, -0.04)]. Vitamin B12 was significantly lower in children with ADHD [SMD -0.29, 95% CI (-0.42, -0.16)]. However, due to high heterogeneity (I2 = 93%), sensitivity analysis was used, I2 fell to 21%, and significant difference was observed between the two groups [SMD -0.19, 95% CI (-0.34, -0.04)]. Conclusion: The results of this systematic review showed that the level of vitamins B9 and B12 in children with ADHD was significantly lower than that in healthy children.

Explorative case control study on the associations of serum vitamin D3, folic acid and vitamin B12 levels on Kawasaki disease and coronary artery lesions.

Background: Kawasaki Disease (KD) is a pediatric vasculitic disorder characterized by systemic small vasculitis, notably coronary arteritis, with unclear pathogenesis. This explorative case-control study investigated the association between folic acid (FA), vitamin D3 (VD3), and vitamin B12 (VB12) levels and the different types of Kawasaki Disease, as well as the incidence of coronary artery lesions (CALs). Methods: In this explorative case control study, 365 KD children admitted to our hospital from January 1, 2022 to June 30, 2023 were included as the KD group. Simultaneously, 365 healthy children who received physical examination during the same period were included as the control group. The KD group was divided into typical KD group and incomplete KD group (IKD group), CALs group and non-CALS group, and IVIG sensitive group and IVIG resistant group. The children with CALs were divided into small tumor group, medium tumor group and large tumor group. Serum levels of FA, VB12, and VD3 were compared across all groups. Results: Serum levels of FA and VD3 were significantly decreased in both the KD and CALs groups (p < 0.05), and both factors were identified as independent risk factors for KD and CALs. Similarly, reduced serum VD3 levels were observed in the IKD and IVIG-resistant groups (p < 0.05), with VD3 also being an independent risk factor for both IKD and IVIG resistance. Additionally, lower serum FA levels were noted in the group with large aneurysms (p < 0.05), establishing FA as an independent risk factor for aneurysm size. Conclusion: Serum levels of folic FA and vitamin VD3 were significantly reduced in children with KD. Furthermore, these reductions were more pronounced in children with IKD and CALs. This pattern suggests that lower FA and VD3 levels may increase the risk of more severe coronary lesions in KD patients. Therefore, monitoring these biomarkers could provide valuable insights for early clinical diagnosis and intervention.

Linking the relationship between dietary folic acid intake and risk of osteoporosis among middle-aged and older people: A nationwide population-based study.

Among middle-aged and older people, balanced and nutritious diets are the foundation for maintaining bone health and preventing osteoporosis. This study is aimed at investigating the link between dietary folic acid intake and the risk of osteoporosis among middle-aged and older people. A total of 20,686 people from the National Health and Nutritional Examination Survey (NHANES) 2007-2010 are screened and included, and 5312 people aged ≥45 years with integral data are ultimately enrolled in evaluation. Demographics and dietary intake-related data are gathered and analyzed, and the odds ratio (OR) and 95% confidence interval (CI) of each tertile category of dietary folic acid intake and each unit increase in folic acid are assessed via multivariate logistic regression models. On this basis, the receiver operating characteristic (ROC) curve is used to identify the optimal cutoff value of dietary folic acid intake for indicating the risk of osteoporosis. Of 5312 people with a mean age of 62.4 ± 11.0 years old, a total of 513 people with osteoporosis are screened, and the dietary folic acid intake amount of the osteoporosis group is significantly lower than that of the non-osteoporosis group (p < .001). The lowest tertile category is then used to act as a reference category, and a higher dietary folic acid intake amount is observed to be positively related to lower odds for risk of osteoporosis. This trend is also not changed in adjustments for combinations of different covariates (p all < .05). Based on this, a dietary folic acid intake of 475.5 µg/day is identified as an optimal cutoff value for revealing osteoporosis. Collectively, this nationwide population-based study reveals that a higher daily dietary folic acid intake has potential protective effects on osteoporosis in middle-aged and older people.

In vitro biological evaluation of a novel folic acid-targeted receptor quantum dot-ß-cyclodextrin carrier for C-2028 unsymmetrical bisacridine in the treatment of human lung and prostate cancers.

BACKGROUND: Traditional small-molecule chemotherapeutics usually do not distinguish tumors from healthy tissues. However, nanotechnology creates nanocarriers that selectively deliver drugs to their site of action. This work is the next step in the development of the quantum dot-ß-cyclodextrin-folic acid (QD-ß-CD-FA) platform for targeted and selected delivery of C-2028 unsymmetrical bisacridine in cancer therapy. METHODS: Herein, we report an initial biological evaluation (using flow cytometry and light microscopy) as well as cell migration analysis of QD-ß-CD(C-2028)-FA nanoconjugate and its components in the selected human lung and prostate cancer cells, as well as against their respective normal cells. RESULTS: C-2028 compound induced apoptosis, which was much stronger in cancer cells compared to normal cells. Conjugation of C-2028 with QDgreen increased cellular senescence, while the introduction of FA to the conjugate significantly decreased this process. C-2028 nanoencapsulation also reduced cell migration. Importantly, QDgreen and QDgreen-ß-CD-FA themselves did not induce any toxic responses in studied cells. CONCLUSIONS: In conclusion, the results demonstrate the high potential of a novel folic acid-targeted receptor quantum dot-ß-cyclodextrin carrier (QDgreen-ß-CD-FA) for drug delivery in cancer treatment. Nanoplatforms increased the amount of delivered compounds and demonstrated high suitability.

Serum Folate, Red Blood Cell Folate, and Zinc Serum Levels Are Related with Gestational Weight Gain and Offspring's Birth-Weight of Adolescent Mothers.

BACKGROUND: Gestational weight gain below or above the Institute of Medicine recommendations has been associated with adverse perinatal and neonatal outcomes. Very few studies have evaluated the association between serum and red blood cell folate concentrations and gestational weight gain in adolescents. Additionally, zinc deficiency during pregnancy has been associated with impaired immunity, prolonged labor, preterm and post-term birth, intrauterine growth restriction, low birth weight, and pregnancy-induced hypertension. OBJECTIVE: The purpose of our study is to evaluate the association between serum concentrations of zinc, serum folate, and red blood cell folate, with the increase in gestational weight and the weight and length of the newborn in a group of adolescent mothers from Mexico City. RESULTS: In our study, 406 adolescent-neonate dyads participated. The adolescents' median age was 15.8 years old. The predominant socioeconomic level was middle-low (57.8%), single (57%), 89.9% were engaged in home activities, and 41.3% completed secondary education. Excessive gestational weight gain was observed in 36.7% of cases, while insufficient gestational weight gain was noted in 38.4%. Small for gestational age infants were observed in 20.9% of the sample. Low serum folate (OR 2.1, 95% CI 1.3-3.3), decreased red blood cell folate (OR 1.6, 95% CI 1.0-2.6), and reduced serum zinc concentrations (OR 3.3, 95% CI 2.1-5.2) were associated with insufficient gestational weight gain. Decreased serum zinc levels (OR 1.2, 95% CI 1.2-3.4) were linked to an increased probability of delivering a baby who is small for their gestational age. CONCLUSIONS: Low serum folate, red blood cell folate, and serum zinc concentrations were associated with gestational weight gain and having a small gestational age baby. Both excessive and insufficient gestational weight gain, as well as having a small gestational age baby, are frequent among adolescent mothers.

Placenta-Related Parameters at Delivery in Relation to Folic Acid Supplementation in Different Pregnancies.

Folic acid plays an important role in the synthesis, repair, and methylation of deoxyribonucleic acid (DNA). Currently, most studies have focused on the effects of periconceptional folic acid (FA) supplementation on fetal development, and there is still a lack of population-based research exploring the association between FA use during pregnancy and placental development. This study aimed to investigate the impacts of FA supplementation in different pregnancies on placenta-related parameters at delivery. The study included 2708 pregnant women recruited from Ma'anshan City, Anhui Province, China, between May 2013 and September 2014. Information on FA use from one month before conception to delivery was collected. Placental length, width, and thickness were measured. Multivariable logistic regression analysis was used to assess the effects of FA supplementation in different pregnancies on placenta-related parameters. Based on multiple regression analysis, propensity score weighting was adopted to enhance comparability between different FA supplementation groups. Compared with FA non-users, FA supplementation before conception was associated with increased placental width (0.241 cm, 95%CI: 0.052-0.429, p = 0.013) and increased placental surface area (6.398 cm2, 95%CI: 1.407-11.389, p = 0.012), and FA use in early/middle pregnancy was, respectively, related with increased placental thickness (0.061 cm, 95%CI: 0.004-0.117, p = 0.036; 0.066 cm, 95%CI: 0.004-0.129, p = 0.038). FA use before conception could increase placental width and area, and FA use in early/middle pregnancy could increase placental thickness. To confirm the findings, further investigations are needed.

Therapeutic and Diagnostic Potential of Folic Acid Receptors and Glycosylphosphatidylinositol (GPI) Transamidase in Prostate Cancer.

Due to the proliferation-induced high demand of cancer cells for folic acid (FA), significant overexpression of folate receptors 1 (FR1) is detected in most cancers. To our knowledge, a detailed characterization of FR1 expression and regulation regarding therapeutic and diagnostic feasibilities in prostate cancer (PCa) has not been described. In the present study, cell cultures, as well as tissue sections, were analyzed using Western blot, qRT-PCR and immunofluorescence. In addition, we utilized FA-functionalized lipoplexes to characterize the potential of FR1-targeted delivery into PCa cells. Interestingly, we detected a high level of FR1-mRNA in healthy prostate epithelial cells and healthy prostate tissue. However, we were able to show that PCa cells in vitro and PCa tissue showed a massively enhanced FR1 membrane localization where the receptor can finally gain its function. We were able to link these changes to the overexpression of GPI-transamidase (GPI-T) by image analysis. PCa cells in vitro and PCa tissue show the strongest overexpression of GPI-T and thereby induce FR1 membrane localization. Finally, we utilized FA-functionalized lipoplexes to selectively transfer pDNA into PCa cells and demonstrate the therapeutic potential of FR1. Thus, FR1 represents a very promising candidate for targeted therapeutic transfer pathways in PCa and in combination with GPI-T, may provide predictive imaging in addition to established diagnostics.

Family Planning and Preconception Care Service Management: The Key Role of Bulgarian GPs.

Assisting women in attaining their reproductive goals is crucial for improving the well-being of families and children. As the first point of contact for healthcare, general practitioners (GPs) are ideal for family planning (FP) and preconception care (PCC). However, primary care interventions' efficacy is unclear. The aim of this study was to examine GPs' knowledge, attitudes, and perspectives on FP and PCC service management. Most GPs were aware of FP and PCC services and held a firm conviction that they should be primarily accountable together with obstetrician-gynaecologists. However, it is worth noting that less than 50% of respondents reported receiving thorough and comprehensive knowledge of their respective specialities. Those with general medicine qualifications demonstrated a high level of commitment to providing such services. The women's GPs and those with training in general medicine prescribed birth control pills and emergency contraception three times more frequently than the other doctors who suggested condoms or traditional methods or referred patients to another specialist (p < 0.05). In conclusion, PCC is of the utmost importance, and its effective implementation demands the collaboration of policymakers, healthcare providers, and individuals. GPs are essential in managing FP and PCC. They must incorporate more in-depth PCC into their clinical practice.

Development and Characterization of Quercetin-Loaded Polymeric Liposomes with Gelatin-Poly(ethylene glycol)-Folic Acid Coating to Increase Their Long-Circulating and Anticancer Activity.

Liposomes as drug-delivery systems have been researched and applied in multiple scientific reports and introduced as patented products with interesting therapeutic properties. Despite various advantages, this drug carrier faces major difficulties in its innate stability, cancer cell specificity, and control over the release of hydrophobic drugs, particularly quercetin, a naturally derived drug that carries many desirable characteristics for anticancer treatment. To improve the effectiveness of liposomes to deliver quercetin by tackling and mitigating the mentioned hurdles, we developed a strategy to establish the ability to passively target cancerous cells, as well as to increase the bioavailability of loaded drugs by incorporating poly(ethylene glycol), gelatin, and folic acid moieties to modify the liposomal system's surface. This research developed a chemically synthesized gelatin, poly(ethylene glycol), and folic acid as a single polymer to coat drug-loaded liposome systems. Liposomes were coated with gelatin-poly(ethylene glycol)-folic acid by electrostatic interaction, characterized by their size, morphology, ζ potential, drug loading efficiency, infrared structures, differential scanning calorimetry spectra, and drug-releasing profiles, and then evaluated for their cytotoxicity to MCF-7 breast cancer cells, as well as cellular uptake, analyzed by confocal imaging to further elaborate on the in vitro behavior of the coated liposome. The results indicated an unusual change in size with increased coating materials, followed by increased colloidal stability, ζ potential, and improved cytotoxicity to cancer cells, as shown by the cellular viability test with MCF-7. Cellular uptake also confirmed these results, providing data for the effects of biopolymer coating, while confirming that folic acid can increase the uptake of liposome by cancer cells. In consideration of such results, the modified gelatin-poly(ethylene glycol)-folic acid-coated liposome can be a potential system in delivering the assigned anticancer compound. This modified biopolymer showed excellent properties as a coating material and should be considered for further practical applications in the future.

Curcumin loaded ß-cyclodextrin-magnetic graphene oxide nanoparticles decorated with folic acid receptors as a new theranostic agent to improve prostate cancer treatment.

This article presents a novel approach to treating prostate cancer using a nanocarrier composed of folic acid (FA), ß-cyclodextrin (ß-CD), and magnetic graphene oxide (MGO) as a theranostic agent. The carrier is designed to improve the solubility and bioavailability of curcumin, a potential therapeutic substance against prostate cancer. Folic acid receptors overexpressed on the surface of solid tumors, including prostate cancer, may facilitate targeted drug delivery to tumor cells while avoiding nonspecific effects on healthy tissues. The anticancer efficacy of Folic acid-curcumin@ß-CD-MGO in vitro was also examined on LNCaP (an androgen-dependent) and PC3 (an androgen-independent) prostate cancer cells. The relaxivity of nanoparticles in MRI images was also investigated as a diagnostic factor. The results showed a concentration-dependent inhibitory effect on cell proliferation, induction of oxidative damage, and apoptotic effects. Also, nanoparticle relaxometry shows that this agent can be used as a negative contrast agent in MRI images. Overall, this study represents a promising theranostic agent to improve the delivery and trace of curcumin and enhance its therapeutic potential in the treatment of prostate cancer.

Impact of vitamin B12 supplement intake cessation on vitamin B12 status in a healthy vegan: A close interval monitoring case study.

BACKGROUND: Healthy plant-based diets, such as the lacto-ovo-vegetarian and the vegan diet, offer numerous benefits to human health. Poorly designed plant-based diets, however, bear the risk for vitamin- and micronutrient deficiencies. Vitamin B12 (B12, cobalamin) is a nutrient of particular concern in both diets, and should be readily supplemented on a continuous basis to ensure adequate B12 levels and to prevent deficiencies. CASE REPORT: This case reports describes the history of a healthy man in his mid-30s who adopted a vegan diet approximately 10 y ago. Well informed about the risks of vitamin B12 deficiency on a plant-based diet, he regularly supplemented methylcobalamin for years (single oral dose: 500 µg, 3-4 times a week) in order to maintain an adequate vitamin B12 status. In late 2023, however, he decided to cease B12 supplementation for undisclosed reasons. Subsequent to this decision, we closely monitored his B12 status and longitudinally measured serum B12, homocysteine, and holotranscobalamin (holo-TC). Total serum folate was also determined as it is a modifier of homocysteine concentration. A gradual decrease in holo-TC and vitamin B12 levels was observed after 4 weeks and supplements had to be re-introduced after 16 weeks. Homocysteine increased concomitantly up to 18.2 µmol/L after 20 weeks. CONCLUSIONS: While a short-term B12 supplement intake cessation might be well tolerated by vegans with an adequate B12 status, an interruption of more than 8 weeks could signify B12 loss approaching suboptimal status. This case report reiterates the need for continuous B12 supplementation in persons following an unfortified plant-based diet.

Acyloxyacyl Hydrolase Protects against Kidney Injury via Inhibition of Tubular CD74-Macrophage Crosstalk.

Renal fibrosis is the common pathway in the progression of chronic kidney disease (CKD). Acyloxyacyl hydrolase (AOAH) is expressed in various phagocytes and is highly expressed in proximal tubular epithelial cells (PTECs). Research shows that AOAH plays a critical role in infections and chronic inflammatory diseases, although its role in kidney injury is unknown. Here, we found that AOAH deletion led to exacerbated kidney injury and fibrosis after folic acid (FA) administration, which was reversed by overexpression of Aoah in kidneys. ScRNA-seq revealed that Aoah-/- mice exhibited increased subpopulation of CD74+ PTECs, though the percentage of total PTECs were decreased compared to WT mice after FA treatment. Additionally, exacerbated kidney injury and fibrosis seen in Aoah-/- mice was attenuated via administration of methyl ester of (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1), an inhibitor of macrophage inhibition factor (MIF) and CD74 binding. Finally, AOAH expression was found positively correlated with estimated glomerular filtration rate while negatively correlated with the degree of renal fibrosis in kidneys of CKD patients. Thus, our work indicates that AOAH protects against kidney injury and fibrosis by inhibiting renal tubular epithelial cells CD74 signaling pathways. Targeting kidney AOAH represents a promising strategy to prevent renal fibrosis progression.

Folic acid supplementation for stroke prevention: A systematic review and meta-analysis of 21 randomized clinical trials worldwide.

BACKGROUND & AIMS: The AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical trials, and an additional 13 folate trials have been published since then. This meta-analysis aims to fill in critical evidence gaps by comprehensively evaluating 21 published trials with particular attention given to identifying the true influences through stratification. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 4, 2023. This study included all randomized controlled trials (RCTs) of folic acid with stroke as one of the reporting endpoints. Relative risks and 95% confidence intervals were used to assess the association between folic acid supplementation and the risk of stroke in a random-effects model. RESULTS: Results from the 21 pooled RCTs totaling 115,559 participants showed that folic acid supplementation significantly reduced the risk of stroke by 10% (RR 0.90, 95%CI 0.83 to 0.98). Subgroup analyses showed that folic acid efficacy was greater in areas without fortified grain or with partially-fortified grain (RR = 0.83, 95% CI 0.75 to 0.93; RR = 1.04 in areas with grain fortification, P-interaction = 0.003). In this group, folic acid supplementation was most efficacious in those without a history of stroke or myocardial infarction (RR = 0.77, 95% CI 0.68 to 0.86; RR = 0.94 for participants with a history of stroke or myocardial infarction, P-interaction = 0.008). The efficacy of folic acid remained consistent regardless of baseline folate levels, folic acid dosage, baseline vitamin B12 levels, vitamin B12 dosage, homocysteine reduction, intervention duration, and whether folic acid was taken alone or in combination (all P-interaction>0.05). All 21 trials were free of attrition bias and reporting bias, and there was no significant publication bias. CONCLUSIONS: This is by far the largest meta-analysis of RCTs regarding folic acid supplementation and stroke, demonstrating the overall benefit of folic acid for stroke prevention. Grain fortification and history of stroke or myocardial infarction may be the most important influences on the efficacy of folic acid for stroke prevention.

Investigating the relationship between health literacy and preconceptual care components during the first 14 weeks of pregnancy: a cross-sectional study.

BACKGROUND AND AIM: Preconceptual care aiming to improve health is influenced by various factors including health literacy. Considering the importance and necessity of high quality preconceptual care, this study aimed to determine the relationship between health literacy and receiving components of preconceptual care prior to pregnancy. METHODS: This cross-sectional study included 693 participants with pregnancies of less than 14 weeks gestation referred to health centers and gynecologists in Shiraz city, Iran. Multi-stage sampling was done from May 2021 to February 2022 in 18 comprehensive urban health centers and 20 gynecology offices via proportional allocation method. The data collection tool comprised a questionnaire consisting of 3 parts: (1) individual and fertility characteristics, (2) information related to the components of preconceptual care and (3) health literacy for Iranian adults. This was completed by individual participants via the self-reporting method. RESULTS: The majority of participants were between 30 and 34 years old. They also identified as women with a university education and were predominantly unemployed. The mean health literacy of participants was 76.81%. Health literacy obtained the highest mean score in the dimension of 'understanding' and the lowest mean score in the dimension of 'access'. The frequency of preconceptual counseling, folic acid supplement consumption, exercise, blood testing, dental visits, genetic counseling, Pap smear testing and rubella, diphtheria, and hepatitis vaccinations prior to pregnancy was 66.8%, 53.8%, 45.6%, 71.86%, 44.44%, 12%, 53.4%, 10.83%, respectively. Many (> 64%) received preconceptual care at specialist gynecology offices. Results demonstrated that health literacy had a statistically significant relationship with preconceptual care, folic acid consumption, exercise and dental care, (p < 0.001), along with blood testing and Pap smear testing (p < 0.05). CONCLUSION: Overall, our results demonstrate that despite health literacy being optimal, uptakes of some components of preconceptual care are low. As such, it will be important to further raise awareness of the importance of preconceptual care for people prior to pregnancy as a priority in health promotion and education.