bims-vitmet 2025-06-08 papers

bims-vitmet

Biomed News

on Vitamin metabolism

Issue of 2025–06–08
nine papers selected by
Onurkan Karabulut, Berkeley City College

Vitamin D and Neurodegenerative Diseases Such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS): A Review of Current Literature.
Prevention of chronic disease using vitamins-a case study of the vitamin D and cardiovascular disease hypothesis using evidence from randomised controlled and prospective cohort studies.
The genetic landscape of CYP24A1 polymorphisms in cancer risk: evidence from a systematic review.
Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysis.
Dietary vitamin K intake associates with reduced all-cause mortality in non-alcoholic fatty liver disease patients.
Vitamin C supplementation mitigates mild cognitive impairment in mice subjected to D-galactose: Insights into intestinal flora and derived SCFAs.
Vitamin D promotes wound healing in aged skin by modulating inflammation, angiogenesis, and EMT via the Hippo pathway.
Inflammatory mischief managed: How retinoic acid calms heart attacks at the (marrow) source.
Folate intake, tissue levels, and colorectal cancer deaths in a national cohort established before folic acid fortification.

Curr Nutr Rep. 2025 Jun 04. 14(1): 77

Vitamin D and Neurodegenerative Diseases Such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS): A Review of Current Literature.

Zehra Savran, Saltuk Bugra Baltaci, Tugce Aladag, Rasim Mogulkoc, Abdulkerim Kasim Baltaci.

   PURPOSE OF REVIEW: This review explores the role of Vitamin D3 and its derivatives as inhibitors of pathological metabolic modifications in neurodegenerative diseases. The manuscript investigates how Vitamin D3 impacts neuronal calcium regulation, antioxidative pathways, immunomodulation, and neuroprotection during detoxification, beyond its known functions in intestinal, bone, and kidney calcium and phosphorus absorption, as well as bone mineralization.
RECENT FINDINGS: Recent studies have highlighted the synthesis of the active metabolite 1,25(OH)2D3 (vitamin D) in glial cells via the hydroxylation process of CY-P24A1, an enzyme in the cytochrome P450 system in the brain. The effects of vitamin D occur through the vitamin D receptor (VDR), a nuclear steroid receptor, which has been identified in various brain regions, including the cerebellum, thalamus, hypothalamus, basal ganglia, hippocampus, olfactory system, temporal, and orbital regions. Neurodegeneration is primarily associated with oxidative stress, protein aggregation, neuroinflammation, mitochondrial dysfunction, apoptosis, and autophagy changes, all of which Vitamin D and VDR are believed to influence. Vitamin D and VDR are recognized as both environmental and genetic factors in the etiopathogenesis of neurodegenerative diseases such as Multiple Sclerosis (MS), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS). A deficiency in Vitamin D is postulated to have detrimental effects on the brain and other diseases throughout various stages of life. This review consolidates findings from clinical and experimental studies, as well as past publications, focusing on the implications of Vitamin D deficiency in these neurodegenerative conditions. Current articles published in PubMed were extensively considered for this review.

Keywords:  Alzheimer’s disease; Amyotrophic lateral sclerosis; Multiple sclerosis; Neurodegenerative diseases; Parkinson’s disease; Vitamin D

DOI:  https://doi.org/10.1007/s13668-025-00663-y
Eur J Nutr. 2025 May 31. 64(5): 199

Prevention of chronic disease using vitamins-a case study of the vitamin D and cardiovascular disease hypothesis using evidence from randomised controlled and prospective cohort studies.

Working Group 1 of the Federation of European Nutrition Societies (FENS) Presidential Activity

   PURPOSE: The hypothesis that vitamin supplementation may prevent cardiovascular disease (CVD) has been supported by compelling mechanistic and observational data. However, most large-scale randomized controlled trials (RCT) of vitamins and CVD are null, leading to the conclusion that vitamins have no role in CVD prevention. Our objective was to examine challenges inherent in single nutrient trials using vitamin D and CVD as a case study.
METHODS: We conducted a systematic scoping review of the literature published since 2011 on vitamin D and CVD, including RCTs, prospective cohort studies (PCS) and systematic reviews from Medline, Web of Science and Cochrane. Studies were conducted in adults and included CVD outcomes with a minimum sample of 500 for RCTs and 10,000 for PCS. We applied Bradford Hill criteria for the establishment of causality in biological systems.
RESULTS: The search yielded 4170 papers, of which 40 were eligible, including 6 RCTs and 7 PCS. The Bradford Hill analysis of a causal relationship between vitamin D and CVD was mixed, with strong mechanistic support and reasonable strength and consistency in observational data but weak evidence of temporality. There was sufficient justification for trialling a benefit for CVD prevention but RCTs were inconsistent with the mechanistic and observational studies and reported mostly null results. Contextual factors were key, including baseline vitamin D status among participants, background supplementation and underlying participant disease profiles.
CONCLUSION: This example illustrates the complexity of conducting nutrient trials and raises questions about RCTs of single nutrients for complex chronic diseases. The core challenge common to all nutrient trials is the absence of a zero-intake placebo group and variable background exposures. Alternative approaches and interpretation paradigms are required.

Keywords:  Bradford hill; Cardiovascular disease; Nutrition science; Randomised controlled trials; Vitamin D; Vitamins

DOI:  https://doi.org/10.1007/s00394-025-03706-w
Discov Oncol. 2025 Jun 04. 16(1): 998

The genetic landscape of CYP24A1 polymorphisms in cancer risk: evidence from a systematic review.

Ssarvinna Haran Manoharan, Vithiya Dewarajan, Sau Har Lee, Yin Sim Tor.

  Cancer remains a significant global health challenge, with a multifaceted etiology that includes genetic factors. Among these, CYP24A1 stands out for its pivotal role in vitamin D metabolism and regulates biological processes influencing cancer risk. Single nucleotide polymorphisms in CYP24A1 are associated with variations in vitamin D bioavailability, potentially impacting the initiation and progression of cancer. To date, no comprehensive review has been conducted on this topic. Therefore, this systematic review aims to investigate the association between common CYP24A1 polymorphisms and cancer susceptibility, by analyzing studies retrieved from PubMed, Scopus, Cochrane Library, and Web of Science databases up to January 2024. Using PRISMA guidelines and quality assessments with the Newcastle Ottawa Scale (NOS), 22 studies, with 28,132 participants (12,751 cases and 15,381 controls) were included. The reported odds ratio and p-value were used to assess the association between CYP24A1 SNPs (rs2296241, rs6068816, rs927650, rs2181874 and rs2585428) with various cancer risks. Key findings revealed that SNP rs2296241 was linked to increased risk of follicular thyroid cancer but lower risks in papillary thyroid cancer, esophageal squamous cell carcinoma, oral cancer, and prostate cancer. SNP rs6068816 correlated with reduced breast and lung cancer risks, while rs927650 and rs2181874 were associated with lower risks in papillary thyroid cancer and prostate cancer, respectively. SNP rs2585428 showed a lower risk in breast and prostate cancers suggesting a protective effect against these malignancies. These results highlight CYP24A1 polymorphisms as potential molecular markers for cancer susceptibility, underscoring their clinical relevance in risk assessment and personalized interventions.

Keywords:  CYP24A1; Cancer; Risk; Single nucleotide polymorphisms; Systematic review

DOI:  https://doi.org/10.1007/s12672-025-02784-w
Res Pract Thromb Haemost. 2025 Mar;9(3): 102847

Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysis.

Anusak Sakwit, Pongpak Pongphitcha, Patcharee Komvilaisak, Masayuki Ochiai, Daijiro Takahashi, Shutaro Suga, Ampaiwan Chuansumrit, Marisol Betensky, Stephen P Pereira, Amber Afzal, C Heleen van Ommen, Neil Goldenberg, Sasivimol Rattanasiri, Nongnuch Sirachainan.

  Vitamin K deficiency (VKD) in cholestatic liver disease affects up to 23% of pediatric patients. While several vitamin K (VK) prophylaxis regimens have been proposed, optimal therapeutic strategies remain undefined. The study aimed to identify the most effective VK prophylaxis for children with cholestatic liver disease. We conducted a systematic review of articles focusing on studies of children aged <18 years with cholestatic liver disease who reported outcomes of either VKD or vitamin K deficiency bleeding (VKDB) after VK prophylaxis. The articles were sourced from PubMed, Scopus, and Embase. A meta-analysis was performed to determine the prevalence of VKD and the efficacy of each prophylactic protocol in preventing VKD/VKDB. The study was registered on PROSPERO (CRD 42021270048). Of the 889 articles, 37 were selected (2 comparative studies, 6 noncomparative studies, and 29 case reports/series). The results from the comparative studies indicated a lower incidence of VKD in the parenteral than that in the oral VK. The meta-analysis of the noncomparative studies showed the prevalence of VKD in high prothrombin induced by vitamin K absence-II group was 56% (95% CI, 45%-68%; I 2 = 0.0%; H 2 = 1.0; Q test: χ2 = 1.93; P = .38) and a prevalence of VKD in abnormal coagulation test was 10% (95% CI, 5%-14%; I 2 = 0%, H 2 = 1.0; Q test: χ2 = 0.82; P = .66), respectively. Among the 3 administrative routes, the analysis from case reports/series showed the median onset of VKDB in cholestatic infants was the earliest in the oral (44.5 days; IQR, 13.0-240.0 days) compared with intramuscular (86.0 days; IQR, 36.0-120.0) and intravenous routes and intravenous (97.0 days; IQR, 74.0-120.0 days) VK prophylaxis. Available studies to determine the optimal route of VK administration in children with cholestatic liver disease were limited. The result from the review indicated that parenteral VK demonstrated a noticeable advantage over oral VK for VKD/VKDB prevention in cholestatic children.

Keywords:  bleeding; children; cholestatic liver disease; prophylaxis; vitamin K

DOI:  https://doi.org/10.1016/j.rpth.2025.102847
Sci Rep. 2025 Jun 02. 15(1): 19272

Dietary vitamin K intake associates with reduced all-cause mortality in non-alcoholic fatty liver disease patients.

Yu Huang, Xianfeng Zhu, Liang Han, Hulan Hu.

  This study aimed to investigate the association between dietary vitamin K intake and all-cause mortality in individuals with non-alcoholic fatty liver disease (NAFLD). We analyzed data from 7857 NAFLD participants in the National Health and Nutrition Examination Survey (NHANES 2005-2018) linked to mortality outcomes from the National Death Index (NDI). Dietary vitamin K intake was log-transformed (ln[VK]) for analysis. Multivariable Cox proportional hazards models and restricted cubic splines were used to evaluate dose-response relationships. Sensitivity analyses, subgroup analyses, and receiver operating characteristic (ROC) curves were performed to validate findings. Over 180 months of follow-up, 842 deaths occurred. Higher ln[VK] was associated with reduced mortality risk, demonstrating an adjusted hazard ratio (HR) of 0.81 per 1-unit increasement (95% confidence interval CI 0.67-0.98, P-trend = 0.028). Restricted cubic splines revealed a U-shaped relationship (P-nonlinear = 0.0009), with an optimal threshold at 121 µg/day (ln[VK] = 4.71). Below this threshold, each unit increase in ln[VK] corresponded to a 33% lower mortality risk (HR = 0.67; 95% CI 0.55-0.81), whereas no significant association was observed above it (HR 1.07; 95% CI 0.67-1.71). The fully adjusted prediction model showed robust discriminative ability, with an area under the curve (AUC) of 0.832. Results remained consistent across sensitivity analyses. Moderate dietary vitamin K intake (up to 121 µg/day) is associated with reduced all-cause mortality in NAFLD patients, with a threshold effect informing tailored dietary recommendations. This study provides novel evidence for optimizing vitamin K intake in NAFLD management.

Keywords:  All-cause mortality; Dietary vitamin K; NHANES; Non-alcoholic fatty liver disease

DOI:  https://doi.org/10.1038/s41598-025-03258-3
Eur J Pharmacol. 2025 May 29. pii: S0014-2999(25)00541-2. [Epub ahead of print] 177787

Vitamin C supplementation mitigates mild cognitive impairment in mice subjected to D-galactose: Insights into intestinal flora and derived SCFAs.

Siju Li, Pengyu Yang, Xiaoyin Cai, Menghui He, Ying He, Feng He.

   BACKGROUND: With the acceleration of population ageing, there has been increasing attention to ageing-related diseases, especially mild cognitive impairment (MCI). Vitamin C (VC), known as ascorbic acid, has demonstrated potential anti-ageing effects and may offer protection against MCI. The study sought to investigate the underlying mechanisms by which VC protects against MCI induced by D-galactose (D-gal).
APPROACHES: ICR mice were subjected to D-gal to elicit MCI and were subsequently administered VC for 8 weeks. The therapeutic effects of VC were assessed by behavioural evaluations and hippocampal pathology. To investigate the potential mechanisms, 16S rDNA sequencing, gas chromatography, and Spearman correlation analysis were employed.
RESULTS: VC supplementation significantly improved spatial learning and memory functions while mitigating hippocampal neuronal damage in D-gal-induced mice. Additionally, VC enhanced cognitive-related anti-inflammatory properties and antioxidant capacity. VC markedly mitigated the colonic pathological damage. Notably, VC led to increased microbial diversity, particularly the enrichment of genera that produce short-chain fatty acids (SCFAs), such as Akkermansia, Ruminococcus, and Butyricicoccus. Interestingly, levels of SCFAs (acetic acid, propionic acid, and butyric acid, etc.) were elevated following VC administration. The Spearman correlation analysis revealed that SCFAs levels were positively correlated with the abundance of the probiotics (Ruminococcus and Butyricicoccus) in response to VC.
CONCLUSIONS: VC supplementation may mitigate MCI, potentially through modulation of intestinal flora and SCFAs production. These results establish a foundation for the application of VC in the management of MCI and underscore its potential as a therapeutic strategy for ageing-related diseases.

Keywords:  SCFAs; Vitamin C; intestinal flora; mild cognitive impairment

DOI:  https://doi.org/10.1016/j.ejphar.2025.177787
J Steroid Biochem Mol Biol. 2025 Jun 02. pii: S0960-0760(25)00127-X. [Epub ahead of print]252 106799

Vitamin D promotes wound healing in aged skin by modulating inflammation, angiogenesis, and EMT via the Hippo pathway.

Yiting Gong, Yurong Ren, Ning Jia, Xiaoming Zhang, Ye Li, Xueyuan Zhi.

  Age-related impairment in skin wound healing represents a significant healthcare challenge. Vitamin D (VD) has been shown to enhance diabetic wound healing. However, its therapeutic potential in age-related wound healing deficits remains unexplored. Here, we investigated VD's impact on wound healing in aged mice and the underlying mechanisms. Twelve-month-old C57BL/6 J mice received VD supplementation for 3 months before full-thickness excisional wounds were created. Wound healing was evaluated through multiple aspects, including inflammation, angiogenesis, epithelial-mesenchymal transition (EMT), and the Hippo signaling pathway. We also examined responses to 1α,25(OH)2D3 in HaCaT cells. VD supplementation significantly accelerated wound closure by modulating several key processes. It promoted inflammation resolution by suppressing pro-inflammatory factors (IL-6, TNF-α), elevating IL-10 levels, and facilitating M1-to-M2 macrophage polarization. VD enhanced angiogenesis through increased CD31-positive vessel formation and upregulation of angiogenic factors (VEGF, VEGFR2, PDGF). It also promoted EMT, as evidenced by reduced epithelial markers, increased mesenchymal markers, and upregulated EMT-related transcription factors. Mechanistically, VD inactivated the Hippo pathway, shown by downregulated Mst1 and Lats1 expressions, decreased p-YAP protein levels, increased YAP and TAZ protein levels, and upregulated target gene expressions (Cyr61). In vitro studies using HaCaT cells confirmed that 1α,25(OH)2D3 promoted cell migration and EMT through Hippo pathway modulation, as these effects were abolished after verteporfin (YAP inhibitor) treatment. Our findings demonstrated that VD supplementation effectively accelerated wound healing in aged skin by modulating inflammation, increasing angiogenesis, and promoting EMT via the Hippo pathway, suggesting VD as a promising therapeutic strategy for managing age-related wound healing deficits.

Keywords:  Aged skin; EMT; Hippo signaling pathway; Vitamin D; Wound healing

DOI:  https://doi.org/10.1016/j.jsbmb.2025.106799
Sci Immunol. 2025 Jun 06. 10(108): eadz3400

Inflammatory mischief managed: How retinoic acid calms heart attacks at the (marrow) source.

Sahily Reyes-Esteves, Christopher A Hunter.

Targeting vitamin A metabolism limits emergency hematopoiesis and promotes resolution of inflammation in myocardial infarction.

DOI: https://doi.org/10.1126/sciimmunol.adz3400
Eur J Nutr. 2025 Jun 02. 64(5): 202

Folate intake, tissue levels, and colorectal cancer deaths in a national cohort established before folic acid fortification.

Anunay Bhattachary, Marian Tabi, Jingjing Yin, Logan Cowan, Jian Zhang.

   OBJECTIVES: The relationship between folate and the risk of colorectal cancer (CRC) remains inconclusive. To control for the interference from folic acid fortification, we assessed the relationship between folate intake, serum folate, and red blood cell (RBC) folate levels and the risk of CRC death in a cohort established before fortification.
METHODS: We analyzed the data of 14,528 adults aged 19 years or older who participated in the National Health and Nutrition Examination Survey (1988-1994) as the baseline examination and were followed through December 31, 2006. Hazard ratios (HR) of CRC deaths were estimated for individuals with different folate intake and biomarker levels. Covariates included age, sex, family income, race/ethnicity, cigarette smoking, alcohol drinking, serum cotinine, vitamin supplements, and dietary energy intake.
RESULTS: After 192,973 person-years (pys) of follow-up with a mean of 14 years, 78 CRC deaths were recorded. The CRC death rate was 0.75/1000 pys, 0.39/1000 pys, and 0.29/1000 pys for adults with low (lower quarter), moderate, and high (upper quarter) total dietary folate equivalent (tDFE, including both dietary and supplemental intake of folate); the adjusted HR was 0.12 (95% CI = 0.03, 0.45) for adults with high, and 0.51 (0.24, 1.11) for moderate tDFE compared to adults with low tDFE (p for trend = 0.09). Similar trends appeared with statistical significance for serum folate but not for dietary folate intake and RBC folate.
CONCLUSION: With minimum interference from folic acid fortification, high folate intake was found to be associated with a reduced risk of CRC death.

Keywords:  Colorectal cancer; Folate; Follow-up studies; Mortality; NHANES

DOI:  https://doi.org/10.1007/s00394-025-03720-y