bims-vitmet 2025-07-13 papers

bims-vitmet

Biomed News

on Vitamin metabolism

Issue of 2025–07–13
ten papers selected by
Onurkan Karabulut, Berkeley City College

Vitamin D and Diabetes: Exploring the Link, Prevention, and Management.
Association of Vitamin Deficiency With Pulmonary Arterial Hypertension: A Review.
Key genes of vitamin D metabolism and their roles in the risk and prognosis of cancer.
Vitamin D in Disease Prevention and Cure-Part I: An Update on Molecular Mechanism and Significance on Human Health.
Vitamin A deficiency triggers colonic methylation potentially impairing colonic neuron via downregulation SGK1/FOXO pathway.
Vitamins K2 and D3 enhance guided bone regeneration in rat calvarial bone defects.
Hypophosphatasia and neuropathic pain: related to vitamin B6 metabolism?
Vitamin C prevents nickel accumulation in rat brain through affecting its transport via serum albumin.
Rescue of the Stargardt Disease phenotype in Abca4 knockout mice through dietary modulation of the vitamin A receptor RBPR2.
Letter to the editor: vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis.

Curr Med Chem. 2025 Jul 09.

Vitamin D and Diabetes: Exploring the Link, Prevention, and Management.

Geir Bjørklund, Monica Butnariu, Leonard Gurgas, Tony Hangan.

  Vitamin D is a crucial nutrient that plays a significant role in various aspects of health. This review explores the importance of vitamin D and its cofactors in preventing and managing diseases, mainly focusing on diabetes and its complications. The evidence reveals a strong link between low vitamin D levels and increased risks of type 2 diabetes (T2D), gestational diabetes, and type 1 diabetes. Vitamin D supplementation, which has shown promising results in reducing the incidence of these diseases and improving outcomes, offers hope in the fight against diabetes. Additionally, vitamin D deficiency has been linked to an increased risk of complications in diabetes, including depression, cancer, peripheral neuropathy, and diabetic foot ulcers. Adequate vitamin D levels have been shown to prevent and treat these complications, improving symptoms and overall outcomes. The review also highlights the global vitamin D deficiency pandemic. It explores strategies for optimizing vitamin D levels, including sun exposure, dietary sources, supplementation, and the role of cofactors such as magnesium and vitamin K2. It underscores the importance of raising awareness about the significance of vitamin D optimization and the need for everyone to play a role in implementing these strategies, as it can profoundly impact disease prevention and management.

Keywords:  Vitamin D; deficiency.; diabetes. gestational diabetes; type 1 diabetes; type 2 diabetes

DOI:  https://doi.org/10.2174/0109298673360987250621042131
Nutr Rev. 2025 Jul 11. pii: nuaf119. [Epub ahead of print]

Association of Vitamin Deficiency With Pulmonary Arterial Hypertension: A Review.

Yansheng Jin, Lan Ding, Maoxiao Fan, Ning Kong.

  Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular syndrome characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, which may lead to right-heart failure and death. Nutritional deficiencies have been identified in patients with PAH. However, a comprehensive characterization of vitamin deficiencies in patients with PAH and their potential roles remains lacking. Consequently, this review aims to synthesize existing literature on the roles of vitamins in PAH, encompassing the epidemiology of vitamin deficiencies, observational and interventional studies investigating the therapeutic potential of vitamins in patients with PAH, and the molecular mechanisms through which vitamins may influence endothelial dysfunction and pulmonary vascular remodeling.

Keywords:  pulmonary arterial hypertension; vitamin A; vitamin C; vitamin D; vitamin E; vitamin deficiency

DOI:  https://doi.org/10.1093/nutrit/nuaf119
Front Genet. 2025 ;16 1598525

Key genes of vitamin D metabolism and their roles in the risk and prognosis of cancer.

Sijie Zheng, Lizhu Zhu, Yufei Wang, Yixin Hua, Jie Ying, Jianxiang Chen.

  Vitamin D is an essential vitamin for normal human metabolism and plays pivotal roles in various biological processes, such as maintaining calcium and phosphorus balance, regulating immune responses, and promoting cell differentiation while inhibiting proliferation. Vitamin D is obtained through sunlight exposure and diet, and is metabolized into its active form via hydroxylation in liver and kidney. Vitamin D deficiency is linked to various diseases, including skeletal disorders, diabetes, and cardiovascular diseases. Recent epidemiology and oncology research have demonstrated that serum vitamin D level, as well as genetic polymorphisms and expression dysregulation of genes related with vitamin D metabolism, have significantly influences on the incidence and prognosis of various types of cancer, including breast cancer, prostate cancer, liver cancer, gastrointestinal malignancy, and hematologic malignancies. The mechanisms linking vitamin D metabolism dysregulation to malignancy are multifactorial, such as the alteration in cell metabolism, proliferation, differentiation, and tumor microenvironment. These findings suggest potential therapeutic benefits of targeting the vitamin D signaling pathway for the diagnosis and treatment of cancer. However, there is still a lack of clinical applications regarding the knowledge of vitamin D metabolic pathway, and future research is urgently needed to illustrate the underlying mechanisms for the rationale design of clinical trials. Therefore, this review summarizes the metabolic pathways of vitamin D and its association with cancer, highlighting the importance of genetic polymorphisms and expression dysregulation of genes involved in vitamin D metabolism in cancer susceptibility and prognosis.

Keywords:  cancer; genetic polymorphisms; metabolism; microenvironment; vitamin D

DOI:  https://doi.org/10.3389/fgene.2025.1598525
Indian J Clin Biochem. 2025 Jul;40(3): 339-381

Vitamin D in Disease Prevention and Cure-Part I: An Update on Molecular Mechanism and Significance on Human Health.

Shailendra Dwivedi, Vijay Singh, Aniruddha Sen, Dharamveer Yadav, Ruchika Agrawal, Surekha Kishore, Sanjeev Misra, Praveen Sharma.

  Vitamin D, a versatile secosteroid hormone, continues to captivate scientific interest due to its multifaceted influence on human health. This comprehensive review, part 1 of a series, provides an up-to-date exploration of the molecular mechanisms governing Vitamin D's impact on various aspects of health. Focusing on its pivotal role in the central nervous system (CNS), neurodevelopmental disorders, and neurodegenerative diseases, the review also delves into its intriguing correslations with oral, prostate, breast, and colon cancers. Beyond these domains, Vitamin D's reach extends to viral infections and reproductive health, affecting fertility in both males and females and playing a crucial role throughout pregnancy. The article offers an in-depth examination of the complex molecular pathways and signaling cascades through which Vitamin D exerts its physiological effects. Importantly, it provides a detailed overview of Vitamin D's involvement in a spectrum of diseases, laying the foundation for the upcoming second part of the article. This forthcoming article (part II) will expand on the role of Vitamin D in additional diseases, contributing to a more comprehensive understanding of its therapeutic potential. In summary, this article serves as a valuable resource for researchers and healthcare professionals, offering insights into the diverse roles of Vitamin D and setting the stage for further exploration in part II.

Keywords:  Cancers; Immunity; Infertility; Inflammation; Pregnancy; Schizophrenia; Viral diseases; Vitamin D

DOI:  https://doi.org/10.1007/s12291-024-01251-7
Pediatr Discov. 2024 Dec;2(4): e86

Vitamin A deficiency triggers colonic methylation potentially impairing colonic neuron via downregulation SGK1/FOXO pathway.

Bei Tong, Junyan Yan, Zhujun Sun, Ruifang Luo, Fang Lin, Riqiang Hu, Ting Yang, Yuting Wang, Jie Chen.

  DNA methylation is widely involved in the modification of intestinal function, but the methylation mechanism in the enteric nervous system has not been studied in vitamin A deficiency (VAD). Herein, we firstly found that in the VAD group, gastrointestinal transit time was delayed compared with the vitamin A normal (VAN) group. RNA sequencing between VAD and VAN rats identified enriched pathways associated with enteric nerves and methylation transferase complexes. Then expression levels of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) were validated to significant increase in the VAD group. Representative reduced bisulfate sequencing showed that the VAD rats had high levels of DNA methylation in promoters and exons compared with the VAN rats. A combined methylomic and transcriptomic analysis identified that methylation levels of Sgk1, a key gene associated with enteric neural development, were elevated in the VAD group, and the activity of the SGK1/FOXO signaling axis was reduced. Furthermore, the colonic neuronal morphology and synaptic architecture were impaired in the VAD offspring. Interestingly, the above alterations in the VAD group were alleviated by vitamin A (VA) supplementation in the early postnatal period. These data suggest that VAD triggers colonic hypermethylation, which probably downregulates the SGK1/FOXO signaling pathway to cause colonic transfer dysfunction.

Keywords:  SGK1/FOXO pathway; enteric neurons; methylation; vitamin A deficiency; vitamin A supplementation

DOI:  https://doi.org/10.1002/pdi3.86
J Periodontol. 2025 Jul 08.

Vitamins K2 and D3 enhance guided bone regeneration in rat calvarial bone defects.

Gülce Nil Varlıhan, Ömer Birkan Ağralı, Hatice Selin Güngörmek, Sibel Demirci Delipınar, Leyla Kuru, Hafize Öztürk Özener.

   BACKGROUND: Vitamins K2 and D3 exhibit anabolic effects on bone metabolism, but their effectiveness in guided bone regeneration (GBR) is unclear. The present study aimed to investigate the impacts of vitamins K2 and D3 administration on GBR of calvarial critical-size defect (CCSD) in rats.
METHODS: A total of 48 defects were obtained by creating two bilateral 5 mm CCSDs in each of 24 rats: the right-side defect was treated using a collagen-based resorbable membrane and a bovine bone graft (GM defect), the left side remained empty (empty defect). The rats were assigned to four groups and administered distilled water (Control), vitamin K2 (K), vitamins K2 and D3 (KD), or vitamin D3 (D) for 8 weeks. Rats were sacrificed after 8 weeks. Histomorphometric and immunohistochemical analyses were performed.
RESULTS: The new bone area was greater in GM defects versus empty defects of all groups (p < 0.05), higher in vitamin groups than the control group in both defects (p < 0.05). Osteocalcin levels were elevated in GM defects than empty defects (p < 0.0001). Within GM defects, levels were higher in the vitamin groups compared with the control group (p < 0.05). Runx2 expression was increased in GM defects compared with empty defects and in vitamin groups compared with the control group (p < 0.05). IL-1β levels were greater in empty defects compared with GM defects in vitamin groups (p < 0.05).
CONCLUSION: The administration of vitamins K2 and D3 in GBR enhanced bone healing in CCSD of rats, indicating that the adjunctive use of these vitamins may represent a promising therapeutic strategy for bone regeneration.
PLAIN LANGUAGE SUMMARY: Vitamin K2 and vitamin D3 are known to play important roles in bone metabolism. Previous research revealed that vitamins K2 and D3 supplements might be effective as a therapeutic approach to bone regeneration. Although there are several methods of bone regeneration, each has limits. Thus, we aimed to investigate the effects of administering vitamins K2 and D3 alone or in combination to restore bone defects. In this study, each rat had two critical-size cranial bone defects (defined as the smallest bone defect that cannot restore naturally throughout life); one was filled with bone grafts and barrier membranes, while the other was left empty. Then rats were divided into groups administered either distilled water, vitamin K2, vitamin D3 or both. More bone was found in the regenerated bone defects compared with those left empty and vitamin-administered rats had more bone in defects than vitamin-unadministered rats. Moreover, the highest amount of bone was observed in regenerated bone defects of rats that received combined vitamins K2 and D3. Therefore, we conclude that administration of vitamins K2 and D3 improves bone healing in critical-size cranial bone defects in rats. The use of vitamins K2 and D3 as adjuncts to guided bone regeneration may be beneficial in clinical applicability. This approach may serve as a promising foundation for future research on clinical relevance.

Keywords:  bone regeneration; cholecalciferol; rats; vitamin K2

DOI:  https://doi.org/10.1002/jper.11372
JBMR Plus. 2025 Aug;9(8): ziaf086

Hypophosphatasia and neuropathic pain: related to vitamin B6 metabolism?

Zografia Zervou, Evert F S van Velsen, M Carola Zillikens.

  Hypophosphatasia (HPP) is caused by pathogenic variant(s) of the ALPL gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). Diminished enzyme activity results in elevated serum concentrations of pyridoxal 5'-phosphate (PLP), the main circulating form of vitamin B6. Neuropathy has been associated with HPP, but the prevalence, pathogenesis, and symptoms remain inadequately understood. Here, we describe 5 adult HPP patients with symptoms suggestive of neuropathic pain, and speculate about potential mechanisms, related to the vitamin B6 metabolism. They reported burning pain sensations, primarily in their lower extremities. One patient was diagnosed with nociceptive pain, but he also experienced numbness and tingling sensations in his hands and feet. All patients exhibited reduced serum ALP levels along with elevated levels of serum vitamin B6 and urine phosphoethanolamine, aligning with the diagnosis of HPP. Regarding treatment, one patient received asfotase alfa which had a remarkable effect with her pain significantly decreasing already within 3 wk of starting the therapy. Another patient received nortriptyline and participated in a rehabilitation program, leading to a reduction in pain within 10 mo. Gabapentin appeared to reduce the pain in one patient, although her symptoms did not fully disappear. Mechanistically, TNSALP is essential for the transformation of PLP, the active form of vitamin B6, into pyridoxal, which is required for crossing the cell membrane and the blood-brain barrier. The deficient catalytic activity of TNSALP could lead to PLP excess extracellularly or deficiency intracellularly. Lack of PLP in the brain may result in changes to metabolites, such as adenosine, which is involved in myelin synthesis. We hypothesize that neuropathic pain could be caused by defective myelination. Alternatively, several cases of polyneuropathy linked to vitamin B6 supplementation have been reported, with a mechanism that may resemble the excess of PLP extracellularly, although the exact mechanism remains unclear.

Keywords:  ALPL; hypophosphatasia; neuropathic pain; tissue-nonspecific alkaline phosphatase; vitamin B6

DOI:  https://doi.org/10.1093/jbmrpl/ziaf086
Biochem Biophys Res Commun. 2025 Jul 05. pii: S0006-291X(25)01029-0. [Epub ahead of print]777 152314

Vitamin C prevents nickel accumulation in rat brain through affecting its transport via serum albumin.

Saima Parveen, Asim Rizvi, Imrana Naseem.

  Nickel (Ni2+) exposure has been linked to oxidative stress, reproductive toxicity, and neurotoxicity. Human serum albumin (HSA), a major plasma transport protein, that plays a critical role in the systemic distribution of xenobiotics, including heavy metals. This study aimed to investigate how vitamin C affects the interaction between Ni2+ and HSA, and whether this interaction influences nickel accumulation in the brain. Male rats were divided into three groups: a control group receiving vitamin C alone, a group exposed to nickel, and a group receiving both nickel and vitamin C. Atomic absorption spectroscopy revealed that co-treatment with vitamin C significantly reduced nickel accumulation in brain tissue compared to nickel exposure alone. To elucidate the underlying mechanism, in vitro and in silico approaches were employed. Spectroscopic analyses-including fluorescence quenching, site marker displacement, synchronous fluorescence, and circular dichroism (CD)-revealed that vitamin C competitively interferes with Ni2+ binding to HSA and protects the native structure of the protein from nickel-induced conformational changes. Notably, the binding affinity of Ni2+ to HSA was lower in the presence of vitamin C. Molecular dynamics simulations supported these findings, indicating structural destabilization of the Ni-HSA complex when vitamin C was present. Together, these results suggest that vitamin C modulates Ni2+ transport by altering its binding to HSA, which may partly explain its protective effect against nickel-induced neurotoxicity. Further research is needed to fully elucidate transport mechanisms of nickel across the blood-brain barrier.

Keywords:  HSA; Molecular simulation; Neurotoxicity; Nickel; Vitamin C

DOI:  https://doi.org/10.1016/j.bbrc.2025.152314
bioRxiv. 2025 Jul 02. pii: 2025.06.27.662034. [Epub ahead of print]

Rescue of the Stargardt Disease phenotype in Abca4 knockout mice through dietary modulation of the vitamin A receptor RBPR2.

Rakesh Radhakrishnan, Matthias Leung, Drew Yochim, Heidi Roehrich, Scott W McPherson, Glenn P Lobo.

Mutations in the ABCA4 gene in Stargardt disease (STGD1) causes accumulation of cytotoxic lipofuscin, resulting in RPE atrophy and photoreceptor dysfunction. One component of lipofuscin is the all- trans -retinal derivative, bisretinoid N- retinylidene- N- retinylethanolamine (A2E). Since ocular A2E biosynthesis relies on circulating all- trans -retinol bound to retinol binding protein 4 (RBP4-ROL), we hypothesized that modulating vitamin A receptors, such as the retinol binding protein receptor 2, RBPR2, which regulate serum RBP4-ROL concentration, should attenuate A2E production. In-silico analysis revealed multiple retinoic acid response element (RARE) binding sites on the murine Rbpr2 gene promotor, which was confirmed in vitro by EMSA and ChIP assays. In vitro luciferase assays showed that Rbpr2 promotor activity was induced by exogenous β-carotene (BC) metabolites. Dietary BC supplementation of Abca4 -/- mice, a mouse model for STGD1, increased hepatic all- trans -retinoic acid and 9- cis -retinoic acid production, which induced Rbpr2 mRNA expression. This mechanism decreased serum RBP4 protein levels, fundus autofluorescence (AF) and ocular A2E accumulation, altogether improving photoreceptor and RPE function. Conversely, such a rescue was not observed in either Abca4 -/- mice fed a diet devoid of BC or in double knockout Rbpr2 -/- ; Abca4 -/- mice. Thus, there was a significant inverse correlation between dietary BC supplementation and Rbpr2 gene presence in Abca4 -/- mice, to that of lipofuscin accumulation in Abca4 -/- mice on diets devoid of BC or in Rbpr2 -/- ; Abca4 -/- mice. Our results provide impetus to pursue BC supplemented diets as therapeutic interventions for STGD1 patients with ABCA4 gene mutations and identifies a novel role for the vitamin A receptor RBPR2 in this process.

DOI: https://doi.org/10.1101/2025.06.27.662034
Expert Rev Gastroenterol Hepatol. 2025 Jul 10. 1-2

Letter to the editor: vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis.

Santiago Barón Gutiérrez, Jonathan Camilo Ramírez Cruz.



Keywords:  Proton pump inhibitors; letter; meta-analysis; systematic review; vitamin B 12 deficiency

DOI:  https://doi.org/10.1080/17474124.2025.2530602