bims-vitmet 2025-09-07 papers

Issue of 2025–09–07
six papers selected by
Onurkan Karabulut, Berkeley City College

Georgian Med News. 2025 Jun; 23-30

IMPACT OF VITAMIN D METABOLISM DISORDERS ON THE DEVELOPMENT OF AUTOIMMUNE KIDNEY DISEASES: A SYSTEMATIC REVIEW.

T Abilov, I Ismailova, Zh Shaimbetov, N Imanbayev, Y Iztleuov.

INTRODUCTION: Vitamin D plays a crucial role in immune regulation and renal physiology. It acts as a modulator of both the innate and adaptive immune systems. Vitamin D enhances the differentiation of monocytes into macrophages, thereby strengthening their phagocytic and chemotactic functions. Its deficiency has been associated with the pathogenesis of autoimmune renal diseases; however, the clinical and molecular mechanisms underlying this association remain insufficiently understood.
AIM: This systematic review focused on systemic lupus erythematosus with lupus nephritis (LN), IgA nephropathy (IgAN), and ANCA-associated vasculitis (AAV). The objective was to identify and synthesize available literature addressing the association between autoimmune kidney diseases and the dysregulation of vitamin D metabolism.
METHODS: Studies published between 2020 and 2025 were retrieved from the Cochrane Library, Google Scholar, Scopus, Web of Science, and PubMed. The inclusion criteria emphasized investigations assessing vitamin D status and metabolism within the context of autoimmune kidney diseases.
RESULTS: The analysis demonstrated that patients with LN, IgAN, and AAV exhibit a high prevalence of vitamin D deficiency, with rates frequently exceeding 70 percent. These values serve as descriptive summaries rather than as combined or pooled estimates.

J Nutr Sci Vitaminol (Tokyo). 2025 ;71(4): 290-299

Active Vitamin D Corrects Cerebrovascular Dysfunction and Aberrant Vasopressin Expression in the Hypertension Phenotype of 1α-Hydroxylase Knockout Mice.

Wei Zhang, Yingying Hu, Luqing Zhang, Ping Dong, Dongmei Li, Ronghui DU.

Vitamin D has a protective effect on the brain under hypertensive conditions. Studies have shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) can negatively regulate hypertension and central renin-angiotensin system activation through a central anti-oxidative mechanism in 1α-hydroxylase knockout mice. To confirm whether endogenous or exogenous 1,25(OH)2D3 deficiency or supplementation alters cerebrovascular function and vasopressin expression through anti-oxidation, researchers provided 1α(OH)ase-/- mice and their wild-type littermates with regular diet, a high-calcium, high-phosphorus rescue diet with N-acetyl-L-cysteine supplementation, or 1,25(OH)2D3 subcutaneous injection. The results showed that the hypertension phenotype was present in the 1α(OH)ase-/- mice, with upregulated vasopressin expression and increased brain/blood oxidative stress. These pathologic changes were corrected by 1,25(OH)2D3 or N-acetyl-L-cysteine plus rescue diet. The findings suggest that 1,25(OH)2D3 may be a promising protective intervention to reduce brain impairment induced by oxidative stress in the hypertension phenotype of 1α(OH)ase-/- mice.

Keywords: 1α-hydroxylase; cerebral blood flow; oxidative stress; vasopressin; vitamin D

DOI: https://doi.org/10.3177/jnsv.71.290

J Blood Med. 2025 ;16 391-411

Multifaceted Clinical Spectrum of Vitamin B12 Deficiency - a Case Report and Literature Review.

Ewa Pustelnik, Katarzyna Pikora, Magdalena Zofia Hartman, Marta Kurzeja, Joanna Czuwara, Paweł Łaguna.

Background: Vitamin B12 (cobalamin) deficiency is a well-known cause of hematologic and neurological disorders; however, its presentation can be highly variable, leading to diagnostic challenges. The etiology is diverse: while the most common cause is dietary insufficiency, other potential causes include malabsorption syndromes, autoimmune gastritis, gastrointestinal disorders, chronic infections, and genetic defects. Clinical presentation varies significantly, ranging from clinically silent macrocytosis to life-threatening anemia or pancytopenia. Neurological and psychiatric manifestations may include vision and gait impairment, depression, and cognitive dysfunction. Given this complexity, vitamin B12 deficiency can mimic other conditions, often leading to a delay in diagnosis.
Case Presentation: A 15-year-old male was admitted in critical condition with severe anemia, thrombocytopenia, jaundice, progressive weight loss, fatigue, gait disturbances, and vision impairment. Initially, Evan's syndrome was suspected, but further laboratory investigations, including a peripheral blood smear and elevated mean corpuscular volume (MCV), led to the diagnosis of profound vitamin B12 deficiency. Additional workup revealed chronic atrophic gastritis as the underlying cause. The patient was treated with vitamin B12 injections, leading to significant hematologic and neurological improvement, weight gain, and resolution of psychiatric symptoms. However, optic nerve atrophy was detected as a late complication.
Conclusion: This case emphasizes the need to consider vitamin B12 deficiency in pediatric patients with unexplained hematologic, neurological, and psychiatric symptoms, particularly when associated with chronic atrophic gastritis. Early recognition and intervention are crucial to preventing irreversible complications, such as optic neuropathy. Given the multidisciplinary nature of its presentation, this case serves as an important reminder for pediatricians, hematologists, gastroenterologists, and neurologists to maintain a high index of suspicion for vitamin B12 deficiency in complex clinical scenarios.

Keywords: atrophic gastritis; cobalamin; hemolytic anemia; thrombocytopenia

DOI: https://doi.org/10.2147/JBM.S524466

FASEB Bioadv. 2025 Aug;7(8): e70044

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) cause enhanced accumulation of cytotoxic lipofuscin, manifesting in RPE atrophy and photoreceptor dysfunction. One component of lipofuscin is the all-trans-retinal derivative, pyridinium bisretinoid A2E. Since ocular A2E biosynthesis relies on all-trans-retinal, which is obtained from circulating all-trans-retinol bound to retinol binding protein 4 (RBP4-ROL), we hypothesized that modulating vitamin A receptors, such as RBPR2, which regulate serum RBP4-ROL homeostasis, should in principle attenuate A2E production. In silico analysis revealed multiple retinoic acid response element (RARE) binding sites on the murine Rbpr2 gene promoter, which was confirmed in vitro by EMSA and ChIP assays. In vitro luciferase assays showed that Rbpr2 promoter 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 lipofuscin autofluorescence, 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 include dietary obtained BC for STGD1 patients with ABCA4 gene mutations and identify a novel role for the vitamin A receptor RBPR2 in this process.

Keywords: ABCA4; RBP4; RBPR2; RPE; Stargardt disease; all‐trans‐retinol; lipofuscin; retinoic acid; retinoic acid response elements; β‐carotene

DOI: https://doi.org/10.1096/fba.2025-00173

bioRxiv. 2025 Aug 30. pii: 2025.05.19.654973. [Epub ahead of print]

Vitamin B12 supports skeletal muscle oxidative phosphorylation capacity in male mice.

Luisa F Castillo, Katarina E Heyden, Abigail R Williamson, Wenxia Ma, Olga V Malysheva, Nathaniel M Vacanti, Anna E Thalacker-Mercer, Martha S Field.

OBJECTIVES: Vitamin B12 plays a vital role in folate-mediated one-carbon metabolism (FOCM), a series of one-carbon transfer reactions that generate nucleotides (thymidylate (dTMP) and purines) and methionine. Inadequate levels of B12 impair FOCM, depressing de novo thymidylate (dTMP) synthesis, which in turn leads to uracil accumulation in DNA. This phenomenon has been well documented in nuclear DNA. Our previous work in liver tissue has shown that mitochondrial DNA (mtDNA) is more sensitive to FOCM impairments in that mtDNA exhibits elevated uracil levels before uracil concentrations in nuclear DNA change. However, the functional consequences of uracil accumulation in mtDNA are largely unknown. The purpose of this study was to determine how a functional B12 deficiency (induced by reduced levels of the B12-dependent enzyme methionine synthase (MTR)) and dietary B12 deficiency affects mtDNA integrity and mitochondrial function in energetic and mitochondria-rich tissues such as skeletal muscle.
METHODS: Male Mtr+/+ and Mtr+/- mice were weaned to either an AIN93G-based control (C) diet containing 25 μ/kg vitamin B12 or a B12-deficient (-B12) diet containing 0 μ/kg vitamin B12 to explore the effects of functional (Mtr+/-) and dietary B12 deficiency on muscle weight, uracil content in mtDNA, mtDNA content, and oxidative phosphorylation complex capacity in skeletal muscle. Aged (20-22mo) male C57BL6/N mice were acclimated to an AIN93G control diet four weeks, then received either weekly injections of saline (vehicle control [30 uL 0.9% NaCl]) or B12 (0.65mg per 30uL 0.9% NaCl) in each of two hindleg muscles [1.25 mg B12 total]) for 8 weeks.
RESULTS: The tibialis anterior (TA) muscle from Mtr+/- mice exhibited lowered maximal respiratory capacity of complex I, II, and IV of the electron transport chain than did TA from Mtr+/+ mice. Exposure to the -B12 diet lowered maximal capacity of complex I in red, mitochondrially rich muscle (soleus and mitochondria-rich portions of quadriceps and gastrocnemius) (p=0.02). Levels of uracil accumulation in mtDNA in red muscle and gastrocnemius were elevated ~10 fold with exposure to -B12 diet (p=0.04 and p<0.001, respectively). In aged mice gastrocnemius complex IV activity increased with intramuscular B12 supplementation (p=0.04).
CONCLUSIONS: Exposure to a B12-deficient diet led to uracil accumulation in mtDNA and impaired maximal oxidative capacity in two different types of skeletal muscle. B12 supplementation improved complex IV maximal capacity in gastrocnemius from aged mice.

DOI: https://doi.org/10.1101/2025.05.19.654973

Front Psychiatry. 2025 ;16 1569826

Exploring neuropsychiatric manifestations of vitamin B complex deficiencies.

Anamaria Han, Leandro Almeida, Nikhilesh Anand, Ihsan M Salloum, Salim Kanaan, Bharathi S Gadad, João Paulo Lima Daher.

B complex vitamins, a group of eight water-soluble vitamins, play interconnected roles in maintaining nervous system health. Thiamine (B1), riboflavin (B2), and niacin (B3) are essential as co-enzymes in numerous metabolic reactions related to energy production. Thiamine is involved in the Krebs cycle, riboflavin in the electron transport chain, and niacin plays a key role in both glycolysis and the Krebs cycle. These metabolic processes are vital for sustaining the integrity of the nervous system, as the energy produced is critical for the functioning of nerve cells. Deficiencies in these vitamins can lead to significant neurological and psychiatric conditions, including Wernicke Korsakoff syndrome, Parkinson's disease, and various mental illnesses. Additionally, pyridoxine (B6), folate (B9), and cobalamin (B12) are indispensable coenzymes for the methylation of homocysteine to methionine, a process critical to nervous system function. Elevated homocysteine levels, resulting from deficiencies of these vitamins, are associated with higher risks of depression and dementia. Thus, imbalances in these vitamins can disrupt key biochemical pathways, leading to neuropsychiatric disorders. The literature reviewed underscores the importance of daily intake of B complex vitamins to maintain normal serum levels and optimal neuronal function. This review aims to elucidate the neuropsychiatric manifestations associated with deficiencies in these vitamins.

Keywords: cobalamin; complex B vitamins; folate; neuropsychiatric manifestations; niacin; pyridoxine; riboflavin; thiamine

DOI: https://doi.org/10.3389/fpsyt.2025.1569826