bims-vitmet 2025-07-06 papers

bims-vitmet

Biomed News

on Vitamin metabolism

Issue of 2025–07–06
twelve papers selected by
Onurkan Karabulut, Berkeley City College

Exploring the association of vitamin B12 deficiency and dental health in older adults.
Assessment of the Relationship Between Serum Vitamin D Level and Its Cardiovascular Outcomes: A Systematic Review and Meta-analysis Study.
Neglected micronutrients - considering a broader set of vitamins and minerals in public health nutrition programs worldwide: A narrative review.
Metformin is associated with low levels of vitamin B12 with no effect on other vitamin levels. A selective action of metformin.
Role of vitamin D in the pathogenesis of early-onset preeclampsia: a narrative review.
NMR-guided Identification of CYP11A1-Adrenodoxin Interactions that Differentially Govern Cholesterol and Vitamin D3 Metabolism.
The efficacy of calcium and vitamin D3 supplementation in improving pregnancy and neonatal outcomes.
The protective role of vitamin E against the effects of hyperthyroidism on the rat pituitary-ovary axis.
Reply to letter to the Editor: Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis.
The Modulatory Effects of Statins, Vitamin E, and Moringa Oleifera Extract on CD3 Expression in Ribociclib-Induced Hepatotoxicity in Rats.
Role of Vitamin B₆ in Testosterone Synthesis.
Computational Strategies to Enhance Vitamin B12 Biosynthesis Potential of Microbes.

Front Nutr. 2025 ;12 1589062

Exploring the association of vitamin B12 deficiency and dental health in older adults.

Man Hung, Amir Mohajeri, Jacob Marx, Corban Ward, Martin S Lipsky.

   Background: Vitamin B12 plays a crucial role in overall health, yet its impact on dental health, particularly dental caries, remains underexplored. Older adults are at an increased risk of vitamin B12 deficiency and dental disease, but the relationship between these two factors is not well understood. This study examines the association between serum vitamin B12 levels and dental health in older adults using data from the NHANES 2011-2014 cycles.
Methods: A cross-sectional analysis was conducted using NHANES data from 1,907 participants aged 65 and older. Serum vitamin B12 levels were categorized as normal (>221 pmol/L), marginal (148-221 pmol/L), and deficient (<148 pmol/L). Dental status was assessed using the Decayed, Missing, and Filled Teeth (DMFT) index based on NHANES dental health examinations. Poisson regression models evaluated associations between vitamin B12 levels and DMFT scores, adjusting for age, sex, race/ethnicity, education, and income.
Results: Lower vitamin B12 levels were significantly associated with higher DMFT scores (p < 0.05). Participants with marginal and deficient vitamin B12 levels exhibited increased DMFT scores compared to those with normal vitamin B12 levels, and these differences persisted after adjusting for demographic and socioeconomic factors. The findings suggest that inadequate vitamin B12 status may contribute to a greater cumulative burden of dental disease in older adults.
Conclusion: These findings suggest that vitamin B12 deficiency may contribute to a greater lifetime burden of dental disease in older adults. Further research is needed to explore causal mechanisms and assess whether vitamin B12 supplementation could be a preventive measure for maintaining dental health in aging populations.

Keywords:  NHANES; dental caries; dental health; older adults; oral health; vitamin B12

DOI:  https://doi.org/10.3389/fnut.2025.1589062
J Saudi Heart Assoc. 2025 ;37(2): 14

Assessment of the Relationship Between Serum Vitamin D Level and Its Cardiovascular Outcomes: A Systematic Review and Meta-analysis Study.

Reza Madadi, Sina Bakhshaei, Arian Tavasol, Mahmood Gorjizad, Rouhollah Hemmati, Masood Zangi.

   Introduction: Cardiovascular events are the most common cause of mortality worldwide. Various studies have shown the relationship between serum 25-hydroxyvitamin D [25(OH)Vit D] levels and cardiovascular events. The purpose of this study is to investigate the meta-analysis of the relationship between serum 25(OH)Vit D levels and the risk of cardiovascular diseases (CVD), including stroke, coronary heart disease, peripheral arterial disease, and aortic disease in the population.
Method: Using valid keywords and searching the Medline, Science Direct, Scopus, and Web of Science databases, 22 papers were compiled. Data analysis was performed in the group of people with low serum 25(OH)Vit D levels (<75 nmol/L). The data were analyzed using a random-effects meta-analysis model with R and Stata Version 17.0 software.
Results: In this study, 22 papers were included. This meta-analysis of 12 cohort studies (n = 39,396) found that lower serum vitamin D levels were significantly associated with increased risk of cardiovascular disease (HR = 1.38, 95 % CI: 1.24-1.53) and all-cause mortality (HR = 1.64, 95 % CI: 1.33-2.03). Dose-response analysis showed that each 10 nmol/L increase in vitamin D reduced CVD risk by 8.2 % (HR = 0.992, 95 % CI: 0.990-0.993). A non-linear inverse association was observed for all-cause mortality, with stronger protective effects at lower vitamin D levels. These results, in addition to most of the studies included in the systematic review, support a potential protective role of higher vitamin D concentrations.
Conclusion: The results of this study showed a relationship between serum 25(OH)Vit D levels and cardiovascular outcomes; the lower the serum 25(OH)Vit D level, the higher the risk of cardiovascular disease.

Keywords:  CHD; Cardiovascular; MI; Meta-analysis; Vitamin D

DOI:  https://doi.org/10.37616/2212-5043.1432
Am J Clin Nutr. 2025 Jul 02. pii: S0002-9165(25)00387-9. [Epub ahead of print]

Neglected micronutrients - considering a broader set of vitamins and minerals in public health nutrition programs worldwide: A narrative review.

Kenneth H Brown, Sonja Y Hess, Sophie E Moore, Gerald F Combs, Kevin D Cashman, Helene McNulty, Lindsay H Allen, Nancy F Krebs, Christine M Pfeiffer, Michael E Rybak, Saskia Jm Osendarp.

  Several essential vitamins and minerals whose deficiencies are associated with metabolic and functional disorders, including increased morbidity and mortality from both communicable and non-communicable diseases, are not being adequately addressed by large-scale, public health nutrition programs worldwide. These neglected micronutrients include thiamine, riboflavin, niacin, pyridoxine, vitamin B12, vitamin D, vitamin K, calcium, selenium, and possibly others. In this narrative review, our objectives are to describe briefly the health implications of each of these deficiencies, summarize the limited available information on their epidemiology, and suggest possible approaches to address them. We conclude that more information, based on dietary assessments, nutritional biomarker surveys, and systematic surveillance of associated health conditions, is needed. Appropriate intervention programs, including changes in food systems to provide wider access to nutrient-rich foods, food fortification and targeted supplementation, should be implemented in settings where these deficiencies are confirmed.

Keywords:  B vitamins; calcium; public health nutrition; riboflavin; selenium; thiamine; vitamin B12; vitamin D; vitamin K; vitamin and mineral deficiency

DOI:  https://doi.org/10.1016/j.ajcnut.2025.06.030
Nutr Metab Cardiovasc Dis. 2025 Jun 11. pii: S0939-4753(25)00347-3. [Epub ahead of print] 104193

Metformin is associated with low levels of vitamin B12 with no effect on other vitamin levels. A selective action of metformin.

Nicolò Vigolo, Anna Toffalini, Nicoletta Rolli, Elisa Paviati, Matteo Gelati, Maddalena Trombetta, Elisa Danese, Giacomo Zoppini.

   BACKGROUND AND AIMS: Metformin is frequently used in type 2 diabetes. Long-term treatment is associated with low blood levels of vitamin B12. No studies have evaluated whether metformin affects the blood levels of other vitamins with different mechanisms of intestinal absorption. Thus, the aim of this study was to measure vitamin B12 and other vitamin levels in metformin treated type 2 diabetes patients.
METHODS AND RESULTS: In 200 ambulatory patients with type 2 diabetes, vitamins B12, A, B1, B6, B9, C and E were measured. Subjects were divided into those taking and those not taking metformin. Vitamin levels were compared in these two groups. Metformin significantly reduced the levels of vitamin B12 compared to patients not taking the drug (227.1 ± 96.9 vs 325.6 ± 176.8 pmol/L, p < 0.001), without affecting the levels of all other measured vitamins. A deficiency of vitamin B12 was found in 21.1 % of patients. Metformin tripled the risk of vitamin B12 deficiency in the multivariate logistic regression model.
CONCLUSIONS: To the best of our knowledge, this is the first study that shows a specific effect of metformin in reducing the level of vitamin B12 without affecting other vitamin levels.

Keywords:  Deficiency; Metformin; Type 2 diabetes; Vitamin B12

DOI:  https://doi.org/10.1016/j.numecd.2025.104193
Front Nutr. 2025 ;12 1598691

Role of vitamin D in the pathogenesis of early-onset preeclampsia: a narrative review.

Shu Zheng, Shuai Dong, Huimin Shen, Peng Xu, Chang Shu.

  Early-onset Preeclampsia (EOPE) is a severe pregnancy complication that poses significant risks to both maternal and fetal health, often leading to fetal growth restriction and maternal morbidity. Despite extensive research, the etiology of EOPE remains unclear, though emerging evidence suggests that vitamin D (VD) may play an important role in placental development and function. Recent studies associate VD deficiency with adverse pregnancy outcomes, including EOPE, through mechanisms such as impaired trophoblast invasion and immune dysregulation at the maternal-fetal interface. This review aimed to synthesize current literature on the role of VD in the pathogenesis of EOPE. We reviewed in vitro, in vivo, and clinical studies to evaluate the impact of VD on immune modulation, angiogenesis, oxidative stress, and trophoblast migration and invasion in the placenta. This comprehensive review aims to provide insights into how VD deficiency exacerbates placental dysfunction, contributing to the development of EOPE. These insights support the rationale for VD supplementation as a potential preventive strategy and highlight the need for further clinical investigation.

Keywords:  early-onset preeclampsia; immune modulation; oxidative stress; placental angiogenesis; vitamin D

DOI:  https://doi.org/10.3389/fnut.2025.1598691
J Biol Chem. 2025 Jun 26. pii: S0021-9258(25)02278-1. [Epub ahead of print] 110428

NMR-guided Identification of CYP11A1-Adrenodoxin Interactions that Differentially Govern Cholesterol and Vitamin D3 Metabolism.

Janie E McGlohon, Jacob Logothetis, D Fernando Estrada.

  Cytochromes P450 (CYPs) are heme-containing enzymes essential for a range of biochemical processes, including steroidogenesis and vitamin D metabolism. Among mitochondrial CYPs, CYP11A1 catalyzes both cholesterol side-chain cleavage, producing pregnenolone, and hydroxylation of vitamin D3, producing 20(OH)D3. Previous studies have shown that substrates can modulate CYP11A1 protein-protein interactions with the redox partner Adrenodoxin (Adx), but the structural basis of the substrate-specific modulation towards Adx is not known. In this study, we investigated whether there exist contact(s) between CYP11A1 and Adx that are differentially influenced by cholesterol and vitamin D3, and whether these substrate-specific contacts are important for CYP11A1 monooxygenation of vitamin D3 or side chain cleavage of cholesterol. Utilizing 2D NMR spectroscopy in combination with solubilization of substrates with hydroxypropyl-β-cyclodextrin, we were able to isolate M77 of Adx α helix-3 as a substrate-specific contact towards CYP11A1. Site-directed mutagenesis of Adx M77 into M77L and M77S and mutagenesis of the corresponding CYP11A1 contact (W418A) revealed differential effects towards cholesterol and vitamin D3 metabolism. These data suggest that CYP11A1 protein-protein interactions with Adx are uniquely driven by substrate specificity and shed light on potential substrate-sensitive recognition in other mitochondrial CYPs. These findings are further discussed in the context of a modeled interaction between CYP11A1 and the reduced (functional) form of Adx in which Adx M77-CYP11A1 W418 is the driving constraint. Moreover, this study describes an NMR-based protocol that is broadly applicable towards the investigation of other substrate-sensitive CYP-redox partner interactions.

Keywords:  Adrenodoxin; CYP11A1; NMR; P450scc; cholesterol; cholesterol side-chain cleavage enzyme; vitamin D3

DOI:  https://doi.org/10.1016/j.jbc.2025.110428
Front Pediatr. 2025 ;13 1605489

The efficacy of calcium and vitamin D3 supplementation in improving pregnancy and neonatal outcomes.

Fei Wang, Mengqing Shen, Ting Wu, Yang Zhang, Yun Wang, Congyun Zhou.

   Objective: This study aims to evaluate the effects of combined calcium and vitamin D3 supplementation on maternal, pregnancy, and neonatal outcomes.
Methods: Clinical data from 122 pregnant women were retrospectively analyzed and categorized into three groups based on their actual intake: control (n = 48), Calcium 600-Vitamin D (600 mg calcium + 1,000 IU vitamin D daily, n = 41), and Calcium 1,200-Vitamin D (1,200 mg calcium + 1,000 IU vitamin D daily, n = 33). Baseline characteristics and outcomes including gestational diabetes, preeclampsia, gestational hypertension, birth weight, and Apgar scores were collected and analyzed.
Results: Calcium and vitamin D₃ supplementation was associated with significantly lower rates of gestational diabetes (P = 0.035), preeclampsia (P = 0.032), and gestational hypertension (P = 0.047), as well as reduced leg cramp frequency (P < 0.001). Neonatal outcomes improved with higher birth weights (P < 0.001) and better 1-minute Apgar scores (P < 0.001). Multivariable logistic regression confirmed that high-dose supplementation (Calcium 1,200-Vitamin D) was independently associated with reduced risks of gestational diabetes (OR = 0.423, 95% CI: 0.123-0.869, P = 0.043) and gestational hypertension (OR = 0.342, 95% CI: 0.126-0.875, P = 0.012). Both supplementation groups significantly reduced leg cramp frequency: Calcium 600-Vitamin D (OR = 0.507, 95% CI: 0.355-0.723, P < 0.001) and Calcium 1,200-Vitamin D (OR = 0.512, 95% CI: 0.256-0.985, P = 0.012). No significant differences were found in other outcomes including preterm birth, neonatal infection, or NICU admission (P > 0.05).
Conclusion: This study suggests that combined calcium and vitamin D₃ supplementation during pregnancy may help reduce the risk of pregnancy-related complications and improve neonatal outcomes, supporting its potential as an adjunct to prenatal care. Further large-scale and long-term studies are warranted to confirm these findings.

Keywords:  calcium; maternal health; neonatal outcomes; pregnancy; vitamin D

DOI:  https://doi.org/10.3389/fped.2025.1605489
Histochem Cell Biol. 2025 Jul 03. 163(1): 72

The protective role of vitamin E against the effects of hyperthyroidism on the rat pituitary-ovary axis.

Elfide Gizem Bakırhan, Süleyman Kaplan.

  This study investigated the effects of an experimentally induced hyperthyroidism model on the pituitary-ovarian axis and the possible protective role of vitamin E against these adverse effects. Wistar albino rats were divided into five groups of eight animals each: control ("Cont," no any treatment); hyperthyroidism ("Hypert," L-thyroxine at 0.3 mg/kg/day); "Sham" (1 ml/day corn oil); "Hypert + vit E" (L-thyroxine (0.3 mg/kg/day and 100 mg/kg/day/1 ml vitamin E); and "Vit E" (100 mg/kg/day/1 ml vitamin E) groups. At the end of the experiment, ovarian tissues were exposed to electron microscopic and stereological analyses. Thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), and superoxide dismutase (SOD) levels, as well as catalase (CAT) enzyme activity, were also determined in blood serum samples. Ovarian follicle numbers and volumes; corpus luteum and cortex volume; body weights; and TSH, FSH, and SOD levels decreased significantly in the Hypert group compared with the Cont group. However, connective tissue volume, CAT enzyme activity, and FT4 levels increased in the Hypert group compared with the Cont group. Vitamin E supplementation was observed to play a protective role on antral follicle, corpus luteum, and connective tissue volumes, CAT activity, and SOD and FSH levels. Hyperthyroidism reduces the number of ovarian follicles and may cause infertility problems. The adverse effect of hyperthyroidism on the pituitary-ovarian axis can be ameliorated by means of vitamin E, since this may have a homeostatic effect on this axis, as shown by the biochemical, histopathological, and stereological analyses in this study.

Keywords:  Hyperthyroidism; Ovary; Pituitary; Rat; Vitamin E

DOI:  https://doi.org/10.1007/s00418-025-02399-w
Expert Rev Gastroenterol Hepatol. 2025 Jul 04.

Reply to letter to the Editor: Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis.

Arup Choudhury, Vishal Sharma.



Keywords:  PPI; Proton pump inhibitor; Vitamin B12; systematic review; vitamin deficiency

DOI:  https://doi.org/10.1080/17474124.2025.2530608
Acta Inform Med. 2025 ;33(2): 90-95

The Modulatory Effects of Statins, Vitamin E, and Moringa Oleifera Extract on CD3 Expression in Ribociclib-Induced Hepatotoxicity in Rats.

Suha Khayri Ababneh, Alia Khwaldeh, Ali Ata Alsarhan, Israa Yousef, Ramadan Al-Shdefat, Aiman Shoiab, Sokiyna Ababneh.

   Background: The use of Ribociclib leads to hepatotoxicity that may be evaluated by the presence of infiltrated CD3 cells.
Objective: To evaluate the expression level of CD3 in the liver tissue of the control group and other groups exposed to Ribociclib and groups received Ribociclib and other treatments including vitamin E, statin, and and Moringa Olifera.
Methods: This experiment utilized fifty adult male albino rats (9 - 10 weeks old). The rats were randomly assigned into five groups (N = 10). Rats in the Group 1 (control) were given 2 ml normal saline. Group 2 rats received 5 mg/kg of ribociclib, while Group 3 rats received the same dose of ribociclib in conjunction with a daily dose of 200 mg/kg of a statin. Group 4 rats were given ribociclib treatment, alongside a daily dose of Vitamin E. Group 5 rats were given daily doses of 5 mg/kg ribociclib and a 200 mg/kg extract of Moringa Olifera. Following the end of the experiment, all rats were terminated and the liver tissues wee excised and fixed in formalin for 24 hours, processed, and stained for CD3 using indirect immunoperoxidase stain. Liver tissues were examined microscopically and the expression level was evaluated employing Adope photoshop. The relationships between groups were computed by independent T test.
Results: The study showed ribociclib caused hepatotoxicity of liver through the increased expression of CD3 in comparison to the control group. Treatment with statin and vitamin E lowered the expression of CD3, but this was not statistically significant (p>0.05), while the treatment with Moringa Olifera extract lowered significantly the expression of CD3 in the liver (p=0.043).
Conclusion: Giving Statin, Vitamin E, or Moringa Olifera extract can protect the liver from the liver toxicity that ribociclib causes.

Keywords:  CD3; Hepatotoxicity; Moringa Olifera Extract; Ribociclib; Statin

DOI:  https://doi.org/10.5455/aim.2025.33.90-95
World J Mens Health. 2025 Jun 25.

Role of Vitamin B₆ in Testosterone Synthesis.

Saleem Ali Banihani.

  Boosting testosterone production and maintaining its adequate concentrations in males is still a critical area of the ongoing research. Vitamin B₆ (VB6), also named pyridoxine, is an essential nutrient and biochemically an organic cofactor in various enzymatic reactions that activate several catabolic and anabolic processes, including energy production, neurotransmitter synthesis, immune system function. While various studies have revealed an indirect association between testosterone and VB6, a collective and comprehensive review of its role in testosterone synthesis has been lacking. Here, we review and summarize the involvement of VB6 in testosterone production and regulation. To achieve this, a thorough search of the PubMed and Scopus databases was conducted, identifying English-language articles published from August 1956 to the present using the keywords "vitamin B₆" and "pyridoxine" versus testosterone. Relevant studies contributing to a mechanistic understanding of this relationship were also included. In summary, VB6 is essential for testosterone production and regulation through various indirect mechanisms. These include its impact on hormonal signaling pathways like GnRH and prolactin, its role in activating enzymatic processes that affect testosterone synthesis, its modulation of androgen receptor sensitivity, and its protection against oxidative stress and homocysteine toxicity. Such critical role of VB6 in regulating testosterone levels in men is considered a strong incentive for researchers to conduct interventional studies.

Keywords:  Luteinizing hormone; Pyridoxine; Testosterone; Vitamin B₆

DOI:  https://doi.org/10.5534/wjmh.240250
Curr Microbiol. 2025 Jul 04. 82(8): 362

Computational Strategies to Enhance Vitamin B12 Biosynthesis Potential of Microbes.

Vidhyashri Nelliyan, Uma Doraisamy, Saranya Nallusamy, Bharathi Nathan, Uma Maheswari Thiyagamoorthy, Hemalatha Ganapathyswamy, Raghu Rajasekaran.

Vitamin B12 is a vital nutrient for the normal functioning of many metabolic processes. It has a characteristic corrinoid ring structure with a cobalt ion. Its complex chemical structure demands 30 enzyme-catalyzed steps for synthesis. Deficiency of this vitamin is common among individuals who are predominantly on a strict vegetarian diet. Large-scale production of this vitamin for dietary supplementation is primarily through microbial fermentation. This review discusses various computational approaches to improve vitamin B12 biosynthesis in microbes, namely metabolic engineering, synthetic biology, comparative genomics and molecular docking. Recent advancements, such as CRISPR-Cas9-based genome editing, artificial intelligence-driven pathway optimization, and the integration of multi-omics data, have revolutionized microbial engineering for enhanced cobalamin production. How these strategies maximize cobalamin biosynthesis in response to the increasing demand for this essential nutrient is discussed in this review. Using relevant case studies and references, the evaluation explores the unique advantages, disadvantages, features, and initiatives of each approach. The conclusion emphasizes the central role of these methods in advancing the field of microbial biotechnology addressing industrial challenges, and generating new ideas to improve vitamin B12 biosynthesis for global nutritional and therapeutic applications.

DOI: https://doi.org/10.1007/s00284-025-04325-8