bims-vitmet 2025-08-03 papers

bims-vitmet

Biomed News

on Vitamin metabolism

Issue of 2025–08–03
seven papers selected by
Onurkan Karabulut, Berkeley City College

Folate, vitamin B12, one carbon metabolism and the nervous system.
Global Trends in Vitamin D Research From 1985 to 2024.
Vitamin E is associated with inflammatory biomarkers and metabolic syndrome: insights from a population study.
Vitamin A5: Evidence, Definitions, Gaps, and Future Directions.
Vitamin K and women's health: a review.
Associations between vitamin K and systemic immune and inflammation biomarkers: a population-based study from the NHANES (2007-2020).
Vitamin B Therapy, Methionine Synthase and Cystathionine Beta-Synthase (CBS) Gene Polymorphisms, and Their Impact on Homocysteine and Cardiovascular Events in Ischemic Stroke With Normal Renal Function: A Randomized Controlled Trial.

J Neurol Sci. 2025 Jul 17. pii: S0022-510X(25)00244-8. [Epub ahead of print]476 123627

Folate, vitamin B12, one carbon metabolism and the nervous system.

Edward H Reynolds.

  Folate, vitamin B12 and one carbon metabolism are fundamental to genetics and epigenetics, and to nervous system development and brain health at all ages. The neuropsychiatric complications of deficiency or inborn errors of folate and vitamin B12 are well documented but there has been controversy about whether excess folic acid is also harmful to the nervous system, especially in the presence of vitamin B12 deficiency. There is now substantial and consistent clinical, epidemiological and experimental evidence that excess folic acid is potentially harmful to the nervous system. Recent experimental evidence confirms that both folate deficiency and excess impair cortical neurogenesis and is greatest when vitamin B12 deficiency is combined with excess folic acid. Excess folic acid increases the demand for vitamin B12 and aggravates the block in the folate cycle resulting from vitamin B12 deficiency. The balance between folate and vitamin B12 is crucial to methylation and to genetics and epigenetics. Both folate deficiency and excess may impair cellular differentiation and nervous system development by hypomethylation or hypermethylation of genes. In countries with folic acid fortification policies many subjects are exposed to excess folate. The long term genetic, epigenetic and transgenerational implications are yet to be clarified. The safe UL of folic acid should be reconsidered in relation to the vitamin B12 status of individuals and populations. The combination of a natural folate together with vitamin B12 would greatly improve the benefits and reduce the harms of current fortification policies.

Keywords:  Epigenetics; Folate; Fortification; Methylation; Nervous system; One carbon; Vitamin B12

DOI:  https://doi.org/10.1016/j.jns.2025.123627
PRiMER. 2025 ;9 33

Global Trends in Vitamin D Research From 1985 to 2024.

Mudasir Umer, Syed Mustafa Ali Shah, Camille Moeckel, Erum Azhar, Faisal Aziz, Abdul Waheed.

Introduction: Despite the importance of vitamin D, the number of vitamin D-related research publications has declined since 2020. This study examines trends in vitamin D-related research and National Institutes of Health (NIH) funding over 4 decades.
Methods: We conducted a PubMed search using medical subject headings terms to identify vitamin D-related papers published between 1985 and 2024. NIH funding data were from NIH Reporter; statistical significance was determined using negative binomial regression.
Results: Vitamin D-related publications rose steadily from 1985 to 2000, surged from 2008 to 2021, peaked at 6,019 in 2021, and then declined. A similar trend was seen in research on vitamin D-associated diseases. NIH funding for vitamin D research peaked at $52.4 million in 2013 but decreased to $10.5 million by 2024. A negative binomial regression showed a significant difference in publication rates (P<.001) in Vitamin D-related publications with "year" being a significant predictor across all models (P<.05). Negative binomial regression across 4 decades showed an annual publication growth of Vitamin D-related papers of 1.44% (P=.002) from 1985 to 1994, 4.78% (P<.001) from 1995 to 2004, and 12.88% (P<.001) from 2005 to 2014. In contrast, during the years 2015 to 2024, the annual increase dropped to 0.63% (P=.389), indicating a decline in publication activity.
Conclusions: Vitamin D research output surged through 2014 but has since lost momentum, declining from its 2021 peak and showing no significant annual growth from 2015 to 2024 (P=.389). These findings regarding vitamin D-related research raise important questions that remain unanswered.

DOI: https://doi.org/10.22454/PRiMER.2025.538113
Nutr Res. 2025 Jul 01. pii: S0271-5317(25)00087-9. [Epub ahead of print]140 161-172

Vitamin E is associated with inflammatory biomarkers and metabolic syndrome: insights from a population study.

Marcela Larissa Costa, Cristiane Hermes Sales, João Valentini Neto, Flávia Mori Sarti, Marcelo Macedo Rogero, Regina Mara Fisberg.

  Vitamin E is a potent antioxidant with anti-inflammatory properties and has been proposed as a promising agent in mitigating conditions associated with metabolic syndrome (MetS). We hypothesize that vitamin E is inversely associated with inflammatory biomarkers and low-grade systemic inflammation while showing a direct association with anti-inflammatory biomarkers. Additionally, we hypothesize that vitamin E will also be inversely associated with the risk of developing MetS. This population-based, cross-sectional study used data from the 2015 ISA-Nutrition survey, which included 368 adults and 212 older adults residing in urban São Paulo. Plasma vitamin E concentration was measured using high-performance liquid chromatography, and MetS was diagnosed based on International Diabetes Federation criteria. Biochemical and anthropometric parameters were assessed using standardized protocols. Restricted cubic spline regression models were applied to evaluate nonlinear associations between vitamin E, inflammation, and MetS. In the linear association between IL-6 and vitamin E, there is an interaction with HDL-c. Our findings also revealed a nonlinear J-shaped association between vitamin E and hepcidin (P < .0001), IL-1β (P < .0001), and adiponectin (P < .001), as well as an inverse association with low-grade systemic inflammation (P < .05). Additionally, vitamin E demonstrated a nonlinear association with MetS (P < .01). These results suggest that vitamin E may play a protective role in modulating inflammation and MetS within this specific urban population. Understanding the interactions between vitamin E, inflammation, and MetS risk is essential for developing prevention and dietary management strategies. Future research should explore the underlying mechanisms and assess optimal vitamin E intake to support metabolic health.

Keywords:  Alpha-tocopherol; Antioxidant; Inflammation; Metabolic syndrome; Vitamin E

DOI:  https://doi.org/10.1016/j.nutres.2025.06.009
Nutrients. 2025 Jul 14. pii: 2317. [Epub ahead of print]17(14):

Vitamin A5: Evidence, Definitions, Gaps, and Future Directions.

Torsten Bohn, Sascha Rohn, Volker Böhm, Marta Despotovic, Angel R de Lera, Wojciech Krezel, Omer Kucuk, Diána Bánáti, Ralph Rühl.

  With the emergence of a new vitamin concept-vitamin A5-it is essential to first clarify the basic definition of vitamins, particularly vitamin A. This article summarizes the foundational concepts and definitions of vitamins with particular relevance to the discovery, establishment, and categorization of new vitamin concepts. Vitamin A5 was discovered 80 years after the last vitamin was identified. It serves as an umbrella term for the dietary precursors 9-cis-β,β-carotene and 9-cis-13,14-dihydroretinol for the endogenous activator of the nuclear hormone receptor RXR, 9-cis-13,14-dihydroretinoic acid. However, several questions arise: Which criteria are typically used to identify a substance as a vitamin? How does vitamin A5 fit into the sometimes misleading definition of vitamin A? This review summarizes key findings and provides a comprehensive assessment of the current understanding, concluding that (a) vitamin A5 is a newly identified micronutrient that plays an important role in the prevention of diet-related diseases and (b) vitamin A5 is an important micronutrient that provides a plausible, mechanistic explanation for why a Western lifestyle diet low in vegetables and especially leafy vegetables can lead to a high prevalence of Western-lifestyle diseases, particularly neurological diseases and poor mental health.

Keywords:  healthy diet; leafy vegetables; longevity; mental health; neurodegenerative diseases

DOI:  https://doi.org/10.3390/nu17142317
Front Glob Womens Health. 2025 ;6 1590414

Vitamin K and women's health: a review.

Sharifa AlBlooshi.

  Vitamin K is a fat-soluble vitamin essential in various physiological functions such as blood coagulation, bone metabolism, cardiovascular health, glucose regulation, immune function, neuroprotection, and vascular health. In this narrative review, studies from databases including PubMed, Google Scholar, Scopus, and the institutional database of Zayed University were selected. The role of vitamin K in women's health, with a focus on osteoporosis, postmenopausal health, cardiovascular health, diabetes, cancer, kidney health, brain health, vascular health, and pregnancy were explored. The role of vitamin K in activating vitamin K-dependent proteins is essential for many of its functions. Vitamin K-dependent proteins such as osteocalcin and matrix gla protein are crucial to many physiological processes such as bone mineralization, vascular calcification, and cardiovascular health. It also modulates glucose metabolism by enhancing insulin sensitivity, reducing oxidative stress, and influencing β-cell function. Vitamin K exhibits anti-cancer properties in cancer research, particularly in breast, cervical, and ovarian cancer models. It also plays a role in brain health including cognitive function, neuroinflammation reduction, and neurodegenerative disease prevention. Similarly in kidney diseases, vitamin K has been linked to chronic kidney disease progression and vascular calcification. Vitamin K's role in pregnancy includes its impact on neonatal coagulation and neurodevelopmental outcomes. Despite the promising role of vitamin K, findings are mixed on its role in bone mineral density and fracture prevention, cardiovascular protection, protection against vascular calcification, diabetes prevention, cancer risk, kidney dysfunction, and its role in maternal and child health. These highlight the need for further research, particularly longitudinal and randomized controlled trials, to determine optimal intake, efficacy of supplementation, and long-term health impacts of vitamin K in women.

Keywords:  bone health; cancer; cardiovascular disease; diabetes; immune system; menopause; vitamin K; women's health

DOI:  https://doi.org/10.3389/fgwh.2025.1590414
Front Nutr. 2025 ;12 1625209

Associations between vitamin K and systemic immune and inflammation biomarkers: a population-based study from the NHANES (2007-2020).

Wenjiao Luo, Dong Ye, Kun Zhao, Liang Zhou, Yanfei Wu, Qiuhua Ge.

   Background: With the aging of the population, finding effective interventions and treatments to delay chronic inflammation-related diseases is an urgent problem to be solved. Previous studies on animals have proposed that vitamin K can inhibit inflammation and may be a potential regulator of the immune inflammatory response. These findings suggested that increasing intake of vitamin K might also help reduce inflammation.
Methods: This study included 36,895 people from the National Health and Nutrition Examination Survey (2007-2020). Multivariate linear regression and restricted cubic spline analyses were conducted to explore the association between vitamin K intake and various immune inflammatory factors. Subgroup analyses were performed based on age, gender, ethnicity, BMI, hyperlipidemia, diabetes and hypertension.
Results: After multivariable adjustment, vitamin K intake is negatively correlated with SII, SIRI, SIIRI, NLR, white blood cell, neutrophil, and monocyte. When the level of vitamin K intake was less than 237.7 mcg/d, RAR showed a significant decreasing trend with the increase of vitamin K. When the vitamin K intake level was lower than 75.1 mcg/d, the basophil showed a downward trend with the increase of intake. However, when vitamin K levels exceed the inflection point, the above association no longer exists.
Conclusion: These findings reveal that vitamin K intake is associated with reduced inflammatory status and improvements in immune inflammatory biomarkers. Vitamin K may modulate systemic immune and inflammatory markers, which may play a role in the development of chronic inflammation.

Keywords:  neutrophil-tolymphocyte ratio; systemic immune inflammatory index; systemic immune-inflammation response index; systemic inflammatory response index; vitamin K

DOI:  https://doi.org/10.3389/fnut.2025.1625209
Cureus. 2025 Jun;17(6): e86727

Vitamin B Therapy, Methionine Synthase and Cystathionine Beta-Synthase (CBS) Gene Polymorphisms, and Their Impact on Homocysteine and Cardiovascular Events in Ischemic Stroke With Normal Renal Function: A Randomized Controlled Trial.

Neetu Kataria, Vasantha C Kalyani, Shashi Ranjan Mani Yadav, Mritunjai Singh, Anissa A Mirza, Nitesh Kumar, Niraj Kumar.

   BACKGROUND: Hyperhomocysteinemia cases were found to be higher in hilly regions due to factors such as high altitude and dehydration. There is limited research on methionine synthase (MS) and cystathionine beta-synthase (CBS) gene polymorphisms among stroke patients in Southeast Asia. The primary objective of the study was to determine the efficacy of vitamin B therapy in lowering homocysteine levels, and the secondary objective was to investigate the prevalence and impact of MS and CBS gene polymorphisms on treatment outcomes and cardiovascular events.
METHODS: A randomized controlled trial was conducted on 90 ischemic stroke patients at a tertiary care hospital, Rishikesh, India. Participants received either vitamin B therapy (B6, B9, B12) or standard therapy for four months. Tools were genetic polymorphisms (polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)) testing, National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS) scores, mean homocysteine, mean vitamin B12, and mean folate levels.
RESULTS: The prevalence of MS-AG and CBS-TT polymorphism frequencies was 6% and 12%, respectively. At four months, the vitamin group showed a significant reduction in homocysteine as 8.6 vs. 19 µmol/L in standard therapy, improved mRS scores, and improved vitamin B12 and folate levels with p < 0.001. Vitamin B12 deficiencies and green vegetable intake were key predictors of hyperhomocysteinemia. Clinical outcomes included one recurrent stroke, eight cardiovascular events, and six vascular deaths.
CONCLUSION: Our observations indicated that vitamin B therapy effectively reduced homocysteine and addressed deficiencies in ischemic stroke patients. However, genetic polymorphism was found to be less prevalent in this hilly region. Combining the role of vitamin B on homocysteine, along with reducing stroke severity and functional disability, leads to early recovery of the stroke patient and reduces rehospitalisation.

Keywords:  gene polymorphisms; homocysteine; ischemic stroke; recurrent cardiovascular events; vitamin b supplementations

DOI:  https://doi.org/10.7759/cureus.86727