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Nutrients
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Exploring the Effect of Folate and Other B Vitamins on...
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Exploring the Effect of Folate and Other B Vitamins on Brain Health and Disease

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: 15 December 2025 | Viewed by 10031

Special Issue Editor

Dr. Edward Quadros

E-Mail Website
Guest Editor
Department of Medicine, SUNY Downstate Medical Center, New York, NY 11203, USA
Interests: vitamin B12 and folate metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vitamins of the B complex group play critical roles in cellular metabolism, and their deficiency leads to specific disorders. This is of utmost significance in embryonic development, especially in the development of the brain and the structural refinement and metabolic functioning of the neonatal and adult brain.

This Special Issue will focus on the role of these vitamins in brain development and function, the disruption of this process, and potential strategies for the prevention and treatment of brain disorders resulting from the deficiency or disrupted metabolism of B vitamins. Special emphasis will be placed on B12 and folate because of their role in fetal and neonatal brain development and in adult brain functional disorders such as depression, dementia, and schizophrenia. We also aim to explore genetic and epigenetic influences on developmental disorders, as well as the role that methyl donors play in regulating this process.

Dr. Edward Quadros
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • folate
  • vitamin B12
  • brain development
  • brain metabolism
  • brain function
  • epigenetics
  • gene regulation
  • genetic disorders

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Published Papers (3 papers)

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14 pages, 933 KiB  
Article
Safety and Efficacy of High-Dose Folinic Acid in Children with Autism: The Impact of Folate Metabolism Gene Polymorphisms
by Caiyun Zhang, Yanlin Chen, Fang Hou, Yanzhi Li, Wanxin Wang, Lan Guo, Caixia Zhang, Li Li and Ciyong Lu
Nutrients 2025, 17(9), 1602; https://doi.org/10.3390/nu17091602 - 7 May 2025
Viewed by 341
Abstract
Background/Objectives: Research on the safety and efficacy of high-dose folinic acid in Chinese children with autism spectrum disorder (ASD) is limited, and the impact of folate metabolism gene polymorphisms on its efficacy remains unclear. This trial aimed to evaluate the safety and efficacy [...] Read more.
Background/Objectives: Research on the safety and efficacy of high-dose folinic acid in Chinese children with autism spectrum disorder (ASD) is limited, and the impact of folate metabolism gene polymorphisms on its efficacy remains unclear. This trial aimed to evaluate the safety and efficacy of high-dose folinic acid intervention in Chinese children with ASD and explore the association between folate metabolism gene polymorphisms and efficacy. Methods: A 12-week randomized clinical trial was conducted, including 80 eligible children with ASD, randomly assigned to an intervention group (n = 50) or a control group (n = 30). The intervention group was administered folinic acid (2 mg/kg/day, max 50 mg/day) in two divided doses. Efficacy was measured using the Psycho-Educational Profile, Third Edition (PEP-3) at baseline and 12 weeks by two trained professionals blind to the group assignments. Methylenetetrahydrofolate reductase (MTHFR C677T, MTHFR A1298C), methionine synthase (MTR A2756G), and methionine synthase reductase (MTRR A66G) were genotyped by the gold standard methods in the intervention group. Results: 49 participants in the intervention group and 27 in the control group completed this trial. Both groups showed improvements from baseline to 12 weeks across most outcome measures. The intervention group demonstrated significantly greater improvements in social reciprocity compared to the control group. Children with MTHFR A1298C or MTRR A66G mutations demonstrated greater improvements in various developmental domains than wild type. Folinic acid may be more effective in certain genotype combinations, such as MTHFR C677T and A1298C. No significant adverse effects were observed during the intervention. Conclusions: High-dose folinic acid may be a promising intervention for children with ASD, and its efficacy is associated with folate metabolism gene polymorphisms. High-dose folinic acid intervention may promote better neurodevelopmental outcomes by alleviating folate metabolism abnormalities caused by single or combined mutations in folate metabolism genes. Full article
(This article belongs to the Special Issue Exploring the Effect of Folate and Other B Vitamins on Brain Health and Disease)
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9 pages, 1774 KiB  
Article
Dietary Choline Intake Is Beneficial for Cognitive Function and Delays Cognitive Decline: A 22-Year Large-Scale Prospective Cohort Study from China Health and Nutrition Survey
by Feifei Huang, Fangxu Guan, Xiaofang Jia, Jiguo Zhang, Chang Su, Wenwen Du, Yifei Ouyang, Li Li, Jing Bai, Xiaofan Zhang, Yanli Wei, Bing Zhang, Yuna He and Huijun Wang
Nutrients 2024, 16(17), 2845; https://doi.org/10.3390/nu16172845 - 26 Aug 2024
Cited by 2 | Viewed by 5949
Abstract
Pre-clinical studies have discovered the neuroprotective function and the benefit for cognitive function of choline. However, it remains unclear whether these benefits observed in animal studies also work in humans. The aims of this study are to examine the effects of dietary choline [...] Read more.
Pre-clinical studies have discovered the neuroprotective function and the benefit for cognitive function of choline. However, it remains unclear whether these benefits observed in animal studies also work in humans. The aims of this study are to examine the effects of dietary choline intake on cognitive function and cognitive decline during ageing in middle-aged and elderly Chinese. We included 1887 subjects aged 55~79 years with 6696 observations from the China Health and Nutrition Survey cohort study. The subjects were followed up for 6 to 21 years, with an average of 12.2 years. A dietary survey was conducted over 3 consecutive days with a 24 h recall, using household weight-recording methods. Based on the China Food Composition, data from USDA, and published literature, the dietary choline intake was calculated as the sum of free choline, phosphocholine, phosphatidylcholine, sphingomyelin, and glycerophosphocholine. Cognitive function was assessed using a subset of the Telephone Interview for Cognitive Status-modified (TICS-m) items. In order to eliminate the different weight of scores in each domain, the scores were converted by dividing by the maximum score in each domain, which ranged from 0 to 3 points. Higher cognitive scores represented better cognition. We used two-level mixed effect models to estimate the effects of dietary choline intake on cognitive score and cognitive decline rate in males and females, respectively. The average dietary choline intake was 161.1 mg/d for the baseline. After adjusting for confounders, the dietary choline intake was significantly associated with higher cognitive score in both males and females. The cognitive score in the highest quartile group of dietary choline was 0.085 for males and 0.077 for females–higher than those in the lowest quartile group (p < 0.01 for males, p < 0.05 for females). For every 10-year increase in age, the cognitive score decreased by 0.266 for males and 0.283 for females. The cognitive score decline rate of the third quartile group of dietary choline was 0.125/10 years lower than that of the lowest quartile group in females (p < 0.05). Dietary choline intake not only improves cognitive function, but also postpones cognitive decline during the aging process. The findings of this study highlight the neuroprotective benefit of choline in the middle-aged and elderly Chinese population, especially among females. Full article
(This article belongs to the Special Issue Exploring the Effect of Folate and Other B Vitamins on Brain Health and Disease)
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29 pages, 353 KiB  
Brief Report
Bibliometric Analysis and a Call for Increased Rigor in Citing Scientific Literature: Folic Acid Fortification and Neural Tube Defect Risk as an Example
by Brynne Boeck and Cara J. Westmark
Nutrients 2024, 16(15), 2503; https://doi.org/10.3390/nu16152503 - 1 Aug 2024
Viewed by 3119
Abstract
The health benefits of vitamin B9 (folate) are well documented, particularly in regard to neural tube defects during pregnancy; however, much remains to be learned regarding the health effects and risks of consuming folic acid supplements and foods fortified with folic acid. In [...] Read more.
The health benefits of vitamin B9 (folate) are well documented, particularly in regard to neural tube defects during pregnancy; however, much remains to be learned regarding the health effects and risks of consuming folic acid supplements and foods fortified with folic acid. In 2020, our laboratory conducted a population-based analysis of the Food Fortification Initiative (FFI) dataset to determine the strength of the evidence regarding the prevalence of neural tube defects (NTD) at the national level in response to mandatory fortification of cereal grains with folic acid. We found a very weak correlation between the prevalence of NTDs and the level of folic acid fortification irrespective of the cereal grain fortified (wheat, maize, or rice). We found a strong linear relationship between reduced NTDs and higher socioeconomic status (SES). Our paper incited a debate on the proper statistics to employ for population-level data. Subsequently, there has been a large number of erroneous citations to our original work. The objective here was to conduct a bibliometric analysis to quantitate the accuracy of citations to Murphy and Westmark’s publication entitled, “Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset”. We found a 70% inaccuracy rate. These findings highlight the dire need for increased rigor in citing scientific literature, particularly in regard to biomedical research that directly impacts public health policy. Full article
(This article belongs to the Special Issue Exploring the Effect of Folate and Other B Vitamins on Brain Health and Disease)
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