ReviewFood and nutrition bulletin2024
Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?
Review in Food and nutrition bulletin, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed.
- Dietary Patterns, Micronutrient Adequacy, and Metabolic Vulnerability in Alzheimer's Disease: A Critical Narrative Review.Nutrients · 2026Review
- Nutrient and Discretionary Food Intake in Vegan Adult Australians: A Cross-Sectional Study.Nutrition bulletin · 2026Article
- Oxidative Stress and Male Infertility: A Critical Analysis of Current Diagnostic and Therapeutic Methods.Antioxidants (Basel, Switzerland) · 2026Review
- Canine Idiopathic Epilepsy as a Natural Animal Model for Human Epilepsy: A Scoping Review Highlighting Metabolic Perspectives Beyond the Brain.Nutrients · 2026Article
- Associations Between Concentrations of Vitamin D3, Vitamin B12, and Folate and the Well-Being of Medical Students.Nutrients · 2026Article
- B vitamins and cardiovascular health: mechanisms, clinical evidence, and precision prevention strategies.Nutrition & metabolism · 2026Review
- Vitamins as Modulators of Neurodegenerative Disease Pathways: Mechanisms and Therapeutic Perspectives.Nutrients · 2026Review
- Taurine and Betaine, Alone and in Combination, Mitigate Lysis of Canine Erythrocytes in an In Vitro Model of Iron-Deficiency Anemia.Veterinary and animal science · 2026Article
- Longitudinal Trends and Analytical Consistency of Folate and Vitamin BBiomedicines · 2026Article
- Skin Hyperpigmentation as Initial Manifestation of Vitamin BCase reports in medicine · 2026Article
- B Vitamins and Ocular Health.Clinical ophthalmology (Auckland, N.Z.) · 2026Review
- Fortification, folate and vitamin B12 balance, and the nervous system. Is folic acid excess potentially harmful?European journal of clinical nutrition · 2025Review
- Homocysteine in the Cardiovascular Setting: What to Know, What to Do, and What Not to Do.Journal of cardiovascular development and disease · 2025Review
- Fresh Genetic Insights Into Micronutrients Influences on Restless Legs Syndrome Risk.Food science & nutrition · 2025Article
- Scientific and Public Health Challenges in Folic Acid Supplementation: Insights from Brazil and Global Implications.Nutrients · 2025Review
- Article
- Folate from probiotic bacteria and its therapeutic applications.Archives of microbiology · 2025Review
- Recent Advances on the Role of B Vitamins in Cancer Prevention and Progression.International journal of molecular sciences · 2025Review
- Perinatal nutrition as a key regulator of genomic imprinting: a new paradigm for maternal-child health.Frontiers in nutrition · 2025Article
- Toxic Effects of Excess Vitamins A, B6, and Folic Acid on the Nervous System.Behavioural neurology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
backgroundIn the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements.
objectivesThe objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians.
resultsCognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency.
conclusionThe evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.