Trial reportEuropean journal of nutrition2016
Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial.
Trial report in European journal of nutrition, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01105351 (Effect of Mild Increase in Folic Acid Intake on the Distribution of Folate Forms in Relation to a Common Polymorphism in One Folate Catabolising Enzyme), which is not on this map. Cited by 16 papers, 3 of them syntheses that pooled it.
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.
Effect of Mild Increase in Folic Acid Intake on the Distribution of Folate Forms in Relation to a Common Polymorphism in One Folate Catabolising Enzyme
Who cites it
16 citing papers in PubMed, 3 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Unmetabolized Folic Acid: Biology, Epidemiology, and Clinical Consequences: A Systematic Review.Nutrients · 2026Pooled it
- Prenatal Folic Acid Supplements and Offspring's Autism Spectrum Disorder: A Meta-analysis and Meta-regression.Journal of autism and developmental disorders · 2022Pooled it
- The impact of MTHFR 677 C/T genotypes on folate status markers: a meta-analysis of folic acid intervention studies.European journal of nutrition · 2017Pooled it
- Serum Concentrations of Folate Forms Following Supplementation of Multimicronutrients with 400 µg or 800 µg Mix of (6S)-5-Methyltetrahydrofolate and Folic Acid (1:1) in Women of Childbearing Age.Molecular nutrition & food research · 2024Trial
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- How Increased Dietary Folic Acid Intake Impacts Health Outcomes Through Changes in Inflammation, Angiogenesis, and Neurotoxicity.Nutrients · 2025Review
- Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review.Nutrients · 2023Review
- The acute postprandial response of homocysteine to multivitamin and mineral supplementation with a standard meal is not impaired in older compared to younger adults.European journal of nutrition · 2023Article
- Article
- Article
- Review
- Unmetabolized folic acid is associated with TNF-α, IL-1β and IL-12 concentrations in a population exposed to mandatory food fortification with folic acid: a cross-sectional population-based study in Sao Paulo, Brazil.European journal of nutrition · 2021Article
- Maternal Haplotypes inGenes · 2019Article
- High dietary folate in pregnant mice leads to pseudo-MTHFR deficiency and altered methyl metabolism, with embryonic growth delay and short-term memory impairment in offspring.Human molecular genetics · 2017Article
- Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.Nutrients · 2016Article
- Association between Serum Unmetabolized Folic Acid Concentrations and Folic Acid from Fortified Foods.Journal of the American College of NutritionArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeUnmetabolized folic acid (UMFA) is common in serum of elderly individuals receiving folic acid (FA)-fortified foods or supplements. We studied the effect of supplementing FA or B-complex on serum concentrations of (6S)-5-methyltetrahydropteroylglutamate [(6S)-5-CH3-H4Pte] and UMFA in elderly people and explored factors associated with detectable UMFA post-supplementation.
methodsThis is a randomized single-blind non-controlled trial on 58 elderly people using daily 400 µg FA (n = 31) or 400 µg FA, 10 µg cyanocob(III)alamin and 8 mg pyridoxine (n = 27) for a median of 23 days. Main outcome includes changes in concentrations of serum (6S)-5-CH3-H4Pte and UMFA.
resultsTotal homocysteine declined by a median of 1.6 (p = 0.074) in the FA and 1.3 µmol/L (p = 0.009) in the B-complex arms (p = 0.66 between the arms). Serum (6S)-5-CH3-H4Pte significantly (p < 0.001 vs. baseline) increased by a median of 9.2 and 6.5 nmol/L in the FA and B-complex groups, respectively (p = 0.152 between the groups). Compared to FA, B-complex reduced cystathionine and caused lower post-intervention serum UMFA, percentage of UMFA to (6S)-5-CH3-H4Pte and prevalence of UMFA ≥ 0.21 nmol/L. Higher serum cystathionine and whole-blood folate predicted higher post-intervention serum UMFA.
conclusionsFA caused higher UMFA as compared to B-complex. Pyridoxine appears to improve folate recycling. Data on serum UMFA should be interpreted in relation to other vitamins involved in folate metabolism. Serum UMFA is suggested to play a sensory role through which the cell recognizes FA available for metabolism via dihydrofolate reductase.
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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.