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Open research questions in Folate and B Vitamins Research

41 unresolved questions extracted from the limitations and future-work sections of 478 Folate and B Vitamins Research papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Moreover, the immunotherapy-related analysis was validated only in the public IMvigor210 cohort of metastatic urothelial carcinoma; therefore, this represents a cross-cancer exploratory validation rather than disease-specific confirmation in STAD, and the generalizability of the immunotherapy findings remains to be further verified in real-world STAD immunotherapy cohorts. Therefore, future studies are warranted to validate the model in large-scale prospective clinical cohorts, thereby excluding potential data selection bias and cohort heterogeneity.

    Construction of a risk model based on folate metabolism-related genes to predict prognosis and immunological characteristics of stomach adenocarcinoma · 2026 · DOI

  • Studies assessing dietary intake frequently report an inverse association, particularly for rectal cancer, whereas analyses of circulating vitamin B12 concentrations yield heterogeneous, and often conflicting findings.

    VITAMIN B12 AND COLORECTAL CANCER: FRIEND OR FOE? A NARRATIVE REVIEW OF AVAILABLE EVIDENCE · 2026 · DOI

  • The 2024 NICE guidelines acknowledge that treatment frequency should be guided by individual symptom response rather than current one-size-fits-all schedules; however, the symptom heterogeneity underpinning this recommendation remains poorly characterized.

    Patient-reported symptom profiles in vitamin B12 deficiency and pernicious anaemia: A cross-sectional study using latent class analysis · 2026 · DOI

  • Despite identified positive relationships between vitamin B12 (B12) and mitochondrial biology, the impact of B12 supplementation on skeletal muscle mitochondria, in advanced age, has not been examined.

    Vitamin B12 improves skeletal muscle mitochondrial biology in aged mice · 2026 · DOI

  • BackgroundMaternal micronutrient deficiencies (MNDs) and inflammation contribute to adverse birth outcomes While the individual effects of MNDs have been studied, the consequence of co-occurring MNDs remains unclear.

    Maternal micronutrient deficiencies and inflammation and their associations with adverse birth outcomes: The BRINDA project · 2026 · DOI

  • The main strengths of this study include a large sample size, high follow-up rate, and blood sampling in both the second and third tri- mesters. Serum retinol was measured using HPLC, the gold standard method. Few studies have assessed vitamin A status in pregnant women in high-income countries, highlighting the relevance of our work. However, the post-hoc design of this study may limit its conclu- sions. Also, the study population was relatively homogenous, well- educated Caucasian women with high socioeconomic status and low-risk pregnancies, which may limit generalizability due to poten- tial selection bias. Participation in the original trial may have been influenced by the exercise intervention, possibly attracting healthier individuals. Additionally, most participants did not exceed the rec- ommended pregnancy weight gain, further limiting generalizability. While serum retinol is useful for detecting deficiency, it may not reflect marginal vitamin A status due to homeostatic regulation and limited correlation with intake or clinical symptoms (34, 52). Lastly, multiple comparisons increase the risk of false positives, so findings should be interpreted with caution. 4.2007.81). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin.

    Maternal vitamin A levels during second and third trimester and associations with offspring’s birth weight: a longitudinal cohort post-hoc study · 2026 · DOI

  • Randomized controlled school based interventions to prevent childhood obesity: systematic review from 2006 to 2009 M.E. Pérez-Morales, M. Bacardí-Gascón, A. Jiménez-Cruz y A. Armendáriz-Anguiano..........................................

    Micronutrient supplementation may reduce symptoms of depression in Guatemalan women · 2026 · DOI

  • This study has several strengths. First, the use of complete enumeration rather than probability sampling - every eligible patient seen at the center during the 30-month study period was included - eliminates sampling bias and yields narrow 95% CIs (margin of error ≤ ±4% for every major prevalence estimate), supporting the precision of the reported figures. Second, the large sample size, comprehensive multi- parameter nutritional assessment, application of standardized international deficiency criteria, and examination of gender- and age-stratified patterns, including multiple concurrent deficiencies, allow a granular description of the nutritional landscape in this clinical population. Third, the study characterizes nutritional status among patients actively seeking nutrition-focused healthcare, a population that is poorly represented in community-based surveys but increasingly relevant as nutrition clinics expand in tertiary care. Several limitations should also be acknowledged. Although the census approach removes sampling bias, the study population was restricted to patients self-referred or clinically referred to a specialized nutrition center at a tertiary institution; the prevalence estimates are therefore conditional on clinical presentation and are not directly generalizable to the source community (Berkson's bias). The subsamples tested for 25(OH)D and vitamin B12 were smaller than the full cohort because biochemical testing was performed on clinical indication rather than universally; post hoc precision nevertheless remained acceptable (±2.9% and ±4.0%, respectively, at 95% CI). The cross-sectional design with retrospective data acquisition precludes inference about temporal relationships or causality. On account of high patient load, difficulty in digitalizing, Twenty-four-hour dietary recall data were available for only a small convenience subset of participants; although gender comparisons using the Mann-Whitney U test showed no statistically significant differences, these analyses are severely underpowered, and the results should not be interpreted as evidence for the absence of a gender gap in dietary intake. Definitive inference will require a prospective study with universal dietary assessment. Detailed data on potential confounders - including socioeconomic status, education, occupation, and habitual dietary patterns - were not collected, limiting our ability to adjust for these variables in the multivariable analyses.

    Prevalence of Nutritional Deficiencies Among Patients Attending a Nutrition Clinic at a Tertiary Care Hospital in Andhra Pradesh, South India: A Retrospective Cross-Sectional Study · 2026 · DOI

  • The association between MTHFR gene polymorphism and complications related to a hypercoagulable state in patients with thalassemia remains controversial: some scientists report a statistically significant relationship, while others largely refute this claim.

    Impact of methylenetetrahydrofolate reductase gene polymorphism on cancer and thalassemia incidence · 2025 · DOI

  • However, the impacts on the genetic variation of methylene tetrahydrofolate reductase (MTHFR) on plasma homocysteine levels in the Northeast Chinese population have not been studied.

    The relationship between plasma homocysteine levels and MTHFR gene variation, age, and sex in Northeast China · 2019 · DOI

  • CONCLUSIONS: The evidence derived from these limited studies suggests that 2000 microg doses of oral vitamin B(12) daily and 1000 microg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short-term haematological and neurological responses in vitamin B(12)-deficient patients.

    Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials · 2006 · DOI

  • BACKGROUND: An association between depression and folate status has been demonstrated in clinical studies, whereas data are sparse on the relationship between depression and other components of 1-carbon metabolism such as vitamin B12, homocysteine, and the methylenetetrahydrofolate reductase 677C-->T polymorphism.

    Folate, Vitamin B12, Homocysteine, and the MTHFR 677C→T Polymorphism in Anxiety and Depression · 2003 · DOI

  • This high degree of correlation between increased serum unsaturated vitamin B12 binding capacity and fibrolamellar hepatocellular carcinoma has not been reported before.

    High serum vitamin B12 binding capacity as a marker of the fibrolamellar variant of hepatocellular carcinoma. · 1982 · DOI

  • It remains to be shown whether the malabsorption of B12 is due to competitive inhibition by metformin in the distal ileum or whether the enzyme system involved in the active absorp- tetracycline therapy after 687 tion of B12 is inactivated by the drug.

    Vitamin-B <sub>12</sub> Status of Patients on Long-term Metformin Therapy · 1971 · DOI

  • Although its potential protective role in colorectal carcinogenesis is biologically based, it remains insufficiently confirmed, emphasising the need for further integrated research.

    VITAMIN B12 AND COLORECTAL CANCER: FRIEND OR FOE? A NARRATIVE REVIEW OF AVAILABLE EVIDENCE · 2026 · DOI

  • These preliminary findings support further investigation of amniotic-fluid metabolomics as a potential tool for studying the fetal biochemical environment.

    Maternal Nutritional Adherence and Second-Trimester Amniotic-Fluid Metabolomic Profiles: An Exploratory Study · 2026 · DOI

  • Despite the evident role of nutrients, integrated strategies for personalized nutritional correction are still lacking in domestic gynecological practice.

    Nutritional support for women’s health under chronic stress (micronutrient supplementation) · 2026 · DOI

  • Iron deficiency is an underrecognized independent risk factor for CVD, and multiple concurrent deficiencies synergistically increase risk.

    Micronutrient Deficiencies and Cardiovascular Disease: A Binational Analysis of NHANES and CHARLS · 2026 · DOI

  • Background Lipoprotein(a) [Lp(a)] is a causal driver of atherosclerosis, yet the interaction between Lp(a)-driven lipid accumulation and a prothrombotic state induced by hyperhomocysteinemia has not been systematically investigated in this high-risk population.

    Prognostic impact of the combined effects of lipoprotein(a) and homocysteine in patients with premature myocardial infarction: a prospective cohort study · 2026 · DOI

  • Further research is necessary to elucidate effects of high doses and long-term consumption of amino acid supplements on immune system, brain function, muscle protein balance, synthesis of toxic metabolites, and tumor growth and examine their suitability under certain circumstances.

    Side Effects of Amino Acid Supplements · 2022 · DOI

  • Urgent public health responses are warranted in high-risk regions, considering the contribution of thiamine deficiency to infant mortality and research suggesting that even subclinical thiamine deficiency in childhood may have lifelong neurodevelopmental consequences.

    Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs · 2018 · DOI

  • Food fortification and maternal and/or infant thiamine supplementation have proven effective in raising thiamine status and reducing the incidence of infantile beriberi in regions where thiamine deficiency is prevalent, but trial data are limited.

    Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs · 2018 · DOI

  • Neurobiological studies are warranted to document the effect of maternal vitamin D insufficiency during pregnancy on the foetal brain and the window of vulnerability.

    Prevalence of autism according to maternal immigrant status and ethnic origin · 2011 · DOI

  • Studies of the C677T allele in relation to oral clefts, Down syndrome, and fetal anticonvulsant syndrome either have yielded conflicting results or have not been yet replicated.

    5, 10-Methylenetetrahydrofolate Reductase Gene Variants and Congenital Anomalies: A HuGE Review · 2000 · DOI

  • Vitamin supplements are an effective means of obtaining adequate folate but little is known about vitamin use during the postpartum period, a time when women may be at risk of folate deficiency and associated health risks.

    Postpartum Supplemental Vitamin Use among Hispanic Women on the US/Mexico Border: Need for Community Health Education · 1999 · DOI

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41 open questions have been extracted from the limitations and future-work passages of 478 Folate and B Vitamins Research papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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