Evidence map›Paper›PMID 32860400›Full record

ArticleThe American journal of clinical nutrition2020

High folic acid or folate combined with low vitamin B-12 status: potential but inconsistent association with cognitive function in a nationally representative cross-sectional sample of US older adults participating in the NHANES.

Regan L Bailey, Shinyoung Jun, Lisa Murphy, Ralph Green, Jaime J Gahche, Johanna T Dwyer, Nancy Potischman, George P McCabe, Joshua W Miller

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of clinical nutrition, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05896878 (The Effects of Daily Anti-inflammatory Supplementation on Foundation Pain Index Scores in Chronic Opiate Patients), which is not on this map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
9.1field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT05896878 naterminatednot on this mapstarted 2023, after this paper: background citation

The Effects of Daily Anti-inflammatory Supplementation on Foundation Pain Index Scores in Chronic Opiate Patients

TypeinterventionalSponsorHudson MedicalRan2023 to 2024Enrolled1ConditionsPain, Chronic, Opioid Dependence, Opioid Use, Inflammation ChronicArmsRoot.Health Dietary Supplement
3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

  1. Pooled it
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  4. Higher vitamin BAlzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 1 country.

Regan L BaileyDepartment of Nutrition Science, Purdue University, West Lafayette, IN, USA.
Shinyoung JunDepartment of Nutrition Science, Purdue University, West Lafayette, IN, USA.
Lisa MurphyDepartment of Nutrition Science, Purdue University, West Lafayette, IN, USA.
Ralph GreenDepartment of Pathology and Laboratory Medicine, University of California, Davis, Davis, CA, USA.
Jaime J GahcheOffice of Dietary Supplements, NIH, Bethesda, MD, USA.
Johanna T DwyerOffice of Dietary Supplements, NIH, Bethesda, MD, USA.
Nancy PotischmanOffice of Dietary Supplements, NIH, Bethesda, MD, USA.
George P McCabeDepartment of Statistics, Purdue University, West Lafayette, IN, USA.
Joshua W MillerDepartment of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA.
Purdue University West Lafayette · USOffice of Dietary Supplements · USRutgers, The State University of New Jersey · USTufts University · USUniversity of California, Davis · US

Funding

Translational Research Support CoreP30ES005022 · NIEHS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI PANOS G. GEORGOPOULOS · 1988 to 2026
$47.4M
Development of a Total Nutrient IndexU01CA215834 · NCI · TEXAS A&M AGRILIFE RESEARCH · PI REGAN BAILEY, JANET A. TOOZE · 2017 to 2026
$2.2M
NCI NIH HHS U01 CA215834NIEHS NIH HHS P30 ES005022
6 · The paper itself

Abstract

backgroundPotential safety concerns relative to impaired cognitive function may exist when high folic acid exposures are combined with low vitamin B-12 status.

objectivesWe aimed to examine the relation of the coexistence of high folate and low vitamin B-12 status with cognitive function, utilizing various definitions of "high" folate status.

methodsCross-sectional data from older adults (≥60 y; n = 2420) from the 2011-2014 NHANES were analyzed. High folate status was defined as unmetabolized serum folic acid (UMFA) > 1 nmol/L or serum total folate > 74.1 nmol/L, and low vitamin B-12 status as methylmalonic acid > 271 nmol/L or serum vitamin B-12 < 150 pmol/L. Logistic regression models estimated ORs of scoring low on 1 of 4 cognitive tests: the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease Delayed Recall (CERAD-DR) and Word Learning tests, and the Animal Fluency test (AF).

resultsA significant interaction was observed relative to scoring low on the DSST (<34; UMFA; P-interaction = 0.0071) and AF (serum folate; P-interaction = 0.0078) for low vitamin B-12 and high folate status. Among those with low vitamin B-12, high UMFA or high serum total folate was associated with higher risk of scoring low on the DSST (OR: 2.16; 95% CI: 1.05, 4.47) and the AF (OR: 1.93; 95% CI: 1.08, 3.45). Among those with "normal" vitamin B-12, higher UMFA or serum total folate was protective on the CERAD-DR. In noninteraction models, when high folate and normal vitamin B-12 status was the reference group, low vitamin B-12 combined with high UMFA was associated with greater risk based on the DSST (<34, OR: 2.87; 95% CI: 1.85, 4.45; <40, OR: 2.22; 95% CI: 1.31, 3.75) and AF (OR: 1.97; 95% CI: 1.30, 2.97); but low vitamin B-12 and lower UMFA (OR: 1.69; 95% CI: 1.16, 2.47) was also significantly associated for DSST < 40 risk.

conclusionsLow vitamin B-12 was associated with cognitive impairment both independently and in an interactive manner with high folate for certain cognitive performance tests among older adults.

Indexed as

CognitionVitamin B 12 DeficiencyAgedCross-Sectional StudiesDose-Response Relationship, DrugFemaleFolic AcidHumansMaleMiddle AgedNutrition SurveysUnited StatesVitamin B 12Folic AcidVitamin B 12cognitive functionfolateinteractionNHANESolder adultsunmetabolized folic acidvitamin B-12

Identifiers

PMID32860400
PMCPMC8184300
OpenAlexW3082398495

What OpenQuestion holds

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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.