scholarly journals 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

2020 ◽  
Vol 112 (6) ◽  
pp. 1547-1557 ◽  
Author(s):  
Regan L Bailey ◽  
Shinyoung Jun ◽  
Lisa Murphy ◽  
Ralph Green ◽  
Jaime J Gahche ◽  
...  
Keyword(s):  
Older Adults ◽  
Folic Acid ◽  
Cognitive Function ◽  
Serum Folate ◽  
Vitamin B ◽  
Digit Symbol Substitution Test ◽  
Cross Sectional ◽  
Folate Status ◽  
Normal Vitamin ◽  
Vitamin B 12

ABSTRACT Background Potential safety concerns relative to impaired cognitive function may exist when high folic acid exposures are combined with low vitamin B-12 status. Objectives We 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. Methods Cross-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). Results A 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. Conclusions Low 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.

Plasma concentrations of vitamin B12 and folate and global cognitive function in an older population: cross-sectional findings from The Irish Longitudinal Study on Ageing (TILDA)

2020 ◽  
Vol 124 (6) ◽  
pp. 602-610 ◽  
Author(s):  
Deirdre M. A. O’Connor ◽  
Eamon J. Laird ◽  
Daniel Carey ◽  
Aisling M. O’Halloran ◽  
Robert Clarke ◽  
...  
Keyword(s):  
Older Adults ◽  
Folic Acid ◽  
Longitudinal Study ◽  
Cognitive Function ◽  
Cognitive Performance ◽  
Vitamin B ◽  
Plasma Vitamin ◽  
Cross Sectional ◽  
Folate Status ◽  
Global Cognitive Function

AbstractThe uncertainty surrounding high intakes of folic acid and associations with cognitive decline in older adults with low vitamin B12 status has been an obstacle to mandatory folic acid fortification for many years. We estimated the prevalence of combinations of low/normal/high vitamin B12 and folate status and compared associations with global cognitive function using two approaches, of individuals in a population-based study of those aged ≥50 years in the Republic of Ireland. Cross-sectional data from 3781 men and women from Wave 1 of The Irish Longitudinal Study on Ageing were analysed. Global cognitive function was assessed by the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Prevalence estimates for combinations of vitamin B12 (plasma vitamin B12 < or ≥258 pmol/l) and folate (plasma folate ≤ or >45·3 nmol/l) concentrations were generated. Negative binomial regression models were used to investigate the associations of vitamin B12 and folate status with global cognitive function. Of the participants, 1·5 % (n 51) had low vitamin B12 (<258 pmol/l) and high folate (>45·3 nmol/l) status. Global cognitive performance was not significantly reduced in these individuals when compared with those with normal status for both B-vitamins (n 2433). Those with normal vitamin B12/high folate status (7·6 %) had better cognitive performance (MMSE: incidence rate ratio (IRR) 0·82, 95 % CI 0·68, 0·99; P = 0·043, MoCA: IRR 0·89, 95 % CI 0·80, 0·99; P = 0·025). We demonstrated that high folate status was not associated with lower cognitive scores in older adults with low vitamin B12 status. These findings provide important safety information that could guide fortification policy recommendations in Europe.

scholarly journals High Folate and Vitamin Low B12 Status: Potential Interactions with Cognitive Function Among U.S. Older Adults, NHANES 2011–2014

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1189-1189
Author(s):  
Regan Bailey ◽  
Shinyoung Jun ◽  
Lisa Murphy ◽  
Ralph Green ◽  
Josh Miller
Keyword(s):  
Older Adults ◽  
Folic Acid ◽  
Cognitive Function ◽  
Vitamin B12 ◽  
Cognitive Performance ◽  
High Serum ◽  
Serum Folate ◽  
Cognitive Test ◽  
Digit Symbol Substitution Test ◽  
Cut Points

Abstract Objectives Potential safety concerns may exist with high folate/folic acid exposures combined with low vitamin B12 (B12) status relative to cognitive function; therefore, we investigated this relationship, leveraging cognitive test performance with folate and B12 biomarker data among a nationally-representative survey of U.S. older adults. Methods We analyzed data from 2420 older adults (≥60 y) from the 2011–2014 NHANES. High folate status was defined as unmetabolized serum folic acid (UMFA) &gt; 1 nmol/L or serum folate &gt; 74.1 nmol/L. Low B12 status was defined using age-specific cut-points for serum B12 [≤429 pmol/L (in 60–69 y) and ≤370 pmol/L (in ≥70 y)] or using a combination of traditional cut-points [elevated methylmalonic acid (&gt;271 nmol/L) and deficient serum B12 (&lt; 150 pmol/L)]. Multivariable logistic regression models estimated odds ratios (OR) of scoring low on one of four cognitive tests: Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer's Disease [CERAD; Word Learning (WL) and Delayed Recall (DR)], and Animal Fluency Test (AF). Results Among older adults with low B12 status, high UMFA was associated with a higher OR of having a low score on the DSST (&lt;34, OR 2.16; 95% CI 1.05–4.47) and high serum folate was associated with a higher OR of having a low score on the AF (&lt;14, OR 1.93; 95% CI 1.08–3.45), only when using traditional cut-points for B12. Among those with normal B12 status, having a high UMFA was protective on the CERAD-DR, regardless of B12 status being defined using age-specific or traditional cut-points. Compared to those with normal B12 (using traditional cut-points) and high UMFA, those with low B12 and high UMFA had a higher risk of scoring low on the DSST (&lt;40, OR 2.22; 95% CI 1.31–3.75) and AF (&lt;14, OR 1.97; 95% CI 1.30–2.97), those with low B12 and lower UMFA had a higher risk of scoring low on the DSST (&lt;40, OR 1.69; 95% CI 1.16–2.47), and those with normal B12 and lower UMFA had a higher risk of scoring low on the CERAD-DR (&lt;17, OR 1.38; 95% CI 1.02–1.85); similar patterns were found with serum folate. Conclusions In older adults, high folate was associated with better cognitive performance when vitamin B12 status is normal, whereas high folate was associated with poorer cognitive performance when vitamin B12 status is low. Funding Sources N/A.

scholarly journals Folate and vitamin B12status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK

2008 ◽  
Vol 100 (5) ◽  
pp. 1054-1059 ◽  
Author(s):  
Robert Clarke ◽  
Paul Sherliker ◽  
Harold Hin ◽  
Anne M. Molloy ◽  
Ebba Nexo ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Folic Acid ◽  
Older People ◽  
Serum Folate ◽  
Vitamin B ◽  
Cross Sectional ◽  
Folic Acid Fortification ◽  
Folate Status ◽  
Cross Sectional Studies ◽  
The Uk

Concerns about risks for older people with vitamin B12deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15·8 (sd14·7) nmol/l in 1995 to 31·1 (sd26·2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12status was unaffected by highv.low folate status (>30 nmol/l) (OR 1·50 (95 % CI 0·91, 2·46)v.1·45 (95 % CI 1·19, 1·76)), respectively. The associations of cognitive impairment with low B12status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2·46; 95 % CI 0·90, 6·71)v.(1·56; 95 % CI 1·30, 1·88)). There was no evidence of modification by high folate status of the associations of low B12with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.

scholarly journals Interpretation of vitamin B-12 and folate concentrations in population-based surveys does not require adjustment for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

2020 ◽  
Vol 111 (4) ◽  
pp. 919-926 ◽  
Author(s):  
Melissa F Young ◽  
Junjie Guo ◽  
Anne Williams ◽  
Kyly C Whitfield ◽  
Sabiha Nasrin ◽  
...  
Keyword(s):  
Survey Design ◽  
Serum Vitamin ◽  
Correlation Coefficients ◽  
Population Based ◽  
Reproductive Age ◽  
Serum Folate ◽  
Vitamin B ◽  
Cross Sectional ◽  
Population Prevalence ◽  
Vitamin B 12

ABSTRACT Background Vitamin B-12 and folate deficiencies in women and children have important public health implications. However, the evidence is conflicting and limited on whether the influence of inflammation on biomarker concentrations may be sufficiently and consistently influenced by inflammation to require adjustment for interpreting concentrations or estimating population prevalence of deficiencies. Objective We examined correlations between concentrations of the inflammation biomarkers C-reactive protein (CRP) and α1-acid glycoprotein (AGP) and serum vitamin B-12 and serum and RBC folate among nonpregnant women of reproductive age (WRA; 15–49 yr) and preschool children (PSC; 6–59 mo). Methods We analyzed cross-sectional data from 16 nationally representative nutrition surveys conducted in WRA (n = 32,588) and PSC (n = 8,256) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Spearman correlations between CRP or AGP and vitamin B-12 or folate concentrations were examined, taking into account complex survey design effects. Results Correlations between inflammation and vitamin B-12 or folate were weak, with no clear pattern of association in either WRA or PSC. Correlation coefficients between CRP and vitamin B-12 for WRA and PSC ranged from −0.25 to 0.16, and correlations between AGP and vitamin B-12 ranged between −0.07 and 0.14. Similarly, correlations between CRP and serum folate ranged from −0.13 to 0.08, and correlations between AGP and serum folate between −0.21 and 0.02. Only 3 surveys measured RBC folate, and among them, correlations for WRA ranged from −0.07 to 0.08 for CRP and −0.04 for AGP (1 country). Conclusions Based on the weak and inconsistent correlations between CRP or AGP and vitamin B-12 or folate biomarkers, there is no rationale to adjust for inflammation when estimating population prevalence of vitamin B-12 or folate deficiencies in WRA or PSC.

scholarly journals Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial

2006 ◽  
Vol 84 (2) ◽  
pp. 361-370 ◽  
Author(s):  
Simone J Eussen ◽  
Lisette C de Groot ◽  
Liesbeth W Joosten ◽  
Rubia J Bloo ◽  
Robert Clarke ◽  
...  
Keyword(s):  
Folic Acid ◽  
Cognitive Function ◽  
Older People ◽  
Controlled Trial ◽  
Vitamin B ◽  
Oral Vitamin ◽  
Vitamin B 12

scholarly journals B-vitamins and prevention of dementia

2008 ◽  
Vol 67 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Robert Clarke
Keyword(s):  
Folic Acid ◽  
Cognitive Function ◽  
Meta Analysis ◽  
B Vitamins ◽  
Vitamin Supplementation ◽  
Vitamin B ◽  
Cross Sectional ◽  
Principal Investigators ◽  
Individual Participant ◽  
B Vitamin

Elevated plasma homocysteine (Hcy) concentrations have been implicated with risk of cognitive impairment and dementia, but it is unclear whether low vitamin B12 or folate status is responsible for cognitive decline. Most studies reporting associations between cognitive function and Hcy or B-vitamins have used a cross-sectional or case–control design and have been unable to exclude the possibility that such associations are a result of the disease rather than being causal. The Hcy hypothesis of dementia has attracted considerable interest, as Hcy can be easily lowered by folic acid and vitamin B12, raising the prospect that B-vitamin supplementation could lower the risk of dementia. While some trials assessing effects on cognitive function have used folic acid alone, vitamin B12 alone or a combination, few trials have included a sufficient number of participants to provide reliable evidence. An individual-patient-data meta-analysis of all randomised trials of the effects on cognitive function and vascular risk of lowering Hcy with B-vitamins will maximise the power to assess the epidemiologically-predicted differences in risk. Among the twelve large randomised Hcy-lowering trials for prevention of vascular disease, data should be available on about 30 000 participants with cognitive function. The principal investigators of such trials have agreed to combine individual-participant data from their trials after their separate publication.

scholarly journals Voluntary fortification is ineffective to maintain the vitamin B12and folate status of older Irish adults: evidence from the Irish Longitudinal Study on Ageing (TILDA)

2018 ◽  
Vol 120 (1) ◽  
pp. 111-120 ◽  
Author(s):  
Eamon J. Laird ◽  
Aisling M. O’Halloran ◽  
Daniel Carey ◽  
Deirdre O’Connor ◽  
Rose A. Kenny ◽  
...  
Keyword(s):  
Older Adults ◽  
Folic Acid ◽  
Longitudinal Study ◽  
Geographic Location ◽  
Sampling Period ◽  
Vitamin B ◽  
Folate Status ◽  
Health Lifestyle ◽  
Supplement Use ◽  
Negative Predictor

AbstractMandatory fortification of staple grains with folic acid and/or vitamin B12(B12) is under debate in many countries including Ireland, which has a liberal, but voluntary, fortification policy. Older adults can be at risk of both deficiency and high folate status, although little is known on the actual prevalence and the major predictors. Population prevalence estimates from older adults (n5290 ≥50 years) from the Irish Longitudinal Study on Ageing (TILDA) (Wave 1) are presented here. Measures included plasma total vitamin B12and folate, whereas predictors included detailed demographic, socio-economic, geographic, seasonal and health/lifestyle data. The prevalence of deficient or low B12status (<185 pmol/l) was 12 %, whereas the prevalence of deficient/low folate status was 15 %. High folate status (>45 nmol/l) was observed in 8·9 %, whereas high B12status was observed in 3·1 % (>601 pmol/l). The largest positive predictor of B12concentration was self-reported B12injection and/or supplement use (coefficient 51·5 pmol/; 95 % CI 9·4, 93·6;P=0·016) followed by sex and geographic location. The largest negative predictor was metformin use (−33·6; 95 % CI −51·9, −15·4;P<0·0001). The largest positive predictor of folate concentration was folic acid supplement use (6·0; 95 % CI 3·0, 9·0 nmol/l;P<0·001) followed by being female and statin medications. The largest negative predictor was geographic location (−5·7; 95 % CI −6·7, −4·6;P<0·0001) followed by seasonality and smoking. B-vitamin status in older adults is affected by health and lifestyle, medication, sampling period and geographic location. We observed a high prevalence of low B12and folate status, indicating that the current policy of voluntary fortification is ineffective for older adults.

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