Interactions between plasma concentrations of folate and markers of vitamin B12status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study

A combination of high folate with low vitamin B12plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72–74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-ɛ4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12in relation to cognitive performance. Plasma vitamin B12concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12concentrations in the lower range, the association between plasma folate and cognitive performance was strongest.

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Plasma free choline, betaine and cognitive performance: the Hordaland Health Study

British Journal Of Nutrition ◽

10.1017/s0007114512001249 ◽

2012 ◽

Vol 109 (3) ◽

pp. 511-519 ◽

Cited By ~ 22

Author(s):

Eha Nurk ◽

Helga Refsum ◽

Ingvar Bjelland ◽

Christian A. Drevon ◽

Grethe S. Tell ◽

...

Keyword(s):

Regression Model ◽

Cognitive Performance ◽

Word Association ◽

Block Design ◽

Plasma Concentrations ◽

Cognitive Testing ◽

Health Study ◽

Vitamin B ◽

Plasma Vitamin ◽

Free Choline

Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70–74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0v. 61·5,P= 0·004), m-DST (10·5v. 9·8,P= 0·005) and m-MMSE (11·5v. 11·4,P= 0·01). A generalised additive regression model showed a positive dose–response relationship between the m-MMSE and choline (P= 0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B12( ≤ 257 pmol/l) concentrations (RRKOLT= 2·6, 95 % CI 1·1, 6·1; RRm-MMSE= 2·7, 95 % CI 1·1, 6·6; RRCOWAT= 3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) ( ≥ 3·95 μmol/l) concentrations (RRm-BD= 2·8, 95 % CI 1·3, 6·1). Low betaine ( ≤ 31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RRKOLT= 2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B12or high MMA on cognitive performance.

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Folate, vitamin B-12, and cognitive function in the Boston Puerto Rican Health Study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa293 ◽

2020 ◽

Vol 113 (1) ◽

pp. 179-186

Author(s):

Tahani Boumenna ◽

Tammy M Scott ◽

Jong-Soo Lee ◽

Natalia Palacios ◽

Katherine L Tucker

Keyword(s):

Folic Acid ◽

Cognitive Function ◽

Puerto Rican ◽

High Plasma ◽

Health Study ◽

Vitamin B ◽

Plasma Vitamin ◽

Cognitive Score ◽

Plasma Folate ◽

Vitamin B 12

ABSTRACT Background There is evidence that low plasma vitamin B-12 and folate individually, as well as an imbalance of high folic acid and low vitamin B-12 status, may be associated with lower cognitive function. Objectives We examined dietary and plasma folate and vitamin B-12 status, and their interaction, in relation to cognitive function in a cohort of older Puerto Rican adults. Methods The design is cross-sectional, with 1408 participants from the Boston Puerto Rican Health Study (mean ± SD age: 57.1 ± 7.9 y). Cognitive function was assessed with a comprehensive test battery and a global composite score was derived. Plasma folate, vitamin B-12, and methylmalonic acid (MMA) were assessed in fasting blood samples. Results After adjusting for covariates, high plasma folate and high plasma vitamin B-12 were each positively associated with global cognitive score (β: 0.063; 95% CI: −0.0008, 0.127; P = 0.053 and β: 0.062; 95% CI: 0.009, 0.12; P = 0.023, respectively, for logged values, and β: 0.002; 95% CI: 0.00005, 0.004; P-trend = 0.044 and β: 0.00018; 95% CI: 0.00001, 0.0003; P-trend = 0.036, respectively, across tertiles). Nine percent of participants had vitamin B-12 deficiency (plasma vitamin B-12 < 148 pmol/L or MMA > 271 nmol/L), but none were folate deficient (plasma folate < 4.53 nmol/L). Deficient compared with higher vitamin B-12 was significantly associated with lower cognitive score (β: −0.119; 95% CI: −0.208, −0.029; P = 0.009). We could not examine the interaction for vitamin B-12 deficiency and high plasma folate, because there were too few individuals (<1% of the cohort) in this category to draw conclusions. Conclusions Low plasma vitamin B-12 and low plasma folate were each associated with worse cognitive function in this population. Vitamin B-12 deficiency was prevalent and clearly associated with poorer cognitive function. More attention should be given to identification and treatment of vitamin B-12 deficiency in this population. Additional, larger studies are needed to examine the effect of vitamin B-12 deficiency in the presence of high exposure to folic acid.

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

British Journal Of Nutrition ◽

10.1017/s0007114508958001 ◽

2008 ◽

Vol 100 (5) ◽

pp. 1054-1059 ◽

Cited By ~ 38

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.

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Effects of folic acid and vitamin B12 supplements on folate and homocysteine metabolism in pigs during early pregnancy

British Journal Of Nutrition ◽

10.1079/bjn2002653 ◽

2002 ◽

Vol 88 (3) ◽

pp. 253-263 ◽

Cited By ~ 19

Author(s):

Frédéric Guay ◽

J. Jacques Matte ◽

Christiane L. Girard ◽

Marie-France Palin ◽

Alain Giguère ◽

...

Keyword(s):

Folic Acid ◽

Present Experiment ◽

Binding Capacity ◽

Plasma Concentrations ◽

Total Content ◽

Plasma Homocysteine ◽

Vitamin B ◽

Plasma Vitamin ◽

Diet Supplements ◽

Uterine Secretions

The present experiment aimed to determine the effects of supplements of folic acid (FA) alone or in combination with vitamin B12 on folate and homocysteine metabolism in gestating nulliparous Yorkshire–Landrace (YL) and multiparous Landrace (LD) occidental sows and multiparous Chinese Meishan–Landrace (ML) sows. LD sows were randomly assigned to two treatments: 0 or 15 mg FA/kg diet while YL and ML sows were assigned to three treatments: 0 mg FA/kg diet, 15 mg FA/kg or 15 mg FA+160 μg vitamin B12/kg diet. Supplements were given from the oestrus preceding insemination up to slaughter on day 15 of gestation. At slaughter, a uterine flush was collected to determine uterine contents of homocysteine, methionine, tetrahydrofolate (THF), 5-methyl-THF, pyridoxal 5-phosphate (P5P) and vitamin B12. Blood samples were taken at first oestrus, at insemination and on days 5, 10 and 15 of gestation to determine plasma concentrations of homocysteine, methionine, THF, 5-methyl-THF, P5P, vitamin B12 and relative total folate-binding capacity. In occidental sows (YL and LD), the FA supplement tended to decrease uterine flush content of homocysteine (P=0·06) and concentrations of plasma homocysteine (P=0·09). Nulliparous YL sows had lower concentrations of plasma homocysteine, methionine, THF and 5-methyl-THF (P<0·05) than multiparous LD sows. Multiparous ML and LD sows had similar concentrations of plasma THF, 5-methyl-THF, methionine and vitamin B12, but ML sows had lower concentrations of plasma homocysteine (P<0·05). The vitamin B12 supplement increased concentrations of plasma vitamin B12 (P<0·05) both in multiparous ML and nulliparous YL sows, but had no effect on the composition of either uterine flush or plasma. The present results showed also that sows had a low vitamin B12 status (<200 pg/ml) and high circulating homocysteine levels (>15 μM) during the first 15 d of gestation. Furthermore, the vitamin B12 content in uterine secretions represented between 180 and 300 % of the total content in plasma. The low plasma concentrations of homocysteine in multiparous ML sows suggest a more efficient remethylation pathway which may not be dependent upon dietary supply of FA or vitamin B12. In nulliparous YL sows, low concentrations of both homocysteine and methionine suggest that the methionine requirement for protein deposition might have reduced the amount of methionine available for the methylation pathway. The results of the present experiment suggest that the reduction of uterine homocysteine may be an important aspect of the role of FA supplement on the uterine environment in occidental sows. The presence of high levels of vitamin B12 in uterine secretions merits further investigation in relation to embryonic development.

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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)

British Journal Of Nutrition ◽

10.1017/s0007114520001427 ◽

2020 ◽

Vol 124 (6) ◽

pp. 602-610 ◽

Cited By ~ 3

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.

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Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification

American Journal of Clinical Nutrition ◽

10.1093/ajcn/85.1.193 ◽

2007 ◽

Vol 85 (1) ◽

pp. 193-200 ◽

Cited By ~ 386

Author(s):

Martha Savaria Morris ◽

Paul F Jacques ◽

Irwin H Rosenberg ◽

Jacob Selhub

Keyword(s):

Cognitive Impairment ◽

Folic Acid ◽

Vitamin B ◽

Older Americans ◽

Folic Acid Fortification ◽

Vitamin B 12

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Folate Nutritional Status among Psoriasis Patients not Exposed to Antifolate Drug

Current Nutrition & Food Science ◽

10.2174/1573401314666180702100301 ◽

2020 ◽

Vol 16 (4) ◽

pp. 543-553

Author(s):

Luciana Y. Tomita ◽

Andréia C. da Costa ◽

Solange Andreoni ◽

Luiza K.M. Oyafuso ◽

Vânia D’Almeida ◽

...

Keyword(s):

Folic Acid ◽

Linear Regression ◽

Multiple Linear Regression Model ◽

Folate Intake ◽

Serum Folate ◽

Linear Regression Models ◽

Cross Sectional ◽

Folic Acid Fortification ◽

Plasma Folate ◽

Psoriasis Severity

Background: Folic acid fortification program has been established to prevent tube defects. However, concern has been raised among patients using anti-folate drug, i.e. psoriatic patients, a common, chronic, autoimmune inflammatory skin disease associated with obesity and smoking. Objective: To investigate dietary and circulating folate, vitamin B12 (B12) and homocysteine (hcy) in psoriatic subjects exposed to the national mandatory folic acid fortification program. Methods: Cross-sectional study using the Food Frequency Questionnaire, plasma folate, B12, hcy and psoriasis severity using the Psoriasis Area and Severity Index score. Median, interquartile ranges (IQRs) and linear regression models were conducted to investigate factors associated with plasma folate, B12 and hcy. Results: 82 (73%) mild psoriasis, 18 (16%) moderate and 12 (11%) severe psoriasis. 58% female, 61% non-white, 31% former smokers, and 20% current smokers. Median (IQRs) were 51 (40, 60) years. Only 32% reached the Estimated Average Requirement of folate intake. Folate and B12 deficiencies were observed in 9% and 6% of the blood sample respectively, but hyperhomocysteinaemia in 21%. Severity of psoriasis was negatively correlated with folate and B12 concentrations. In a multiple linear regression model, folate intake contributed positively to 14% of serum folate, and negative predictors were psoriasis severity, smoking habits and saturated fatty acid explaining 29% of circulating folate. Conclusion: Only one third reached dietary intake of folate, but deficiencies of folate and B12 were low. Psoriasis severity was negatively correlated with circulating folate and B12. Stopping smoking and a folate rich diet may be important targets for managing psoriasis.

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Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2005.183 ◽

2005 ◽

Vol 43 (10) ◽

Cited By ~ 57

Author(s):

Ralph Green ◽

Joshua W. Miller

Keyword(s):

United States ◽

Folic Acid ◽

Vitamin B12 Deficiency ◽

The United States ◽

Community Dwelling ◽

Vitamin B ◽

Prevalence Rates ◽

Total Vitamin ◽

Folic Acid Fortification ◽

B12 Deficiency

AbstractPrevalence rates for folate deficiency and hyperhomocysteinemia have been markedly reduced following the introduction of folic acid fortification in the United States. We report the prevalence of hyperhomocysteinemia in a population of community-dwelling elderly Latinos in the post-folic acid fortification era. We measured homocysteine, total vitamin B

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Folic acid and vitamin B12 status of vervet monkeys used for nutritional research

Laboratory Animals ◽

10.1258/002367793781082386 ◽

1993 ◽

Vol 27 (1) ◽

pp. 59-64 ◽

Cited By ~ 5

Author(s):

F. S. Venter ◽

H. Cloete ◽

J. V. Seier ◽

M. J. Faber ◽

J. E. Fincham

Keyword(s):

Folic Acid ◽

Inverse Relationship ◽

Atherogenic Diet ◽

The Other ◽

Vitamin B ◽

Plasma Vitamin ◽

Vervet Monkeys ◽

Adult Males ◽

Competitive Protein Binding ◽

Apparently Healthy

Plasma and red blood cell (RBC) folic acid levels, as well as plasma vitamin B12 levels were determined in Vervet monkeys ( Cercopithecus aethiops). All the vervets were apparently healthy and without symptoms or lesions typical of folic acid and/or vitamin B12 deficiencies. Competitive protein binding radioassays were used to determine folate and vitamin B12 values in animals fed 4 different diets. The B12 levels for all the groups ranged between 866 and 5867 pg/ml and showed an inverse relationship with the FA measurements. The lowest mean RBC folic acid content in a group fed an atherogenic diet for 3 years was 12·8 ng/ml. For the other 3 diets, mean RBC folic acid levels were 90·7, 132·3 and 152·8 ng/ml, respectively. A megadose of 25·6 mg of folic acid per day for 99 days was given to 3 adult males. No obvious toxic effects were observed in these animals although mean RBC folic acid levels increased to 1013 ng/ml.

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