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

2012 ◽  
Vol 109 (3) ◽  
pp. 511-519 ◽  
Author(s):  
Eha Nurk ◽  
Helga Refsum ◽  
Ingvar Bjelland ◽  
Christian A. Drevon ◽  
Grethe S. Tell ◽  
...  

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.

2013 ◽  
Vol 111 (6) ◽  
pp. 1085-1095 ◽  
Author(s):  
Esmée L. Doets ◽  
Per M. Ueland ◽  
Grethe S. Tell ◽  
Stein Emil Vollset ◽  
Ottar K. Nygård ◽  
...  

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.


1989 ◽  
Vol 62 (3) ◽  
pp. 729-738 ◽  
Author(s):  
F.P.M. O'Harte ◽  
D. G. Kennedy ◽  
W. J. Blanchflower ◽  
D. A. Rice

Eight lambs were fed on a cobalt-deficient whole-barley diet supplemented with urea, vitamins and minerals. Four control lambs were fed on the same diet which had been further supplemented with Co. Plasma vitamin B12 levels in the Co-depleted group declined rapidly, falling below the normal range within 5 weeks. Differences between the live weights of the animals in the two groups approached statistical significance by week 14. However, methylmalonic acid (MMA) rose above normal levels in the Co-depleted group within 7 weeks. This suggested that an elevated plasma concentration of MMA is a comparatively early indicator of functional vitamin B12 deficiency. It is recommended that 10 μmol/l be the upper level of normality for plasma MMA concentration in barley-fed animals, in contrast with the level of 5 μmol/l for grass-fed animals. Changes in the plasma concentrations of MMA and ethylmalonic acid associated with feeding the barley-based diet per se did not significantly affect the validity of the gas-liquid chromatographic assay for MMA.


2000 ◽  
Vol 84 (5) ◽  
pp. 645-653 ◽  
Author(s):  
G. I. Stangl ◽  
F. J. Schwarz ◽  
H. Müller ◽  
M. Kirchgessner

This investigation was designed to estimate the Co requirement of growing cattle on the basis of plasma and liver levels of vitamin B12 and folate, plasma levels of homocysteine and methylmalonic acid (MMA) and haematological variables. For this purpose thirty-four male intact cattle of the German Simmental breed (236 kg) were assigned randomly to ten groups and were fed corn silage-based diets which contained 70, 90, 109, 147, 184, 257, 327, 421, 589 or 689 μg Co/kg DM for 40 weeks. One-slope broken-line model analysis and a quadratic model with plateau were used to estimate the Co requirement. The broken-line model estimated the dietary Co requirement of growing cattle to be 257 (SE 29) ΜG/KG DIETARY DM BASED ON PLASMA VITAMIN B12 AS RESPONSE CRITERION. THE DIETARY CO LEVELS NEEDED TO MAXIMISE THE LIVER VITAMIN B12 AND LIVER FOLATE WERE 236 (se 8) and 190 (se 8) μg/kg dietary DM respectively. Plasma folate did not show any response to the different Co levels. The dietary Co was inversely correlated with the plasma concentrations of homocysteine and MMA. Estimates of the dietary Co concentration required to minimise homocysteine were 161 (se 10) μg/kg DM. When MMA was used as response criterion, the linear model yielded a Co requirement of 124 (se 3) μg/kg dietary DM. The quadratic model did not provide a better closeness of regression fit and yielded similar requirements to the linear model. Haemoglobin concentration and haematocrit tended to have a slight response to increasing dietary Co and were only decreased in cattle on diets containing less than 100 μg Co/kg DM. On the basis of the present data, recommended levels of dietary Co for normal folate metabolism and minimum homocysteine and MMA levels can be set to be 150–200 μg/kg DM; for maximum vitamin B12 levels, the desired Co content in the diet seems to be 250 μg/kg DM.


2002 ◽  
Vol 88 (3) ◽  
pp. 253-263 ◽  
Author(s):  
Frédéric Guay ◽  
J. Jacques Matte ◽  
Christiane L. Girard ◽  
Marie-France Palin ◽  
Alain Giguère ◽  
...  

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.


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 ◽  
...  

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.


2019 ◽  
Vol 149 (4) ◽  
pp. 635-641 ◽  
Author(s):  
Natalia Palacios ◽  
Tammy Scott ◽  
Neha Sahasrabudhe ◽  
Xiang Gao ◽  
Katherine L Tucker

ABSTRACT Background Despite its important role in cognitive development and regulation of nervous system function, vitamin B-6 has been under-studied in relation to cognitive aging. Objective We investigated whether plasma pyridoxal-5'-phosphate (PLP, vitamin B-6) concentrations were associated with cognitive function and subsequent cognitive decline. Methods In a longitudinal study of 949 participants (aged 45–75 y at baseline; 70% women) from the Boston Puerto Rican Health Study cohort, we examined the association between baseline plasma PLP and baseline cognitive function and 2-y cognitive decline. Cognitive function was assessed with an in-person 7-test cognitive battery, at baseline and 2-y follow-up. We also used logistic regression to estimate the odds of major 2-y decline in global cognitive function (defined as decline ≥1 SD below the mean), as well as decline in executive function and memory. We also used multivariable linear regression to calculate adjusted mean differences in cognitive scores, and 95% CIs, across tertiles of plasma PLP at baseline, as well as cross-sectional and longitudinal associations with individual test scores. Results In analyses adjusted for potential confounders, the OR of having a major 2-y decline in global cognitive function was 2.46 (95% CI: 1.49, 4.05; P-trend: 0.001) among participants in the lowest tertile of PLP compared with those in the top tertile of PLP. The association of PLP with cognition was stronger in participants older than 55 y at baseline (OR for bottom to top tertile: 4.58; 95% CI: 2.02, 10.35; P-interaction: 0.01) compared with those 55 y old or younger, as well as in ever smokers (OR for bottom to top tertile: 2.99; 95% CI: 1.45, 6.19; P-interaction: 0.02) compared with never smokers. Conclusions Lower baseline plasma PLP was associated with increased odds of 2-y cognitive decline in a cohort of Boston area Puerto Ricans. The association was stronger among older participants and among ever smokers.


2020 ◽  
Vol 113 (1) ◽  
pp. 179-186
Author(s):  
Tahani Boumenna ◽  
Tammy M Scott ◽  
Jong-Soo Lee ◽  
Natalia Palacios ◽  
Katherine L Tucker

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 &lt; 148 pmol/L or MMA &gt; 271 nmol/L), but none were folate deficient (plasma folate &lt; 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 (&lt;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.


2021 ◽  
Vol 58 (5) ◽  
pp. 567-576
Author(s):  
Ronald G. Munger ◽  
Rajarajeswari Kuppuswamy ◽  
Jyotsna Murthy ◽  
Kalpana Balakrishnan ◽  
Gurusamy Thangavel ◽  
...  

Background and Objective: The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case–control study in Tamil Nadu state, India. Methods: Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case–control status. Results: Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B12 status (OR = 3.65 95% CI, 1.21-11.05). Case–control status was not consistently associated with folate or tHcy levels. Low vitamin B12 status, when defined by a combination of both plasma vitamin B12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09). Conclusions: Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B12 or folate levels or their interactions are causally related to CL±P.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 483
Author(s):  
Olaf Sommerburg ◽  
Susanne Hämmerling ◽  
S. Philipp Schneider ◽  
Jürgen Okun ◽  
Claus-Dieter Langhans ◽  
...  

Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy. Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years (p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L (p < 0.01). Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.


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