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


Nurk, Eha, Refsum, Helga, Bjelland, Ingvar, Drevon, Christian A., Tell, Grethe S., Ueland, Per M., Vollset, Stein E., Engedal, Knut, Nygaard, Harald A., Smith, David A.


The British Journal Of Nutrition, Volume: 109, No.: 3, Pages.: 511-519

Year of Publication



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 (56·0 v. 61·5, P=0·004), m-DST (10·5 v. 9·8, P=0·005) and m-MMSE (11·5 v. 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 (RR(KOLT)=2·6, 95 % CI 1·1, 6·1; RR(m-MMSE)=2·7, 95 % CI 1·1, 6·6; RR(COWAT)=3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) (≥3·95 μmol/l) concentrations (RR(m-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 (RR(KOLT)=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 B₁₂ or high MMA on cognitive performance.;

Bibtex Citation

@article{Nurk_2012, doi = {10.1017/s0007114512001249}, url = {}, year = 2012, month = {may}, publisher = {Cambridge University Press ({CUP})}, volume = {109}, number = {03}, pages = {511--519}, author = {Eha Nurk and Helga Refsum and Ingvar Bjelland and Christian A. Drevon and Grethe S. Tell and Per M. Ueland and Stein E. Vollset and Knut Engedal and Harald A. Nygaard and David A. Smith}, title = {Plasma free choline, betaine and cognitive performance: the Hordaland Health Study}, journal = {British Journal of Nutrition} }


adverse effects, aged, aging, b, betaine, biological markers, blood, choline, choline deficiency, cohort studies, diet, epidemiology, etiology, female, geriatric assessment, humans, male, methylmalonic acid, mild cognitive impairment, norway, physiopathology, risk factors, statistics as topic, vitamin b 12, vitamin b 12 deficiency

Countries of Study


Types of Study

Cohort Study

Type of Outcomes


Type of Interventions

Risk Factor Modification

Risk Factor Modifications

General population health promotion

Pharmaceutical Interventions

Herbal remedies, vitamins, dietary supplements