Optimal Dietary Intake Composition of Choline and Betaine Is Associated with Minimized Visceral Obesity-Related Hepatic Steatosis in a Case-Control Study

Few studies on humans have comprehensively evaluated the intake composition of methyl-donor nutrients (MDNs: choline, betaine, and folate) in relation to visceral obesity (VOB)-related hepatic steatosis (HS), the hallmark of non-alcoholic fatty liver diseases. In this case–control study, we recruited 105 patients with HS and 104 without HS (controls). HS was diagnosed through ultrasound examination. VOB was measured using a whole-body analyzer. MDN intake was assessed using a validated quantitative food frequency questionnaire. After adjustment for multiple HS risk factors, total choline intake was the most significant dietary determinant of HS in patients with VOB (Beta: −0.41, p = 0.01). Low intake of choline (<6.9 mg/kg body weight), betaine (<3.1 mg/kg body weight), and folate (<8.8 μg/kg body weight) predicted increased odds ratios (ORs) of VOB-related HS (choline: OR: 22, 95% confidence interval [CI]: 6.5–80; betaine: OR: 14, 95% CI: 4.4–50; and folate: OR: 19, 95% CI: 5.2–74). Combined high intake of choline and betaine, but not folate, was associated with an 81% reduction in VOB-related HS (OR: 0.19, 95% CI: 0.05–0.69). Our data suggest that the optimal intake of choline and betaine can minimize the risk of VOB-related HS in a threshold-dependent manner.

Habitual Choline Intakes across the Childbearing Years: A Review

Choline is an important nutrient during the first 1000 days post conception due to its roles in brain function. An increasing number of studies have measured choline intakes at the population level. We collated the evidence focusing on habitual choline intakes in the preconceptual, pregnancy, and lactation life stages. We conducted a review including studies published from 2004 to 2021. Twenty-six relevant publications were identified. After excluding studies with a high choline intake (>400 mg/day; two studies) or low choline intake (<200 mg/day; one study), average choline intake in the remaining 23 studies ranged from 233 mg/day to 383 mg/day, even with the inclusion of choline from supplements. Intakes were not higher in studies among pregnant and lactating women compared with studies in nonpregnant women. To conclude, during the childbearing years and across the globe, habitual intakes of choline from foods alone and foods and supplements combined appear to be consistently lower than the estimated adequate intakes for this target group. Urgent measures are needed to (1) improve the quality of choline data in global food composition databases, (2) encourage the reporting of choline intakes in dietary surveys, (3) raise awareness about the role(s) of choline in foetal–maternal health, and (4) consider formally advocating the use of choline supplements in women planning a pregnancy, pregnant, or lactating.

Choline intake and associations with egg and dairy consumption among pregnant women attending a high-risk antenatal clinic in South Africa: the NuEMI study

Background The importance of adequate choline intake during pregnancy has been well documented, but low intake is common. Total choline intake, main food sources of choline, as well as associations between choline intake and egg and dairy consumption were determined in a sample of pregnant women attending the high-risk antenatal clinic at a regional hospital in Bloemfontein, South Africa. Methods A cross-sectional study design was used. Trained fieldworkers collected dietary intake data using a validated quantified food frequency questionnaire (QFFQ), after which all food items were matched to foods in the USDA Database for the Choline Content of Common Foods (Release 2) to quantify choline intake. Logistic regression with backward selection (p < 0.05) was used to determine whether egg and dairy consumption were independently associated with a choline intake below the adequate intake (AI) level. Results The median daily intake of choline was 275 mg (interquartile range 185 mg – 387 mg) (N = 681). Most participants (84.7%) consumed less than the AI of 450 mg/day for choline. Meat and meat products, cereals, eggs and dairy contributed mostly to choline intake. Food items that contributed most to choline intake included full-cream milk, maize porridge, brown bread, deep-fried potatoes and deep-fried dough (vetkoek). A choline intake below the AI was significantly associated with lower egg and dairy intakes (p < 0.0001 and p = 0.0002 respectively). Conclusion Most pregnant women in the current study had choline intakes below the AI. It is recommended that public health messaging targeted at pregnant women promote the consumption of foods that can significantly contribute to choline intake, such as eggs and dairy.

Choline intake effects on psychophysiological indicators of students in the pre-exam period

Introduction. Choline has a wide range of physiological functions. It has a neuroprotective effect on brain dysfunctions, while its deficiency has a negative effect on antenatal development of the nervous system. We aimed to study the impact of exogenous choline on the psychophysiological indicators in students. Study objects and methods. 87 students were surveyed by questionnaire to determine their background intake of dietary choline. One month before the exams, we measured their simple and complex visual-motor reaction times, functional mobility and balance of nervous processes, as well as indicators of their short-term memory, attention, health, activity, and mood. Then, we divided the students into a control and an experimental group, regardless of their choline intake. The experimental group took 700 mg choline supplements on a daily basis for one month, followed by a second psychophysiological examination. Results and discussion. Students with a low choline intake had lower functional mobility and balance of nervous processes, but better attention stability than students with a high choline intake. The second examination showed improved short-term memory, health, and activity indicators in the experimental group, compared to the control. The visual-motor reaction times also increased, but only in students with an initially low level of choline intake. Conclusion. Choline supplementation can be recommended to students under pre-exam stress to enhance the functional state of their central nervous system.

Choline Intake Correlates with Cognitive Performance among Elder Adults in the United States

Objective. This research attempted to explore the neuroprotective effect of choline and establish evidence for future dietary recommendations and nutritional interventions to maintain a proper cognitive function among elders aged >60 years in the US. Method. This cross-sectional study retrieved data of 2,393 eligible elderly participants from the 2011-2014 National Health and Nutrition Examination Survey. Combining dietary and supplement choline intake, total choline intake was evaluated using the 24-hour dietary recall method and the dietary supplement questionnaire. Total choline intake was categorized into tertiles, which ranged at <187.60 mg/day (T1), 187.60-399.50 mg/day (T2), and >399.50 mg/day (T3). The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word Learning subtest, Animal Fluency (AF) test, and Digit Symbol Substitution test (DSST) was used to measure cognitive function. Participants who scored the lowest 25th percentile in each cognitive test were classified in the low cognitive function (LC) group. Logistic regression models were implemented to examine the association between total choline intake and the incidence of LC. Results. In the CERAD test, the risk of LC was significantly lower in T2 than T1 (OR: 0.668, 95% CI: 0.493-0.904, and P = 0.006 ) when adjusted for age, gender, BMI, alcohol consumption, and hypertension. Similarly, T2 was associated with a significantly lower risk of LC when assessed by the AF test (OR: 0.606, 95% CI: 0.580-0.724, and P < 0.001 ) and DSST (0.584, 95% CI: 0.515-0.661, and P < 0.001 ). In all three cognitive measures, the T3 of the total choline intake was not associated with cognitive function compared to T1. Conclusion. Total choline intake at 187.06-399.50 mg/day reduces the risk of LC by approximately 50% compared to intake at <187.6 mg/day. The findings of this research may be used to establish dietary recommendations and nutritional interventions to optimize the cognitive function among elders.

Maternal Choline Supplementation as a Potential Therapy for Down Syndrome: Assessment of Effects Throughout the Lifespan

Maternal choline supplementation (MCS) has emerged as a promising therapy to lessen the cognitive and affective dysfunction associated with Down syndrome (DS). Choline is an essential nutrient, especially important during pregnancy due to its wide-ranging ontogenetic roles. Using the Ts65Dn mouse model of DS, our group has demonstrated that supplementing the maternal diet with additional choline (4-5 × standard levels) during pregnancy and lactation improves spatial cognition, attention, and emotion regulation in the adult offspring. The behavioral benefits were associated with a rescue of septohippocampal circuit atrophy. These results have been replicated across a series of independent studies, although the magnitude of the cognitive benefit has varied. We hypothesized that this was due, at least in part, to differences in the age of the subjects at the time of testing. Here, we present new data that compares the effects of MCS on the attentional function of adult Ts65Dn offspring, which began testing at two different ages (6 vs. 12 months of age). These data replicate and extend the results of our previous reports, showing a clear pattern indicating that MCS has beneficial effects in Ts65Dn offspring throughout life, but that the magnitude of the benefit (relative to non-supplemented offspring) diminishes with aging, possibly because of the onset of Alzheimer's disease-like neuropathology. In light of growing evidence that increased maternal choline intake during pregnancy is beneficial to the cognitive and affective functioning of all offspring (e.g., neurotypical and DS), the addition of this nutrient to a prenatal vitamin regimen would be predicted to have population-wide benefits and provide early intervention for fetuses with DS, notably including babies born to mothers unaware that they are carrying a fetus with DS.

Associations of choline intake with hypertension and blood pressure among older adults in cross-sectional 2011 – 2014 NHANES differ by body mass index and comorbidity status

Blood pressure (BP) is a known cardiovascular risk factor that is hypothesized to be inversely related to choline intake. A previous study suggested that this association may be more apparent in older adults and may differ according to demographic and health characteristics. The primary study objectives are to investigate the cross-sectional associations of total choline intake with BP (n=843) and prevalent hypertension (n=2,113) among U.S. adults aged ≥65 y using the sample from the 2011–2014 National Health and Nutrition Examination Survey. Logistic and multiple linear regression models for complex surveys were employed for hypertension status and BP respectively. Effect modification by sex, race, body mass index (BMI) and comorbidity status were separately investigated using an interaction term. Choline intake interacted with BMI (P-interaction=0.04) such that choline intake tended to be associated with lower odds of hypertension among people with BMI <18.5 kg/m2 (OR [95% CI]: 0.64 [0.4,1.00]; P=0.052). Choline intake was not associated with systolic BP (mean±SEM change per 100 mg of choline: −1.03±0.74 mmHg; P=0.16). In contrast, its relation to diastolic BP differed by cardiovascular comorbidity (P-interaction=0.03) with a non-significant (P=0.13) negative direction of association observed among those who were free of comorbidities and a non-significant (P=0.26) positive direction observed among those with comorbidities. Collectively, these results suggested that the associations of choline intake with BP levels and hypertension risk among older adults are dependent on other risk factors.

School-Aged Children in Vancouver, Canada Do Not Meet Dietary Choline Recommendations but Meet Recommendations for Folate and Vitamin B12

Objectives Nutrients such as choline, betaine, folate, and vitamin B12 are required for proper growth and development, but little is known about these nutrients in children. Our objective was to determine intakes and biomarkers of these nutrients in school-aged children (5 to 6 years old). Methods A cross-sectional study of healthy children (n = 285) recruited from Vancouver, Canada were assessed. Dietary information was collected using three 24-hour recalls. Nutrient intakes were estimated using the Canadian Nutrient File and USDA database for choline; supplement use was collected by questionnaire. Plasma biomarkers were quantified by mass spectrometry and immunoassay. Results Daily dietary intakes were (mean ± SD) choline 250 ± 96 mg, betaine 88 ± 41 mg, folate 335 ± 126 µg DFE, and vitamin B12 3.78 ± 2.71 µg. Top food sources were dairy and eggs (42–57%) for choline and vitamin B12, and cereal and grains (41–60%) for betaine and folate. Only 40% of children met the choline adequate intake (AI) recommendation for North America (≥250 mg/d); 81.5% met the European AI (≥170 mg/d). Plasma free choline, betaine, and dimethylglycine concentrations were (mean ± SD) 8.62 ± 2.13 µmol/L, 45.3 ± 13.7 µmol/L, 3.34 ± 1.03 µmol/L, respectively. Dietary choline intake and plasma free choline were not related. However, dietary choline intake was positively associated with plasma dimethylglycine. Less than 5% of children had inadequate folate and vitamin B12 intakes. More than half of the children (59.4%) were consuming a supplement containing B-vitamins, but none included choline or betaine. Some children (5.26%) had total folic acid intakes above the North American upper limit (UL; &gt;400 µg/d); 10.90% had intakes above the European UL (&gt;300 µg/d). Vitamin B12 intake was positively associated with plasma total vitamin B12 (mean ± SD; 594 ± 158 pmol/L) in an adjusted model (sex, age, total energy intake, and supplement use; p &lt; 0.05). Conclusions Our findings suggest that many school-aged children are not meeting dietary choline recommendations. Some children may have excessive folic acid intakes. The impact of imbalanced methyl nutrient intakes during this active period of growth and development needs to be determined in the future. Funding Sources CIHR, NSERC, and BC Children's Hospital Research Institute.