Self-reported choline intake and associations with circulating parameters of one-carbon and lipid metabolism in a healthy Norwegian population
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- Master theses 
Introduction: Choline is an essential nutrient even though it to some extent can be endogenously synthesized in the liver. It is required for the synthesis of phospholipids in cell membranes and for optimal transmembrane signaling, as a central part of the neurotransmitter acetylcholine, and it is closely related to the one-carbon metabolism through its metabolite betaine. In food and in the body, choline occurs in water-soluble forms, including free choline (FC), phosphocholine (PC) and glycerophosphocholine (GC), and in the lipid-soluble forms phosphatidylcholine (PtdCho) and sphingomyelin (SM). PtdCho connects choline to the lipid metabolism as it is essential for VLDL synthesis in the liver. Indeed, choline deficiency has been shown to cause liver damage. Other severe health outcomes associated with choline deficiency are muscle damage, aberrant gene expression, birth defects, decreased cognitive function, carcinogenesis, and cardiovascular disease. Choline is abundant in animal food sources, such as eggs, milk, meat, poultry, and fish, in addition to plant based sources including leafy vegetables, wholegrain products and legumes. So far, only the National Academy of Medicine (NAM) and the European Food Safety Authority (EFSA) have established Adequate Intakes (AI) for choline (respectively 425 mg/d for women and 550 mg/d for men or 400 mg/d for adults). For now there are no nationally representative estimates on choline intake in Norway and recommended dietary intake of choline for the Nordic countries has yet not been established. Aim and hypothesis: To investigate the intake of total choline and individual choline forms in a healthy Norwegian population and map the food items contributing to the intake. Additionally, associations between choline intake and plasma concentrations of eleven metabolites involved in the one-carbon metabolism and serum lipids will be assessed. Materials and methods: Data from the Hordaland Health study ́97- ́99 was used for analyzing the intake of choline in a Norwegian population. Participants were born in 1925-27 or 1950-51 and were settled in Hordaland county (now part of Vestland). Baseline characteristics were retrieved through self-administered questionnaires and a non-fasting blood sample was taken at attendance. Dietary data was obtained using a semi-quantitative 169-item food frequency questionnaire (FFQ) designed according to a Norwegian habitual meal pattern. The intake of total choline and choline forms was analyzed from the FFQ using the USDA Database for the Choline Content of Common Foods 2008. Choline intakes were energy-adjusted using the residual method and reported as means with standard deviations. Dietary intakes were energy-adjusted using the nutrient density method and were reported as g/1000 kcal or in energy percentage. To explore the relationship between choline intake and circulating levels of one-carbon metabolites and lipid metabolites, choline intake was modeled as a polynomial spline in a model with sex as an interaction term and adjusted for age, BMI and smoking. Results: After exclusion, 5746 participants (43.6% men) were considered eligible for analysis. Nearly half of them (48.5%) were born in 1925-27, while the rest were born in 1950- 51. The mean (SD) total choline intake was 265.2 (±55.9) mg/d in the total study population, and intakes were similar between men and women after energy-adjustment. The major food groups contributing to the intake of total choline were dairy, eggs, vegetables, grain products, and meat. Nearly half of the choline intake (43.5%) came from the lipid-soluble form PtdCho, which was mainly retrieved trough the intake of eggs, meat, grain products and vegetables. The intake of choline was inversely associated with plasma concentrations of homocysteine (Hcy), glycine, and serine, and positively associated with methionine, cystathionine, cysteine, trimethyllysine, trimethylamine N-oxide (TMAO), and dimethylglycine, as well as plasma choline in men. In both men and women, a higher choline intake was associated with increased concentrations of total cholesterol (TC), LDL- cholesterol and triglycerides (TG). Conclusion: To our knowledge, this study is the first to assess the intake of total choline and individual choline forms in a healthy Norwegian population. Compared to the AIs set by NAM and EFSA, most participants did not achieve the recommended intakes, even prior to energy-adjustment. Our findings suggest that choline intake affects the concentration of most metabolites involved in one-carbon metabolism, and has a Hcy-lowering effect, but increases the concentration of TML and TMAO in healthy men and women. A high intake of choline could also negatively affect lipid-profile, by increasing the serum concentrations of TC, LDL- cholesterol, and TG.
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