ID 3090 - Cholina

PL: Cholina
EN: Choline
Pdf: choline

Oświadczenie (4)

Oświadczenie (2)

1. Charakterystyka żywności / składnika

The food constituent that is the subject of the health claim is choline.
Choline (2-hydroxyethyl-N,N,N-trimethylammonium chloride) is a quaternary ammonium cation generally present in foods either with a chloride counterion (chloride salt) or bound to an acetyl group (acetylcholine), to a cytidine diphosphate group (citicoline) or, mainly, to a phosphatidyl group (lecithin) as in milk, liver, eggs and peanuts. Choline is also synthesised in the body. In supplements, choline is mostly present as choline chloride or as phosphatidylcholine, isolated from soy or egg yolk.
Choline is measurable in foods by established methods. This evaluation applies to choline present in foods, and to those forms consumed as food supplements.
The Panel considers that the food constituent, choline, which is the subject of the health claims, is sufficiently characterised.

2.3. Udział w prawidłowym metabolizmie homocysteiny (ID 3090)

The claimed effect is “reduction in homocysteine levels”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and the references provided, the Panel assumes that the claimed effect refers to the maintenance of normal blood concentrations of homocysteine by contributing to normal homocysteine metabolism.
The Panel considers that contribution to normal homocysteine metabolism is a beneficial physiological effect.

3. Naukowe uzasadnienia wpływu na zdrowie człowieka - 

Choline is a dietary component which is also formed endogenously in the body by methylation of phosphatidylethanolamine using S-adenosylmethionine as the methyl donor. Choline functions as a precursor of acetylcholine, phospholipids and betaine, and plays a role in the structural integrity of cell membranes, in methyl metabolism, in cholinergic neurotransmission, and in lipid and cholesterol transport and metabolism. Demand for dietary choline is dependent on the metabolic methyl-group exchange relationships between choline and methionine, folate and vitamin B12. With this type of
nutrient interdependence, the designation of the essential nature of a nutrient will depend on whether de novo synthesis rates are adequate to meet the demand when other nutrients are available in amounts sufficient to sustain normal growth and function. In men with adequate folate and vitamin B12 status fed a choline-deficient diet, endogenous synthesis of choline may not be sufficient to cover needs, whereas little information is available with respect to other population subgroups (e.g. women, children and elderly subjects). The primary criterion to estimate adequate intakes of choline in the United States is the prevention of liver damage, as assessed by measuring serum alanine aminotransferase activity in the blood (IoM, 1998).
No dietary reference values for choline have been established in the EU. There are no reliable intake data, and no indications of inadequate choline intakes, available in the EU.

3.3. Udział w prawidłowym metabolizmie homocysteiny (ID 3090)

It is well established that choline can function as a precursor for the formation of betaine, and that betaine can act as a methyl donor in the remethylation of homocysteine in the liver by the enzyme betaine-homocysteine methyltransferase (IoM, 1998).
A claim on betaine and contribution to normal homocysteine metabolism has already been assessed with a favourable outcome (EFSA Panel on Dietetic Products Nutrition and Allergies (NDA), 2011).
Most of the references provided in the consolidated list were narrative reviews from textbooks and scientific journals referring to the biochemical functions and metabolism of choline, or human and animal studies addressing the effects of choline depletion or supplementation relative to the status of other methyl donors (e.g. folate, vitamin B12 and betaine) on health outcomes other than homocysteine concentrations or metabolism (e.g. liver steatosis, muscle function and cancer).
Two human intervention studies on the effects of choline supplementation on blood concentrations of homocysteine were provided (da Costa et al., 2005; Olthof et al., 2005).
In a placebo-controlled cross-over study, Olthof et al. (2005) investigated the effect of supplemental choline (2.6 g/day as phosphatidylcholine) for two weeks on plasma homocysteine concentrations after an overnight fast, as well as after an oral methionine load in 26 men with mildly elevated
homocysteine concentrations (14.7 3.4 mol/L). Phosphatidylcholine supplementation for two weeks
significantly decreased mean fasting plasma homocysteine concentrations by 18 % (-3.0 mol/L;
95 % CI: -3.9, -2.1 mol/L). A single dose of phosphatidylcholine containing 1.5 g choline
significantly reduced the postmethionine-loading increase in homocysteine by 15 % (-4.8 mol/L;
95 % CI: -6.8, -2.8 mol/L) on the first day of supplementation, and phosphatidylcholine supplementation for two weeks significantly reduced the postmethionine-loading increase in
homocysteine by 29 % (-9.2 mol/L; 95 % CI: -11.3, -7.2 mol/L). All changes were relative to placebo. The Panel notes that the doses of choline used in this study are several times above the proposed conditions of use.
In one small (pilot) depletion study, eight men were fed a “choline-sufficient” diet providing 550 mg choline per day for 10 days followed by a choline-deficient diet (<50 mg/day) for 42 days, or until the subjects were clinically judged to be choline deficient (i.e. evaluated as the development of hepatic steatosis assessed by magnetic resonance imaging), whichever came first (da Costa et al., 2005). Plasma concentrations of homocysteine were assessed in fasting and four hours after an oral methionine load (100 mg/kg body weight) on day 10 of the diet containing 550 mg choline per day, and after 42 days of the choline-deficient diet (or when deficiency was diagnosed). The diets met or exceeded the estimated average requirement for methionine plus cysteine and the daily reference intake for vitamin B6, vitamin B12, and folate (400 dietary folate equivalents per day). Four subjects developed hepatic steatosis during the choline depletion phase, and four subjects did not by day 42. In all eight human subjects, plasma choline and betaine concentrations fell 30 % and 47 %, respectively, at the end of the depletion phase (P<0.005). Subjects who were judged to be clinically depleted had
decreases in plasma choline and betaine concentrations which were not different from those observed in subjects not deemed to be clinically depleted. At the end of the depletion phase, plasma concentrations of homocysteine at fast and four hours after an oral methionine load significantly increased only in subjects clinically choline-depleted, as compared to the “choline sufficient” phase.
Two human observational studies addressed the association between dietary choline and blood concentrations of homocysteine (Cho et al., 2006; Dalmeijer et al., 2008).
In a cohort of the Framingham Offspring Study (Cho et al., 2006) an inverse association was observed between choline, betaine, and choline plus betaine intakes measured by validated food frequency questionnaires (FFQ) and plasma total homocysteine concentrations in 1,960 subjects (1,040 women) independent of age, sex, smoking, alcohol intake, caffeine intake, hypertensive medication use, serum creatinine concentrations and intakes of folate, vitamin B6 and vitamin B12. The energy-adjusted mean (±SD) intakes of choline and betaine were 313±61 mg/day (314 mg per day for women and 312 mg per day for men) and 208±90 mg per day (216 mg per day for women and 200 mg per day for men), respectively.
In a prospective cohort study (Dalmeijer et al., 2008) which investigated the association between dietary intakes of folate, betaine and choline and the risk of cardiovascular disease (CVD) in a cohort of 16,165 women, aged 49-70 years, without prior CVD, intakes of folate, betaine and choline were assessed using a validated FFQ at baseline. Median follow-up period was 97 months. Homocysteine concentrations were assessed in the blood of a randomly selected sample of women (n=910). High folate and choline intakes were statistically significantly associated with lower homocysteine concentrations, whereas no statistically significant association was observed for betaine. Mean intakes
of betaine, choline and folate were 214 74, 300 51 and 195 40 mg/day, respectively.
In weighing the evidence, the Panel took into account that choline can be a precursor for the formation of betaine, that betaine can act as a methyl donor in the remethylation of homocysteine in the liver by the enzyme betaine-homocysteine methyltransferase, that choline depleted diets tend to increase plasma concentrations of homocysteine, that a human intervention study showed a significant decrease in plasma concentrations of homocysteine following choline administration, and that two observational studies supported the inverse association between dietary choline and blood concentrations of homocysteine.
The Panel concludes that a cause and effect relationship has been established between the consumption of choline and contribution to normal homocysteine metabolism.

4.3. Udział w prawidłowym metabolizmie homocysteiny (ID 3090)

The Panel considers that the following wording reflects the scientific evidence: “Choline contributes to normal homocysteine metabolism”.

5. Warunki i możliwe ograniczenia stosowania oświadczenia

The Panel notes that no dietary reference values for choline have been established in the EU. There are no reliable intake data and there are no indications of inadequate choline intakes available in the EU. The Panel also notes that dietary references values (adequate intakes) have been established outside the EU for different population subgroups (IoM, 1998). A nutrient content claim has been authorised in the United States based on the adequate intake for adult males (550 mg of choline per day).

Warunki i możliwe ograniczenia stosowania oświadczenia

The product must contain at least 15% of the AI (AI for adult males and females varies is 550 and 425 mg/day, respectively) To also present a statement that excess choline consumption (=3.5 g/day), may be associated with hypotension and/or a fishy body odour.