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Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998)
Institute of Medicine (IOM)

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. "12 Choline." Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: The National Academies Press, 1998.

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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline

TOLERABLE UPPER INTAKE LEVELS

Hazard Identification

Adverse Effects

Choline doses that are orders of magnitude greater than estimated intake from food have been associated with body odor, sweating, salivation, hypotension, and hepatotoxicity in humans (LSRO/ FASEB, 1975, 1981). There are no indications in the literature that excess choline intake produces any additional adverse effects in humans. The animal data provide supportive evidence for a low degree of toxicity of choline. However, some animal studies have indicated growth suppression at high intakes (LSRO/FASEB, 1975). Because of the large doses and routes of administration used (e.g., intravenous and intraperitoneal injection), they were considered not relevant to human intakes from food and supplements (Davis, 1944; Hodge, 1945; Sahu, 1989; Sahu et al., 1986).

Body Odor, Sweating, and Salivation. High doses of choline have been associated with fishy body odor, vomiting, salivation, sweating, and gastrointestinal effects (LSRO/FASEB, 1981). These symptoms were reported in patients with tardive dyskinesia and cerebellar ataxia treated with choline chloride at 150 and 220 mg/kg of body weight/day for 2 to 6 weeks (10 and 16 g/day, respectively) (Davis et al., 1975; Growdon et al., 1977b; Lawrence et al., 1980). Studies of the production of methylamines from ingested choline suggest that fishy odor would have been observed in healthy populations (Zeisel et al., 1983). Fishy body odor results from the excretion of excessive amounts of trimethylamine, a choline metabolite, as the result of bacterial action. Lecithin, a choline-containing phospholipid, does not present a risk of fishy body odor because it generates little methylamine because the bacterial enzyme cannot cleave the ester (Zeisel et al., 1983).

Hypotension. Oral administration of 10 g/day of choline chloride (which is equivalent to 7.5 g [72 mmol] of choline alone) had a slight hypotensive effect in humans (Boyd et al., 1977). Choline could be acting by increasing vagal tone to the heart or by dilating arterioles. Although added choline increases acetylcholine release from in vitro preparations of heart (Loffelholz, 1981), changes in cardiac rate have not been observed in healthy humans treated with choline.

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408
Front Matter (R1-R24)
Summary (1-16)
1 Introduction to Dietary Reference Intakes (17-26)
2 The B Vitamins and Choline: Overview and Methods (27-40)
3 A Model for the Development of Tolerable Upper Intake Levels (41-57)
4 Thiamin (58-86)
5 Riboflavin (87-122)
6 Niacin (123-149)
7 Vitamin B6 (150-195)
8 Folate (196-305)
9 Vitamin B12 (306-356)
10 Pantothenic Acid (357-373)
11 Biotin (374-389)
12 Choline (390-422)
13 Uses of Dietary Reference Intakes (423-436)
14 A Research Agenda (437-442)
A Origin and Framework of the Development of Dietary Reference Intakes (443-447)
B Acknowledgments (448-450)
C Système International d'Unités (451-452)
D Search Strategies (453-455)
E Methodological Problems Associated with Laboratory Values and Food Composition Data for B Vitamins (456-459)
F Dietary Intake Data from the Boston Nutritional Status Survey, 1981–1984 (460-465)
G Dietary Intake Data from the Continuing Survey of Food Intakes by Individuals (CSFII), 1994–1995 (466-477)
H Dietary Intake Data from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994 (478-501)
I Daily Intakes of B Vitamins by Canadian Men and Women, 1990, 1993 (502-506)
J Options for Dealing with Uncertainties in Developing Tolerable Upper Intake Levels (507-511)
K Blood Concentrations of Folate and Vitamin B12 from the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994 (512-519)
L Methylenetetrahydrofolate Reductase (520-522)
M Evidence from Animal Studies on the Etiology of Neural Tube Defects (523-526)
N Estimation of the Period Covered by Vitamin B12 Stores (527-530)
O Biographical Sketches (531-536)
P Glossary and Abbreviations (537-540)
Index (541-567)