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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
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.