Conversion of dietary choline to trimethylamine and dimethylamine in rats: dose-response relationship.
Trimethylamine (TMA) and dimethylamine (DMA) are normal components of human urine and are precursors of dimethylnitrosamine, a potent carcinogen. In part, DMA and TMA are products of the metabolism of dietary choline by intestinal bacteria. Most TMA formed in the intestinal tract is later oxidized and excreted as trimethylamine oxide (TMAO). Humans treated with large doses of choline smell "fishy" (the odor of TMA). Humans ingest choline as part of foods, and yet rarely smell fishy, suggesting that TMA formation must depend upon the dose of choline ingested. We found that, in adult rats, at low doses of choline (1.5 mmol/kg body wt) only 9 mumol choline (6% of the dose) reached the part of the intestine which is colonized by bacteria (the cecum and colon). After administration of 15 mmol choline/kg body wt, 237 mumol (16% of the dose) reached the cecum and colon. At both doses, 64-65% of the administered choline was absorbed from the intestine by 3 h after the dose. We found that orally administered choline slightly increased TMA and TMAO excretion at doses of choline smaller than 7 mmol/kg body wt, but that there was a disproportionately large increase in TMA excretion per 24 h when larger doses were administered (from 11 mumol TMA and 100 mumol TMAO per kg body wt in controls to 226 mumol TMA and 3617 mumol TMAO per kg body wt in rats treated with 15 mmol choline/kg body wt).(ABSTRACT TRUNCATED AT 250 WORDS)
Zeisel
S H
SH
Department of Pathology, Boston Unversity School of Medicine, MA 02118.
daCosta
K A
KA
Youssef
M
M
Hensey
S
S
D000818:Animals; D002794:Choline / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D004032:Diet; D004123:Dimethylamines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008744:Methylamines / Q000096:biosynthesis* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D004123:Dimethylamines; D008744:Methylamines; C034516:dimethylamine; C005855:trimethyloxamine; C023336:trimethylamine; D002794:Choline