Conversion of Dietary Choline to Trimethylamine and Dimethylamine in Rats: Dose-Response Relationship

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Abstract
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 µmol 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 µmol (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 µmol TMA and 100 µmol TMAO per kg body wt in controls to 226 µmol TMA and 3617 µmol TMAO per kg body wt in rats treated with 15 mmol choline/kg body wt). DMA excretion increased in a linear fashion as the daily choline dose was increased (from 48 ± 3 µmol/kg body wt in controls to 106 ± 9 µmol/kg body wt in rats treated with 15 mmol choline/kg body wt). These observations support the hypothesis that it is only when intestinal transport systems for the absorption of choline are overloaded that appreciable amounts of this nutrient reach the large bowel and are metabolized to form TMA by intestinal bacteria. DMA formation did not increase in proportion to TMA excretion, suggesting that there is no simple product-precursor relationship between these two amines.

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