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Studies in Nicotinic Acid Metabolism

I. The Fate of Nicotinic Acid in Man¹

Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina

Trigonelline and nicotinuric acid are the two known end products of nicotinic acid metabolism found in human urine.

For a study of normal trigonelline excretion in man, a diet free of coffee, peas, beans and other legumes is necessary. On such a diet, rigorously controlled, three individuals excreted 9 to 13 mg. of trigonelline per day. On less rigorously controlled diets, twenty-six students excreted an average of 15 mg. of trigonelline per day. Three individuals, after 3 days of fasting, excreted 8 to 12.6 mg. trigonelline per day.

The normal daily excretion of acid hydrolyzable nicotinic acid derivatives (NA) by thirty-six subjects on different diets and under fasting conditions was 0.7 to 2.2 mg. This level was not affected by smoking.

There is a constant loss of at least 10 mg. of known nicotinic acid derivatives in the urine daily, regardless of diet.

Of 200 mg. oral doses of nicotinic acid, 25 to 90 mg. could be accounted for by the increase in urinary trigonelline and nicotinuric acid. Trigonelline accounted for 55 to 84% of this increase. The remainder was nicotinuric acid. The feeding of glycine and choline with 200 mg. doses of nicotinic acid did not change the proportions of trigonelline and nicotinuric acid excreted.

Of 200 mg. doses of nicotinamide, 36 to 60 mg. could be accounted for by the increase in urinary trigonelline. There was no increased excretion in the acid hydrolyzable nicotinic acid fractions.

Trigonelline is not utilized by man when taken orally, and is excreted almost completely as such. Nicotinuric acid when ingested is excreted to the extent of about 60%, unchanged, and without an accompanying increase in trigonelline.⁹

After six daily doses of 500 mg. of nicotinamide the urinary excretion of NA and trigonelline in six subjects accounted for 27 to 42% of the ingested dose, compared to 5 to 21% which could be accounted for after the first day. Over 90% of this added excretion was in the form of trigonelline. Of the remaining NA fraction, 65 to 80% was nicotinuric acid.

The extra excretion of NA and trigonelline after a test dose of nicotinamide may serve as an indication of the nutritional status of an individual with respect to nicotinic acid.

A preliminary report was made by the authors before the meeting of the American Society of Biological Chemists at Chicago, April, 1941.

⁹ Since this paper has gone to press it has been determined that nicotinuric acid given intravenously in 100 mg. doses to three subjects was excreted to the extent of 96, 94 and 97%.

² Upjohn Fellow in Biochemistry.

Manuscript received 18 August 1941.

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