Temporal influence of ascorbic acid dose on the endogenous formation of N-nitrosoproline and N-nitrosothiazolidine-4-carboxylic acid in humans

Abstract

The temporal effect of ascorbic acid intake on the endogenous formation of N-nitrosoproline and N-nitrosothiazolidine-4-carboxylic acid was determined over 15 days in 10 ascorbate depleted men consuming a low nitrate and ascorbic acid (<23 μmol) diet. N-nitrosoproline precursors were given as follows: days 3–15, nitrate (5.24 mmol); days 2–15, l-proline (4.35 mmol) 30 min following the nitrate; days 5–11, ascorbic acid (2.62 mmol) 6, 5, 4, 3, 2, 1, and 0.5 hr before the proline, concurrent with the proline on day 12, and 0.5, 1 and 2 hr following the proline on days 13–15. Urine was analyzed for N-nitrosoamino and ascorbic acids. Gastric pH and residence time were measured on days 3–4 concurrently with the proline challenge. Excretion of N-nitrosoproline on nitrate and proline only days was 42.2 ± 16.0 nmol. Significant ( P < 0.05) inhibition was observed when ascorbic acid was given 5 hr before proline (29.1 ± 10.5 nmol). These data suggest that the ascorbic acid content of the stomach due to secretion is sufficient to partially inhibit gastric nitrosation. Diets high in ascorbic acid could reduce gastric formation of N-nitroso compounds even if ascorbic acid is not consumed at the same time as the precursors. No correlation between gastric pH and gastric residence time with N-nitrosoproline and N-nitrosothiazolidine-4-carboxylic acid excretion was observed over the pH range observed. Several subjects consistently excreted high or low levels of N-nitrosoproline or N-nitrosothiazolidine-4-carboxylic acid compared to the mean, regardless of the ascorbic acid intake. This suggests that physiological differences between subjects may account for their endogenous nitrosation capacity.