Impact of methionine on net ketoacid production in humans

Abstract

An exogenous acid load (NH 4Cl) inhibits net ketoacid production in the first week of starvation and the fourth to eighth weeks of ketogenic dieting. To determine whether an acid load produced by amino acid metabolism can similarly modify ketosis, five overweight volunteers ingested methionine (H 2SO 4), NH 4Cl, and NaCl (control), in varying order, each day for seven days during weeks 5 to 8 of hypocaloric ketogenic dieting. During days 5 to 7 of each phase, blood pH, bicarbonate, and pCO 2 were stable but lower in the NH 4Cl phase (7.32 ± 0.02, 18.1 ± 1.2 mmol/L, 35.8 ± 1.4 mmHg) and the methionine phase (7.33 ± 0.01, 17.1 ± 0.9 mmol/L, 34.0 ± 2.0 mmHg) than in the NaCl phase (7.38 ± 0.01, 22.3 ± 0.2 mmol/L, 37.6 ± 1.6 mmHg), P < .05. Over this period, blood acetoacetate concentration was lower during the methionine and NH 4Cl phases than during NaCl, P < .05. In addition blood β-hydroxybutyrate and total ketone-body concentrations were lower in the methionine than NaCl phases, P < .05. Urinary acetoacetate and β-hydroxybutyrate excretion fell with both acid loads, P < .05. Compared with control values, urinary total ketone excretion was suppressed by 67 ± 10% in the NH 4Cl and 89 ± 3% in the methionine periods. When NaCl was ingested after either of the acid loads, urinary ketone excretion increased by 300% to 700%. Thus, methionine ingestion, which results in an acid challenge equivalent to that of a large protein load, has an impact on net ketoacid production similar to that of NH 4Cl. This observation suggests that endogenous as well as exogenous acid loads can influence organic acid production in a direction that helps maintain acid-base equilibrium.