Protein wasting due to acidosis of prolonged fasting

Abstract

During a total fast in obese subjects, the daily rate of nitrogen excretion undergoes only a small further decline after 2 wk, the excretion rate being about 5 g N/day. At this time, ammonium and urea each constitute about one-half of this excretion. The purpose of this study was to consider two alternative hypotheses: first, that the near plateau in nitrogen excretion represents an irreducible minimum rate of net protein breakdown in order to supply essential organs with calories in the form of glucose; second, that protein breakdown could be further reduced by minimizing the requirement to provide nitrogen for ammonium excretion during the ketoacidosis of fasting. Because ammonium excretion is largely controlled by acid-base balance, 150 mmol of sodium bicarbonate plus 60 mmol of potassium chloride were administered daily to decrease ammonium excretion in eight obese subjects who were totally fasting for more than 14 days. Urine ammonium nitrogen fell with this treatment (from 3.8 +/- 0.4 to 2.0 +/- 0.4 g N/g creatinine). In addition, there was a smaller fall in the rate of urea excretion (from 2.5 +/- 0.2 to 2.1 +/- 0.3 g N/g creatinine) together with a fall in the blood urea nitrogen. Therefore, it appears that ammonium excretion contributes to the negative nitrogen balance of a prolonged total fast, as assessed over a 3-day period of observation, is responsible for about one-third of the net lean body mass loss.

Interorgan Coordination of the Murine Adaptive Response to Fasting

“…Muscle catabolism is a major source of amino acids in this phase. When fasting is continued, muscle protein catabolism declines, and hepatic uptake of amino acids decreases, which is reflected in a decline of endogenous glucose production (6) and urinary nitrogen excretion (4,7). Lipid catabolism and the (hepatic) production of ketone bodies also increases rapidly and is quantitatively similar after 3 days and 5-6 weeks of starvation (8), but plasma levels increase only gradually to plateau after 4 weeks (4,9).…”

“…Lipid catabolism and the (hepatic) production of ketone bodies also increases rapidly and is quantitatively similar after 3 days and 5-6 weeks of starvation (8), but plasma levels increase only gradually to plateau after 4 weeks (4,9). The associated increase in urinary ketone body (organic-acid) excretion requires a compensatory increase in ammonia production and urinary excretion (4,7,10), which is met by an increased renal amino acid uptake and gluconeogenesis (5,6). As a result, the kidney and the liver produce similar amounts of glucose (4,6) and ammonia/urea (7) after 2-3 weeks of fasting.…”

High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses

“…Besides this effect on bone, metabolic acidosis has also been demonstrated to contribute to increases in whole body protein turnover and concomitant decreases in whole body protein content (9,10,54). In certain groups such as patients with renal failure and obese subjects who were on a weight-loss diet, metabolic acidosis has also been linked to protein wasting (26,32); in acidotic rats, impaired growth, abnormal nitrogen utilization, and increased muscle protein degradation were found (48,71). Several investigations have shown that the correction of acidosis compensates for those losses (27-29, 45, 53).…”

Comments on metabolic needs for glucose and the role of gluconeogenesis

“…Why should glutamine be metabolized in the kidney, obliging the urinary loss of ketones, when it may just as readily be metabolized in the liver, the carbon skeleton converted to glucose and the nitrogen to urea, at a much lower energy cost? The classical idea that NH 4 excretion is obligated by ketoacid loss and is required for acid-base homeostasis receives support from the study of Hannaford et al (1982) who showed that provision of sodium bicarbonate and potassium chloride to starved obese patients greatly reduced urinary NH 4 excretion even though ketonuria was not decreased. Nevertheless the very existence of starvation ketonuria, when conservation of calories ought to be a priority, is a challenge.…”

“…In this regard, Kamel et al (1988) point out that the excretion of 150 mMoles of NH 4 and 150 mMoles of ketoacid per day can provide these osmoles and, in terms of conserving lean body mass, is much more effective (by a factor of four) than the provision of the same number of osmoles in the form of urea. That urinary nitrogen loss during starvation can be reduced appreciably by factors that have little or nothing to do with glucose provision to the brain is apparent from the experiments of Hannaford et al (1982) where sodium bicarbonate and potassium chloride were provided to the starved obese patients. Not only was ammonium excretion decreased, as expected from acidbase considerations, but total urinary excretion (urea ammonium) was decreased by a third, indicating a proportional decrease in proteolysis.…”