Faecal ammonia and pH during lactulose administration in man: comparison with other cathartics

Abstract

SUMMARY The effect of lactulose on faecal pH and ammonia has been studied in three normal subjects with the aid of dialysis of faeces in vivo. Observations were also made with sodium sulphate and the two hexahydric alcohols, mannitol and sorbitol, given in doses sufficient to cause a similar increase in stool weight.All four cathartics rendered the stool more acid, but there was no increase in the concentration of faecal ammonia. Lactulose, despite increasing faecal volume, did not cause an increase in the absolute amount of ammonia lost in the faeces, but the other purgatives did show a modest rise.The results are inconsistent with the theory that lactulose benefits the clinical picture of portosystemic encephalopathy by trapping ammonia in an acid stool. An alternative suggestion is advanced, namely, that any cathartic (including lactulose) reduces ammonia absorption from the colon by decreasing colonic transit time, and so reducing the amount of ammonia generated by autolysis of colonic bacteria.Lactulose (1-4 ,B galactosido-fructose) was introduced in 1966 by Bircher, Muller, Guggenheim, and Haemmerli, in the treatment of portosystemic encephalopathy. This step had been suggested by Ingelfinger (1964-65) who recognized that the disaccharide is not hydrolysed in the ileum and when taken by mouth will reach the colon unchanged, where it promotes the growth of lactobacilli, organisms which lack urease, and other ammonia-generating enzymes (Phear and Ruebner, 1956;Macbeth, Kass, and McDermott, 1965). Ingelfinger (1964) suspected that a reduction in the number of proteolytic bacteria in the colon, in favour of lactobacilli, would reduce the formation of ammonia, leading to a decrease in portal venous ammonia.Clinical trials have since tended to confirm the value of lactulose in portosystemic encephalopathy (Bircher, Haemmerli, Scollo-Lavizzari, and Hoffmann, 1971a). Lactulose has also been shown to lower faecal pH (Mayerhofer and Petuely, 1959), a finding which has led to an alternative suggestion, that its effect on non-ionic diffusion of ammonia might explain its efficacy in portosystemic encephalopathy. It was argued (Elkington, Floch, and Conn,

Effects of lactulose and other laxatives on ileal and colonic pH as measured by a radiotelemetry device

“…The present results suggest that acceptable doses of lactulose will not consistently reduce faecal pH. Agostini et al (1972) showed that, even when faecal pH was lowered by lactulose, there was no demonstrable increase in the faecal excretion of ammonia. It seems unlikely that the trapping of ammonia in an acid stool is relevant in this context.…”

“…In the third subject, the faecal volume was more than doubled, compared with the control period, and the mean pH was significantly reduced by 0.7 unit. In clinical trials of patients with hepatic encephalopathy, much more striking acidification of faeces has been reported in some studies (Elkington et al, 1969;Bircher et al, 1971) but the dose of lactulose used was generally greater than that used by Agostini et al (1972) and the stool volumes were probably larger. Zeegen et al (1970) measured the pH of faecal dialysates and faecal volume in four subjects taking lactulose and extremely variable results were obtained.…”

“…First, magnesium sulphate was used because it does not acidify faeces and may even produce an alkaline pH (Zeegan et al, 1970). Secondly, sodium sulphate was examined because this produces a more consistent acidification of faeces than lactulose, probably by a totally different mechanism (Down, Agostini, Morison, and Wrong, 1972;Agostini et al, 1972). Finally, the effects of a mixture of lactulose and sodium sulphate 999 were investigated in an attempt to produce uniform acidification along the length of the colon.…”

Colon Cancer: A Disease of Fibre Depletion or of Dietary Excess ?

“…The amount of urinary secondary amine was also unchanged during the high fibre period. Agostini et al [1] showed that the amount of urea hydrolysed in the colon by the gut flora was not reduced by the administration of dietary lactulose at a dose high enough to give two stools per day and a fecal pH of 5-6; this is despite the fact that the transit time must have been reduced considerably from the normal. There is certainly no support, therefore, for the contention that a decreased transit time necessarily results in decreased bacterial action on the gut contents.…”

Comparative Study of Basal Arterial Ammonemia and of Orally-Induced Hyperammonemia in Chronic Portal Systemic Encephalopathy, Treated with Neomycin, Lactulose, and an Association of Neomycin and Lactulose

“…Recent experimental findings [10][11][12], in agreement with the nonionic diffusion of ammonia, tend to confirm that lactulose decreases ammonia resorption by acidifying the colonic content and thereby lowering the intralumen proportion of nonionized ammonia. However, this generally accepted mechanism contradicts the inability of lactulose to increase the absolute quantity of ammonia in the feces [13].…”