Lactulose production

FOS mixtures are commercialized with a purity level above 95%, while commercial GOS mixtures contain between 40% and 70% of tri- and tetrasaccharides, except for the purified TOS-100 powder, commercialized byYakult that contains more than 99% GOS. In Europe, FOS synthesized using enzymes are only commercialized by Beghin-Meiji Industries while inulin and oligofructose extracted from the chicory root are produced by Beneo-Orafti, Cosucra, and Sensus. A compilation of the fruc-tans, GOS, and lactulose products currently produced and commercially available is presented in (Table 19.6). 

Very precise kinetic experiments were performed with sponge Ni and Ru/C catalysts in a laboratory-scale pressurized slurry reactor (autoclave) by using small catalyst particles to suppress internal mass transfer resistance. The temperature and pressure domains of the experiments were 20-70 bar and 110-130°C, respectively. Lactitol was the absolutely dominating main product in all of the experiments, but minor amounts of lactulose, lactulitol, lactobionic acid, sorbitol and galactitol were observed as by-products on both Ni and Ru catalysts. The selectivity of the main product, lactitol typically exceeded 96%. 

Figure 12.3. Lactose hydrogenation at 120°C and 50 bar on Ru/C (main product lactitol, by-product with maximum lactulose). Fit of model (1-3, 4b).

These products cause water to enter the lumen of the colon. Lactulose and sorbitol are osmolar, non-absorbable sugars. Magnesium containing products increase secretion of electrolytes... 

Both dietary and endogenous ammoniagenic substrates are removed from the intestinal lumen by the osmotic cathartic action of nonabsorbable disaccharides such as lactulose and lactitol. These compounds are currently the main therapeutic agents for chronic HE. The efficacy of oral lactulose for the treatment of HE has been established in controlled trials [41-43]. Besides having a cathartic effect, lactulose lowers the colonic pH as a result of the production of organic acids by bacterial fermentation. The decrease in pH creates an environment that is hostile to the survival of urease-producing intestinal bac-... 

Antibiotics with activity against urease-producing bacteria, such as neomycin [42], paromomycin [44] or metronidazole [45], also reduce the production of intestinal ammonia and have proved to be of value. Vancomycin has also been used in patients with lactulose-resistant chronic encephalopathy [46]. The efficacy of neomycin is similar to that of lactulose [42]. However, a small percentage of this drug is absorbed from the gastrointestinal tract and may cause ototoxic and nephrotoxic effects, especially with continuous use over several months [47]. This drug should be used with particular caution by patients with renal insufficiency. The efficacy of metronidazole for... 

Treatment approaches include (1) reduction of blood ammonia concentrations by dietary restrictions, and drug therapy aimed at inhibiting ammonia production or enhancing its removal (lactulose and antibiotics) and (2) inhibition of y-aminobutyric acid-benzodiazepine receptors by flumazenil. 

Kuncewicz. A., Panfil-Kuncewicz, H. and Michalak, J. (2000). Lactulose and furosine as indices of the degree of heating of milk and other food products, Przemysl Spozywczy, 5, 20-22. 

Osmotic laxative effects are also produced by the polyhydric alcohols, mannitol and sorbitol, which unlike glucose cannot be transported through the intestinal mucosa, as well as by the non-hydrolyzable disaccharide, lactubse. Fermentation of lactulose by colon bacteria results in acidification of bowel contents and microfloral damage. Lactulose is used in hepatic failure in order to prevent bacterial production of ammonia and its subsequent absorption (absorbable NH3 nonabsorbable NH4+), so as to forestall hepatic coma. 

Figure 2.19 Concentration of lactulose in heated milk products (modified from Andrews, 1989).

Lactulose is unstable in alkaline solution, degrading by alkaline peeling and /3-elimination reactions to yield galactose, isosaccharinic acids, and other acid products (Corbett and Kenner 1954). Amines can bring about dehydration and degradation reactions (Hough et al. 1953). Lactulose is similar to sucrose in humectant properties (Huhtanen et al. 1980). 

Cerbulis et al. (1978) studied the chemical characteristics of the reaction of lactose with urea. Maximal yields (40%) of lactosylurea were obtained at an initial pH of 2.0 (final pH, 3.0). At this pH, lactose was partially hydrolyzed to D-glucose and D-galactose, which also reacted with urea to yield minor urea-containing compounds. Lactulose was the principal secondary product formed above pH 4.0. 

Adachi, S. and Patton, S. 1961. Presence and significance of lactulose in milk products A review. J. Dairy Sci. 44, 1375-1393. 

Sec also Carbohydrates and Milk and Milk Products. LACTULOSE. See Sweeteners. 

The network as depicted in the figure is a very simplified one. It does not incorporate epi-lactose (C-2 epimer of lactose, 4-0-p-D-galacto-pyranosyl-D-mannose) and further reactions of D-galactose. However, it does describe the major events the interconversion of lactose and lactulose, the formation of D-galactose by an elimination reaction and the simultaneous formation of acidic by-products from the glucose moiety. 

Although up to now the commercial product generally is a sugar mixture containing lactulose, there is a trend to further purification. 

Data from Table I point out that other milk-based products are likely to form Amadori products, in this case lactulose-lysine and fructose-lysine, even under moderate thermal treatments. The furosine content, originating from the acid hydrolysis of Amadori products, was high in a whipping agent made from sugar and Na caseinate. It is surprising, however, that cheeses have also relatively high furosine levels. 

Another lactose heat-derived compound is lactulose (4-0-6-D-galactopyranosyl-D-fructofuranose) which was first reported by Montgomery and Hudson (37). This compound can be found in heated milk products, heat processed lactose-containing foods, and alkaline lactose solutions via the isomerization of lactose. It is of interest due to claimed beneficial effects on the gut flora of infants. It has also been proposed as an indicator of the severity of heat treatment in processed dairy products (5). Apparently, it can be present in two forms in heated milks, namely in free solution and covalently bound to protein amino groups. 

Thiazolium salt XTT has been used to evaluate the extent of the Maillard reaction in UHT (ultra-high-temperature)-treated milk, where it proved more rapid and convenient than determination of lactulose, HMF, or furosine.451 To establish the nature of the Maillard reaction products (MRP) involved, the interaction of the aminoreductone from lactose and n-butylamine (Amax = 319.5 nm) with MRP was studied. Excellent correlation (r = 0.967, n = 19) was found between the increased absorbance at 319.5 nm and XTT reducibility, as measured at 492 nm, near Alliax for the formazan, the reduction product of XTT. 

Treatment approaches include (1) reduction of blood ammonia concentrations by dietary restrictions, and drug therapy aimed at inhibiting ammonia production or enhancing its removal (lactulose and antibiotics) and (2) inhibition of y-aminobutyric acid-benzodiazepine receptors by flumazenil. Approaches to reducing blood ammonia concentrations include In patients with acute HE, limit protein intake to 10 to 20 g/day while maintaining the total caloric intake. Protein intake can be titrated by increasing 10 to 20 g/day every 3 to 5 days to a total of 0.8 to 1 g/kg/day. With chronic HE, restrict protein intake to 40 g/day. 

Suppression of bowel flora is thought by some to be useful in hepatic encephalopathy. Here, absorption of products of bacterial breakdown of protein (ammonium, amines) in the intestine lead to cerebral symptoms and even to coma. In acute coma, neomycin 6 g/d should be given by gastric tube as prophylaxis, 1-4 g/d may be given to patients with protein intolerance who fail to respond to dietary protein restriction (see also lactulose, p. 640). 

Intestinal detoxiflcation by means of lactulose, which, among other things, delays the production and/or portal uptake of endotoxins, is another important therapy step. 

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