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Effect of exogenous β-galactosidase in patients with lactose malabsorption and intolerance: a crossover double-blind placebo-controlled study



To evaluate the efficacy of the addition to milk, 5 min and 10 h before its consumption, of a lactase obtained from Kluyveromyces lactis in lactose malabsorbers with intolerance.


Double-blind, placebo-controlled, crossover study.


University Hospital.


In total, 11 male and 19 female (aged from 18 to 65 y, mean age 43.3 y) lactose malabsorbers with intolerance participated.


Each patient underwent three H2 breath tests, in a random order. We used 400 ml of cow's semiskimmed milk as substrate and a β-galactosidase obtained from K. lactis. The test A was carried out adding to the milk the enzyme (3000 UI), 10 h before its consumption; the test B was performed adding the β-galactosidase (6000 UI) 5 min before milk ingestion and the test C was made using placebo. We evaluated the maximum breath H2 concentration, the cumulative H2 excretion and a clinical score based on intolerance symptoms (bloating, abdominal pain, flatulence and diarrhoea).


Our study showed a significant reduction of the mean maximum H2 concentration after both test A (12.07±7.8 p.p.m.) and test B (13.97±7.99 p.p.m.) compared with test C (51.46±16.12 p.p.m.) (ANOVA F=54.33, P<0.001). Similarly, there was a significant reduction of the mean cumulative H2 excretion after both test A (1428±1156 p.p.m.) and test B (1761±966 p.p.m.) compared with test C (5795±2707 p.p.m.) (ANOVA F=31.46, P<0.001). We also observed a significant reduction of the mean clinical score after both test A (0.36±0.55) and test B (0.96±0.85) compared with test C (3.7±0.79) (ANOVA F=106.81, P<0.001). Moreover, with regard to the mean clinical score, there was a significant reduction after test A with respect to test B (Bonferroni's P=0.03).


Our study shows that in lactose malabsorbers with intolerance, the lactase obtained from K. lactis can represent a valid therapeutic strategy, with objective and subjective efficacy and without side effects.

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  • Barillas C & Solomons NW (1987): Effective reduction of lactose maldigestion in preschool children by direct addition of b-galactosidase to milk at mealtime. Pediatrics 79, 766–772.

    CAS  PubMed  Google Scholar 

  • Briet F, Pochart P, Marteau P, Flourie B, Arrigoni E & Rambaud JC (1997): Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect? Gut 41, 632–635.

    Article  CAS  Google Scholar 

  • Corazza GR, Benati G, Sorge M, Strocchi A, Calza G & Gasbarrini G (1992): Beta-galactosidase from Aspergillus niger in adult lactose malabsorption: a double-blind crossover study. Aliment. Pharmacol. Ther. 6, 61–66.

    Article  CAS  Google Scholar 

  • Di Stefano M, Veneto G, Malservisi S, Cecchetti L, Minguzzi L, Strocchi A & Corazza GR (2002): Lactose malabsorption and intolerance and peak bone mass. Gastroenterology 122, 1793–1799.

    Article  CAS  Google Scholar 

  • Gilat T, Russo S, Gelman-Malachi E & Aldor TA (1972): Lactase in man: a non-adaptable enzyme. Gastroenterology 62, 1125–1127.

    CAS  PubMed  Google Scholar 

  • Gudmand-Hoyer E (1994): The clinical significance of disaccharide maldigestion. Am. J. Clin. Nutr. 59, 735S–741S.

    Article  CAS  Google Scholar 

  • Kotler DP, Holt PR & Rosensweig NS (1982): Modification of the breath hydrogen test increased sensitivity for the detection of carbohydrate malabsorption. Lab. Clin. Med. 100, 798–805.

    CAS  Google Scholar 

  • Lami F, Callegari C, Tatali M, Graziano L, Guidetti C, Miglioli M & Barbara L (1988): Efficacy of addition of exogenous lactase to milk in adult lactase deficiency. Am. J. Gastroenterol. 83, 1145–1149.

    CAS  PubMed  Google Scholar 

  • Lin MY, Dipalma JA, Martini MC, Gross CJ, Harlander SK & Savaiano DA (1993): Comparative effects of exogenous lactase (beta-galactosidase) preparations on in vivo lactose digestion. Dig. Dis. Sci. 38, 2022–2027.

    Article  CAS  Google Scholar 

  • Onwulata CI, Rao DR & Vankineni P (1989): Relative efficiency of yogurt, sweet acidophilus milk, hydrolyzed-lactose milk, and a commercial lactase tablet in alleviating lactose maldigestion. Am. J. Clin. Nutr. 49, 1233–1237.

    Article  CAS  Google Scholar 

  • Peuhkuri K, Vapaatalo H, Nevala R & Korpela R (1999): Influence of the pharmacological modification of gastric emptying on lactose digestion and gastrointestinal symptoms. Aliment. Pharmacol. Ther. 13, 81–86.

    Article  CAS  Google Scholar 

  • Rask Pedersen E, Jensen BH, Jensen HJ, Keldsbo IL, Hylander Moller E & Norby Rasmussen S (1982): Lactose malabsorption and tolerance of lactose-hydrolyzed milk. A double-blind controlled crossover study. Scand. J. Gastroenterol. 17, 861–864.

    Article  CAS  Google Scholar 

  • Rosado JL, Solomons NW, Lisker R, Bourges H, Anrubio G, Garcia A, Perez-Briceno R & Aizupuru E (1984): Enzyme replacement therapy for primary adult lactase deficiency. Gastroenterology 87, 1072–1082.

    CAS  PubMed  Google Scholar 

  • Saltzman JR, Russell RM, Golner B, Barakat S, Dallal GE & Goldin BR (1999): A randomized trial of Lactobacillus acidophilus BG2FO4 to treat lactose intolerance. Am. J. Clin. Nutr. 69, 140–146.

    Article  CAS  Google Scholar 

  • Shaw AD & Davies GJ (1999): Lactose intolerance: problems in diagnosis and treatment. J. Clin. Gastroenterol. 28, 208–216.

    Article  CAS  Google Scholar 

  • Solomons NW, Guerrero AM & Torun B (1985a): Dietary manipulation of the postprandial colonic lactose fermentation: II. Addition of exogenous microbial beta-galactosidase at mealtime. Am. J. Clin. Nutr. 41, 209–221.

    Article  CAS  Google Scholar 

  • Solomons NW, Guerrero AM & Torun B (1985b): Effective in vivo hydrolysis of milk lactose by beta-galactosidase in the presence of solid foods. Am. J. Clin. Nutr. 41, 222–227.

    Article  CAS  Google Scholar 

  • Suarez FL, Savaiano DA & Levitt MD (1995): The treatment of lactose intolerance. Aliment. Pharmacol. Ther. 9, 589–597.

    Article  CAS  Google Scholar 

  • Szilagyi A (2002): Lactose: a potential prebiotic. Aliment. Pharmacol. Ther. 16, 1591–1602.

    Article  CAS  Google Scholar 

  • Szilagyi A, Salomon R & Seidman E (1996): Influence of loperamide on lactose handling and oral-coecal transit time. Aliment. Pharmacol. Ther. 10, 765–770.

    Article  CAS  Google Scholar 

  • Szilagyi A, Torchinsky A & Calacone A (2000): Possible therapeutic use of loperamide for symptoms of lactose intolerance. Can. J. Gastroenterol. 14, 581–587.

    Article  CAS  Google Scholar 

  • Swagerty DL, Walling AD & Klein RM (2002): Lactose intolerance. Am. Fam. Physician 65, 1845–1850.

    PubMed  Google Scholar 

  • Wang Y, Harvey CB, Hollox EJ, Phillips AD, Poulter M, Clay P, Walker-Smith JA & Swallow DM (1998): The genetically programmed down-regulation of lactase in children. Gastroenterology 114, 1230–1236.

    Article  CAS  Google Scholar 

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Correspondence to M Montalto.

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Guarantor: M Montalto.

Contributors: MM designed the study, wrote the manuscript and recruited the patients with the help of GN. LS, VC, MV, LC, RM, AG and GG participated in clinical assessment, data management and editing of the paper. MC carried out statistical calculations. All authors reviewed the manuscript and approved the final version.

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Montalto, M., Nucera, G., Santoro, L. et al. Effect of exogenous β-galactosidase in patients with lactose malabsorption and intolerance: a crossover double-blind placebo-controlled study. Eur J Clin Nutr 59, 489–493 (2005).

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  • lactose malabsorption
  • lactose intolerance
  • enzyme replacement
  • β-galactosidase
  • Kluyveromyces lactis

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