Table 3.
Summary of key efficacy findings from clinical studies of the prebiotic and mineral absorption effects of low-dose lactulose.
| Study population, age | N | Aims | Design | Treatment regimen | Key efficacy findings | References |
|---|---|---|---|---|---|---|
| Prebiotic effects | ||||||
| Healthy M and F 8–22 y | 8 | Assess the effects of lactulose on the composition and metabolic activity of fecal microbiota | Open-label, single-arm study | Lactulose 3 g/D for 2 W |
↑ (~7%) in populations of bifidobacteria (p < 0.001) ↓ (slight) in populations of Bacteroidaceae and lecithinase-positive clostridia (both p < 0.05) ↓ fecal indole, phenol (both p < 0.05), and skatol (in 4/8 volunteers) ↓β-glucuronidase, nitroreductase, and azoreductase activities (all p < 0.05) ↓ fecal pH 7.0 → 6.4 ↑ fecal moisture content by 4.3–5.3% |
(63) |
| Healthya M and F 13–66 y | 304 | Assess the effects of lactulose on intestinal function and fecal character | Open-label study in three groups | n = 8 healthy volunteers: lactulose 4 g/D for 3 W n = 296a: lactulose 3 or 5 g/D for 10 D | Lactulose 4 g/D: ↑ populations of bifidobacteria (p < 0.05) ↓ populations of Bacteroidaceae, eubacteria, and clostridia (mean ratio to total bacteria when compared with after lactulose intake; all p < 0.05) ↓ fecal pH (compared with after lactulose intake; p < 0.05) ↓ fecal indole (compared with before lactulose intake; p < 0.05) Lactulose 3 or 5 g/D: ↑ defecation frequency and feces became more watery, yellowish, and softer (compared with before and after lactulose intake for both 3 and 5 g/D groups; p < 0.05 or p < 0.01, respectively) Results were consistent between patients with low and normal defecation frequencies |
(60) |
| Healthyb 18–50 y | 20 | Assess the effects of lactulose on colonic microbiota | Randomized, double-blind, PBO-controlled study | R 1:1 to lactulose 10 g/D (n = 10) or PBO (glucose/lactose; n = 10) for 26–33 D | With lactulose: ↑ populations of Bifidobacterium spp. vs. pre-tx levels (p < 0.01) ↑ populations of Bifidobacterium spp. vs. PBO (p < 0.01) ↓ populations of Clostridium spp. vs. pre-tx levels (p < 0.01) |
(64) |
| Healthy M and F 19–42 y | 16 | Assess the effects of prolonged lactulose on fecal bifidobacteria and metabolic indices potentially involved in colonic carcinogenesis | Randomized, double-blind, PBO-controlled, parallel-group study | R 1:1 to lactulose 10 g/D (n = 8) or PBO (sucrose; n = 8) for 6 W | With lactulose: ↑ fecal Bifidobacterium counts from D0 to D21 and D42 (p = 0.048) and vs. PBO (p = 0.03) Neither group showed significant changes in total anaerobes, lactobacilli, pH, or other study variables |
(59) |
| Healthyb 24–31 y | 36 | Assess the comparative efficacy of lactulose and lactitol on colonic microbiota and fecal biochemistry | Randomized, double-blind, PBO-controlled study | R 1:1:1 to lactulose 20 g/D (n = 12), lactitol 20 g/D (n = 12), or PBO (sucrose/lactose; n = 12) for 4 W | Lactulose vs. PBO: ↑ populations of probiotic bacteria (p < 0.01) ↓ populations of putrefactive bacteria (p < 0.01) Beneficial changes greater with lactulose vs. lactitol Effect onset more rapid with lactulose vs. lactitol (1 vs. 2 W) Both lactulose and lactitol led to significant changes in fecal biochemistry compared with PBO |
(16) |
| Healthy postmenopausal F 55–64 y | 10 | Assess the effects of lactulose on intestinal microbiota and SCFA production | In-vivo effect on fecal samples and computer-controlled in-vitro model of the proximal large intestine | Lactulose 10 g/D for 7 D. Microbiota obtained from volunteers before and after lactulose consumption were adapted to an in-vitro model of the proximal colon and then fed lactulose 10 g/D introduced gradually over a 48-h period | Following in-vivo lactulose consumption: no changes in fecal pH, dry weight, or mean molar SCFA ratios in the fecal samples ↑ populations of Bifidobacterium (p < 0.05) Following adaptation of the in-vivo samples (before and after lactulose consumption) to the in-vitro culture system:clear effect of in-vivo lactulose consumption on Lactobacillus and Enterococcus (both ↑) clear effect of in-vivo lactulose consumption on SCFA ratios ( ↓ butyrate; p < 0.001) |
(65) |
| Healthy F 18–21 y | 26 | Assess the prebiotic effects of lactulose on defecation frequency | Open-label, single-arm, before-after study | Lactulose 1, 2, and 3 g/D for 2 W each. Crossed over after a 2-W washout period | Lactulose 1, 2, and 3 g/D: ↑ defecation frequency ↑ defecation D ↑ fecal bifidobacteria counts |
(61) |
| Healthy F mean (± SD): 20.2 (± 2.4) y | 52 | Assess the prebiotic effects of lactulose on defecation frequency | Randomized, double-blind, PBO-controlled, crossover study | R 1:1 to lactulose 2 g/D or PBO (glucose) for 2 W. Crossed over after a 3-W washout period | Lactulose vs. PBO: ↑ populations of Bifidobacterium in feces ↑ proportion of Bifidobacterium in feces ↑ defecation frequency ↑ number of defecation D improved fecal character (consistency and volume) |
(62) |
| Chronically constipated M and F mean (± SD): 57 (± 18) y | 65 | Assess the comparative efficacy of lactulose and PEG-4000 on colonic microbiota | Prospective, multicenter, randomized, single-blind, active-controlled, parallel-group study | R 1:1 to lactulose or PEG-4,000 for 4 W. W1 dose fixed (20 g/D); W2 dose could vary (10–30 g/D); W3–4 dose fixed (10–30 g/D) | With lactulose (D −1 to D28): ↑ populations of fecal bifidobacteria and anaerobes (p < 0.02) no significant differences in SCFAs With PEG-4000 (D−1 to D28): no significant differences in populations of fecal bifidobacteria/anaerobes ↓ total SCFAs (p = 0.02), acetate (p = 0.02), and butyrate (p = 0.04) |
(54) |
| Mineral absorption effects | ||||||
| Healthy M 23–42 y | 24 | Assess the effect of lactulose on Ca and Mg absorption | Randomized, double-blind, three-period, three-group crossover study | R 1:1:1 to PBO, lactulose 2 or 4 g/D, plus CaCO3 300 mg (20 mg 44Ca) and MgO 150 mg (28 mg 25Mg). Crossed over after a 2-W washout period between each tx | Lactulose 2 or 4 g/D enhanced Ca and Mg absorption vs. PBO Urinary stable isotopes ratios (44Ca/40Ca and 25Mg/24Mg) ↑ with lactulose dose and were significantly different for lactulose vs. PBO for Ca (lactulose 4 g/D) and Mg (lactulose 2 and 4 g/D) (all p < 0.01) |
(66) |
| Healthy postmenopausal F 56–64 y | 12 | Assess the effect of lactulose on Ca absorption | Randomized, double-blind, PBO-controlled crossover study | R 1:1:1 to lactulose 5 or 10 g/D or PBO (aspartame) for 9 D. 44Ca and 48Ca given on D8. Crossed over after a 19-D washout period between each tx | Lactulose 5 or 10 g/D dose-dependently ↑ intestinal Ca absorption without ↑ urinary excretion |
(67) |
| Postmenopausal, with osteopenia F 52–67 y | 41 | Assess the effect of lactulose on BMD maintenance | Randomized, double-blind, PBO-controlled parallel-group study | R 1:1 to lactulose 10 g/D plus CaCO3 500 mg/D or PBO plus CaCO3 1,000 mg/D for 12 months | Lactulose plus CaCO3 500 mg/D was as effective as lactulose plus CaCO3 1,000 mg/D | (68) |
a
69 patients could be considered mildly constipated (defecation frequency < 1.0/D).
b
Sex of participants not stated.
↓, decreased; ↑, increased; BMD, bone mineral density; Ca, calcium; D, day(s); F, female; M, male; Mg, magnesium; n, number of participants; N, total number of participants; PBO, placebo; PEG-4000, polyethylene glycol-4000; R, randomized; SCFA, short-chain fatty acid; SD, standard deviation; spp., species (plural); tx, treatment; W, week(s); y, years.