Table 4.
Summary of key safety/tolerability findings from clinical studies of lactulose.
| Design and study population | Key safety findings | References |
|---|---|---|
| Prebiotic effects of lactulose | ||
| Open-label study in 304 healthy adult volunteers (one group non-constipated; one group mildly constipated) | Lactulose was generally well-tolerated at all doses Most participants reported that treatment had no significant tolerability effect (59–80% of all abdominal symptom comments were “nothing significant”) However, small increases in abdominal gaseous symptoms (flatulence, abdominal distension, passing flatus) were observed in both treatment groups | (60) |
| Randomized, double-blind, PBO-controlled study in 20 healthy adult volunteers | Lactulose 10 g/day was generally well-tolerated One participant reported a moderate to severe change in flatulence, bloating, and accompanying abdominal pain | (64) |
| Randomized, double-blind, PBO-controlled, parallel-group study in 16 healthy adult volunteers | Prolonged low-dose lactulose (10 g/day) was well-tolerated and was associated with mild digestive symptoms Excess flatus was more common in the lactulose group vs. PBO (p = 0.03) but was very mild. Bloating, borborygmi, and abdominal pain did not differ between the groups | (59) |
| Open-label, single-arm, before-after study in 26 healthy women | Low-dose lactulose (1, 2, and 3 g/day) was well-tolerated No side effects or SAEs were reported Secondary abdominal symptoms were predominantly GI in nature; however, their incidence did not differ significantly between pre-observation/washout periods and respective lactulose intake periods | (61) |
| Randomized, double-blind, PBO-controlled, crossover study in 52 healthy women | No side effects or SAEs were reported The main tolerability symptoms were GI in nature, but these were similar for low-dose lactulose (2 g/day) and PBO | (62) |
| Prospective, multicenter, randomized, single-blind, active-controlled, parallel-group study in 65 adults with chronic constipation | The proportion of patients reporting at least 1 day of moderate-to-severe borborygmi and bloating decreased in both the lactulose and PEG-4000 treatment groups Eight patients in the lactulose group and five in the PEG-4000 group reported a total of 17 AEs (events assessed included borborygmi, bloating, abdominal pain, and excess flatus); however, there were no SAEs | (54) |
| Mineral absorption effects of lactulose | ||
| Randomized, double-blind, three-period, three-group crossover study in 24 healthy men | Low-dose lactulose (2 or 4 g/day) was well-tolerated, with no side effects reported | (66) |
| Randomized, double-blind, PBO-controlled crossover study in 12 healthy postmenopausal women | Low-dose lactulose (5 and 10 g/day) was well-tolerated There were no significant differences in GI complaints between low-dose lactulose and aspartame PBO treatment in a postmenopausal population | (67) |
AE, adverse event; GI, gastrointestinal; PBO, placebo; PEG-4000, polyethylene glycol-4000; SAE, serious adverse event.