Studies conducted in Japan and Europe have shown that LcS improves self-reported severity and stool consistency in chronic idiopathic constipation, reduces incidence of hard lumpy stools among healthy subjects, and increases stool frequency among subjects with low stool frequency. In the present study, however, within a 4-week treatment period, administration of 3.0 × 1010 CFU per day of LcS in adults with functional constipation did not bring about statistically significant improvement in any of the four efficacy outcomes when compared with a placebo nutrient drink at α = 5% level. The α = 5% level is conventionally used for clinical trials of medical prescriptions. The present study involved a fermented milk beverage that is not a prescribed pharmaceutical agent, and the purpose of supplementation is for long-term effect. Thus, α = 10% level is not considered critical, and re-evaluation at this α level was attempted, which revealed statistically significant improvement in constipation severity score at week 4 of treatment. It should be noted that the probiotics improved stool consistency significantly compared with baseline, while the placebo did not, and the magnitude of the probiotic treatment effect on stool consistency was small but statistically significant. This effect size also grew larger over time. These findings provide an indication that time could have been a limiting factor in the observation of the full effects of the probiotics on the earlier mentioned parameters. Further investigation with a longer duration of treatment of between 6 and 8 weeks is warranted in order to obtain conclusive results.
Previous studies found significant improvement in certain constipation-related parameters with 4-week administration of a variety of probiotic strains, which was the basis for deciding the present study's duration of intervention. However, the duration of time required for probiotics to exert their effects are still uncertain. There are studies that show significant results with a longer intervention period of 6 weeks. In an 8-week intervention study with prebiotic isomalto-oligosaccharides in constipated elderly people, it was observed that the effects of the prebiotic on defecation was time-dependent. An increase in frequency of spontaneous defecation occurred only in the 4th to 8th week of intervention and not in the first 4 weeks. As both probiotics and prebiotics are thought to exert their beneficial effects on bowel movement through modulation of the gut microflora, it is possible that in the case of probiotics as well, a certain amount of time is needed for the changes in gut microflora to translate to changes in bowel movement. In fact, many recent chronic constipation studies apply intervention periods of between 8 and 12 weeks,[24,25] which is in line with recommendations for trial design in functional gut disorders.[26,27]
Besides the duration of intervention, the positive response toward the placebo drink in control group was another limitation of the present study. Versus baseline values, the control group showed sustained significant improvement in terms of constipation severity score and stool frequency. Whether this response was due to variations in day-to-day diet, a laxative effect of the placebo drink itself or a placebo effect, is not known. Malaysians typically consume spicy food containing capsaicin on a regular basis that may irritate the digestive system resulting in a laxative effect. Both probiotic and placebo drink contained approximately 1 g of lactose. Although lactose intolerance is common among Malaysians, the low levels of lactose in the study drinks would not normally cause digestive disturbances in the lactose-intolerant. However, there is a possibility that even low amounts of lactose could produce a mild softening of stools not amounting to diarrhea that the subjects may have regarded as improvement to their constipation. For future studies, use of a lactose-free probiotic preparation and placebo is recommended. Nevertheless, placebo effect has been noted to be particularly strong in gut-related conditions and can sometimes persist for the first 2–3 weeks of intervention. This presents an ongoing challenge to researchers in evaluating treatments in functional gut disorders.
The present study is the first to test LcS as treatment in otherwise-healthy subjects with Rome-defined functional constipation, as well as in non-Japanese Asian sample. It is unclear whether the vastly different diets of South East Asian subjects compared with the Japanese or Europeans would have bearing on the effects of this probiotic in constipation, although diet has been shown to influence gut microflora composition that may be part of the mechanism through which probiotics exert their effects.
Volunteers in the present study were not actively seeking treatment for their condition and thus could be considered as having relatively mild constipation, also reflected by their low severity scores at baseline (5.06 and 5.21 points in probiotics and control groups, respectively), which was close to the 5-point cut-off between healthy and constipated subjects. The relatively low severity scores may have also contributed partly to the failure to achieve statistical significance.
Post-hoc exploratory analysis showed improvement in severity of incomplete evacuation in probiotic group that might suggest that this symptom may improve with LcS intake, although further investigation is necessary to verify this. Improvement in severity of incomplete evacuation has been previously reported with interventions using LcS as well other strains of probiotics. The sensation of incomplete evacuation is an integral component of constipation. Efficacy parameters involving the measurement of "completeness" of evacuation in each defecation combined with stool frequency, namely complete, spontaneous bowel movements (CSBMs), has been acknowledged to have clinical importance in chronic constipation and Irritable Bowel Syndrome with constipation. The effect of LcS on CSBM has yet to be investigated and thus remains a focal issue for future studies involving not only LcS but other probiotic strains as well.
The present study is the first to use a severity scoring tool as an outcome measurement in an intervention with LcS in constipation. The tool used, CCQ, was assessed in a review of self-report measures for constipation severity, where out of seven tools evaluated, only CCQ and Patient Assessment of Constipation—Symptom were found to be satisfactory in terms of validity and reliability. Results of the present study support utilization of CCQ severity score as a useful indicator to detect changes in severity of constipation over time with an intervention.
J Gastroenterol Hepatol. 2013;28(7):1141-1147. © 2013 Blackwell Publishing