Effect of Vitamin D3 (Cholecalciferol) Supplementation on Gastrointestinal Symptoms in Patients with Irritable Bowel Syndrome Attending El-Mahsama Family Practice Center, Ismailia, Egypt: A Randomized Clinical Trial

INTRODUCTION

Irritable bowel syndrome (IBS) is a recurrent chronic functional gastrointestinal disorder. Patients with IBS suffer from abdominal pain, distention, and change in bowel habits with either predominate constipation, diarrhea or both. ^{1, 2} IBS is diagnosed clinically using the Rome IV criteria after excluding any warning signs, without the need for any biochemical markers.³

Worldwide, IBS affects around 10%–25% of the population, which can burden any health care system and impair patients' quality of life. ^{2, 4} IBS symptoms are among the most common causes of primary health care consultations. ⁴

The exact etiology of IBS is still undefined. However, many multifactorial theories were proposed including psychosocial disturbance, visceral hypersensitivity, dietary factors, bacterial overgrowth, genetic factors, and brain-gut interaction.⁵ To date, treatment strategies for IBS are only directed to alleviate symptoms, with no specific cure. ⁵

Vitamin D₃ (Cholecalciferol) has immunological, anti-inflammatory, and antimicrobial properties which encouraged researchers to investigate its therapeutic effects on different chronic diseases such as, multiple sclerosis and cardiovascular diseases. ⁶, ⁷ To the best of our knowledge, only one study was conducted in Egypt to evaluate the effect of vitamin D₃ on IBS symptoms in pediatric and adolescent patients, ⁸ but no similar studies were performed for adult patients. Therefore, this study aimed to evaluate the effect of vitamin D supplementation on IBS symptoms in adult patients attending a rural primary health care setting using a randomized controlled trial.

PATIENT AND METHODS

Participants and study setting

The study participants (100) were enrolled from patients attending a family practice center in El-Mahsama village, Ismailia, Egypt from October 2018 to March 2019. The study setting is a rural primary health care center, which provides medical health services at a reduced cost. Out of the enrolled sample, 20 were excluded (15 not fulfilling Rome IV criteria, 2 pregnant and 3 already taking vitamin D supplementations). The included sample was male and female adults aged 18 years or more, who met the diagnostic criteria of irritable bowel syndrome (Rome IV) which include frequent abdominal pain associated with two or more of the following: (1) defecation, (2) altered stool frequency; (3) or altered stool consistency. These symptoms should occur for at least 1 day per week in the last 3 months.³

Baseline sociodemographic characteristics

The sociodemographic status of participants was assessed at the baseline, using a valid and reliable questionnaire in Arabic. The overall score of sociodemographic scale was 84, from which it is sub-grouped into very low (score = 21 or less), medium (score 22-42), high (score= 43-63) and very high levels(64-84).⁹

Study design and follow-up

A randomized control double-blinded trial was designed. Participants were allocated by simple random technique, where every participant had an equal chance to be included in any of the study groups. The intervention group (40 participants) received oral 4000 IU vitamin D₃ pearls once daily for 12 weeks, while the control group (40 participants) received oral placebo pearls containing edible paraffin once daily for the same period. Both vitamin D and placebo pearls had the same shape, size, weight, texture, and packing. Allocation of the participant to either vitamin D or placebo had been done by an independent colleague. Double-blinding, to both the participants and the researcher, was applied. In the follow-up period, two participants discontinued the study (one in the intervention group, who became pregnant after 2 months and one in the placebo group, who was lost after one month of follow up). The study steps are illustrated in figure 1.

IBS symptoms and severity scoring system

At baseline and post-intervention, the total irritable bowel syndrome symptom severity scale (IBSSSS) was assessed in both groups, by a valid and reliable tool. Participants were asked to assess five items related to abdominal pain severity and frequency, distension, bowel habits satisfaction, and impact of IBS in general. The maximum score for each item is 100, while the minimum score is 0, with a total score ranged from 0 to 500. Accordingly, the IBSSSS was classified as: mild (75-175), moderate (176-300), and severe (above 300). A post-intervention score became below 75 or reduced by 50 or more was considered a clinically significant improvement. ^10,11 The questionnaire was translated into Arabic, then the Arabic version was back-translated into English by two independent translators.

Statistical analysis

The statistical analysis of the results was performed using the 22^nd version of the ''Statistical Package of Social Science'' program. Qualitative results were presented as frequencies and percentages, and comparison between them was done using Chi-square or Fisher’s test. The quantitative variables were presented as means ± standard deviations, and independent sample t-test or Mann-Whitney U test were used to compare these variables. The pre- and post-intervention data were compared using the dependent t-test or Mann-Whitney U test. Results with P values

RESULTS

The socioeconomic and household characteristics were studied in both groups. The mean age was 37.64 ± 11.13 years in the intervention group and 38.03 ± 6.37 years in the placebo group. Seventy percent of the participants were females. About half of the study participants had secondary education and worked in semi-professional occupations. The percentages of participants depending on free governmental health services were 51.3% and 43.6% for the intervention and control groups, respectively. In both study groups, more than half of the participants reported that they have more than one person per room with percentages of 51.3% for the intervention group, and 64.1% for the control group. About half of the participants can just meet their routine expenses in both groups.  The baseline characteristics were not statistically significantly different between the two study groups, which implies that these two groups are more or less the same, which can be a matching equivalent.

According to the categories of the socioeconomic scale, figure 2 showed that the majority of the participants in the studied sample belonged to the middle socioeconomic level (80%).

Table 1 compares the symptoms of irritable bowel syndrome among the intervention group and the placebo group after intervention. Results showed that the five items of IBS, related to abdominal pain severity and frequency, distension, bowel habits satisfaction, and impact of IBS in general, were statistically significantly improved (p<0.001) for patients who received vitamin D compared to those who received placebo (Table 1). 

Table 2 presents IBSSSS for the two study groups in the pre and post-intervention. Results showed that the baseline difference between the intervention and the control groups regarding IBSSSS was statistically insignificant (p=0.078). However, after the intervention, patients receiving vitamin D₃ had statistically significantly lower (p<0.001) IBSSSS (114.36 ± 67.36) compared to participants who received a placebo (292.13 ± 74.77). The IBSSSS difference was statistically significantly higher (p<0.001) for patients receiving vitamin D (-164.72 ± 67.77) compared to participants who took a placebo (-12.13 ± 50.78) (Table 2).

*IBSSSS: Irritable bowel syndrome severity score

Figure 1. Steps of the study

Figure 2. Socioeconomic levels of the total study sample