A rapid, simple questionnaire to assess gastrointestinal symptoms after oral ferrous sulphate supplementation

Abstract

Background: Oral iron supplementation is often associated with rapid onset of gastrointestinal side-effects. The aim of this study was to develop and trial a short, simple questionnaire to capture these early side-effects and to determine which symptoms are more discriminating.

Methods: The study was a double-blind placebo-controlled randomized parallel trial with one week treatment followed by one week wash-out. Subjects were randomized into two treatment groups (n = 10/group) to receive either ferrous sulphate (200 mg capsules containing 65 mg of iron) or placebo, both to be taken at mealtimes twice daily during the treatment period. Subjects completed the questionnaires daily for 14 days. The questionnaire included gastrointestinal symptoms commonly reported to be associated with the oral intake of ferrous iron salts (i.e. nausea, vomiting, heartburn, abdominal pain, diarrhoea, and constipation).

Results: Seventy five per cent of participants reporting the presence of one or more symptoms in the first week of the study were in the ferrous sulphate group. In the second week of the study (i.e. wash-out), 67% of the participants reporting one or more symptom(s) were in the ferrous sulphate group. In the first week of the study (treatment) the number of symptoms reported by participants in the ferrous sulphate group (mean ± SEM = 6.7 ± 1.7) was significantly higher than that for participants in the placebo group (1.2 ± 0.5) (p = 0.01). In the second week of the study (wash-out) the number of symptoms reported by participants in the ferrous sulphate group (4.6 ± 2.0) appeared higher than for participants in the placebo group (1.0 ± 0.7) although this did not reach significance (p = 0.12). Events for which the gastrointestinal symptom questionnaire was most discriminatory between ferrous sulphate and placebo groups were: heartburn, abdominal pain and the presence of black stools (all p ≤ 0.03).

Conclusions: A tool for the detection of commonly-occurring side effects should not require large study numbers to be effective. With just 10 subjects per group (iron or placebo), this simple questionnaire measures gastrointestinal side-effects associated with oral iron (ferrous sulphate) supplementation, and would be appropriate for use in intervention studies or clinical trials.

Trial registration: ClinicalTrials.gov Identifier: NCT02146053 (21/05/2014).

Figure 1

One-page symptom questionnaire to assess gastrointestinal adverse effects after oral iron supplementation. The letters ‘A’ to ‘J’ are not present on the actual questionnaire but are herein shown for ease of reference throughout this manuscript.

Figure 2

Mean (SEM) incidence per participant of symptoms, from ‘box C’ of the questionnaire, in in week 1 (treatment) and week 2 (wash-out) of the iron and placebo groups. The mean incidence of symptoms for the week as mild (stripped part of columns), moderate (closed) and severe (open) is shown.

Figure 3

Incidence of individual symptoms in the iron and placebo groups. A, percentage of participants in each group reporting nausea, heartburn, abdominal pain (ABD pain), constipation, change in bowel movements (Bowel mov) or the presence of black stool movements on at least one day of each week of the intervention or wash-out periods (i.e. data from boxes ‘C’ and ‘H’ on the questionnaire (Figure 1)). The number of participants reporting symptoms in the iron group was significantly higher than that of the placebo group (p = 0.01). B, mean number of black bowel movements per day, obtained from box ‘H’ of the questionnaire (Figure 1), in the iron group (no black bowel movements were reported in the placebo group). Error bars represent standard error of mean (SEM). *p < 0.05; **p < 0.01 for comparison between each treatment day and the baseline (i.e. day 0). ^##p < 0.01 for comparison between each wash-out day and the end of the treatment period (i.e. day 7).