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Expert Critique
FROM THE ASCO Reading Room
Adding vitamin D supplementation to IBS management could be a useful clinical tool, given that many patients with IBS do not respond to conventional pharmacological and dietary interventions. Recent intervention studies report that vitamin D supplementation has the potential to improve IBS symptoms and quality of life, which has prompted researchers to recommend assessment and treatment of vitamin deficiency as part of routine IBS care. Despite this emerging evidence, there is insufficient research to draw firm conclusions. Further investigation is warranted to elucidate if vitamin D supplementation has robust therapeutic value for this population.
Add irritable bowel syndrome (IBS) to the list of conditions associated with vitamin D deficiency. Although data are limited, emerging evidence suggests that vitamin D is a factor in IBS, with deficiency widely reported in adult and pediatric patients, and supplementation studies starting to point to improved severity scores. That has led some researchers to say that physicans should already be considering vitamin D supplementation as part of for IBS, even in the absence of an established optimal dose.
So far, only seven published articles have addressed vitamin D in IBS – four observational studies and three randomized controlled trials.
For example, earlier this year, a review article by , from the University of Sheffield in the U.K., confirmed a high prevalence of deficiency in IBS sufferers, regardless of ethnicity, and recommended that all IBS patients have their serum vitamin D levels tested. Based on two intervention studies, the review also suggested that supplements might ease symptoms such as pain, bloating, diarrhea, and constipation. The authors called for large, adequately powered studies to explore a possible therapeutic role for adjunctive vitamin D.
In 2015, the Sheffield group reported that 82% of 51 IBS patients tested as vitamin-D deficient. Interest had been sparked by a 2012 of a 41-year-old female Sheffield researcher, whose active diarrhea symptoms responded positively to adding 3,000 IU daily of vitamin D. Data from 37 IBS sufferers commenting online about the effect of vitamin D supplementation on their own condition subsequently revealed that approximately 70% of these IBS patients reported that high-dose vitamin D had improved their symptoms.
The Sheffield group also conducted a three-arm randomized (placebo, vitamin D alone, and vitamin D+probiotic) in 2015, but found no symptom improvement with vitamin D supplementation.
Most promising so far is a 2016 randomized, double-blind, controlled study by reporting on 90 Iranian IBS patients randomly assigned to receive very high-dose (50,000 IU) of vitamin D3 or a placebo every 2 weeks for 6 months. During the intervention period, a significantly greater improvement in IBS symptoms such as abdominal pain and distention, flatulence, rumbling, and overall gastrointestinal symptoms occurred in the vitamin D arm versus the placebo group. Only dissatisfaction with bowel habits remained unaltered.
Severity and quality of life (QoL) scores significantly improved in the intervention versus the placebo group. The mean IBS severity score system change was -53.82±23.3 versus -16.85± 25.01 (P<0.001), respectively, while the IBS-QoL score change was 14.26±3 versus 11±2.34 (P<0.001), respectively.
Meanwhile, mounting evidence indicates that vitamin D levels are often lower in IBS. A 2015 by Khayyat and Attar reported that 82% of 60 IBS patients were vitamin D-deficient compared with 31% of 100 healthy controls. In addition, the mean serum level of 25(OH)D in IBS patients was 21+12 nmol/L compared with the control group (31+16 nmol/L).
And in the pediatric population, a by Nwosu and associates found significantly lower vitamin D concentrations in 55 IBS patients than in 116 controls with similar body mass index. Only 7% of IBS children were vitamin D-sufficient, while more than 50% were deficient in the vitamin, which was a much higher prevalence than in inflammatory bowel disease and other malabsorption conditions. The authors called for randomized controlled trials to explore the use of supplementation in pediatric IBS.
At the pathophysiologic level, some researchers say the link between IBS and vitamin D deficiency may, at least theoretically, be due to alterations in immune response and/or in serotonin production. In a 2018 article, reported that compared with controls, IBS patients had differential expression of genes associated with serotonin metabolism, exhibiting lower levels of TPH1, the enzyme that catalyzes the rate-limiting step in serotonin biosynthesis.
"The expression of select IBS genetic biomarkers was shown to be modulated by vitamin D," the researchers wrote. "These results suggest that IBS pathogenesis and pathophysiology may involve dysregulated serotonin production and/or vitamin D insufficiency."
In their study, Khayyat and colleagues noted that vitamin D also inhibits T-cell proliferation and may inhibit immune response. The team also proposed a dietary factor: "Attention needs to be drawn to the psychosocial behavioral patterns of these IBS patients, who often tend to avoid food items like fortified milk, which are rich in vitamin D and calcium, leading us to the conclusion that an altered vitamin D absorption mechanism could be an underlying reason for such observed social behaviours."
The therapeutic potential of adjunctive vitamin D is currently being explored by researchers at Beth Israel Deaconess Hospital in Boston in a randomized study of 90 IBS patients. Led by Judy W. Nee, MD, the study will assign patients with all types of IBS to placebo or 4,000 IU vitamin D per day for 3 months, at which point they will be compared for serum vitamin D levels, IBS symptoms, bowel habits, anxiety, depression, and sleep quality.
"The supplementation D dose of 4,000 IU per day is the upper limit considered safe in healthy people by the Institute of Medicine, so there is no fear of toxicity," Nee told ľ¹ÏÖ±²¥. "It's a low-risk and low-cost way of seeing if IBS symptoms can be improved."