Effect of Vitamin D Supplementation on Severity of Symptoms in Irritable Bowel Syndrome:

A Systematic Review

Rachael M. Costello RDN, LDN

University of New England

Portland, Maine

rcostello@une.edu
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Abstract

Objective: To review the effectiveness of vitamin D supplementation in the treatment of irritable

bowel syndrome. (IBS)

Design: A total of 46 records were identified by searching Pubmed, CINAHL and ProQuest

databases. A total of 4 studies met inclusion and exclusion criteria for analysis. Study

descriptions and outcomes were synthesized to form conclusions.

Setting: Studies took place in outpatient university clinics.

Participants: Patients diagnosed with irritable bowel syndrome using Rome III criteria and 14-75.

Interventions: Participants were supplemented orally with varying levels of vitamin D, from

2000IU daily, 50,000IU once weekly or biweekly, for either six weeks or six months.

Main Outcome Measures: Symptom and severity questionnaires, IBS quality of life

questionnaires, and serum 25(OH)D3 levels.

Analysis; All studies found a significant increase in serum 25(OH)D3 levels and quality of life

scores and significant decreases in symptoms and severity in the treatment groups.

Key words: Irritable bowel syndrome, vitamin d, ergocalciferols, supplementation

Word count: (158)

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INTRODUCTION

Irritable bowel syndrome (IBS) is a functional bowel disorder, affecting between 7-21% of the

population.¹ Diagnosis occurs in the absence of other gastrointestinal disease diagnoses and

symptoms can vary but include constipation, diarrhea or both, abdominal pain, bloating and gas.¹

In the United States, women are affected at a 2:1 ratio when compared to men.¹ People with IBS

suffer higher rates of depression and anxiety and report lower quality of life than the general

population.² Treatment for IBS focuses on controlling symptoms and may involve dietary

interventions, stress-relieving exercises, medication, and physical activity.³ Dietary

modifications are personalized and there is no single food eliminated in IBS.⁴

Diagnosis of IBS cannot be completed with a serum blood test and symptoms guide practitioners

in the decision.⁵ As gastrointestinal diseases became more prevalent worldwide, a committee

was developed to streamline diagnoses of the various disorders, including IBS.⁵ The resulting

guide, currently in its fourth generation, is named Rome IV, and up until recently Rome III has

been used.⁵ The Rome III criteria will be referenced here as it was the version used in the studies

reviewed. These criteria define IBS as:

“recurrent abdominal pain or discomfort (defined as an uncomfortable sensation not described

as pain) for at least 3 days a month in the last three months, associated with 2 or more of the

following:

1. Improvement with defecation

2. Onset associated with a change in frequency in stool

3. Onset associated with a change in the form (appearance) of stool.

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These criteria should be fulfilled for the last 3 months with symptom onset at least 6 months

prior to diagnosis.”⁵

Vitamin D is a fat-soluble vitamin which is also considered a hormone.⁶ Humans can produce

vitamin D when skin is exposed to UV-B light.⁶ Many factors influence the ability of the body

to produce vitamin D, including time of day, latitude, skin color, amount of skin exposed, and

time of year.⁷ Vitamin D is also available in the diet, primarily found in fortified milk products,

fatty fish, and mushrooms.⁷

Vitamin D has long been known important in maintaining bone health.⁶ A vitamin D deficiency

can manifest as rickets in children or osteomalacia in adults. ⁷ These both influence bone

strength and are resolved by increasing vitamin D serum levels, either through sun exposure,

diet, or supplementation.⁷ More recent research has looked at additional roles vitamin D may

play in the body. The discovery of vitamin D receptors (VDR) on most tissues throughout the

body and in particular in the gastrointestinal tract, led to conclusions that vitamin D is important

in various bodily systems.⁸ Anxiety and depression are seen in higher levels in vitamin D

deficient subjects as well as those suffering from gastrointestinal disorders.²

Patients with IBS suffer from lower vitamin D levels than the general population.⁹ This may be

due to various factors including malabsorption, low-dietary choices containing vitamin D,

limited sun exposure, or other unknown reasons.⁹ Since quality of life (QoL) is likely affected

by the experience of gastrointestinal symptoms and the known higher levels of anxiety and

depression in IBS patients,combined with the increased vitamin D deficiency, a possible

treatment may be vitamin D supplementation.

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Measuring quality of life and severity of symptoms can be subjective and difficult to quantify.

There is an accepted and verified tool used in IBS patients to determine the severity of symptoms

called the IBS Severity Scoring System (IBS-SSS) questionnaire.¹⁰ This questionnaire asks

questions regarding the severity of IBS symptoms. It is scored by the practitioner, using specific

guidelines.¹⁰ In addition, the IBS Quality of Life (IBS- QoL) questionnaire is a verified tool used

to in IBS as another measure, more specifically regarding the quality of life.¹¹

If vitamin D supplementation can improve the quality of life and decrease the severity of

symptoms in IBS patients, this could be a useful treatment tool. In order to determine the

effectiveness of vitamin D supplementation in IBS, the question reviewed was:

In people with a diagnosis of irritable bowel syndrome, diagnosed according to the ROME III

criteria, what is the effect of vitamin D supplementation, for at least one month, on the severity

of symptoms as measured with IBS-SSS questionnaire and/or IBS-QOL questionnaire, and

serum levels of 25(OH)D3 when compared to placebo?

METHODS

A graduate student (RC) with experience in the nutritional implications of gastrointestinal

disorders, under the guidance of a graduate professor (JM) conducted the review. The systematic

review focused on studies published from 2014-2019 that measured the effects of vitamin D

supplementation in patients with IBS. The Preferred Reporting Items for Systematic Reviews

and Meta-Analysis (PRISMA) guidelines were followed in this review. The search strategy was

conducted by graduate student (RC). Searches were performed in three databases, PubMed,

CINAHL and ProQuest for studies related to vitamin D supplementation in IBS and the effect on
 Costello 5

severity of symptoms and quality of life. Search terms included: ​irritable bowel syndrome, IBS,

vitamin D, ergocalciferols, supplementation, quality of life.

ARTICLE SELECTION AND INCLUSION CRITERIA

Figure 1: Article Search and Selection Process

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Title and abstract screening were completed by the author. Full-text articles were obtained for

studies selected from the original screening. Studies were included if they used randomized

controlled clinical trials with 10 or more participants in each study group and had a withdrawal

rate of 20% or less. Subjects were non-institutionalized, otherwise healthy and diagnosed with

IBS using Rome III criteria. Studies were excluded on the basis of study design of case study or

cohort study and using less than 10 subjects per study group and with greater than 20% drop out

rate. Subjects without Rome III criteria as a diagnostic tool and those hospitalized or

institutionalized were excluded. A total of four articles met the inclusion criteria.

DATA EXTRACTION AND SYNTHESIS

The author extracted data from the 4 articles and entered it into a table. Information extracted

included study design and purpose, population, intervention, setting and results and conclusions.

See Table 1.

Table 1: Summary of studies included in review

Author, Year,  Quality  Study Purpose Study  Intervention and  Outcome Data Conclusion
Study Design,  Grade  Population Setting s/ Results
Country,  (+, -, Ø)
Funding 
Source

Abbasnezad A (+) To determine the 18-70-year- Setting: University Treatment  Vitamin D

et al effectiveness of old IBS hospital outpatient group:  supplement
2016 vitamin D patients Dx Serum 25(OH)D3 ation of
Randomized supplementation by ROME III Intervention- significantly 50,000IU
Double-blind, on improvement criteria experimental group increased by every two
placebo-controll of symptoms and Treatment received 50,000IU 33.12± 9.65 weeks is
ed clinical trial severity score group: n=45 vitamin D every 3 IBSSS scores beneficial to
Iran and quality of life (28 weeks x 6 months, significantly IBS patients
Funding: in patients females) delivered orally- Visits decreased by on
University grant diagnosed with Control to the 53.82± 23.30 symptoms,
irritable bowel group: n=45 gastroenterologist QoL scores severity and
syndrome as (29 were at baseline, 3mo significantly quality of life
females) and 6 mo to obtain the
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diagnosed by Mean age vitamin D and improved by

ROME III criteria 37.9yo complete the 14.26±3
questionnaires. Blood
testing was at Control group: 
baseline and end of Serum 25(OH)D3
study. increased by
2.28±7.76
Control- received a IBSSS scores
placebo pill similar in significantly
appearance to the decreased by
study 16.85±25.01
QoL scores
significantly
improved by
11±2.34

Jalil M et al (+) To determine the 18-75-year- Setting: University Treatment  Vitamin D

2019 effectiveness of old females hospital outpatient group:  improves
Randomized vitamin D with BMI Significant the
double-blind supplementation 18-25 Intervention- increase in serum symptoms
placebo-controll in patients Diagnosed experimental group 25(OH)D3 from and quality
ed trial diagnosed with by ROME III received 50,000 IU 21.10±5.23 to of life in IBS
Iran irritable bowel criteria with weekly for 6 weeks 36.43±12.34 patients with
Funding: none syndrome IBS delivered orally- IBS-SSS and 6-week
diagnosed ROME “pearl” quality of life supplement
III and low serum Placebo received scores ation
vitamin D on the 10mg MCT in the significantly
improvement of same shape “pearl” as improved more
serum levels of vitamin D than the placebo
vitamin D and group
severity of
symptoms and Control group: 
quality of life No significant
increase in serum
25(OH)D3

Amrousy D et al (+) To determine the Adolescent Setting: Outpatient Treatment  Vitamin D

2018 effectiveness of IBS pt aged university group​: supplement
Randomized vitamin D 14-18 yo Significantly ation can be
Egypt supplementation Diagnosed Intervention: Oral D3 higher 25(OH)D3 effective in
Funding- none in adolescents on by ROME III 2000IU/d delivered by than placebo, treating
the severity of Vitamin D liquid drops (2 drops 17.2±1.3 to adolescents
symptoms and <20ng/dL per day) x 6 months 39±3.3 ng/ml with IBS
quality of life in Placebo: 2 drops IBS-SSS
IBS patients glucose significantly
diagnosed with IBS-SSS and quality improved from
ROME III and of life questionnaires 167.6±46.9 to
vitamin D at baseline, 3mo and 239.3±73
deficiency 6mo There was a
Serum 25(OH)D3 at significant
baseline and 6 mo improvement in
the quality of life
scores
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Control group: 
No significant
change in serum
25(OH)D3 or
IBS-SSS or
quality of life
score

Jalil M et al. (+) To determine the 18-75 year Setting: Outpatient D+S= results not The
2016 effects of vitamin old females university statistically synergistic
Factorial D, soy with BMI significant effects of
Blinded isoflavones and 18-25 4 groups: D= IBS-SSS and vitamin D
randomized their probable Diagnosed -placebo vitamin D, IBS QoL and soy
clinical trial interaction in by ROME III placebo soy statistically isoflavones
Iran women with IBS isoflavones (P+P) significant were not
Funding: none -placebo vitamin D, S= IBS-SSS and supported,
soy isoflavones (P+S) IBS QoL however,
-vitamin D +placebo statistically vitamin d or
soy isoflavones (D+P) significant soy
-vitamin D, soy isoflavones
isoflavones (D+S) alone did
improve
25 subjects per group IBS-SSS
Soy isoflavones was and quality
taken BID, vitamin D of life
50,000IU pearl, every scores
other week for 6
weeks

IBS-SSS and QoL

questionnaires were
taken at baseline, 6
weeks, 10 weeks

QUALITY RATING

All four articles were given a quality rating of positive, negative, or neutral, which follows the

Academy of Nutrition and Dietetics Evidence Analysis Libray’s (EAL) quality criteria checklist

for primary research.¹² The ratings are based on the relevance of the research question to the

population being studied, whether bias was introduced, the clarity of the research question,

whether blinding was used to minimize bias, reliability and validty of outcomes measures, if the

appropriate statistical analyses were used, and whether any funding may have introduced bias.¹²
 Costello 9

The author completed the checklists for each study to determine the ratings. An overall

conclusion grade of Good was determined based on the EAL Conclusion Grading Table.

RESULTS

The 4 studies reviewed were randomized double-blind, or factorial blind, placebo-controlled

clinical trials. Each study supplemented vitamin D and used the IBS-SSS and IBS QoL

questionnaires to determine severity of symptoms and quality of life improvement in the

subjects. Each study varied in dosage and length of study as well as several other factors.

Abbasnezad A¹³, and colleagues supplemented with 50,000 IU vitamin D3 every two weeks for 6

months. Serum 25(OH)D3 levels were drawn at baseline and at 6 months. IBS-SSS and

IBS-QoL questionnaires were completed at baseline, 3 months, and 6 months. Subjects were

adults aged 18-70, living in Iran. Researchers found significant improvement in IBS-SSS of

-53.82±23.3 and QoL scores of +14.26±3 as well as 25(OH)D3 serum levels of 33.12±9.65 in the

treatment group. The placebo group had no significant improvement in serum 25(OH)D3 levels

but did see significant improvement in IBS-SSS and IBS-QoL scores, however, these were much

lower than the treatment group.

Jalili and colleagues¹⁴ supplemented 50,000IU vitamin D3 weekly for 6 weeks. These subjects

were females aged 18-75, with a normal BMI (18-25), vitamin D deficiency and were living in

Iran. Serum 25(OH)D3 levels, IBS-SSS and IBS-QoL questionnaires were taken aat baseline and

close of the 6 week study. IBS-SSS scores decreased by 61.46±14.54, IBS-QoL scores increased

by 48.13±4.24, and serum 25(OH)D3 levels increased from 21.10±5.23 to 36.43±12.34. These
 Costello 10

results were all significant changes. The placebo group did not see any significant changes in

measured outcomes.

Amrousy et al¹⁵ studied 112 adolescents with IBS and vitamin D deficiency in Egypt, aged

14-18 with vitamin D deficiency. Participants in the treatment group received oral vitamin D3

via drops of 2000IU daily for 6 months. Serum 25(OH)D3 was taken at baseline and 6 months.

IBS-SSS and IBS-QoL questionnaires were administered at baseline, 3 months, and 6 months.

The IBS-SSS scores decreased from 239.3±73 to 167.6±46.9, IBS-QoL improved from

59.2±14.7 to 75.2±9.2 and serum 25(OH)D3 increased from 17.2±1.3 to 39±3.3. The placebo

group did not see any significant improvements in any measures.

The last study from Jahili and colleagues¹⁶ was designed slightly differently than the first three

studies. Subjects were again females aged 18-75 with BMI of 18-25, living in Iran. This study

had an additional variable of soy isoflavones. The four study groups received either: placebo

vitamin D and placebo soy isoflavones, placebo vitamin D and soy isoflavones, vitamin D and

placebo soy isoflavones, or soy isoflavones and vitamin D. The dose for vitamin D was

50,000IU vitamin D biweekly, given orally over the course of 6 weeks. This study saw

significant improvement in the vitamin D plus placebo soy isoflavones group as well as in the

soy isoflavones plus placebo vitamin D group, but not in the vitamin D plus soy isoflavones

group. For the purpose of this review, the result of the vitamin D plus soy isoflavones results

will be discussed. In this group, the IBS-SSS scores decreased by 150.31, and IBS-QoL scores

increased by 39.95.

See table 2 for a comparison of all 4 studies.

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Table 2: Results and parameters of studies in review

Author Age/ Total BMI Supplementation IBS-SSS IBS-QoL 25(OH)

gender participant method and dose D3
s

Abbasnez 18-70 90 n/a 50,000IU -53.82±2 +14.26± +33.12±

had A, et Male bi-weekly 3.3 2 9.65
al and Oral pearl
2016 female 6 months

Jahili M, 18-75 116 18-2 50,000IU -61.46±1 +48.13± 21.10±5.

et al female 5 Weekly 4.54 4.24 23 to
2019 Oral pearl 36.43±1
6 weeks 2.34

Amrousy 14-18 112 n/a 2000IU 239.3±7 59.2±14. 17.2±1.3

et al Male Daily 3 to 7 to to
2018 and Oral liquid 167.6±4 75.2±9.2 39±3.3
female drops 6.9
6 months

Jahili M, 18-75 100 18-2 50,000IU -150.31 +39.95 Not

et al female 5 Bi-weekly given
2016 Oral Pearl
6 weeks

DISCUSSION

The studies reviewed had promising results showing positive effects of vitamin D

supplementation in patients diagnosed with IBS. The studies varied in dosing and length of

supplementation, however, IBS-SSS and IBS-QoL scores improved significantly in all treatment

groups. Studies were similar in size, ranging from 90-116 participants, and all were adequately

powered. There were no available systematic reviews available to compare results to. This is
 Costello 12

another indicator that more research needs to be completed in this area. A pilot study was

performed in 2015 in England by Tazzyman et al¹⁷, also looked at vitamin D supplementation in

IBS patients. This study saw improvement in symptoms and quality of life, although the results

were not significant as the study was not adequately powered.¹⁷

Limitations were evident amongst the studies. Location of subjects is the first limitation, as three

of the four were completed in Iran and one in Egypt. This is a small representation of the IBS

population worldwide. Two of the studies only examined women, another limitation. Other

variables such as time of year, amount of sun exposure, and skin color were not taken into

consideration in any study. These studies all excluded those with concurrent gastrointestinal

disorders, and while was important for the parameters of these studies, is an additional area that

should be explored.

In people diagnosed with irritable bowel syndrome (IBS) as diagnosed by ROME III criteria,

oral vitamin D supplementation of 50,000IU bi-weekly or weekly, or 2,000IU daily over 6

weeks-6 months, significantly increases serum 25(OH)D3 when compared to placebo.

Symptoms and severity as measured by IBS-SSS questionnaires were significantly improved in

treatment groups. Quality of Life scores also had a statistically significant improvement.

IMPLICATIONS FOR RESEARCH AND PRACTICE

Patients with IBS suffer from a decreased quality of life due to their symptoms and related

anxiety and depression. These patients are at a greater risk for low serum 25(OH)D3 levels.
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Practitioners working with IBS patients should make regular monitoring and replating of

25(OH)D3 a part of their protocol to increase the quality of life in their patients.

The need for further research in the area of vitamin D supplementation in IBS patients is

warranted. The greater prevalence of vitamin D deficiency needs to be addressed and protocols

for treating the deficiency need designing as well. All four studies reviewed used differing doses

and length of treatment. Future research in this area should focus on the determination of the

ideal amount and length of time to supplement. This may vary by current 25(OH)D3 level,

region, skin color, other concurrent medical diagnoses, age, and gender. All of the

above-mentioned variables are areas where further research can be focused.

References

1. Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: A clinical review. ​JAMA.

2015; 313(9):949-958.

2. Zamani M, Alizadeh-Tabari S, Zamani V. Systematic review with meta-analysis: the

prevalence of anxiety and depression in patients with irritable bowel syndrome. ​Aliment

Pharmacol Ther. ​2019; 00:1-12.

3. Torkzadeh F, Danesh M, Mirbagher L, Daghaghzadeh H, Emami MH. Relations between

coping skills symptom severity, psychological symptoms, and quality of life in patients

with irritable bowel syndrome. ​Int J Prev Med. 2​ 019; 10(72) doi: 10. 4103/ijpvm.IJPVM

464 17.
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4. Ooi SL, Correa D, Pak SC. Probiotics, prebiotics, and lowFODMAP diet for irritable

bowel syndrome. What is the current evidence? ​Complement Ther Med. 2​ 019; 43:73-80.

5. Lacey BE, Patel NK. Rome criteria and a diagnostic approach to irritable bowel

syndrome. ​J Clin Med. ​2017; 6(11) doi: 10.3390/jcm6110099.

6. Margulies SL, Kurian D, Elliott MS, Han Z. Vitamin D deficiency in patients with

intestinal malabsorption syndromes- think in and outside the gut. ​J Dig Dis. ​2015;

16:617-633.

7. Holick MF. Vitamin d deficiency. ​N Engl J Med. 2​ 007; 357(3): 266-281.

8. Dobnig H. A review of the health consequences of the vitamin D deficiency pandemic. ​J

Neurol Sci. 2​ 011; 311:15-18.

9. Khayyat Y, Attar S. Vitamin D deficiency in patients with irritable bowel syndrome:

Does it exist? ​Oman Med J. 2​ 015; 30(2): 115-118.

10. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a

simple method of monitoring irritable bowel syndrome and its progress. ​Aliment

Pharmacol Ther. ​1997; 11:395-402.

11. Drossman DA, Patrick DL, Whitehead WE, et al. Further validation of the IBS-QOL: A

disease-specific quality-of-life questionnaire. ​Am J Gastroenterol. 2​ 000; 95(4):999-1007.

12. Academy of Nutrition and Dietetics.​ Evidence Analysis Manual: Steps in the Academy

Evidence Analysis Process. ​Chicago, IL: Academy of Nutrition and Dietetics; 2016.

13. Abbasnezhad A, Smani R, Hajiani E, Alavinejad P, Cheraghian B, Ghadiri A. Effect of

vitamin D on gastrointestinal symptoms and health-related quality of life in irritable

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bowel syndrome patients: a randomized double-blind clinical trial. ​Neurogastroenterol

Motil. 2​ 016; 28:1533-1544.

14. Jalili M, Vahedi H, Potstchi H, Hekmatdoost A. Effects of Vitamin D supplementation in

patients with irritable bowel syndrome: A randomized, double-blind, placebo-controlled

clinical trial. ​Int J Prev Med.​ 2019; 10:16.

15. El Amrousy D, Hassan S, El Ashry H, Yousef M, Hodeib H. Vitamin D supplementation

in adolescents with irritable bowel syndrom: Is it useful? A randomized controlled trial.

Saudi J Gastroenterol​. 2018; 24:109-114.

16. Jalili M, Hekmatdoost A, Vahedi H, Poustchi H, et al. Co-Administration of soy

isoflavones and vitamin D in management of irritable bowel disease. ​PLOS ONE. 2​ 016;

doi: 10.1371/journal.pone.0158545.

17. Tazzyman S, Richards N, Trueman AR, et al. Vitamin D associates with improved

quality of life in participants with irritable bowel syndrome: outcomes from a pilot trial.

BMJ Open Gastro. 2​ 015; 2 e000052 doi: 10.1136/bmjgast-2015-000052.