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doi:10.1111/jgh.15891

S Y S T E M AT I C R E V I E W

Association between irritable bowel syndrome and

micronutrients: A systematic review

Schin Bek,* Yao Neng Teo,* Xin-Hui Tan,† Kristie H R Fan*,‡,§ and Kewin Tien Ho Siah*,§
*Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, †Department of Dietetics, §Division of Gastroenterology and
Hepatology, Department of Medicine, National University Hospital, ‡FAST and Chronic Programmes, Alexandra Hospital, Singapore

Key words
colonic diseases, functional, irritable bowel
syndrome, micronutrients, trace elements,
vitamins.
Accepted for publication 2 May 2022.
Correspondence
Dr Kewin Tien Ho Siah, Division of
Gastroenterology and Hepatology, University
Medicine Cluster, National University Health
System, Level 10 Tower Block, 1E Kent Ridge
Road, Singapore 119228, Singapore.
Email: kewin_siah@nuhs.edu.sg
Declaration of conflict of interest: The authors
declare that they have no conflicts of interest.
Author contribution: KS conceived and
designed the study. SB and YNT were
responsible for data collection. SB, YNT, and KS
interpreted the data and drafted the manuscript.
SB, YNT, KS, KHF, and TXH contributed to
manuscript revision as well as final review and
approval for publication.
Abstract
Background and Aim: Irritable bowel syndrome (IBS) is a highly prevalent disorder of
gut brain interaction with a multifactorial etiology. Food trigger avoidance is common
among individuals with IBS and exclusion diets are gaining popularity. However, recent
guidelines on IBS management cautioned regarding the use of unsupervised dietary ther-
apy with concerns of development of poor eating habits and even nutritional deficiencies.
We aimed to review the available literature on the effect of habitual and exclusion diets on
micronutrient status as well as the role of micronutrient supplementation in alleviating IBS
symptoms.
Methods: Four electronic databases (PubMed, Embase, Cochrane, Web of Science) were
searched for articles that reported micronutrient data in patients with IBS. Serum micronu-
trient levels and dietary intake of micronutrients in patients with IBS were collected. The
extracted data were tabulated and organized by micronutrient type to observe for trends.
Results: Twenty-six articles were included in this systematic review (12 interventional and
14 observational studies). Studies showed that generally IBS subjects had lower levels of
vitamin B2, vitamin D, calcium, and iron at baseline compared with non-IBS subjects.
Studies also found that exclusion diets were associated with lower intake of micronutrients
especially vitamin B1, B2, calcium, iron, and zinc. There was a lack of interventional stud-
ies on micronutrients.
Conclusion: Irritable bowel syndrome patients are at risk of developing multiple micronu-
trient deficiencies that may have both localized gastrointestinal as well as systemic effects.
Dietary management of IBS patients should include a proper dietitian review to ensure nu-
tritional adequacy where possible.

Introduction individuals with IBS report food-related gastrointestinal

Irritable bowel syndrome (IBS) is one of the commonest disease of
gut-brain interaction (DGBI). It is characterized by recurrent ab-
dominal pain and bowel disturbances without discernible abnor-
malities during routine clinical investigation.1 Results from the
Rome Foundation Global Study found the global prevalence of
ROME IV IBS in adults to be 4.1%.2 The pathophysiology of
IBS is not well understood and is currently referred to as multifac-
torial—attributable to gut dysmotility, visceral hypersensitivity,
dysfunction of the brain-gut axis, immune activation, changes in
gut microbiome, and food sensitivities.3 IBS has a
well-documented significant impact on quality of life (QOL),
resulting in increased psychosocial burdens, healthcare utilization
and wider social and economic consequences. It is associated with
higher rates of psychiatric comorbidities including depression and
anxiety as well as reduced work productivity.4–8
The role of diet has been increasingly identified as an area of im-
portance in the holistic management of IBS. More than half of
symptoms.9,10 Abdominal pain and bloating are common
post-prandial symptoms. Common identified triggers include
foods rich in fermentable carbohydrates and fats, coffee, spices
and alcohol.9 There are multiple proposed mechanisms by which
food may trigger gastrointestinal symptoms in IBS. Some of these
mechanisms include osmotic effects in the gastrointestinal tract,
immune activation, and altered gut microbiome.11,12 Irregular
meal timings have also been related to the habitual diets of IBS
patients.13 Many individuals with IBS are keen to explore dietary
options and up to 90% have attempted to modify their diets to
avoid food triggers.14,15 Recent IBS management guidelines by
the American College of Gastroenterology and the British Society
of Gastroenterology both recommend dietary manipulation and
diet exclusion therapy such as a diet low in fermentable oligosac-
charides, disaccharides and monosaccharides and polyols
(FODMAPs) as first or second line treatment for IBS. However,
they also cautioned regarding the risks of exclusion diets including
the development of overly restrictive eating habits and potential

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Irritable bowel syndrome and micronutrients S Bek et al.

Table 1 PICOS (inclusion and exclusion criteria applied for article inclusion)

PICOS Inclusion criteria Exclusion criteria

Population • Patients with irritable bowel syndrome (IBS)

Intervention • +/ Micronutrient supplementation including vitamins and minerals
Comparison • +/ Comparison of micronutrient supplementation against no supplementation or
against placebo
Outcome • Gastrointestinal symptoms including stool frequency, abdominal pain, stool status
• Quality of life
• IBS score systems including IBS-SSS (Symptom Severity Score), IBS-QoL (Quality of
Life)
• Amount/level of micronutrients in patients with IBS
Study • Articles in English or translated to English • Reviews including systematic reviews and meta-
design • Observational studies analyses
• Clinical trials including randomized controlled trials • Letters
• Editorials
• Perspectives
• Case reports and series
• Studies analyzing non-human subjects
• Conference abstracts

Figure 1 PRISMA flowchart

nutritional deficiencies.16,17 In particular, there have been multiple
studies and case reports that showed the development of micronu-
trient deficiencies in patients with IBS and other DGBI who prac-
ticed restricted diets and consequently had unbalanced and poor
nutrient intake. This could lead to clinical manifestations of micro-
nutrient deficiencies like scurvy,18 pellagra, and hypovitaminosis
A.19
Micronutrients, often referred to as vitamins and minerals, are
not produced in the body (except for vitamin D), and must be
derived from the diet. They are vital to the body’s health and are
essential for the function of many bodily systems. For example, vi-
tamins including vitamins A, B12, and C are necessary for im-
mune function, energy generation and other functions.20,21
Meanwhile, minerals like zinc and calcium contribute to growth,
musculoskeletal health, blood coagulation and fluid homeostasis,
among other processes.22 In the gastrointestinal tract, vitamins
and minerals are important for nutrient absorption, gut motility,
modulation of the human gut microbiome and other functions.23,24

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© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
 Table 2 Study characteristics of included observational studies
S Bek et al.

First author, Type of study Study population Sample size Types of micronutrients Significant findings
country, year of the study

Abbasnezhad, Observational: Controls = 90 180 Vitamin D, calcium Higher prevalence of vitamin D deficiency (VDD) in patients with IBS
Iran, 2019 Cross-sectional IBS = 90 compared with healthy controls. In patients with IBS, there was a significant
study IBS-C = 30 positive association between serum 25(OH)D3 levels and disease-specific
IBS-D = 24 quality of life (IBS-QoL) and a significant negative association between serum
IBS-A = 36 25(OH)D3 concentration and IBS-SSS.
Bahrami, Iran, Observational: No IBS = 376 448 Zinc The mean dietary intake of zinc was significantly lower in patients with IBS
2019 Cross-sectional Adolescent girls (12–18 years old) than those without.
study IBS = 72
IBS subtypes NR
Bohn, Sweden, Observational: Controls = 374 561 Vitamin A, D, B1, B2, B3, Patients with IBS had in total significantly lower intake of vitamin A, riboflavin,
2013 Cross-sectional IBS = 187 B6, B9, B12, calcium, iron, calcium, and potassium, and a higher intake of vitamin E, folate, iron, and

Journal of Gastroenterology and Hepatology 37 (2022) 1485–1497

study IBS-C = 55 zinc vitamin C, compared with the subjects from the national survey.
IBS-D = 62
IBS-nonC-nonD = 70
Cho, South Korea, Observational: Patients with IBS symptoms aged 124 Vitamin A, C, D, B1, The mean 25-OHD level was 16.25 ± 6.58 ng/mL. Among the 124 patients, 88
2018 Cross-sectional 10–17 years from a pediatric B6, B12, calcium, (70.4%) had a vitamin D level <20 ng/mL (vitamin D deficiency). There was a
study gastroenterology clinic iron, zinc significant negative correlation between symptom severity and vitamin D
IBS = 124 level and a significant negative correlation between school absence and
IBS-C = 29 vitamin D level.
IBS-D = 63
IBS-M = 32

© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
Hujoel, USA, 2020 Observational: Civilian and noninstitutionalized 12,328 Vitamin A, C, B1, B12, Individuals with IBS had significantly higher copper–zinc ratio and were more
Cross-sectional individuals in the United States calcium, iron, zinc likely to have ratios above 1.8, indicative of underlying copper–zinc imbalance.
study No IBS = 11,915
IBS = 413
IBS subtypes NR
Khayyat, Saudi Observational: Controls = 100 160 Vitamin D The mean serum level of 25(OH)D was significantly lower in patients with IBS
Arabia, 2015 Case–control IBS = 60 and 82% were vitamin D deficient compared with 31% in healthy controls.
study
Khayyatzadeh, Observational: Adolescent girls (12–18 years) 965 Vitamin D, calcium Patients with IBS had significantly lower serum 25-OH D levels compared
Iran, 2017 Cross-sectional No IBS = 799 with those without IBS. There was a significant inverse association between
study IBS = 166 presence of IBS and serum 25-OH D level.
IBS subtypes NR
Ligaarden, Observational: IBS = 17 17 Vitamin B1, B6, iron, There was a significant inverse association between dietary intake of vitamin
Norway, 2011 Cross-sectional IBS-C = 1 magnesium, zinc B6 and severity of IBS symptoms.
study IBS-D = 7
IBS-A = 9

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 1488
Table 2 (Continued)

First author, Type of study Study population Sample size Types of micronutrients Significant findings
country, year of the study

Nath, USA, 2019 Observational: Patients with medically 229 Vitamin D Vitamin D insufficiency (0 to 29 ng/mL) was associated with a high prevalence
Cohort study complicated obesity considering of bowel symptoms of IBS in people with medically complicated obesity.
bariatric surgery
Irritable bowel syndrome and micronutrients

IBS = 67
Nwosu, USA, Observational: Pediatric patients aged 6–21 years 171 Vitamin D There was a significantly higher prevalence of vitamin D deficiency (25(OH)
2017 Case–control Controls = 116 D ≤ 50 nmol/L) in patients with IBS (53%) compared with controls (27%). 7%
study IBS = 55 of patients with IBS met criterion for vitamin D sufficiency (25(OH)
IBS subtypes NR D ≥ 75 nmol/L) compared with 25% of controls.
Schoen, USA, Observational: Patients with gastrointestinal 151 Vitamin D Patients with functional bowel disease had lower serum mean 25-OHCC
1978 Cross-sectional disease levels (25.5 ± 10.2 ng/mL) compared with healthy controls (33.0 ± 11.5 ng/
study Functional bowel disease = 19 mL).
Stevenson, South Observational: Controls = 19 122 Vitamin A, C, B9, calcium, The dietary intake of particular micronutrients (calcium, iron, and folate) in
Africa, 2014 Cohort study IBS = 103 iron patients with IBS was significantly less than the dietary reference intake.
IBS-D = 34
IBS-C = 69
IBS-M or IBS-alternating = 0
(excluded from this study)
Torres, France, Observational: Controls = 34,578 36,448 Vitamin D, B1, B2, B3, B6, The mean daily dietary intake of micronutrients (calcium, potassium, zinc and
2018 Cross-sectional IBS = 1870 B9, B12, calcium, iron, vitamins B2, B5 and B9) was significantly lower in patients with IBS compared
study IBS-D = 617 magnesium, zinc with healthy controls.
IBS-C = 402
IBS-M = 673
IBS-undefined = 178
Williams, UK, Observational: Participants with IBS 104 Vitamin C, B2, B9, calcium Patients with IBS had adequate and balanced macronutrient intake with
2011 Cross-sectional IBS-D = 39 micronutrient intake exceeding reference nutrient intakes.
study IBS-C = 23
IBS-M = 42

© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
S Bek et al.

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 S Bek et al.

Table 3 Study characteristics of included interventional studies

First author, Type of study Study population Sample size Types of micronutrients Significant findings
country, year

Abbasnezhad, Interventional: Randomized IBS-C = 29 85 Vitamin D, calcium Vitamin D supplementation improved QoL scores and IBS symptom severity.
Iran, 2016 controlled trial (RCT) IBS-D = 22
IBS-A = 34
Amani, Iran, Interventional: RCT IBS-D = 22 85 Vitamin D Vitamin D supplementation significantly reduced interleukin 17 (IL-17) and
2018 IBS-C = 29 malondialdehyde serum levels and increased total antioxidant capacity and IL-10
IBS-A = 34 serum levels in IBS patients compared with placebo group. Across the IBS
subtypes, it was only in IBS-D that vitamin D supplementation significantly
reduced tumor necrosis factor alpha and IL-17 serum levels compared with
placebo group.
Amrousy, Interventional: RCT Treatment = 56 112 Vitamin D IBS-SSS, IBS-QoL and total scores significantly improved in vitamin D treatment

Journal of Gastroenterology and Hepatology 37 (2022) 1485–1497

Egypt, 2018 Placebo = 56 group compared with placebo group.
IBS-C = 63
IBS-D = 29
IBS-M = 11
IBS-U = 9
Eswaran, Interventional: RCT IBS-D = 78 78 Vitamins A, D, B1, B2, B3, Although decrease in several micronutrients was observed with implementation
USA, 2020 B6, B9, B12, calcium, iron, of the low-FODMAP diet relative to the mNICE diet, most of these disappeared
magnesium, zinc after adjusting for energy intake.
Jalili, Iran, Interventional: RCT Women with 100 Vitamin D Co-administration of soy isoflavones with vitamin D did not improve the IBS
2016 IBS symptoms severity scores (IBS- SSS) and IBS-QoL; but improved the total score

© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
(IBS-TS).
Jalili, Iran, Interventional: RCT Patients with 116 Vitamin D, calcium, iron, Vitamin D therapy improved the severity of symptoms and QoL in patients with
2019 IBS magnesium, zinc IBS.
Mazzawi, Interventional: non-RCT IBS-D = 17 17 Vitamins A, D, B1, B2, B6, Following dietary guidance, there were increases in the consumption of dairy
Norway, 2013 B9, B12, calcium, iron, products, β-carotene, retinol equivalents, riboflavin, vitamin B12 and calcium,
magnesium, zinc although only the increase in vitamin B12 consumption was statistically
significant. Dietary guidance also resulted in improvements in IBS total symptom
scores and IBS-QoL.
OBrien, New Interventional: non-RCT Chronic 20 Vitamin B9, B12, calcium, In older adults the low FODMAP diet is clinically effective and does not
Zealand, 2020 functional iron, magnesium jeopardize nutritional intake when supervised by an experienced dietitian.
diarrhea = 20
Sikaroudi, Iran, Interventional: RCT IBS-D = 74 74 Vitamin D Symptoms severity, QoL, hospital anxiety and depression scale (HADs)
2020 depression, visceral sensitivity index (VSI) improved significantly in the vitamin D
group compared with the placebo group.
IBS-D = 80 130

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Irritable bowel syndrome and micronutrients S Bek et al.

Patients affected by IBS seem to have benefitted from a low FODMAP diet but
with the habitual control diet. Selenium and vitamin B12 were both higher after

higher compared with the habitual control diet. 30% met the recommendation
the low FODMAP diet compared with the sham control diet. Vitamin B12 was
(measured using the Healthy Diet Indicator and Healthy Diet Score) compared

not from an SCD, and a low FODMAP diet does not seem to cause vitamin D
Micronutrient deficiency can cause disruption to normal bodily
functions, manifesting as diseases such as beri-beri and scurvy.25

The IBS population exhibited significant levels of Vitamin D insufficiency.

In patients with IBS, a 4-week low FODMAP diet decreases diet quality
Subclinical micronutrient deficiency is more difficult to recognize

for iodine, 39% for magnesium, 48% for iron, and 15% for selenium.
and can lead to pathological changes over time.26 Therefore, it is
integral that doctors and other healthcare professionals managing
individuals with IBS are cognisant of the various diet modification
strategies and recognize the importance of micronutrients. How-
ever, the impact of micronutrients on IBS symptoms remains un-
clear. This present systematic review is aimed at evaluating the
effect of habitual and exclusion diets on micronutrient status in
IBS, as well as the role of micronutrient supplementation in allevi-
ating IBS symptoms.

Methodology
A literature search of 4 electronic databases (PubMed, Embase,
and folic acid deficiencies. Web of Science, Cochrane) was performed on 10th December
2020 for articles published from date of inception to 10th Decem-
Significant findings

ber 2020 reporting baseline serum levels or dietary intake of

micronutrients in IBS patients and articles reporting the effects
of micronutrient supplementation on patients with IBS. Observa-
tional studies and clinical trials were included, while reviews, let-
ters, editorials, perspectives, case reports and series, and
conference abstracts were excluded. Throughout the research pro-
cess, the research team received advice and guidance from medical
Vitamin A, B1, B2, B3, B6,

librarians from the National University of Singapore’s (NUS)

Types of micronutrients

Yong Loo Lin School of Medicine (YLLSOM) and local educa-

B9, B12, calcium, iron,

tional experts and clinicians at the National University Hospital’s

magnesium, zinc

Division of Gastroenterology and Hepatology and Department of

Vitamins D, B9

Dietetics. The PICOS inclusion and exclusion criteria table

Vitamin D

(Table 1) was utilized to guide the search process.

Search strategies used for Embase, Web of Science, and
Cochrane are presented in Table S1.
Serum micronutrient levels and dietary intake of micronutrients
Sample size

in patients with IBS were collected. In studies investigating the ef-

fect of micronutrient supplementation on patients with IBS, out-
come data including gastrointestinal symptoms, IBS score
51

60

systems, and post-intervention micronutrient levels were collected.

The extracted data were tabulated and organized by micronutrient
Study population

type to observe for trends.

Patients with
IBS-M = 50

IBS-M = 28

To ensure the quality of included articles, risk of bias assessment

IBS-D = 14
IBS-C = 9

of included interventional studies was conducted by 2 independent

reviewers using the Cochrane Risk of Bias tool.27 Domains
IBS

assessed comprise random sequence generation, allocation con-

cealment, masking of participants and personnel, blinding of out-
controlled trials were included

come assessment, incomplete outcome data, selective outcome

Data from two randomized

reporting, and other sources of bias. The risk of bias for included
interventional studies is shown in Figure S1. The systematic re-
Interventional: RCT

Interventional: RCT

view was reported according to the Preferred Reporting Items of

for this secondary

Systematic Reviews and Meta-Analyses (PRISMA) guidelines.28

Type of study

The PRISMA checklist is shown in Figure S2.28

analysis
(Continued)

Results
The PRISMA flowchart is presented in Figure 1. Twenty-six arti-
Vincenzi, Italy,
country, year
First author,

cles were analyzed in this systematic review in total. Twelve were

Staudacher,

USA, 2015
Tazzyman,
UK, 2020

interventional and 14 were observational studies. The study char-

Table 3

acteristics of included observational studies and interventional

2017

studies are presented in Tables 2 and 3, respectively.

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© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
 Table 4 Summary of results

Serum level of micronutrient in Dietary intake of micronutrient in Association of micronutrient with IBS QoL or
S Bek et al.

patients with IBS compared patients with IBS compared IBS symptom severity
with healthy controls with healthy controls or dietary
reference values

Higher Lower No Higher Lower No IBS-QoL IBS Symptoms

difference difference
a
Vitamin A Bohn 2013
Vitamin B1 Ligaarden Ligaarden 2011 Torres
b,c
2011 (males) Eswaran 2020 2018
a
Vitamin B2 Ligaarden Bohn 2013 Torres
2011 (males) Ligaarden 2011 2018
Williams 2011 (females)
b,c
Eswaran 2020
Vitamin B3 Ligaarden
2011 (females)

Journal of Gastroenterology and Hepatology 37 (2022) 1485–1497

Ligaarden
2011 (males)
Vitamin B6 Ligaarden 2011 Low intake of B6 associated with a high
symptom score:
Ligaarden 2011
Vitamin B9 Williams 2011 Stevenson 2014
a
Torres 2018
OBrien 2020
c
OBrien 2020
e
Vincenzi 2017

© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
a
Vitamin B12 Staudacher, Bohn 2013 Eswaran
b,c
2020 2020
a e
Vitamin D Abbasnezhad 2019 Vincenzi 2017 Positive association between serum Lower serum vitamin D levels associated
a
Abbasnezhad 2019 vitamin D levels and IBS-QoL: with higher symptom severity:
(IBS-D) Abbasnezhad 2019 Abbasnezhad 2019
Nwosu 2017 Vitamin D supplementation improved Cho 2018
a
Nwosu 2017 (IBS QoL: Nath 2019
with migraines) Amrousy 2018 Vitamin D supplementation improved IBS
Cho 2018 Jalili 2016 symptoms:
(adolescents) Jalili 2019 Amrousy 2018
Khayyatzadeh 2017 Sikaroudi 2020 Jalili 2016
Schoen 1978 Sikaroudi 2020
a
Khayyat 2015 Vitamin D supplementation did not
improve IBS symptoms significantly:
Jalili 2019
Tazzyman 2015

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 1492
Table 4 (Continued)

Serum level of micronutrient in Dietary intake of micronutrient in Association of micronutrient with IBS QoL or
patients with IBS compared patients with IBS compared IBS symptom severity
with healthy controls with healthy controls or dietary
reference values

Higher Lower No Higher Lower No IBS-QoL IBS Symptoms

difference difference

Calcium Williams 2011 Bohn 2013

Irritable bowel syndrome and micronutrients

(females)
a
Bohn 2013
a
Torres 2018
OBrien 2020
c
OBrien 2020
c
Eswaran 2020
d
Eswaran 2020
Stevenson 2014
Iron Bohn 2013^ Stevenson 2014
(females) Ligaarden 2011
Bohn 2013^ (females)
Ligaarden OBrien 2020
c
2011 (males) OBrien 2020
b,c
Eswaran 2020
Magnesium Ligaarden 2011
OBrien 2020
c
OBrien 2020
a a
Zinc Bahrami 2019 Bahrami 2019
a
Torres 2018
Ligaarden 2011
(females)
Ligaarden 2011
(males)
a
Levels at baseline, compared with controls.
b
Proportion of participants meeting/exceeding dietary reference values.
c
After low-FODMAP diet.
d
After mNICE diet.
e
After SCD diet.

© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
S Bek et al.

Journal of Gastroenterology and Hepatology 37 (2022) 1485–1497

14401746, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jgh.15891 by Nat Prov Indonesia, Wiley Online Library on [12/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

S Bek et al.
Serum micronutrients. The only two micronutrients with
serum levels reported were vitamin D and zinc. Of all six articles
reviewed studying the relationship between vitamin D and
IBS,29–34 two studies reported vitamin D3 levels,29,30 whereas
the other four reported vitamin D2 levels.31–34 The results re-
vealed that across the board, serum levels of vitamin D were lower
in IBS patients, when compared with dietary reference values and
when compared with healthy controls. Serum levels of zinc were
also lower in patients with IBS compared with controls.35 Differ-
ent subgroups of patients with IBS were studied, namely the
IBS-D subtype,29 IBS associated with migraines,34 and also ado-
lescents afflicted with IBS.33
Dietary intake of micronutrients. Dietary intake of
micronutrients in patients with IBS were analyzed using food dia-
ries in various interventional and observational studies. Random-
ized controlled trials studied the effect of dietary interventions,
including the low-FODMAP diet,36 the modified National Institute
for Health and Care Excellence guidelines (mNICE) diet,37 and the
Specific Carbohydrate Diet (SCD),38 on micronutrient intake. Ob-
servational studies analyzed baseline micronutrient intake.
Dietary intake for vitamins B1, B2, B9, calcium, iron, and mag-
nesium were reduced after following a low-FODMAP diet.37,39
Dietary intake of calcium was reduced after following the mNICE
diet,37 and levels of vitamins B9 and D intake dropped after the
SCD diet.40 There were no significant changes from baseline in di-
etary intake and levels of other micronutrients. At baseline, intake
of vitamins B1, B2, B6, B9, calcium, iron, magnesium, and zinc in
patients with IBS were significantly lower compared with dietary
reference values.37 The dietary reference values used were the Ref-
erence Nutrient Intake (RNI) in the UK and Dietary Reference In-
takes (DRI) in the USA.26 Compared with healthy controls, intake
of vitamin A, B2, B9, B12, calcium, and zinc were reduced as
well.35,41,42
Effect of vitamin D supplementation on IBS symp-
tom severity and QoL. The relationship between vitamin
D supplementation and IBS symptoms were reported in
Figure 2 Risk of micronutrient deficiency in IBS patients
Journal of Gastroenterology and Hepatology 37 (2022) 1485–1497
© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
14401746, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jgh.15891 by Nat Prov Indonesia, Wiley Online Library on [12/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Irritable bowel syndrome and micronutrients
randomized controlled trials. Outcome measurement was reported
using IBS Symptom Severity Score (IBS-SSS), IBS Quality of
Life (IBS-QOL) questionnaire, and IBS Total Score (IBS-TS). Vi-
tamin D supplementation was shown to alleviate IBS symptoms
such as abdominal pain, distension, and overall gastrointestinal
symptoms compared with placebo. Following vitamin D supple-
mentation, four studies reported an improvement in IBS-QoL
scores,43–47 and three studies reported an improvement in IBS
symptom severity scores.44–46
The summary of results is presented in Table 4.
Discussion
In our systematic review, studies showed that there was an inade-
quate intake of vitamins A, B2, B9, B12, calcium and zinc in the
habitual diet of IBS patients. Habitual diets of IBS patients were
associated with deficiencies in Vitamin A, B6, B12 and zinc, of
which patients with IBS on restrictive diets (low-FODMAP diet,
mNICE diet, SCD diet) also had additional deficiencies in vita-
mins B1, B2, B9, D, as well as calcium, iron and magnesium.
IBS-QoL, IBS-SSS, and IBS-TS scores improved following vita-
min D supplementation. The risk of deficiency in dietary intake
of micronutrients in IBS patients is reflected in Figure 2. However,
it must be noted that while interventional studies may demonstrate
micronutrient deficiencies in IBS patients while they are on their
respective diets, these dietary interventions only span a brief pe-
riod (generally between 4 weeks and 2 months), followed by a
gradual return to a modified diet.48 As a result, any micronutrient
deficiency encountered during the period may only be temporary.
Despite the numerous studies on management of IBS, few ana-
lyzed the role of micronutrients. More specifically, little is known
regarding the effect of micronutrient supplementation in alleviat-
ing IBS symptoms apart from that of vitamin D. Of the 10 random-
ized controlled trials (RCTs) included in our review, 7 investigated
the effects of vitamin D supplementation and 3 studied the effects
of dietary interventions. Interventional studies for IBS have been
largely skewed towards vitamin D supplementation, as many stud-
ies have demonstrated that vitamin D produces benefits in other
gastrointestinal diseases and may interfere in the
1493

Irritable bowel syndrome and micronutrients
pathophysiological pathways of IBS.49 As a result, future RCTs
could evaluate the role of zinc, calcium, and B vitamin supplemen-
tation on IBS symptom severity. Thirteen studies reported dietary
micronutrient levels based on food frequency questionnaires or
food diaries. Of the seven studies reporting serum micronutrient
levels, six were reporting serum vitamin D levels and only one in-
vestigated serum zinc levels.
We will now discuss the role of micronutrients in regulating the
gut mucosa, microbiota, immunity, as well as systemic functioning
in the body and its potential impact on IBS. According to the avail-
able literature, there may be a role for dietary supplementation of
micronutrients zinc, calcium, vitamins B6, B9, B12 and D. Further
interventional studies are required to investigate this subject
matter.
Regarding zinc, its intracellular form contributes to intestinal
tight junction integrity by maintaining occluding and claudin-3
expression,50 and maintains the structural and functional integ-
rity of the intestinal barrier, protecting against invading
pathogens.51 Zinc has also been related to reduced pathogenicity
of gut-specific organisms by causing stress on bacterial
envelopes.52 Calcium deficiency may be attributed to avoidance
of dairy products as they may cause symptoms of bloating and
abdominal pain in IBS-D patients,53 and with dairy products be-
ing high in lactose, the low FODMAP diet recommends that
they be excluded.54 As for magnesium, the Korean Society of
Neurogastroenterology and Motility reports that magnesium salts
can improve stool consistency and frequency, in patients with
normal renal function.55 An interventional study has revealed
the beneficial effect of magnesium oxide (MgO) as first line
treatment of chronic constipation, acting as an osmotic laxative.
The study yielded promising results in the form of improved ab-
dominal symptoms, and significant reduction in straining during
defecation.56
Vitamin B6, pyridoxine, plays an important role in immune
modulation, possessing anti-inflammatory and antioxidant
properties57 and can alter the molecular and histological features
of colonic inflammation,58 a key feature in the pathophysiology
of IBS. Vitamin B9 is also known as folate. Murine studies re-
vealed vitamin B9 plays a part in intestinal immunomodulation.
Deficiency in dietary vitamin B9 causes reduced T regulator cell
population in the small intestine, and this resulted in greater sus-
ceptibility to intestinal inflammation,59 which is implicated in
IBS.60 Vitamin B12, cobalamin, plays a role in reducing the viru-
lence of gut commensal bacteria61 and has immunomodulatory
properties, contributing to the immune response via natural killer
cells and CD8 + T cells,62 which may potentially benefit patients
with IBS who have increased circulating T cells.63 However, a ran-
domized controlled trial investigating the utility of vitamin B12
supplementation revealed that it does not reduce fatigue or im-
prove quality of life in IBS or IBD patients.64 Lastly, vitamin D
plays important roles in immune system regulation,65 electrolyte
reabsorption,66 and maintenance of skeletal health.67 Six random-
ized controlled trials have demonstrated that vitamin D supple-
mentation is beneficial in IBS, whether in improving symptoms
or quality of life.
1494
© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
14401746, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jgh.15891 by Nat Prov Indonesia, Wiley Online Library on [12/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
S Bek et al.
Limitations. The findings of our systematic review should
be interpreted in view of its limitations. Firstly, there is a lack
of representation of micronutrients other than vitamin D in inter-
ventional studies. Of the 12 included interventional studies, five
studies investigated the effects of dietary changes while seven
studies investigated the effects of vitamin D supplementation
in patients with IBS. Owing to the lack of interventional studies
investigating the effect of supplementation involving
micronutrients other than vitamin D, we are unable to draw def-
inite conclusions about the potential benefit of supplementing
for other vitamins and minerals. Secondly, while different IBS
subtypes were included in study populations, many studies did
not report data stratified by IBS subtypes. Hence, we are unable
to find out if different IBS subtypes may present with different
micronutrient dietary intake, serum levels, differences in quality
of life and IBS symptom severity. Thirdly, the majority of in-
cluded studies reported approximate dietary intake values de-
rived from the quantity and types of food consumed as
reported in food diaries, thus, errors in estimation of food can
lead to inaccuracies in data collected.68
Additionally, this systematic review only included fully pub-
lished articles and excluded conference abstracts, and this could
be a source of publication bias. A large proportion of the studies
reported are from Europe, the United States of America, or the
Middle East. There is paucity of dietary studies on IBS in Asia,
and thus a real need is present to explore this area given the vari-
ation in diets between different populations and cultures.
Implications for practice and future research. The
British Society of Gastroenterology’s guidelines on the manage-
ment of IBS recommends dietary advice as first-line treatment.69
Currently, practice guidelines by the British Dietetic Association
remain the only topic specific dietary management of IBS,
recommending dietary and lifestyle assessment targeting intake
of food triggers and healthy eating habits as first-line manage-
ment, followed by dietitian-led low FODMAP diets as
second-line management.70 Future studies should investigate
the potential of iron, calcium, magnesium, vitamins B1, B2,
B6, B9, and B12. Further studies are also warranted for the cre-
ation of standardized, evidence-based guidelines for vitamin D
supplementation in IBS. Dietary guidance by a dietitian trained
in the field of IBS will be helpful to prevent micronutrient defi-
ciencies that result from insufficient knowledge on specific
foods to avoid in exclusion diets.
Conclusion
Patients with IBS are at risk of developing multiple micronutrient
deficiencies that may have local gastrointestinal and systemic ef-
fects from unbalanced diets poor in nutrients. Patients’ habitual di-
ets should be assessed for nutritional adequacy. Dietary
management of IBS patients includes, whenever possible, a proper
dietitian review of dietary habits and nutritional status. Dietary
guidance by a dietitian trained in the field of IBS is recommended
to ensure adequate micronutrient intake.
Journal of Gastroenterology and Hepatology 37 (2022) 1485–1497

S Bek et al.
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