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ORIGINAL ARTICLE: HEPATOLOGY AND NUTRITION

Vitamin and Mineral Status in Patients With


Inflammatory Bowel Disease
Razan H. Alkhouri, Humaira Hashmi, Robert D. Baker, Daniel Gelfond, and Susan S. Baker

ABSTRACT
The aim of the study is to investigate the prevalence of
Objectives: Patients with inflammatory bowel disease (IBD) are at risk for
vitamin and zinc deficiencies in pediatric patients with IBD at the
vitamin and mineral deficiencies because of long-term inflammation in the
time of diagnosis, before initiation of therapeutic intervention, and
gut mucosa and decreased oral intake. The aim of the study is to investigate
compare it to normal controls.
the prevalence of vitamin and zinc deficiencies in patients with newly
diagnosed IBD compared with a control group.
Methods: This is a retrospective chart review of all of the patients diagnosed METHODS
as having IBD from 2006 to 2010, ages 1 to 18 years. Patients who had fat- The study was approved by the Children and Youth Institu-
and water-soluble vitamins (A, E, D 25-OH, folate, and B12) and zinc levels tional Review Board, University at Buffalo, Women and Children’s
obtained at time of diagnosis were included in the study. A total of Hospital, for the retrospective chart review of both the patients with
61 patients with IBD and 61 age- and sex-matched controls were included. IBD and the matched control subjects. Charts for patients who were
Results: None of the 61 patients with IBD had folate or vitamin B12 diagnosed as having IBD between 2006 and 2010 at the Women and
deficiency. Vitamin D deficiency was found in 62% of the patients, Children’s Hospital of Buffalo were retrospectively reviewed. A
vitamin A deficiency in 16%, vitamin E deficiency in 5%, and zinc total of 239 charts were reviewed; 61 patients, ages 1 to 18 years,
deficiency in 40%. The control group had vitamin D and E and zinc with IBD (46 patients with Crohn disease [CD], 12 with ulcerative
deficiency in 75%, 8%, and 19% patients, respectively. colitis, and 3 with indeterminate colitis) had vitamin levels drawn at
Conclusions: We conclude that vitamin B12 and folate deficiencies are rare time of diagnosis and before treatment. The diagnosis of IBD was
in children with newly diagnosed IBD in the United States and we question based on standard clinical, radiographic, endoscopic, and histo-
whether routine monitoring is warranted. Vitamin A and zinc deficiency are logical criteria (5).
common in patients with newly diagnosed IBD and levels should be assessed Vitamin and mineral levels, weight, and height were obtained
at the time of diagnosis so that enteral repletion can commence. Vitamin D from the patient’s initial visit. Body mass index (in kilograms per
deficiency is common in all of the children in the Buffalo, NY, area, and square meter) and body mass index z score were determined using
routine screening for this deficiency is warranted. EpiInfo anthropometric software. The areas involved in inflam-
Key Words: folate, IBD, nutrition, pediatrics, vitamin A, vitamin B12,
mation were recorded for each patient using histological features
vitamin D, vitamin deficiency, vitamin E, zinc
and radiographic findings.
Age- and sex-matched control subjects were selected from
those who had vitamin and mineral levels checked to evaluate their
(JPGN 2013;56: 89–92) nutritional status during an upper endoscopy for abdominal pain.
Patients for whom their biopsies were normal or revealed only
reflux esophagitis were included in the study. Patients with biopsies

I nflammatory bowel disease (IBD) is a chronic intestinal inflam-


matory condition of unknown etiology. Vitamin and mineral
deficiencies have been described in patients with IBD and are
revealing any other inflammatory, infectious, or malabsorption
conditions were excluded.

attributed to gut mucosal inflammation and decreased oral intake


(1). After diagnosis, depending on the choice of medications, Statistical Analysis
patients may have an additional risk for exacerbating folate
All of the statistical analyses were performed in SPSS
deficiency (2,3).
(SPSS Inc, Chicago, IL) and SAS 9.2 (SAS Institute Inc, Cary,
We hypothesized that at the time of diagnosis, patients would
NC) by a professional statistician. Results are expressed as mean
be deficient in fat-soluble vitamins, B12 and zinc. We also hypo-
values  standard deviation. Vitamin deficiency is defined as
thesized that our patients would not be folate deficient because
vitamin A <20 mg/dL (6), vitamin E <5 mg/L (7), vitamin D
grains in the United States are supplemented with folate (4).
<30 nmol/L (8,9), vitamin B12 <200 pg/mL (10), folate <3 ng/mL
(10), and zinc <70 mg/dL (6).
Received January 11, 2012; accepted July 2, 2012.
From the Digestive Disease and Nutrition Center, SUNY at Buffalo,
Buffalo, NY. RESULTS
Address correspondence and reprint requests to Razan H. Alkhouri, MBBS,
A total of 61 patients with IBD and 61 control subjects were
Women and Children’s Hospital of Buffalo, Buffalo, NY 14222
(e-mail: ralkhouri@upa.chob.edu). included in the study. Demographic and clinical characteristics for
The authors report no conflicts of interest. the different IBD subgroups and controls, including anthropometric
Copyright # 2012 by European Society for Pediatric Gastroenterology, data at the time of diagnosis, are presented in Table 1. The mean
Hepatology, and Nutrition and North American Society for Pediatric concentration of each vitamin, erythrocyte sedimentation rate, and
Gastroenterology, Hepatology, and Nutrition albumin obtained at the time of diagnosis  standard deviation are
DOI: 10.1097/MPG.0b013e31826a105d presented in Table 2.

JPGN  Volume 56, Number 1, January 2013 89


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Alkhouri et al JPGN  Volume 56, Number 1, January 2013

TABLE 1. Demographics of patients and controls

Total IBD, N ¼ 61 CD, N ¼ 46 UC, N ¼ 12 IC, N ¼ 3 Control, N ¼ 61

Age, y (mean  SD) 12.3  3.9 12.1  4.1 12.3  3.5 14.6  2.5 12.1  3.6
Sex
M 40 32 6 2 30
F 21 14 6 1 31
Ethnicity
White 48 35 10 3 52
African American 10 9 1 0 4
Other 3 2 1 0 5
Height z score (mean  SD) 0.04  1.4 0.08  1.5 0.002  1.3 0.5  1.1 0.14  1.2
Weight z score (mean  SD) 0.06  1.5 0.15  1.5 0.4  1.3 0.5  1.7 0.7  1.3
BMI z score (mean  SD) 0.03  1.4 0.24  1.3 0.67  1.4 0.12  2.1 0.63  1.3
TI inflammation 37 (80%) None None N/A
Site of inflammation Duodenum Colon Duodenum N/A
(N, % of patients in (13, 28%) (12, 100%) (2, 66%)
the disease group)
Gastric (18, 39%) Gastric (2, 66%)
Colon (40, 87%) Colon (3, 100%)

BMI ¼ body mass index; CD ¼ Crohn disease; IC ¼ indeterminate colitis; N/A ¼ not applicable; SD ¼ standard deviation; TI ¼ terminal ileum;
UC ¼ ulcerative colitis. There was no significant difference among the groups.

None of the 61 patients with IBD had folate or vitamin B12 After the supplementation of grains in the United States with
deficiency, despite the fact that 80% of the patients with CD had folate in 1995, concerns were raised that B12 deficiency could be
terminal ileum inflammation at the time of diagnosis and measure- masked. This is a serious concern in patients who have IBD because
ment of vitamin levels. More than half of the patients had elevated 80% of those with CD in the present study have ileal inflammation.
serum folate levels. Vitamin B12 is primarily absorbed in the terminal ileum bound to
Vitamin E and D deficiencies were found in both groups. No intrinsic factor. Ileal inflammation could prevent adequate vitamin
folate, vitamin B12, or vitamin A deficiency was found in the control B12 absorption, possibly leading to B12 deficiency. High folic acid
group. Vitamin A and zinc deficiencies were statistically more intake is thought to mask the manifestations of vitamin B12
prevalent in the IBD group compared with control group (Fig. 1). deficiency by correcting the megaloblastic anemia, but not the
Zinc deficiency was found in 40% and 19% of IBD and control neurological or cognitive deterioration. Without the presence of
subjects, respectively. anemia, vitamin B12 deficiency may be missed and further advance
No correlation was found between vitamin A deficiency and neurological deterioration (11,12). Our finding is in contrast to that
erythrocyte sedimentation rate levels; however, lower albumin of Yakut et al (13) and Chowers et al (14) who found vitamin B12
levels were found in those with vitamin A deficiency (P < 0.05). and folate deficiency in their studies; however, their studies were
Vitamin levels of patients with CD compared to those with ulcera- done in Europe and Israel, respectively, where fortification of grains
tive colitis are presented in Figure 2. Only 3 patients were noted is not mandated. Similar to the Heyman et al report (2), we found
to have severe vitamin D deficiency (vitamin D <10 nmol/L), that folate was increased both in patients with IBD and in the control
2 patients with IBD and 1 control. group. It is likely that our findings and those of Heyman truly
represent folate status in the United States after supplementation of
DISCUSSION grains. It is important to emphasize that even in the patients with
Nutrition is an integral component of the management of IBD who are vulnerable for vitamin B12 deficiency, no deficiency
patients with IBD. Because vitamin and mineral deficiencies have was identified.
been reported in patients with IBD, multivitamin supplementation is Vitamin D is produced endogenously in the skin by the
generally recommended. photoreduction of 7-dehydrocholesterol by ultraviolet light (15).

TABLE 2. Vitamin levels in IBD and control patients

Total IBD CD UC IC Control

Folate, ng/mL (mean  SD) 20.1  6.5 20.3  7 20.9  5.9 19.3  6.6 20.4  5.5
Vitamin B12, pg/mL (mean  SD) 775  441 781  372 906  669 639  282 727  346
Vitamin A (retinol), mg/dL (mean  SD) 47.5  20 44.7  29.5 50  19.7 48  11.3 40.5  10.1
Vitamin E (a-tocopherol), mg/L (mean  SD) 9.3  3.4 9.5  3.2 9.6  4.3 7  2.6 6.8  1.8
Vitamin D (1,25-dihydroxy-vitamin D), ng/mL (mean  SD) 27.8  15.3 29.9  12.7 32  25.8 21.7  7.5 26.7  9.4
Zinc, mg/dL (mean  SD) 73.6  15 76.4  17.5 74.5  19.2 70  8.5 80.3  13.8
Albumin, g/dL (mean  SD) 3.3  0.6 3.2  0.6 3.5  0.6 3.3  0.5 4.3  0.4
ESR, mm/h (mean  SD) 37  26 38  27 35  25 19  2.6 N/A

CD ¼ Crohn disease; ESR ¼ erythrocyte sedimentation rate; IBD ¼ inflammtory bowel disease; IC ¼ indeterminate colitis; N/A ¼ not obtained;
SD ¼ standard deviation; UC ¼ ulcerative colitis.

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JPGN  Volume 56, Number 1, January 2013 Vitamin and Mineral Status in Patients With IBD

Vitamin deficiencies in IBD and control patients anticipated, in all the study patients (controls and IBD), there
80 75 was less vitamin D deficiency in the summer months compared
70 with spring (P ¼ 0.08), autumn (P ¼ 0.15), and winter (P ¼ 0.08).
62
P value < 0.05 Vitamin D is a fat-soluble vitamin and we expected that vitamin D
Percent deficient

60
stored throughout the summer and synthesized during the autumn,
50 Control one of the sunniest and pleasantest times in western New York,
40
40 IBD would have led to higher levels in this season. Skin pigmentation
P value < 0.05
30 has a dramatic effect on previtamin D3 production. We looked at the
19 self-reported ethnicity of the patients. We found that 79% and 85%
20 16
of IBD and control patients were reported as white, respectively.
10 8
5 We were cautioned, however, that skin pigment varies widely
0
0 within racial groups and there is no clinical tool that allows an
Vitamin A* Vitamin E Vitamin D Zinc* accurate association of skin pigment and vitamin D synthesis
(personal communication with Dr Holick, December 2011).
FIGURE 1. Vitamin deficiencies in inflammatory bowel disease (IBD)
 Other fat-soluble vitamins were also found to be deficient in
and control patients. Vitamin A and zinc were noted to be more
patients with IBD; vitamin A deficiency was found in IBD but not in
deficient in the IBD group compared with control patients (P < 0.05).
the control group. Serum retinol concentration reflects an individ-
ual’s vitamin A status (6,21). Because serum retinol is home-
Owing to concerns regarding the development of cancer, sunlight ostatically controlled, its levels do not drop until the body’s
exposure is limited throughout life and sun screens that block the stores are significantly limited. The serum concentration of retinol
solar radiation and cutaneous synthesis of vitamin D3 are used is affected by several factors, including retinal-binding protein
liberally. A limited number of foods are fortified with vitamin D, synthesis in the liver, infection, nutritional status, and the existing
including milk (100 IU per 8-ounce serving), select orange juice level of other nutrients, such as zinc and carotenoid. Absorption is
(100 IU per 8-ounce serving), other isolated juice products, and influenced by dietary factors, including zinc deficiency, abetalipo-
certain breads and cereals (16). Therefore, children are at risk for proteinemia, and protein deficiency, which is common in patients
developing vitamin D deficiency whether they have a chronic with IBD (6,7). In our patients, there is an association between
disease. The Institute of Medicine recommends a daily intake of serum vitamin A and protein (Table 2).
600 IU/day in individuals 1 to 70 years of age, and calcium 700 to Vitamin E is a fat-soluble vitamin that is thought to function
1300 mg/day based on age to promote healthy skeletal growth (17). primarily as a chain-breaking antioxidant that prevents the propa-
The fact that both our control patients (75%) and those with IBD gation of lipid peroxidation (22). In the present study, we evaluated
(62%) were vitamin D–deficient suggests that children in western vitamin E status by measuring the content of a-tocopherol in the
New York warrant routine screening for vitamin D deficiency. blood plasma and found that a minority of subjects in both groups
Although there is no consensus on optimal levels of have vitamin E deficiency. Vitamin E is found in numerous foods;
25-hydroxyvitamin D (25[OH] D) as measured in serum, levels thus, overt deficiency is rare and is seen in individuals who are
<30 ng/mL were shown to be associated with elevated parathyroid unable to absorb the vitamin, or have inherited abnormalities.
hormone (PTH). Heaney et al (18) demonstrated that maximum Zinc functions as a component of several enzymes such as
calcium absorption occurs at levels of 25(OH) D >32 ng/mL. alkaline phosphatase, and is essential for the integrity of the
Therefore, levels <30 ng/mL may contribute to osteoporosis by immune system. It is difficult to assess zinc deficiency because
decreasing intestinal calcium absorption. Furthermore, in a study serum zinc levels are not considered a good indicator of zinc
involving hip fractures in older adults, a minimum 25(OH) D level deficiency. Inconsistent data exist for the serum zinc concentration
of 32 ng/mL is necessary for optimal protection from fracture and in healthy individuals, and those values depend on the time of the
intestinal absorption of calcium (19). day the sample was collected (6,23). A number of studies have
Skin pigmentation and season were found to be significant reported no association between dietary zinc intake and plasma or
predictors of circulating concentration of serum 25(OH) D (20). We serum zinc concentration (24). We understand the limitations that
examined the season during which vitamin D was drawn on all of the use of serum zinc levels places on these data, but serum zinc is
the patients and controls. Vitamin D assessment spanned all year all that is available on a clinical basis to assess zinc status, and
and deficiency was noted in all of the seasons (Fig. 3.). As patients who have IBD are at risk for zinc deficiency.

Vitamin D deficiency among th four seasons


80.00
Vitamin deficiencies in CD and UC patients
70 70.00
60.00
Percent deficient

60
50 50.00

40 CD 40.00 Percent deficient


UC 30.00
30
20 20.00
10 10.00
0 0.00
Vitamin A Vitamin E Vitamin D Zinc Summer Fall Winter Spring

FIGURE 2. Vitamin deficiencies in patients with Crohn disease (CD) FIGURE 3. Vitamin D deficiency in all of the subjects among the
and ulcerative colitis (UC). There were no significant differences 4 seasons. Vitamin D deficiency is noted in all of the seasons, but there
between the CD and the UC group with respect to vitamins A, E, is less vitamin D deficiency in the summer months as compared with
D, and zinc. spring (P ¼ 0.08), autumn (P ¼ 0.15), and winter (P ¼ 0.08).

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Alkhouri et al JPGN  Volume 56, Number 1, January 2013

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