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Vitamin and Mineral Status in Patients With Inflammatory Bowel Disease

Alkhouri, Razan H.; Hashmi, Humaira; Baker, Robert D.; Gelfond, Daniel; Baker, Susan S.

Journal of Pediatric Gastroenterology and Nutrition: January 2013 - Volume 56 - Issue 1 - p 89–92
doi: 10.1097/MPG.0b013e31826a105d
Original Articles: Hepatology and Nutrition
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Objectives: Patients with inflammatory bowel disease (IBD) are at risk for vitamin and mineral deficiencies because of long-term inflammation in the gut mucosa and decreased oral intake. The aim of the study is to investigate 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 as having IBD from 2006 to 2010, ages 1 to 18 years. Patients who had fat- and water-soluble vitamins (A, E, D 25-OH, folate, and B12) and zinc levels obtained at time of diagnosis were included in the study. A total of 61 patients with IBD and 61 age- and sex-matched controls were included.

Results: None of the 61 patients with IBD had folate or vitamin B12 deficiency. Vitamin D deficiency was found in 62% of the patients, vitamin A deficiency in 16%, vitamin E deficiency in 5%, and zinc deficiency in 40%. The control group had vitamin D and E and zinc deficiency in 75%, 8%, and 19% patients, respectively.

Conclusions: We conclude that vitamin B12 and folate deficiencies are rare in children with newly diagnosed IBD in the United States and we question whether routine monitoring is warranted. Vitamin A and zinc deficiency are common in patients with newly diagnosed IBD and levels should be assessed at the time of diagnosis so that enteral repletion can commence. Vitamin D deficiency is common in all of the children in the Buffalo, NY, area, and routine screening for this deficiency is warranted.

Digestive Disease and Nutrition Center, SUNY at Buffalo, Buffalo, NY.

Address correspondence and reprint requests to Razan H. Alkhouri, MBBS, Women and Children's Hospital of Buffalo, Buffalo, NY 14222 (e-mail: ralkhouri@upa.chob.edu).

Received 11 January, 2012

Accepted 2 July, 2012

The authors report no conflicts of interest.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition of unknown etiology. Vitamin and mineral deficiencies have been described in patients with IBD and are attributed to gut mucosal inflammation and decreased oral intake (1). After diagnosis, depending on the choice of medications, patients may have an additional risk for exacerbating folate deficiency (2,3).

We hypothesized that at the time of diagnosis, patients would be deficient in fat-soluble vitamins, B12 and zinc. We also hypothesized that our patients would not be folate deficient because grains in the United States are supplemented with folate (4).

The aim of the study is to investigate the prevalence of vitamin and zinc deficiencies in pediatric patients with IBD at the time of diagnosis, before initiation of therapeutic intervention, and compare it to normal controls.

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METHODS

The study was approved by the Children and Youth Institutional Review Board, University at Buffalo, Women and Children's Hospital, for the retrospective chart review of both the patients with IBD and the matched control subjects. Charts for patients who were diagnosed as having IBD between 2006 and 2010 at the Women and Children's Hospital of Buffalo were retrospectively reviewed. A total of 239 charts were reviewed; 61 patients, ages 1 to 18 years, with IBD (46 patients with Crohn disease [CD], 12 with ulcerative colitis, and 3 with indeterminate colitis) had vitamin levels drawn at time of diagnosis and before treatment. The diagnosis of IBD was based on standard clinical, radiographic, endoscopic, and histological criteria (5).

Vitamin and mineral levels, weight, and height were obtained from the patient's initial visit. Body mass index (in kilograms per square meter) and body mass index z score were determined using EpiInfo anthropometric software. The areas involved in inflammation were recorded for each patient using histological features and radiographic findings.

Age- and sex-matched control subjects were selected from those who had vitamin and mineral levels checked to evaluate their 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 revealing any other inflammatory, infectious, or malabsorption conditions were excluded.

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Statistical Analysis

All of the statistical analyses were performed in SPSS (SPSS Inc, Chicago, IL) and SAS 9.2 (SAS Institute Inc, Cary, NC) by a professional statistician. Results are expressed as mean values ± standard deviation. Vitamin deficiency is defined as vitamin A <20 μg/dL (6), vitamin E <5 mg/L (7), vitamin D <30 nmol/L (8,9), vitamin B12 <200 pg/mL (10), folate <3 ng/mL (10), and zinc <70 μg/dL (6).

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RESULTS

A total of 61 patients with IBD and 61 control subjects were included in the study. Demographic and clinical characteristics for the different IBD subgroups and controls, including anthropometric data at the time of diagnosis, are presented in Table 1. The mean concentration of each vitamin, erythrocyte sedimentation rate, and albumin obtained at the time of diagnosis ± standard deviation are presented in Table 2.

TABLE 1

TABLE 1

TABLE 2

TABLE 2

None of the 61 patients with IBD had folate or vitamin B12 deficiency, despite the fact that 80% of the patients with CD had terminal ileum inflammation at the time of diagnosis and measurement of vitamin levels. More than half of the patients had elevated serum folate levels.

Vitamin E and D deficiencies were found in both groups. No folate, vitamin B12, or vitamin A deficiency was found in the control group. Vitamin A and zinc deficiencies were statistically more prevalent in the IBD group compared with control group (Fig. 1). Zinc deficiency was found in 40% and 19% of IBD and control subjects, respectively.

FIGURE 1

FIGURE 1

No correlation was found between vitamin A deficiency and erythrocyte sedimentation rate levels; however, lower albumin levels were found in those with vitamin A deficiency (P < 0.05). Vitamin levels of patients with CD compared to those with ulcerative colitis are presented in Figure 2. Only 3 patients were noted to have severe vitamin D deficiency (vitamin D <10 nmol/L), 2 patients with IBD and 1 control.

FIGURE 2

FIGURE 2

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DISCUSSION

Nutrition is an integral component of the management of patients with IBD. Because vitamin and mineral deficiencies have been reported in patients with IBD, multivitamin supplementation is generally recommended.

After the supplementation of grains in the United States with folate in 1995, concerns were raised that B12 deficiency could be masked. This is a serious concern in patients who have IBD because 80% of those with CD in the present study have ileal inflammation. Vitamin B12 is primarily absorbed in the terminal ileum bound to intrinsic factor. Ileal inflammation could prevent adequate vitamin B12 absorption, possibly leading to B12 deficiency. High folic acid intake is thought to mask the manifestations of vitamin B12 deficiency by correcting the megaloblastic anemia, but not the neurological or cognitive deterioration. Without the presence of anemia, vitamin B12 deficiency may be missed and further advance neurological deterioration (11,12). Our finding is in contrast to that of Yakut et al (13) and Chowers et al (14) who found vitamin B12 and folate deficiency in their studies; however, their studies were done in Europe and Israel, respectively, where fortification of grains is not mandated. Similar to the Heyman et al report (2), we found that folate was increased both in patients with IBD and in the control group. It is likely that our findings and those of Heyman truly represent folate status in the United States after supplementation of grains. It is important to emphasize that even in the patients with IBD who are vulnerable for vitamin B12 deficiency, no deficiency was identified.

Vitamin D is produced endogenously in the skin by the photoreduction of 7-dehydrocholesterol by ultraviolet light (15). Owing to concerns regarding the development of cancer, sunlight exposure is limited throughout life and sun screens that block the solar radiation and cutaneous synthesis of vitamin D3 are used liberally. A limited number of foods are fortified with vitamin D, including milk (100 IU per 8-ounce serving), select orange juice (100 IU per 8-ounce serving), other isolated juice products, and certain breads and cereals (16). Therefore, children are at risk for developing vitamin D deficiency whether they have a chronic disease. The Institute of Medicine recommends a daily intake of 600 IU/day in individuals 1 to 70 years of age, and calcium 700 to 1300 mg/day based on age to promote healthy skeletal growth (17). The fact that both our control patients (75%) and those with IBD (62%) were vitamin D–deficient suggests that children in western New York warrant routine screening for vitamin D deficiency.

Although there is no consensus on optimal levels of 25-hydroxyvitamin D (25[OH] D) as measured in serum, levels <30 ng/mL were shown to be associated with elevated parathyroid hormone (PTH). Heaney et al (18) demonstrated that maximum calcium absorption occurs at levels of 25(OH) D >32 ng/mL. Therefore, levels <30 ng/mL may contribute to osteoporosis by decreasing intestinal calcium absorption. Furthermore, in a study involving hip fractures in older adults, a minimum 25(OH) D level of 32 ng/mL is necessary for optimal protection from fracture and intestinal absorption of calcium (19).

Skin pigmentation and season were found to be significant predictors of circulating concentration of serum 25(OH) D (20). We examined the season during which vitamin D was drawn on all of the patients and controls. Vitamin D assessment spanned all year and deficiency was noted in all of the seasons (Fig. 3.). As anticipated, in all the study patients (controls and IBD), there was less vitamin D deficiency in the summer months compared with spring (P = 0.08), autumn (P = 0.15), and winter (P = 0.08). Vitamin D is a fat-soluble vitamin and we expected that vitamin D stored throughout the summer and synthesized during the autumn, one of the sunniest and pleasantest times in western New York, would have led to higher levels in this season. Skin pigmentation has a dramatic effect on previtamin D3 production. We looked at the self-reported ethnicity of the patients. We found that 79% and 85% of IBD and control patients were reported as white, respectively. We were cautioned, however, that skin pigment varies widely within racial groups and there is no clinical tool that allows an accurate association of skin pigment and vitamin D synthesis (personal communication with Dr Holick, December 2011).

FIGURE 3

FIGURE 3

Other fat-soluble vitamins were also found to be deficient in patients with IBD; vitamin A deficiency was found in IBD but not in the control group. Serum retinol concentration reflects an individual's vitamin A status (6,21). Because serum retinol is homeostatically controlled, its levels do not drop until the body's stores are significantly limited. The serum concentration of retinol is affected by several factors, including retinal-binding protein synthesis in the liver, infection, nutritional status, and the existing level of other nutrients, such as zinc and carotenoid. Absorption is influenced by dietary factors, including zinc deficiency, abetalipoproteinemia, and protein deficiency, which is common in patients with IBD (6,7). In our patients, there is an association between serum vitamin A and protein (Table 2).

Vitamin E is a fat-soluble vitamin that is thought to function primarily as a chain-breaking antioxidant that prevents the propagation of lipid peroxidation (22). In the present study, we evaluated vitamin E status by measuring the content of α-tocopherol in the blood plasma and found that a minority of subjects in both groups have vitamin E deficiency. Vitamin E is found in numerous foods; thus, overt deficiency is rare and is seen in individuals who are unable to absorb the vitamin, or have inherited abnormalities.

Zinc functions as a component of several enzymes such as alkaline phosphatase, and is essential for the integrity of the immune system. It is difficult to assess zinc deficiency because serum zinc levels are not considered a good indicator of zinc deficiency. Inconsistent data exist for the serum zinc concentration in healthy individuals, and those values depend on the time of the day the sample was collected (6,23). A number of studies have reported no association between dietary zinc intake and plasma or serum zinc concentration (24). We understand the limitations that the use of serum zinc levels places on these data, but serum zinc is all that is available on a clinical basis to assess zinc status, and patients who have IBD are at risk for zinc deficiency.

Zinc deficiency in patients with IBD is likely due to increased losses of zinc from the gastrointestinal tract. Zinc deficiency also can occur due to inadequate zinc intake or poor absorption. For example, a diet low in meat and high in legumes and whole grains could have a negative effect on zinc status because meat has high levels of bioavailable zinc, and legumes and whole grains contain phytates that bind zinc and inhibit its absorption (25,26).

There are other potential limitations in our study, including inherent nature of selection bias attributed to retrospective chart review methodology. Because there is no effective technique to measure skin pigmentation, we reported the ethnicity of the patients.

We conclude that vitamin B12 and folate deficiency are rare in children newly diagnosed as having IBD and we question whether routine monitoring is warranted. Vitamin A and zinc deficiency are common in patients newly diagnosed as having IBD and levels should be assessed at the time of diagnosis so repletion can commence. Vitamin D deficiency is common in all of the children in the Buffalo, NY, area and routine screening for this deficiency is warranted.

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Acknowledgment

The authors thank Chinxing Ma, PhD, for assisting in the performance of the statistical analysis.

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Keywords:

folate; IBD; nutrition; pediatrics; vitamin A; vitamin B12; vitamin D; vitamin deficiency; vitamin E; zinc

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