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.
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.
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).
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.
The authors thank Chinxing Ma, PhD, for assisting in the performance of the statistical analysis.
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Keywords:Copyright 2013 by ESPGHAN and NASPGHAN
folate; IBD; nutrition; pediatrics; vitamin A; vitamin B12; vitamin D; vitamin deficiency; vitamin E; zinc