Nutrient Deficiencies with Celiac Disease

A recent study (JPGN 2014; 59: 225-28) examined fat-soluble vitamin deficiencies in pediatric patients with newly diagonosed Celiac disease (CD).

Of the 83 patients analyzed between 1995-2012 at the Mayo clinic, the key findings:

  • No patients had vitamin A deficiency
  • Two patients had vitamin E deficiency.  Both of these patients had complete villous atrophy along with a malabsorptive presentation.
  • Nine patients had mild-to-moderate vitamin D deficiency (less than the reported frequency in the general pediatric population)
  • All of these vitamin deficiencies corrected with gluten-free diet and vitamin supplements.

A limitation of the study was a selection bias as not all children underwent vitamin level measurements.

Take-home message (from authors): “fat-soluble deficiencies are uncommon in children with a new diagnosis of CD.  Routine measuring of fat-soluble vitamin levels may not be necessary.”

Related blog posts:


What happens to micronutrient levels in the hospital setting?

When atypical labs need to be obtained, many times this is easier in the hospital setting for logistical reasons including insurance and accessibility to specialty labs.  One group of labs that may be less suited for checking in the hospital, despite convenience, would be micronutrients.  Many of the micronutrients can be affected by systemic inflammatory response (Am J Clin Nutr 2012; 95: 64-71).  Thanks to Kipp Ellsworth for this reference (from his @PedNutritionGuy twitter feed).

Previous studies on systemic inflammatory response (SIR), as assessed by elevated C-reactive protein (CRP) concentrations, has shown that with elective surgery there are transient decreases in plasma concentrations of zinc, selenium, iron, vitamin A, vitamin E, carotenoids, riboflavin, vitamin B-6, vitamin C, and vitamin D.

This current study adds to this body of information.  Between 2001-2011, 2217 whole-blood samples were taken from 1303 patients. Specific micronutrients that were studied: plasma zinc, copper, selenium, vitamins A, B-6, C, and E.  For vitamin D, the authors examined 4327 samples from 3677 patients. The authors did not include manganese, thiamine or riboflavin because these are measured in erythrocytes.

For each analyte, the concentrations were separated according to 6 categories of CRP values: <5, 6-10, 11-20, 21-40, 41-80, and >80 mg/L.

Key finding: Except for copper and vitamin E, all plasma micronutrient concentrations decreased with increasing severity of acute inflammatory response.  For selenium, vitamin B-6, and vitamin C, this occurred with only slight increases in CRP (5 to 10 mg/L).

The magnitude of the SIR effect on micronutrients was quite variable among patients and analytes.  When CRP was >80 mg/L, analyte deficiency rate was noted to be the following:

  • 60 % for selenium (vs. 33% with NL CRP)
  • 48% for vitamin A (vs. 7% with NL CRP)
  • 35% for vitamin B-6 (vs. 14% with NL CRP)
  • 80% for vitamin C (vs. 33% with NL CRP)
  • 88% for vitamin D (vs. 69% with NL CRP)
  • 81% for zinc (vs. 33% with NL CRP)
  • 9% for copper (vs. 4% with NL CRP)
  • 16% for vitamin E (vs. 9% with NL CRP)

**The specific normal value cutoffs and more data at all CRP values are noted in Table 9 of the manuscript.

The implications from this study are clear.  When micronutrient values are derived from plasma during a SIR, a false-positive diagnosis of a micronutrient deficiency is more likely. The study has several limitations and the findings may not be applicable to all types of medical conditions.

Authors conclusion: When CRP concentration is >20 mg/L (>2 mg/dL), “plasma concentrations of selenium, zinc, and vitamins A, B-6, C, and D are clinically uninterpretable.”

Related blog entries:

Fat soluble vitamin deficiency -sometimes the rule rather than the exception

While it is well-known that cholestasis predisposes individuals to develop fat-soluble vitamin (FSV) deficiencies, the exact frequency is not clear.

A recent prospective multi center study of infants with biliary atresia (BA) indicates that FSV deficiency is quite frequent –thanks to Kipp Ellsworth for forwarding this article (DOI: 10.1542/peds.2011-1423;  “Infants with BA are at risk for malabsorption of dietary lipid and fat-soluble vitamins (FSVs) due to insufficient intraluminal bile acid concentrations.”

To determine the frequency of FSV deficiencies, this study examined 92 infants with BA who were enrolled in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after hepatoportoenterostomy (HPE).  This study was conducted by the Biliary Atresia Research Consortium (BARC) between 2005-2008.

All infants were treated with a standardized dose of a liquid multiple FSV/d-α tocopheryl polyethylene glycol-1000 succinate (TPGS; a micelle forming water-soluble form of vitamin E).  Infants received initially ADEKs; later in the study, ∼32 months after start, participants were changed to AquADEKs due to a manufacturer’s change.  In addition, all infants received supplemental vitamin K, initially 2.5 mg three times per week.  As noted in supplement to article, the two study multivitamins have particularly low amounts of vitamin D (800 units) and vitamin E (80-100 units) compared to frequent dosing in clinical practice for severe cholestasis (see below).

TABLE 1 from study: Target FSV Levels and Replacement Regimens

  • Vitamin A (retinol)

Target:  19–77 mg/dL retinol:RBP molar ratio >0.8

Supplement strategy:  Increments of 5000 IU (up to 25–50 000 IU/d) orally or monthly intramuscular administration of 50 000 IU

  • D (25-hydroxy vitamin D)

Target: 15–45 ng/mL

Supplement: Increments of 1200 to 8000 IU orally daily of cholecalciferol or ergocalciferol; alternatively calcitriol at 0.05 to 0.20 mg/kg per day

  • E (α tocopherol) 

Target: 3.8–20.3 mg/mL & vitamin E:total serum lipids ratio >0.6 mg/g

Supplement: Increments of 25 IU/kg of TPGS orally daily (to 100 IU/kg per d)

  • K (phytonadione)

Target: INR ≤1.2

Supplementation Strategy:

  • <1.2-1.5  INR:  2.5 mg vitamin K orally daily
  • 1.5-1.8  INR: 1.8  2.0–5.0 mg vitamin K intramuscular and 2.5 mg vitamin K orally daily
  • >1.8 INR:  2.0–5.0 mg vitamin K intramuscular and 5.0 mg vitamin K orally daily

Results: FSV was common in infants with total bilirubin (TB) ≥2 mg/dL. At three months post HPE, only 3 infants with this degree of cholestasis were sufficient for all four vitamins.; at 6 months post HPE, all 24 infants with TB ≥2 mg/dL had at least one FSV deficiency: “100%, 79%, 50%, and 46%, respectively, for vitamins A, D, E, and K .”   Also, the incidence of vitamin D deficiency would be higher if the authors had chosen a higher target.

Take-home points:

  • FSV deficiencies are common particularly in patients with TB > 2mg/dL; thus careful monitoring is worthwhile
  • There is no current multivitamin that is adequate.  A better strategy is to individualize the dosing for each vitamin and consider injection (except for vitamin E) if needed

Initial individualized dosing of FSV supplementation in clinical practice for severe cholestasis (prior to deficiencies):

Vitamin A: start with ~5000 units daily.

Vitamin D: See previous posts for more information on dosing.  Two options include: Drisdol® (8000 IU/ml) 0.125ml/kg/day (=1000 IU/kg/day) and Bio-D-Mulsion Forte® -each drop = 2,000 IU (also inexpensive)

Vitamin E (Liqui-E®/Nutr-E sol®26.6 IU/ml) 1ml/kg/day
with tocopherol polyethylene glycol succinate.  Alternative is AquaE®(Yasoo

Vitamin K (phytonadione) 2.5mg QOD

Related posts:

Diagnosing biliary atresia earlier

Common to be “D-ficient”

Outcomes of Biliary Atresia

MicroRNAs and biliary atresia

Bleeding due to vitamin K deficiency