April 2, 2014

Vitamin D Supplementation Potentially Helpful for Chronic Urticaria

Study suggests vitamin D may relieve hives
Researchers recently found that high-dose vitamin D boosted the effects of drug therapy for chronic urticaria, but the study was not a home run. Other interventions should also be considered.


Rorie A, Goldner B, Lyden MS, Poole JA. Beneficial role for supplemental vitamin D3 treatment in chronic urticaria: a randomized study. All Asthma Immunol. 2014; Epub ahead of print.


Single-center, prospective, randomized, double-blind trial with 2 arms. Participants in arm 1 were given 4,000 IU vitamin D orally. Participants in arm 2 were given 600 IU per day. Study duration was 12 weeks, and all participants used standard triple therapy care (certrizine, ranitidine, montelukast) as needed.


The study included 42 participants who had idiopathic urticaria and/or idiopathic angioedema for at least 6 weeks. Exclusion criteria included physical urticarial (known physical trigger identified), hereditary or acquired angioedema, hypercalcemia, renal insufficiency, primary hyperparathyroidism, sarcoidosis, granulomatous disease, malignancy, or pregnancy/lactation.

Study Parameters Assessed

Medication use, urticaria severity

Primary Outcome Measures

Urticaria Severity Score (USS). Number and type of medications used (H1, H2 receptor antagonists, leukotriene antagonists)

Key Findings

Triple-drug therapy provided significant relief of symptoms within 1 week, lowering total USS scores by 33% across both arms. The addition of 4,000 IU/d of vitamin D was safe and provided additional symptom relief, with a 40% reduction in total USS scores at 12 weeks. The high-dose vitamin D arm had a trend (P=0.052) toward lower USS scores vs the low-dose group at week 12, with less urticarial body distribution and number of days with hives. In addition, participants reported better sleep and less-intense itching in the high-dose versus low-dose groups. While serum levels of 25-hydroxycholecalciferol were generally higher in the high-dose group, there was no direct correlation with vitamin D levels and symptom improvement (USS scores). The use of allergy medications did not differ between groups.

Practice Implications

Vitamin D deficiency has been linked to asthma and atopic diseases.1,2 This association is biologically plausible; however, the existing clinical data is full of contradictory reports.3,4 At this time, there is insufficient data on the potential causality of D deficiency and the clinical value of vitamin D supplementation for specific allergic and atopic health conditions.

This is the first RCT for chronic, idiopathic urticaria. In this study, the final USS of 24.1 (4.0) in the low-dose and 15.0 (2.9) were only suggestive of being significant (P=0.052) The study has 2 significant limitations: 1) the sample size was small, and 2) the mean 25(OH)D values were significantly higher in the low-dose group (37 ng/ml) than in the high-dose group (29 ng/ml) at the start. At the end of the study, the low-dose group remained unchanged, and the high-dose group increased to a mean of 56 ng/ml.

A value of 37 ng/ml (baseline mean of low-dose group) with a small standard deviation is considered a vitamin D replete population. This is a setup for a classic type II false negative study. That is, supplementing any group with normal levels may not result in any improvement. The unmatched serum levels at the start of the study favored a negative study. This could be resolved if the study had been of longer duration or the participants had been appropriately divided into matched arms.  

This study definitely supports the triple-drug therapy for patient relief. This study suggests that the addition of vitamin D at 4,000 IUs may bring additional relief. The results are not a home run. Clinicians may find significant additional relief by focusing on intestinal function and adverse food reactivity.

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  1. Paul G, Brehm JM, Alcorn JF, Holguín F, Aujla SJ, Celedón JC. Vitamin D and asthma. Am J Respir Crit Care Med. 2012;185(2):124-32.
  2. Sutherland ER, Goleva E, Jackson LP, Stevens AD, Leung DY. Vitamin D levels, lung function, and steroid response in adult asthma. Am J Respir Crit Care Med. 2010;181(7):699-704.
  3. Hyppönen E, Sovio U, Wjst M, et al. Infant vitamin d supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966. Ann N Y Acad Sci. 2004;1037(1):84-95.
  4. Poon AH, Laprise C, Lemire M, et al. Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy. Am J Respir Crit Care Med. 2004;170(9):967-973.