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The value and significance of 25(OH) and 1,25(OH) vitamin D serum levels in adult coeliac patients: A review of the literature.

Vitamin D
Zingone F, Ciaccia C.
Dig Liver Dis (2018), https://doi.org/10.1016/j.dld.2018.04.005

Several studies suggest that newly diagnosed coeliac patients frequently present with low levels of circulating vitamin D, therefore guidelines suggest it’s evaluation at the time of diagnosis. 
This paper sought to review the existing studies that assess vitamin D levels in adult coeliac patients to understand whether a real deficiency exists and whether a routine evaluation of vitamin D, with appropriate supplementation, should be recommended at diagnosis and follow up.

Vitamin D3 is biologically inert prohormone produced in the skin, it is converted to 25-hydroxyvitamin D3 [25 (OH) vitamin D] in the liver, and then to 1,25-dihydroxyvitamin D3 [(1,25 (OH) vitamin D – also known as calcitriol, in the kidney. Calcitriol is the active form of vitamin D, it has a short half-life, a variable concentration dependent on many factors, and a plasma concentration approximately 1000 times smaller than 25 (OH) vitamin D (the storage form of the vitamin). Calcitriol regulates calcium absorption and homeostasis, promotion calcium absorption from the gut and enabling bone mineralisation. Vitamin D deficiency is considered one of the main causes of low bone mineral density (BMD). More than 50% of patients with coeliac disease show low BMD at diagnosis and subsequently have a high risk of fractures. However, no clear data exists regarding the relationship between vitamin D levels and fracture risk in coeliac patients.

In total, 328 papers were identified for possible inclusion within the review. Of these, 20 papers specifically tested vitamin D levels in the serum of adult coeliac patients and were therefore selected for more detailed analysis. The review indicated that most studies report 25 (OH) vitamin D deficiency at diagnosis that improves on a gluten-free diet, independently of supplementation. However, in the few studies that analysed circulating levels of calcitriol, this was found to be higher in newly diagnosed coeliac patients compared to control patients (coeliac on gluten-free diet and healthy controls). Since calcitriol is the active from of vitamin D, these findings may support the theory that calcium malabsorption in coeliac patients does not result from vitamin D deficiency, but rather from reduced numbers of calcium binding proteins in the gut mucosa, secondary to enterocyte loss. This event impairs response to calcitriol, further increasing calcium loss from bone and inducing secondary hyperparathyroidism. For this reason, in most cases a balanced gluten-free diet will eventually normalise calcium absorption. This raises doubt regarding the need for vitamin D supplementation in coeliac patients with bone problems.

The authors of this review noted that the existing literature on vitamin D levels in coeliac patients presents several limitations. For example, most studies use small numbers of subjects, variable methods for assessing serum levels of vitamin D and rarely examine confounding factors that may influence vitamin D level. The main limitation relates to the fact that very few studies analyse calcitriol levels in patients with coeliac disease. This is crucial since low 25 (OH) vitamin D does not necessarily correspond to a deficiency of calcitriol and thus to a calcium imbalance secondary to this. There is a need to conduct more, larger scale studies in order to establish the levels of circulating vitamin D in coeliac patients, alongside the meaning and utility of calcitriol levels in the assessment and management of patients with low bone mass and increased fracture risk.
The authors of this review conclude that they are unable to find adequate evidence of the need for vitamin D supplementation in coeliac patients who are established on a gluten free diet. Therefore healthcare providers should recommend a well-balanced diet including dairy products, alongside education regarding the importance of lifestyle changes, such as exercising on a regular basis, smoking cessation and avoiding excessive alcohol intake.
 
Link to full study: https://www.dldjournalonline.com/article/S1590-8658(18)30702-3/fulltext
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