Vitamin D in the Middle East and North Africa

Abstract

Purpose: The Middle East and North Africa (MENA) region registers some of the lowest serum 25‑hydroxyvitamin D [25(OH)D] concentrations, worldwide. We describe the prevalence and the risk factors for hypovitaminosis D, completed and ongoing clinical trials, and available guidelines for vitamin D supplementation in this region.

Methods: This review is an update of previous reviews published by our group in 2013 for observational studies, and in 2015 for randomized controlled trials (RCTs) from the region. We conducted a comprehensive search in Medline, PubMed, and Embase, and the Cochrane Library, using MeSH terms and keywords relevant to vitamin D, vitamin D deficiency, and the MENA region, for the period 2012-2017 for observational studies, and 2015-2017 for RCTs. We included large cross-sectional studies with at least 100 subjects/study, and RCTs with at least 50 participants per arm.

Results: We identified 41 observational studies. The prevalence of hypovitaminosis D, defined as a 25‑hydroxyvitamin D [25(OH)D] level below the desirable level of 20 ng/ml, ranged between 12-96% in children and adolescents, and 54-90% in pregnant women. In adults, it ranged between 44 and 96%, and the mean 25(OH)D varied between 11 and 20 ng/ml. In general, significant predictors of low 25(OH)D levels were female gender, increasing age and body mass index, veiling, winter season, use of sun screens, lower socioeconomic status, and higher latitude.We retrieved 14 RCTs comparing supplementation to control or placebo, published during the period 2015-2017: 2 in children, 8 in adults, and 4 in pregnant women. In children and adolescents, a vitamin D dose of 1000-2000 IU/d was needed to maintain serum 25(OH)D level at target. In adults and pregnant women, the increment in 25(OH)D level was inversely proportional to the dose, ranging between 0.9 and 3 ng/ml per 100 IU/d for doses ≤2000 IU/d, and between 0.1 and 0.6 ng/ml per 100 IU/d for doses ≥3000 IU/d. While the effect of vitamin D supplementation on glycemic indices is still controversial in adults, vitamin D supplementation may be protective against gestational diabetes mellitus in pregnant women. In the only identified study in the elderly, there was no significant difference between 600 IU/day and 3750 IU/day doses on bone mineral density. We did not identify any fracture studies.The available vitamin D guidelines in the region are based on expert opinion, with recommended doses between 400 and 2000 IU/d, depending on the age category, and country.

Conclusion: Hypovitaminosis D is prevalent in the MENA region, and doses of 1000-2000 IU/d may be necessary to reach a desirable 25(OH)D level of 20 ng/ml. Studies assessing the effect of such doses of vitamin D on major outcomes, and confirming their long term safety, are needed.

Keywords: 25(OH)D, 25‑hydroxyvitamin D; ALKP, alkaline phosphatase; BMC, bone mineral content; BMD, bone mineral density; BMI, body mass index; CARS, Childhood Autism Rating Scale; CDC, Centers for Disease Control; Ca, Calcium; DEQAS, Vitamin D External Quality Assessment Scheme; DXA, dual-energy X-ray absorptiometry; ESCEO, European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis; GDM, Gestational Diabetes Mellitus; HOMA-IR, homeostatic model assessment of insulin resistance; HbA1c, glycated hemoglobin; Hypovitaminosis D; ID LC-MS/MS, isotope dilution liquid chromatography - tandem mass spectrometry; IOM, Institute of Medicine; KSA, Kingdom of Saudi Arabia; LCMS/MS, liquid chromatography-tandem mass spectrometry; MENA, Middle East North Africa; Middle East and North Africa; OSTEOS, Lebanese Society for Osteoporosis and Metabolic Bone Disorders; PO4, phosphorus; PTH, parathyroid hormone; Predictors; RCT, randomized controlled trials; ROB, risk of bias; RR, relative risk; SDp, pooled standard deviation; T2D, type 2 diabetes; UAE, United Arab Emirates; UVB, ultraviolet B; VDDR2, vitamin d dependent rickets type 2; VDR, vitamin d receptor; VDSP, Vitamin D Standardization Program; Vitamin D assays; Vitamin D guidelines; WM, weighted mean.

Fig. 1

Four panel figure of radiographs from a 4-month old boy with nutritional rickets (A–C), and a 2 year old girl with vitamin D dependent rickets type 2 (D). Wrist (A), and knee (B) radiographs reveal cupping and fraying of the metaphysis of the long bones (black arrow). Wrist radiograph (C) post-treatment demonstrates healing at the level of the radius (black arrow) with persistent changes at the ulna. Radiographic changes, with severe cupping extending from the radius to the metacarpals and phalanges (D), may be more severe in patients with vitamin D dependent rickets type 2 (black and white arrows).

Fig. 2

Weighted means (±pooled SD) for serum 25‑hydroxy-vitamin D levels by age group in 4 countries in the Middle East. In adults, the weighted means are based on 2 studies from each of Bahrain (N = 1150), Iran (N = 6842) and KSA (N = 4305) and one from Lebanon (N = 5091, spanning two periods, 2000–2004, and 2007–2008); in children the weighted means are based on 3 studies from Iran (N = 2809) and KSA (N = 5143) and one from Lebanon (N = 494, spanning the 2 same periods); and in pregnant women 3 from Iran (N = 351) and 2 from KSA (N = 1612).

Fig. 3

Percent bias in 160 samples run as part of Center of Diseases C (CDC) Vitamin D Standardization Program (VDSP). The percent bias of the individual reported values is shown for all 160 samples run at our institution over 4 quarters in 2016–2017 using the platform automated Roche Elecsys assay compared with reference values defined by the CDC VDSP reference. Percent bias formula: [(reported value − reference value) / reference value] × 100. Although the mean % bias in our samples was 14%, many individual values fell outside that recommended bias range of −5% to +5% (range framed by dotted lines).