Vitamin D Deficiency and Possible Role in Multiple Sclerosis

European Neurological Review, 2015;10(2):131–8 DOI:


Vitamin D is not only an essential nutrient for bone homeostasis but has also been implicated in many other disorders including cardiovascular disease (CVD) and autoimmune diseases. Here we review the problem of vitamin D deficiency and guidelines to help achieve adequate levels in both the general population and in multiple sclerosis (MS) patients and its role in MS and impact on treatment. Although there is a lack of consensus on vitamin D deficiency and insufficiency, they have been defined as a serum level of 25(OH)D <50 nmol/L or 52.5–72.5 nmol/L, respectively. Deficiency is common in all age groups. Vitamin D is probably involved in the prevention of a number of disease states and 25(OH)D is thought to regulate at least 2,000 genes. Vitamin D toxicity is very rare, with none seen at doses up to 20,000 IU/day. However, the majority of primary care clinicians are not aware of the recommended dose for vitamin D supplementation and optimum serum level in terms of patients with MS. Several organisations have concluded that vitamin D screening cannot be recommended in the general population. Guidelines have been published on treatment and prevention of vitamin D deficiency, particularly for at-risk groups and during pregnancy. There is much evidence for the protective effects of vitamin D in MS. A higher level of sun exposure and intake of vitamin D as well as of serum 25 (OH)D, are associated with a lower risk of MS. It also has a beneficial effect on the clinical course of MS, such as lowering the risk of relapses. Growing evidence indicates that the effects of interferon-beta are additively enhanced by 25(OH)D in MS and this may be due to its modulating vitamin D metabolism.
Keywords: Vitamin D, 25-hydroxyvitamin D, deficiency, supplementation, multiple sclerosis, cardiovascular disease
Disclosure: Michael F Holick serves as a consultant for Bayer HealthCare Pharmaceuticals, Inc. Stuart Cook has received prior grant support from Bayer HealthCare Pharmaceuticals, Inc. and Biogen and has received prior honoraria from Bayer, Biogen and EMD Serono. Gustavo Suarez is an employee of Bayer HealthCare Pharmaceuticals. Mark Rametta is an employee of Bayer HealthCare Pharmaceuticals
Acknowledgments: Medical writing support, including preparation of the drafts under the guidance of the authors, was provided by Ray Ashton, Richmond Medical Communications. and funded by Bayer HealthCare Pharmaceuticals, Inc. All named authors meet the criteria of the International Committee of Medical Journal Editors for authorship for this manuscript, take responsibility for the integrity of the work as a whole and have given final approval for the version to be published.
Received: October 20, 2015 Accepted November 30, 2015
Correspondence: Michael F Holick, Boston University School of Medicine, 85 E. Newton St Fuller Building, Boston, US. E:
Support: The publication of this article was supported by Bayer HealthCare Pharmaceuticals, Inc. The views and opinions expressed in the article are those of the authors and not necessarily those of Bayer HealthCare Pharmaceuticals, Inc.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit.

Vitamin D is an essential nutrient for bone homeostasis that has also been implicated in numerous other disorders, such as cardiovascular disease (CVD) and autoimmune diseases. Originally vitamin D deficiency was associated only with rickets and it was considered that the fortification of food resolved this disorder. However, it is now realised that rickets represents just one manifestation of vitamin D deficiency.1,2 The recommended Dietary Reference Intakes are solely based on the skeletal effects of vitamin D, with the recommended dietary allowance (RDA) ranging from 400 to 800 IU/day depending on age as recommended by the Institute of Medicine to maintain blood levels of 25-hydroxyvitamin D (25[OH]D) of at least 50 nmol/L (20 ng/mL). However to achieve non-skeletal benefits of vitamin D, a multitude of studies have suggested that maintenance of a level of 25[OH]D >30 ng/mL may be required. The majority of primary care clinicians are not aware of the recommended dose for vitamin D supplementation and the optimum level in terms of patients with multiple sclerosis (MS). This article reviews the role of vitamin D in MS and its impact on MS treatment. In addition, the extent and consequences of vitamin D deficiency and guidelines to help the general population and those with MS achieve sufficient levels will be considered.

Vitamin D Deficiency and its Consequences
There is considerable debate on the blood level of 25[OH]D that constitutes deficiency in both the general population and with respect to certain disorders, such as MS. Conflicting recommendations have been published by different organisations. Experts disagree on the optimal 25(OH)D concentration and thus many definitions of deficiency and insufficiency have been proposed. In the general population, a serum level of at least 50 nmol/L 25(OH)D is generally considered to be required for maximum bone health and thus vitamin D deficiency has been defined as a 25(OH)D <50 nmol/L.3,4 The Endocrine Society also recognised that vitamin D had non-skeletal health benefits, and defined vitamin D insufficiency as a 25(OH)D level of 51–74 nmol/L.

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Keywords: Vitamin D, 25-hydroxyvitamin D, deficiency, supplementation, multiple sclerosis, cardiovascular disease