Unfavorable outcomes during treatment of multiple sclerosis with high doses of vitamin D

Fragoso, Yára Dadalti; Adoni, Tarso; Damasceno, Alfredo; Damasceno, Carlos Augusto de Albuquerque; Ferreira, Maria Lúcia Brito; Finkelzstejn, Alessandro; Gomes, Sidney; Gonçalves, Marcus Vinícius Magno; Grzesiuk, Anderson Kuntz; Lins, Suellen; Mendes, Maria Fernanda; Oliveira, Fabiana Sodré de; Parolin, Monica Fiuza Konke; Rocha, Cristiane Franklin; Tauil, Carlos Bernardo

doi:10.1016/j.jns.2014.08.019

Cited by 23 publications

(15 citation statements)

References 5 publications

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“…This is illustrated by a recent report of adverse effects in 21 Brazilian MS cases, 19 of whom had stopped taking their standard disease modifying treatments. They used median 100,000 IU vitamin D daily, reached serum concentrations of around 375 nmol/l, and presented with both signs of insufficient efficacy such as MS relapses and disease progression, and side effects such as renal failure, pseudotumor cerebri, and seizures . Vitamin D treatment should by no means be used as a replacement for standard disease modifying drugs, nor should excessive doses be used.…”

Section: Vitamin D and Ms Preventionmentioning

confidence: 99%

Vitamin D and multiple sclerosis-from epidemiology to prevention

Sundström

Salzer

2015

Acta Neurol Scand

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In the present review, we discuss observational and experimental data suggesting a protective effect from sun exposure and/or vitamin D in multiple sclerosis (MS). These data include geographic variations in MS occurrence, temporal trends, genetics, biobank, and questionnaire data. We look more closely at the differentiation between general effects from UV exposure, and those of vitamin D per se, including plausible mechanisms of action. Finally, primary prevention is touched upon, and we suggest actions to be taken while awaiting the results from ongoing randomized controlled trials with vitamin D in MS. The basis for the sunshine hypothesis in multiple sclerosis (MS) consists of epidemiological data on MS incidence and prevalence. These geographic variations in MS occurrence were commented upon already by Charcot and were early interpreted to show an increasing MS occurrence with increasing distance from the equator (1). Together with data from migration studies, an environmental factor in the etiology of MS was strongly suggested (reviewed in (2)). Sunshine and MS epidemiologyThe most natural factor related to the distance from the equator is sunshine-exposure to UV radiation. This notion has been considerably reinforced by studies showing that latitude is a poor proxy for UV radiation and that satellite-derived data on UV intensity, which provide a more accurate estimate of UV radiation, show a stronger association with MS occurrence (3-5).The latitude gradient in MS has been questioned recently (6), which has thrown some researchers into doubt about the sunshine hypothesis. The majority of MS epidemiological studies have studied prevalence. Prevalence data are less informative when etiological factors are considered, as the prevalence depends not only on the incidence in the last decades, but for chronic diseases like MS also on the mortality. Incidence studies are more difficult to perform and generally contain fewer cases but are superior for generating etiological hypotheses. It has been proposed that while MS prevalence data still show a latitude gradient, global MS incidence data, including Europe, do not, with the exception that the incidence gradient is still apparent in Australia and New Zealand (6).A recent meta-analysis showed that a latitude gradient of MS incidence in Europe does indeed exist (7), and the same tendency was noted in another meta-analysis (8). Two temporal trends were observed regarding the MS incidence: (i) a general increase in MS incidence (6, 7) and (ii) a decreased difference between geographic areas earlier attributed a high and low MS risk, such as northern vs southern Europe (7). Chile is a wellsuited country for studies on latitude gradients due to its elongated shape, and in one study, the incidence of hospitalizations because of MS was compared between regions (9). The authors reported no association between the incidence and latitude or UV radiation index. However, this was true after exclusion of the southernmost region, which 56

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Section: Vitamin D and Ms Preventionmentioning

confidence: 99%

Vitamin D and multiple sclerosis-from epidemiology to prevention

Sundström

Salzer

2015

Acta Neurol Scand

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“…Because of a compounding error by the pharmacy, the woman had taken 600,000 IU (rather than the intended 600 IU) of cholecalciferol daily for more than 3 years, leading to reversible hypercalcemia and partially reversible renal impairment [ 25 ]. Fragoso and colleagues reported considerable vitamin D toxicity in 21 MS patients who were exposed to levels ranging from 8000 IU/day to extremely high, supra-physiological doses of 150,000 IU/day (average 87,000 IU) [ 26 ]. …”

Section: Introductionmentioning

confidence: 99%

“…Fragoso and colleagues reported considerable vitamin D toxicity in 21 MS patients who were exposed to levels ranging from 8000 IU/day to extremely high, supra-physiological doses of 150,000 IU/day (average 87,000 IU) [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D and Multiple Sclerosis: A Comprehensive Review

Sintzel¹,

2017

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Numerous observational studies have suggested that there is a correlation between the level of serum vitamin D and MS risk and disease activity. To explore this hypothesis, a literature search of large, prospective, observation studies, epidemiological studies, and studies using new approaches such as Mendelian randomization was conducted. Available data and ongoing research included in this review suggest that the level of serum vitamin D affects the risk of developing MS and also modifies disease activity in MS patients. Newer Mendelian randomization analyses suggest there is a causal relationship between low vitamin D level and the risk of MS. Post-hoc evaluations from two phase 3 studies, BENEFIT and BEYOND, support the findings of observational trials. Study limitations identified in this review recognize the need for larger controlled clinical trials to establish vitamin D supplementation as the standard of care for MS patients. Though there is increasing evidence indicating that lower vitamin D levels are associated with increased risk of MS and with greater clinical and brain MRI activity in established MS, the impact of vitamin D supplementation on MS activity remains inadequately investigated.

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“…Notably, 17 of 21 patients had clinical disease activity in terms of relapses, new MRI lesions or an increase in disability. Moreover, direct side effects of vitamin D supplementation, such as gastric symptoms, seizures, severe hypercalcemia, kidney failure, nephrolithiasis and nephrocalcinosis were noted [59]. The side effects seen in our patient with uncontrolled intake of ultra-high doses of vitamin D which mimicked the progression of primary progressive MS is discussed in the following chapter [60].…”

Section: Vitamin D Toxicity: a Life-threatening Complicationmentioning

confidence: 75%

Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats

et al. 2020

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in several clinical trials, since hypovitaminosis D was linked to higher disease activity and may even play a role in long-term outcome. Here, we review the current understanding of the molecular effects of vitamin D beyond calcium homeostasis, the potential beneficial action in MS and hazards including complications of chronic and high-dose therapy. In clinical trials, doses of up to 40,000 IU/day were tested and appeared safe as add-on therapy for short-term periods. A recent meta-analysis of a randomized, double-blind, placebo-controlled clinical trial investigating vitamin D as add-on therapy in MS, however, suggested that vitamin D had no therapeutic effect on disability or relapse rate. We recognize a knowledge gap for chronic and high-dose therapy, which can lead to life-threatening complications related to vitamin D toxicity including renal failure, cardiac arrythmia and status epilepticus. Moreover, vitamin D toxicity may manifest as fatigue, muscle weakness or urinary dysfunction, which may mimic the natural course of progressive MS. Given these limitations, vitamin D supplementation in MS is a sensitive task which needs to be supervised by physicians. While there is strong evidence for vitamin D deficiency and the development of MS, the risk-benefit profile of dosage and duration of add-on supplementation needs to be further clarified.

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Unfavorable outcomes during treatment of multiple sclerosis with high doses of vitamin D

Cited by 23 publications

References 5 publications

Vitamin D and multiple sclerosis-from epidemiology to prevention

Vitamin D and multiple sclerosis-from epidemiology to prevention

Vitamin D and Multiple Sclerosis: A Comprehensive Review

Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats

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