Inter-dependence of vitamin D levels with serum lipid profiles in multiple sclerosis

https://doi.org/10.1016/j.jns.2011.07.024Get rights and content

Abstract

Objective

To assess whether vitamin D (VD) levels in multiple sclerosis (MS) patients exhibit inter-dependence with serum lipid profile variables (serum cholesterol, high-density lipoprotein or HDL, low-density lipoprotein or LDL, and triglycerides) and to investigate the associations with clinical disability measures.

Methods

The study population consisted of consecutive 178 MS patients (age: 46.6 ± 10.6 years; disease duration: 13.8 ± 10.3 years). The patients were assessed for fasting lipid profile and VD obtained concomitantly. Neurological disability using the Expanded Disability Status Scale (EDSS) was obtained within ± 6 months of the lipid profile. The associations between the HDL, LDL, total cholesterol and total cholesterol to HDL ratio with deseasonalized VD levels and their relationships with EDSS and the MS Severity Score (MSSS) were analyzed using regression methods.

Results

The cholesterol to HDL ratio was associated with the deseasonalized VD (rp =  0.18, p = 0.019) and VD3 (rp =  0.17, p = 0.028) levels. The probability of VD3 sufficiency was associated with HDL > 60 mg/dl status (p = 0.015, OR = 0.42, 95% CI = 0.20 to 0.86) and with total cholesterol to HDL ratio < 3.5 status (p < 0.001, OR = 4.07, 95% CI = 2.03 to 8.15). In stepwise regression models, EDSS was associated with total cholesterol to HDL ratio (p = 0.008, rp = 0.21) whereas MSSS was associated with deseasonalized 25-hydroxy VD3 (p = 0.021, rp =  0.18). The probability of EDSS  4.0 was also associated with total cholesterol to HDL ratio (p = 0.011, OR = 1.59, 95% CI = 1.11 to 1.26).

Conclusions

The results suggest inter-dependence between the total cholesterol to HDL ratio and deseasonalized vitamin D levels in MS patients. Disability measures in MS are also associated with these inter-dependent variables.

Introduction

Vitamin D (VD) has long been suspected as a potential environmental trigger in multiple sclerosis (MS) [1], [2]. Women who took VD supplements were 40% less likely to develop MS than women who did not take supplements [3] and young adults with the highest levels of 25-hydroxy-VD had a 62% reduction in MS risk [4]. Administration of 1, 25-dihydroxy-VD inhibits experimental allergic encephalomyelitis [5], [6]. Recent data suggest also an association between low VD and increased risk for relapses and MS disease progression [7], [8], [9], [10], [11], [12], [13].

Vitamin D deficiency is very common in many populations worldwide and may play a role in the etiology of many chronic diseases, including diabetes, cardiovascular diseases, common cancers, autoimmune diseases and osteoarthritis [14], [15], [16]. Low sunlight exposure, age-related decreases in cutaneous synthesis and diets low in vitamin D are factors implicated to contribute to the high prevalence of vitamin D insufficiency [17].

The endogenous production of VD in the skin requires 7-dehydrocholesterol as a substrate. This requirement links the VD production to serum cholesterol. In vitro studies have demonstrated that 25-hydroxy-VD inhibits the activity of the cholesterol synthesis enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), and this suggests that higher vitamin D levels could interact with the lipid profile decreasing total cholesterol [18]. Vascular comorbidities and high cholesterol levels were also shown to be associated with increased risk of disease activity and progression in MS [13], [19].

The relationships of VD to the lipid profile and cholesterol system have not been investigated in MS. The aim of this study was to therefore assess the inter-dependence of serum VD to lipid profile variables (serum cholesterol, HDL, LDL and triglycerides) and to clinical disability in a large cohort of consecutive MS patients.

Section snippets

Study design

Single-center, retrospective, longitudinal, cases only chart review study.

Study population

The study population included consecutive patients with clinically definite MS patients according to the McDonald criteria with available baseline EDSS assessment within ± 6 months of lipid profile testing and a follow-up EDSS assessment  6 months from the baseline visit. Patients with clinically isolated syndromes and neuromyelitis optica were not collected. The clinical data collected included statin use, height and weight.

Demographic and clinical characteristics

The clinical, demographic and MRI features of the cohort are summarized in Table 1. The frequency of Caucasian-Americans was 147 (82.6%), African-Americans was 11 (6.2%), Hispanics was 2 (1.1%), Native American was 1 (0.6%), and 17 (9.6%) were Unknown. The median absolute time difference between the lipid profile/vitamin D and EDSS assessments was 22 days (25th–75th percentile inter-quartile range = 10–53 days).

The majority of patients were on disease-modifying therapies: 28% were on

Discussion

In this paper, we have reported results that indicate inter-dependence between the lipid profile and the vitamin D pathways in MS patients. The total cholesterol to HDL ratio was strongly associated with VD sufficiency status (p < 0.001, OR = 4.07). Higher disability as measured with EDSS and the probability of EDSS  4.0 were associated with the cholesterol to HDL ratio whereas MSSS was associated with deseasonalized VD3 levels.

We found that VD sufficiency was associated with the total cholesterol

Financial conflicts

The authors report no conflicts of interest.

Confidentiality

Use of the information in this manuscript for commercial, non-commercial, research or purposes other than peer review is not permitted prior to publication without expressed written permission of the author.

Disclosure

Dr. Weinstock-Guttman received speaker honoraria and consultant fees from Teva Neuroscience, Biogen Idec, EMD Serono, Novartis, Pfizer and Accorda. She also received financial support for research activities from the National Institute of Health, National Multiple Sclerosis Society, National Science Foundation, Department of Defense, EMD Serono, Biogen Idec, Teva Neuroscience, Cyberonics, Accorda, and the Jog for the Jake Foundation. These are unrelated to the research presented in this report.

Acknowledgments

Support from the National Multiple Sclerosis Society (RG3743 and a Pediatric MS Center of Excellence Center Grant) and the Department of Defense Multiple Sclerosis Program (MS090122) is gratefully acknowledged. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

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