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- Leckstroem, Daniel, et al.
(författare)
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The trials and tribulations of vitamin D : time for the ‘sunshine’ vitamin to come in out of the cold – or just more broken promises?
- 2014
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Ingår i: Expert review of Endocrinology & Metabolism. - : Informa Healthcare. - 1744-6651 .- 1744-8417. ; 9:4, s. 327-344
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Tidskriftsartikel (refereegranskat)abstract
- We are presently faced with the competing notions of modern life being a ‘state of vitamin D depletion’, implying a widespread need to supplement with vitamin D, or, the opposite view, which is that the present evidence can only support at best selective targeted vitamin D intervention. This is important as there is evidence that over the last 40–50 years there were downwards global trends in serum 25(OH)D concentrations, while individual consumption of vitamin D as supplements rose. For this reason and many others, a large population-based interventional study, the VITAL trial, was designed to try to establish the health value of vitamin D supplementation. VITAL is a huge primary prevention trial looking at the effects of vitamin D repletion in preventing cancer and cardiovascular disease in a fundamentally healthy population. This may seem an unusual approach given that what we mostly know about vitamin D is that is has some effects on the skeleton. This review looks to explore current knowledge about vitamin D in health and disease, and at how this is now undergoing significant reappraisal and revision. We will carefully critique the VITAL study design to see if it will allow for the construction of the detailed portfolio of clinical evidence so urgently needed to allow us better to understand role of vitamin D supplementation in health and disease.
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| 2. |
- Salzer, Jonatan, 1981-
(författare)
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Environmental risk factors for multiple sclerosis
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. It usually strikes during young adulthood, and 2.5 million individuals are estimated to have the disease worldwide. The causes of MS are not known, but several factors have been shown to be associated with the risk of the disease, including certain genes, vitamin D, smoking and Epstein- Barr virus infection. Little is known about how/if these factors interact.Methods Study I: The risk of MS by month of birth was investigated using MS cases from the Swedish MS registry and using general population controls. Studies II–V: We identified MS cases who had donated blood prior to disease onset, and MS cases whose mothers had donated blood during pregnancy, by cross-linking a database of MS cases, and a database of mothers of MS cases, to two local biobank cohorts. One of them consisted of blood samples collected during early pregnancy, and one with samples collected during health controls. Levels of 25(OH)D (25-hydroxyvitamin D), RBP (retinol binding protein, a surrogate marker for vitamin A), CRP (C- reactive protein), cotinine (a nicotine metabolite) and anti Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibodies were measured in cases and matched controls. The risk of MS by categories of these exposures was estimated in bi- and multivariable matched logistic regression models.Results Subjects born in spring had a higher risk of MS, but no influence of early gestational levels of the measured risk factors on the risk of MS in the offspring was observed. In prospective samples from MS cases and controls, 25(OH)D levels ≥75 nmol/l, intermediate RBP levels, and elevated CRP levels in young were associated with a decreased risk of MS. Elevated cotinine levels (suggestive of smoking) and high antibody reactivity against EBNA-1 were associated with an increased risk of MS. All factors but RBP were more clearly associated with MS in young subjects.Conclusion All factors analyzed in prospectively collected samples were associated with the risk of MS, and taken together, the data indicate that the key etiopathological events that lead to MS occur before the age of 20–30. Study II provides support for trials exploring the primary preventive potential of oral vitamin D supplementation.
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| 3. |
- Salzer, Jonatan, 1981-, et al.
(författare)
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Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank sampels
- 2013
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 19:12, s. 1587-1591
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased antibody reactivity against Epstein-Barr Nuclear Antigen-1 (EBNA-1) has been associated with an increased risk for MS, and high levels of 25-Hydroxyvitamin D (25[OH]D) have been associated with a lower risk for MS. Interaction between these two factors has been proposed.Objectives: To examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk for multiple sclerosis (MS), and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.Methods: Antibody reactivity (as specified above) and 25(OH)D levels were measured using ELISAs in n=192 MS cases and n=384 matched controls. The risk for MS was analysed using matched logistic regression.Results: The risk for MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trend <0.001. The risk increase was most pronounced for EBNA-1385–420. In young individuals (below median age at sampling, <26.4 years) these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains.Conclusions: We confirm that increased antibody reactivity against EBNA-1 is a risk factor for MS. Our findings in young individuals suggest that 25(OH)D status might influence the immune response towards Epstein-Barr virus, and thereby modulate MS risk.
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| 4. |
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| 5. |
- Salzer, Jonatan, 1981-, et al.
(författare)
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Smoking as a risk factor for multiple sclerosis
- 2013
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 19:8, s. 1022-1027
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure.Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples.Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression.Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8).Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.
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| 6. |
- Salzer, Jonatan, 1981-, et al.
(författare)
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Vitamin A and systemic inflammation as protective factors in multiple sclerosis
- 2013
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 19:8, s. 1046-1051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin A is important for the immune system, and might suppress inflammatory activity in multiple sclerosis (MS).Objectives: We aimed to examine if vitamin A levels were associated with MS risk in samples collected prospectively and during gestation.Methods: We measured Retinol Binding Protein (RBP – a surrogate marker for vitamin A) and high-sensitivity C-reactive protein (hs-CRP) levels, in (1) prospectively collected biobank blood samples from MS cases and controls, and (2) gestational samples where the offspring had later developed MS, and gestational control samples. The risk of MS was calculated using matched multivariable logistic regression adjusted for confounders.Results: In prospective samples, RBP levels within the second quintile (vs. the first) were associated with a lower MS risk (OR = 0.38, 95% CI 0.19–0.74). No effect on MS risk in the offspring by gestational RBP levels was found. In young subjects hs-CRP levels ≥10 mg/l in prospective samples were associated with a lower MS risk (OR = 0.36, 95% CI 0.14–0.95).Conclusions: Our results suggest that sub-optimal vitamin A levels may be associated with MS risk. The association between hs-CRP levels and MS risk in young subjects may support the role of the hygiene hypothesis in MS aetiology.
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