scholarly journals On the Nature of Evidence and ‘Proving’ Causality: Smoking and Lung Cancer vs. Sun Exposure, Vitamin D and Multiple Sclerosis

2018 ◽  
Vol 15 (8) ◽  
pp. 1726 ◽  
Author(s):  
Robyn Lucas ◽  
Rachael Rodney Harris
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Lung Cancer ◽  
Vitamin D ◽  
Observational Studies ◽  
Animal Studies ◽  
Disease Risk ◽  
Sun Exposure ◽  
Sufficient Evidence

If environmental exposures are shown to cause an adverse health outcome, reducing exposure should reduce the disease risk. Links between exposures and outcomes are typically based on ‘associations’ derived from observational studies, and causality may not be clear. Randomized controlled trials to ‘prove’ causality are often not feasible or ethical. Here the history of evidence that tobacco smoking causes lung cancer—from observational studies—is compared to that of low sun exposure and/or low vitamin D status as causal risk factors for the autoimmune disease, multiple sclerosis (MS). Evidence derives from in vitro and animal studies, as well as ecological, case-control and cohort studies, in order of increasing strength. For smoking and lung cancer, the associations are strong, consistent, and biologically plausible—the evidence is coherent or ‘in harmony’. For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker, with smaller effect sizes, but coherent across a range of sources of evidence, and biologically plausible. The association is less direct—smoking is directly toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the immune system, which in turn may reduce the risk of immune attack on self-proteins in the central nervous system. Opinion about whether there is sufficient evidence to conclude that low sun exposure/vitamin D increase the risk of multiple sclerosis, is divided. General public health advice to receive sufficient sun exposure to avoid vitamin D deficiency (<50 nmol/L) should also ensure any benefits for multiple sclerosis, but must be tempered against the risk of skin cancers.

scholarly journals On the nature of evidence and 'proving' causality: smoking and lung cancer vs. sun exposure, vitamin D and multiple sclerosis

2018 ◽  
Author(s):  
Robyn Lucas ◽  
Rachael Rodney Harris
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Lung Cancer ◽  
Vitamin D ◽  
Observational Studies ◽  
Animal Studies ◽  
Disease Risk ◽  
Sun Exposure ◽  
Sufficient Evidence

If environmental exposures are shown to cause an adverse health outcome, reducing exposure should reduce the disease risk. Links between exposures and outcomes are typically based on ‘associations’ derived from observational studies, and causality may not be clear. Randomised controlled trials to ‘prove’ causality are often not feasible or ethical. Here the history of evidence that tobacco smoking causes lung cancer – in observational studies – is compared to that of low sun exposure and/or low vitamin D status as causal risk factors for the autoimmune disease, multiple sclerosis. Evidence derives from in vitro and animal studies, as well as ecological, case-control and cohort studies, in order of increasing strength. For smoking and lung cancer, the associations are strong, consistent, and biologically plausible – the evidence is coherent or ‘in harmony’. For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker, with smaller effect sizes, but coherent across a range of sources of evidence, and biologically plausible. The association is less direct – smoking is directly toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the immune system, which in turn may reduce the risk of immune attack on self-proteins in the central nervous system. Opinion about whether there is sufficient evidence to conclude that low sun exposure/vitamin D increase the risk of multiple sclerosis, is divided. General public health advice to receive sufficient sun exposure to avoid vitamin D deficiency (&lt;50nmol/L) should also ensure any benefits for multiple sclerosis.

scholarly journals A framework for measurement and harmonization of pediatric multiple sclerosis etiologic research studies: The Pediatric MS Tool-Kit

2018 ◽  
Vol 25 (8) ◽  
pp. 1170-1177 ◽  
Author(s):  
Sandra Magalhaes ◽  
Brenda Banwell ◽  
Amit Bar-Or ◽  
Isabel Fortier ◽  
Heather E Hanwell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Vitamin D ◽  
Delphi Study ◽  
Sun Exposure ◽  
Small Sample ◽  
Sample Sizes ◽  
Vitamin D Intake ◽  
Measurement Framework ◽  
Small Sample Sizes

Background: While studying the etiology of multiple sclerosis (MS) in children has several methodological advantages over studying etiology in adults, studies are limited by small sample sizes. Objective: Using a rigorous methodological process, we developed the Pediatric MS Tool-Kit, a measurement framework that includes a minimal set of core variables to assess etiological risk factors. Methods: We solicited input from the International Pediatric MS Study Group to select three risk factors: environmental tobacco smoke (ETS) exposure, sun exposure, and vitamin D intake. To develop the Tool-Kit, we used a Delphi study involving a working group of epidemiologists, neurologists, and content experts from North America and Europe. Results: The Tool-Kit includes six core variables to measure ETS, six to measure sun exposure, and six to measure vitamin D intake. The Tool-Kit can be accessed online ( www.maelstrom-research.org/mica/network/tool-kit ). Conclusion: The goals of the Tool-Kit are to enhance exposure measurement in newly designed pediatric MS studies and comparability of results across studies, and in the longer term to facilitate harmonization of studies, a methodological approach that can be used to circumvent issues of small sample sizes. We believe the Tool-Kit will prove to be a valuable resource to guide pediatric MS researchers in developing study-specific questionnaire

scholarly journals Comparison of Antioxidant Status and Vitamin D Levels between Multiple Sclerosis Patients and Healthy Matched Subjects

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Ehsan Hejazi ◽  
Reza Amani ◽  
Naser SharafodinZadeh ◽  
Bahman Cheraghian
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Dietary Intake ◽  
Antioxidant Status ◽  
Sun Exposure ◽  
Total Antioxidant Status ◽  
Serum Levels ◽  
Study Groups ◽  
Vitamin D Levels ◽  
Multiple Sclerosis Patients

Objective. The aim of the present study was to compare the serum levels of total antioxidant status (TAS) and 25(OH) D3 and dietary intake of multiple sclerosis (MS) patients with those of normal subjects.Method. Thirty-seven MS patients (31 women) and the same number of healthy matched controls were compared for their serum levels and dietary intake of 25(OH) D3 and TAS. Sun exposure and the intake of antioxidants and vitamin D rich foods were estimated through face-to-face interview and food frequency questionnaire.Results. Dietary intake of antioxidants and vitamin D rich foods, vitamin C, vitamin A, and folate was not significantly different between the two groups. There were also no significant differences in the mean levels of 25(OH) D3 and TAS between the study groups. Both groups had low serum levels of 25(OH) D3 and total antioxidants.Conclusion. No significant differences were detected in serum levels and dietary intake of vitamin D and antioxidants between MS patients and healthy controls. All subjects had low antioxidant status and vitamin D levels.

Past environmental sun exposure and risk of multiple sclerosis: a role for the Cdx-2 Vitamin D receptor variant in this interaction

2009 ◽  
Vol 15 (5) ◽  
pp. 563-570 ◽  
Author(s):  
JL Dickinson ◽  
DI Perera ◽  
AF van der Mei ◽  
A-L Ponsonby ◽  
AM Polanowski ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Significant Interaction ◽  
Important Determinant ◽  
Sun Exposure ◽  
Population Based ◽  
Vdr Gene ◽  
Increased Risk ◽  
Group 2

Multiple studies have provided evidence for an association between reduced sun exposure and increased risk of multiple sclerosis (MS), an association likely to be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we examine whether the vitamin D receptor ( VDR), an integral component of this pathway, influences MS risk in a population-based sample where winter sun exposure in early childhood has been found to be an important determinant of MS risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and 235 controls, and associations with MS and past sun exposure were examined by logistic regression. No significant univariate associations between the polymorphisms, rs11574010 ( Cdx-2A > G), rs10735810 ( Fok1T >  C), or rs731236 ( Taq1C > T) and MS risk were observed. However, a significant interaction was observed between winter sun exposure during childhood, genotype at rs11574010, and MS risk ( P = 0.012), with the ‘G’ allele conferring an increased risk of MS in the low sun exposure group (≤2 h/day). No significant interactions were observed for either rs10735810 or rs731236, after stratification by sun exposure. These data provide support for the involvement of the VDR gene in determining MS risk, an interaction likely to be dependent on past sun exposure.

scholarly journals Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Justin Killick ◽  
Joanne Hay ◽  
Elena Morandi ◽  
Sonja Vermeren ◽  
Saniya Kari ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
T Cells ◽  
T Cell ◽  
Chronic Inflammatory Disease ◽  
Vitamin D Supplementation ◽  
Type I ◽  
T Cell Migration ◽  
The Impact

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), in which T-cell migration into the CNS is key for pathogenesis. Patients with MS exhibit impaired regulatory T cell populations, and both Foxp3+ Tregs and type I regulatory T cells (Tr1) are dysfunctional. MS is a multifactorial disease and vitamin D deficiency is associated with disease. Herein, we examined the impact of 1,25(OH)2D3 on CD4+ T cells coactivated by either CD28 to induce polyclonal activation or by the complement regulator CD46 to promote Tr1 differentiation. Addition of 1,25(OH)2D3 led to a differential expression of adhesion molecules on CD28- and CD46-costimulated T cells isolated from both healthy donors or from patients with MS. 1,25(OH)2D3 favored Tr1 motility though a Vitamin D-CD46 crosstalk highlighted by increased VDR expression as well as increased CYP24A1 and miR-9 in CD46-costimulated T cells. Furthermore, analysis of CD46 expression on T cells from a cohort of patients with MS supplemented by vitamin D showed a negative correlation with the levels of circulating vitamin D. Moreover, t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis allowed the visualization and identification of clusters increased by vitamin D supplementation, but not by placebo, that exhibited similar adhesion phenotype to what was observed in vitro. Overall, our data show a crosstalk between vitamin D and CD46 that allows a preferential effect of Vitamin D on Tr1 cells, providing novel key insights into the role of an important modifiable environmental factor in MS.

scholarly journals Association of Vitamin D Status with Chronic Disease Risk Factors and Cognitive Dysfunction in 50–70 Year Old Adults

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 141 ◽  
Author(s):  
Japneet Kaur ◽  
Steven Ferguson ◽  
Eduardo Freitas ◽  
Ryan Miller ◽  
Debra Bemben ◽  
...  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Vitamin D ◽  
Chronic Diseases ◽  
Disease Risk ◽  
Serum Vitamin ◽  
Old Adults ◽  
Serum Vitamin D ◽  
Chronic Disease Risk ◽  
Vitamin D Levels

Vitamin D deficiency/insufficiency has been primarily associated with skeletal disorders, however, since vitamin D receptors are found on multiple types of cells, there is also a link to increased chronic disease risk and all-cause mortality. The aim of this study was to examine whether deficient/insufficient vitamin D levels are associated with risk factors of chronic diseases and cognitive dysfunction in 50 to 70 year old adults. Participants completed the health status, three-day dietary record and vitamin D food frequency, sun exposure, and international physical activity questionnaires. Cognitive function of the participants was assessed using the Automated Neuropsychological Assessment Metrics while body composition (percent body fat, android/gynoid ratio) was assessed using Dual Energy X-ray Absorptiometry. Applanation tonometry was used to obtain pressure wave forms at the radial artery to examine arterial stiffness and central pressures. A fasting blood draw was taken to measure vitamin D, blood lipid and glucose levels. Fifty percent of the participants (36/72) were vitamin D deficient/insufficient. Individuals in the low physical activity (PA) group had lower serum vitamin D concentration compared to those in the high PA group (p = 0.04). Moreover, serum vitamin D levels were negatively related to risk factors of chronic diseases; blood glucose (r = −0.38; p = 0.01), triglycerides (r = −0.27; p = 0.02), and android/gynoid ratio (r = −0.32; p = 0.01). Deficient/insufficient vitamin D levels are linked to the risk factors of chronic diseases in men and women aged 50 to 70 years.

scholarly journals Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1488 ◽  
Author(s):  
Anna Mas-Capdevila ◽  
Joan Teichenne ◽  
Cristina Domenech-Coca ◽  
Antoni Caimari ◽  
Josep M Del Bas ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gut Microbiota ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Current Evidence ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Beneficial Effects ◽  
High Interindividual Variability

Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Animal and in vitro studies demonstrate beneficial effects of hesperidin and its derived compounds on CVD risk factors. Thus, hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models. However, there is still controversy about whether hesperidin could contribute to ameliorate glucose homeostasis, lipid profile, adiposity, and blood pressure in humans, as evidenced by several clinical trials reporting no effects of treatments with this flavanone or with orange juice on these cardiovascular parameters. In this review, we focus on hesperidin’s beneficial effects on CVD risk factors, paying special attention to the high interindividual variability in response to hesperidin-based acute and chronic interventions, which can be partly attributed to differences in gut microbiota. Based on the current evidence, we suggest that some of hesperidin’s contradictory effects in human trials are partly due to the interindividual hesperidin variability in its bioavailability, which in turn is highly dependent on the α-rhamnosidase activity and gut microbiota composition.

scholarly journals Vitamin D in the Prevention and Treatment of Osteoarthritis: From Clinical Interventions to Cellular Evidence

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 243 ◽  
Author(s):  
Clara Yongjoo Park
Keyword(s):  
Vitamin D ◽  
Observational Studies ◽  
Pilot Trial ◽  
Clinical Results ◽  
Vitamin D Supplementation ◽  
Vitamin D Status ◽  
Randomized Controlled ◽  
The Relationship

Older adults are recommended vitamin D to prevent fractures. Though this population is also at risk of osteoarthritis (OA), the effect of vitamin D on OA is unclear and may differ by disease state. The relationship between vitamin D and OA during OA initiation and progression were considered in this narrative review of in vivo and in vitro studies. Regarding OA initiation in humans, the small number of published observational studies suggest a lack of association between induction of OA and vitamin D status. Most randomized controlled trials were performed in White OA patients with relatively high vitamin D status (>50 nmol/L). These studies found no benefit of vitamin D supplementation on OA progression. However, subset analyses and one randomized controlled pilot trial indicated that vitamin D supplementation may alleviate joint pain in OA patients with low vitamin D status (<50 nmol/L). As the etiology of OA is recently being more fully uncovered, better animal and cell models are needed. According to currently available clinical results, evidence is lacking to set a vitamin D level to prevent OA, and increasing vitamin D status above 50 nmol/L does not seem to benefit OA patients.

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