Opposing and potentially antagonistic effects of BMP and TGF-ß in multiple sclerosis: The "Yin and Yang" of neuro-immune Signaling.

Bone Morphogenetic Proteins (BMP) and Transforming Growth Factor-beta (TGF-ß) are cytokines with similar receptors and messengers. They are important for immune cell function, with BMPs exerting mainly proinflammatory but also anti-inflammatory effects, and TGF-ß suppressing inflammation. Patients with Multiple Sclerosis exhibit BMP overactivity and suppressed TGF-ß signaling. This dysregulated signaling participates in the crosstalk between infiltrating immune cells and glia, where BMP inhibits remyelination. Reciprocal antagonism between the two pathways takes place via a variety of mechanisms. Although this antagonism has not been studied in the setting of Multiple Sclerosis, it could inform further research and treatment discovery.

Total intake of different minerals and the risk of multiple sclerosis.

OBJECTIVE: To investigate the association between mineral intake (potassium, magnesium, calcium, phosphorus, iron, zinc, manganese, copper) and multiple sclerosis (MS) risk. METHODS: In a prospective cohort study, we assessed dietary and supplemental mineral intake by a validated food frequency questionnaire administered every 4 years to 80,920 nurses in the Nurses' Health Study (1984-2002) and 94,511 in the Nurses' Health Study II (1991-2007). There were 479 new MS cases during follow-up. We estimated hazard ratios and 95% confidence intervals for the association of energy-adjusted mineral intake with MS risk using Cox regression, adjusting for age, residence latitude at age 15, ancestry, body mass index at age 18, supplemental vitamin D, smoking, and total energy intake. RESULTS: We did not find any association between the minerals and MS risk, either for baseline or cumulative intake during follow-up. The associations were null comparing women with highest to those with lowest intakes in quintiles or deciles and there was no significant trend for higher intakes (p trend across baseline quintiles: potassium 0.35, magnesium 0.13, calcium 0.22, phosphorus 0.97, iron 0.85, zinc 0.67, manganese 0.48, copper 0.59). CONCLUSIONS: Our findings suggest that mineral intake is not an important determinant of MS risk.

Diet quality and risk of multiple sclerosis in two cohorts of US women.

OBJECTIVE: To determine the association between measures of overall diet quality (dietary indices/patterns) and risk of multiple sclerosis (MS). METHODS: Over 185,000 women in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) completed semiquantitative food frequency questionnaires every 4 years. There were 480 MS incident cases. Diet quality was assessed using the Alternative Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED) index, and Dietary Approaches to Stop Hypertension (DASH) index. Principal component analysis was used to determine major dietary patterns. We calculated the hazard ratio (HR) of MS with Cox multivariate models adjusted for age, latitude of residence at age 15, body mass index at age 18, supplemental vitamin D intake, and cigarette smoking. RESULTS: None of the dietary indices, AHEI-2010, aMED, or DASH, at baseline was statistically significantly related to the risk of MS. The principal component analysis identified "Western" and "prudent" dietary patterns, neither of which was associated with MS risk (HR, top vs bottom quintile: Western, 0.81 (p = 0.31) and prudent, 0.96 (p = 0.94)). When the analysis was repeated using cumulative average dietary pattern scores, the results were unchanged. CONCLUSION: There was no evidence of an association between overall diet quality and risk of developing MS among women.

No association between dietary sodium intake and the risk of multiple sclerosis.

OBJECTIVE: To prospectively investigate the association between dietary sodium intake and multiple sclerosis (MS) risk. METHODS: In this cohort study, we assessed dietary sodium intake by a validated food frequency questionnaire administered every 4 years to 80,920 nurses in the Nurses' Health Study (NHS) (1984-2002) and to 94,511 in the Nurses' Health Study II (NHSII) (1991-2007), and calibrated it using data from a validation study. There were 479 new MS cases during follow-up. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the effect of energy-adjusted dietary sodium on MS risk, adjusting also for age, latitude of residence at age 15, ancestry, body mass index at age 18, supplemental vitamin D intake, cigarette smoking, and total energy intake in each cohort. The results in both cohorts were pooled using fixed effects models. RESULTS: Total dietary intake of sodium at baseline was not associated with MS risk (highest [medians: 3.2 g/d NHS; 3.5 g/d NHSII] vs lowest [medians: 2.5 g/d NHS; 2.8 g/d NHSII] quintile: HRpooled 0.98, 95% CI 0.74-1.30, p for trend = 0.75). Cumulative average sodium intake during follow-up was also not associated with MS risk (highest [medians: 3.3 g/d NHS; 3.4 g/d NHSII] vs lowest [medians: 2.7 g/d NHS; 2.8 g/d NHSII] quintile: HRpooled 1.02, 95% CI 0.76-1.37, p for trend = 0.76). Comparing more extreme sodium intake in deciles yielded similar results (p for trend = 0.95). CONCLUSIONS: Our findings suggest that higher dietary sodium intake does not increase the risk of developing MS.

Polyunsaturated fatty acids and the risk of multiple sclerosis.

BACKGROUND: Results from previous studies on polyunsaturated fatty acid (PUFA) intake and multiple sclerosis (MS) risk are conflicting. OBJECTIVE: To prospectively investigate the association between dietary intake of PUFA and MS risk. METHODS: We followed 80,920 women from Nurses' Health Study (1984-2004) and 94,511 women from Nurses' Health Study II (1991-2009) who reported on diet using a validated food frequency questionnaire every 4 years and identified 479 incident MS cases during follow-up. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), for the effect of PUFA intake on MS risk adjusting for age, latitude of residence at age 15, ancestry, cigarette smoking, supplemental vitamin D intake, body mass index, and total energy intake. RESULTS: Higher intake of total PUFA at baseline was associated with a lower risk of MS (HR top vs bottom quintile: 0.67, 95% CI: 0.49-0.90, p trend = 0.01). Among the specific types of PUFA, only α-linolenic acid (ALA) was inversely associated with MS risk (HR top vs bottom quintile: 0.61, 95% CI: 0.45-0.83, p trend = 0.001). The long-chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not associated with MS risk. CONCLUSION: Low dietary PUFA intake may be another modifiable risk factor for MS.

Physical activity and the incidence of multiple sclerosis.

OBJECTIVE: To study whether physical activity during adulthood or early life is associated with multiple sclerosis (MS) incidence in 2 prospective cohorts of women. METHODS: Women in the Nurses' Health Study (NHS) (n = 81,723; 1986-2004) and NHS II (n = 111,804; 1989-2009) reported recent physical activity at baseline and in selected follow-up questionnaires. Using this information, we calculated total metabolic equivalent hours of physical activity per week, a measure of energy expenditure. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. To estimate relative rates (RRs) and 95% confidence intervals (CIs), we used Cox proportional hazards models, adjusting for age, latitude of residence at age 15, ethnicity, smoking, supplemental vitamin D, and body mass index at age 18. RESULTS: Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS (RRpooled = 0.73, 95% CI 0.55-0.98; p-trend 0.08); this trend was not present in 6-year lagged analyses. Change in physical activity analyses suggested that women reduced activity before onset of MS symptoms. In NHS and NHS II, higher strenuous activity at ages 18-22 years was weakly associated with a decreased MS rate. However, in NHS II, total early-life activity at ages 12-22 was not associated with MS. CONCLUSIONS: Though higher physical activity at baseline was weakly associated with lower MS risk, this may have been due to women reducing physical activity in response to subclinical MS.