α-Linolenic acid is associated with MRI activity in a prospective cohort of multiple sclerosis patients.

BACKGROUND: The plant-based ω-3 fatty acid α-linolenic acid (ALA) has been associated with lower MS risk. It is currently unknown whether ALA affects disease activity. OBJECTIVE: To investigate the association between ALA levels and disease activity. METHODS: We conducted a cohort study including 87 multiple sclerosis (MS)-patients who originally participated in a randomized trial of ω-3 fatty acids (the OFAMS study). We measured serum levels of ALA during follow-up and used random intercept logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association between ALA levels, new magnetic resonance imaging (MRI) lesions, Expanded Disability Status Scale (EDSS) progression and new relapses adjusting for age at inclusion, sex, and use of interferon beta-1a. RESULTS: In continuous (per 1-SD increase) multivariable-adjusted analyses, higher ALA levels were significantly associated with lower odds of new T2-lesions (OR: 0.59, 95% CI: 0.37-0.95) during follow-up. The effect estimates were similar for new T1Gd + lesions (OR: 0.73, 95% CI: 0.48-1.11), EDSS-progression (OR: 0.62, 95% CI: 0.34-1.16) and new relapses (OR: 0.49, 95% CI: 0.22-1.10), but these estimates did not reach statistical significance. Further adjustment for vitamin D and tobacco use did not materially change the results. CONCLUSION: We found that higher levels of ALA were associated with lower disease activity in MS-patients.

Trans-fatty Acids and Survival in Renal Transplantation.

OBJECTIVE: High consumption of trans-fatty acids (TFAs) is associated with increased mortality. DESIGN AND METHODS: Observational cohort study of 1.988 Norwegian renal transplant recipients with a median follow-up time of 9.6 years. We assessed multivariable adjusted associations between plasma levels of industrial and ruminant TFAs with patient and graft survival. Plasma phospholipid fatty acid levels were determined by gas chromatography at 10 weeks after transplantation. RESULTS: During follow-up, there were 595 deaths, and 805 grafts were lost. Plasma industrial TFA levels dropped from 0.3 wt% in years 1999-2004 to reach a plateau of 0.2 wt% from year 2005 and beyond, whereas plasma levels of ruminant TFAs remained stable throughout the study period. In the former era (years 1999 to 2004, n = 902), we found multivariable adjusted associations between plasma industrial TFA levels and mortality (hazard ratio 4.44, P = .02) and graft loss (hazard ratio 4.22, P = .01). In the latter era (years 2005 to 2011, n = 1,086), there were no associations between plasma industrial TFA levels and patient or graft survival. Plasma ruminant TFAs were not associated with mortality or graft loss in either eras. CONCLUSION: In this Norwegian transplant cohort, plasma industrial TFA levels dropped from around 0.3 wt% in the former era to 0.2 wt% in the latter era. While plasma industrial TFA was significantly associated with survival in the former era, no associations were found with survival in the latter era. This finding suggests that lowering industrial TFA consumption from modest to low levels could possibly influence health beneficially after renal transplantation.

Validation of repeated self-reported n-3 PUFA intake using serum phospholipid fatty acids as a biomarker in breast cancer patients during treatment.

BACKGROUND: The role of n-3 polyunsaturated fatty acids (PUFAs) in breast cancer is not clear and under debate. To explore this relationship it is important to have proper validated dietary assessment methods for measuring the intake of n-3 PUFAs. The aim of the current study is to validate two different methods used to assess the intake of selected n-3 PUFAs as well as food sources of long-chained n-3 PUFAs. Also, we aim to study how stable the intake of fatty acids is during breast cancer treatment. METHODS: The study-population was patients with breast cancer (Stages I-II) or ductal carcinoma in situ (DCIS-grade III) undergoing treatment (n = 49) in Norway. Dietary intake was assessed by two self-administered methods, a 256 food item food frequency questionnaire (FFQ) and a 7-day pre-coded food diary (PFD). The FFQ was administered presurgery and twelve months postsurgery, and the PFD was administered shortly after surgery (10 +/- 2 days), six and twelve months postsurgery. Fasting blood samples (presurgery, six and twelve months postsurgery) were analysed for serum phospholipid fatty acids, a biomarker for intake of n-3 PUFAs. RESULTS: Mean (SD) age was 54.2 (7.8) years at diagnosis, and the mean (SD) body mass index (BMI) was 24.8 (3.4) kg/m2. Correlation coefficients between dietary intakes of n-3 PUFAs measured with the FFQ and the PFD ranged from 0.35 to 0.66. The correlation coefficients between the PFD and the biomarker (serum phospholipid n-3 PUFAs) as well as between the FFQ and the biomarker demonstrated stronger correlations twelve months after surgery (ρ 0.40-0.56 and 0.36-0.53, respectively) compared to around surgery (ρ 0.08-0.20 and 0.28-0.38, respectively). The same pattern was observed for intake of fatty fish. The intake of n-3 PUFAs did not change during treatment assessed by the FFQ, PFD or biomarker. CONCLUSION: These results indicate that the FFQ and the PFD can be used to assess dietary intake of fish and n-3 PUFAs in breast cancer patients during breast cancer treatment. Still, the PFD shortly after surgery should be used with caution. The diet of patients undergoing breast cancer treatment was quite stable, and the intake of n-3 PUFAs did not change.

Serum levels of leptin and adiponectin are not associated with disease activity or treatment response in multiple sclerosis.

Adipokines secreted by fatty tissue have inflammatory properties and are suggested biomarkers of MS disease activity. To assess this, 88 MS patients were followed with nine repeated measurements of leptin and adiponectin and 12 magnetic resonance imaging (MRI) scans for two years; six months without any immunomodulatory treatment followed by 18 months during interferon-beta (IFNB) treatment. Serum levels of leptin dropped and adiponectin increased upon initiation of IFNB-therapy, but were not associated with clinical or MRI disease activity or with treatment response. Our findings indicate that leptin and adiponectin are not useful as biomarkers of MS disease activity.

Development of Kidney Transplant Fibrosis Is Inversely Associated With Plasma Marine Fatty Acid Level.

OBJECTIVE(S): We assessed associations between plasma levels of polyunsaturated fatty acids (PUFAs) and degree of inflammation and interstitial fibrosis in transplanted kidneys. DESIGN: The design of the study was single center cohort study. SUBJECTS: A study population of 156 patients who received a kidney transplant at Oslo University Hospital during 2010. MAIN OUTCOME MEASURE: Kidney transplant biopsies were obtained at 2 months and 1 year after transplantation. Degree of inflammation and interstitial fibrosis in the cortex of transplanted kidneys were estimated semi-quantitatively. Plasma phospholipid fatty acids levels were measured in a stable phase 2 months posttransplant. We used multivariate linear regression to assess associations between plasma levels of PUFAs and degree of inflammation and interstitial fibrosis at 2 months and 1 year postoperatively and change in degree of interstitial fibrosis during the first year after transplantation, adjusting for inflammation and fibrosis risk factors. RESULTS: Higher plasma marine n-3 PUFA levels were associated with less development of interstitial fibrosis in the kidney transplant (unstandardized ß-coefficient -1.12, standardized ß-coefficient -0.18, P = .03) during the first year after transplantation. Plasma levels of alpha linoleic acid, linoleic acid, and arachidonic acid were not associated with development of interstitial fibrosis. No associations were found between plasma levels of PUFAs and inflammation inside fibrotic areas or outside fibrotic areas in the kidney transplant at neither 2 months nor 1 year postoperatively. Linolenic acid levels in plasma were positively associated with change in renal function during the first year after transplantation. CONCLUSION: The inverse association between plasma marine n-3 PUFA levels and development of interstitial fibrosis during the first year after kidney transplantation suggests that marine fatty acid consumption might halt progression of fibrosis.

Gestational diabetes and offspring birth size at elevated environmental pollutant exposures.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased availability of glucose and macronutrients in fetal circulation and macrosomia. Therefore, the role of GDM in the association between metabolism-disrupting chemicals and birth size deserves attention. OBJECTIVE: We examined whether GDM may mediate or modify the associations between maternal environmental pollutant exposures and offspring birth size measures. METHODS: We analyzed 604 Faroese pregnant women and their offsprings born in 1997-2000. Maternal pregnancy serum concentrations of organochlorine compounds (OCs: polychlorinated biphenyl (PCB) congeners and dichlorodiphenyldichloroethylene (DDE)), and five perfluoroalkyl substances (PFASs), and hair and cord blood mercury concentrations were measured. We used regression (single-pollutants) and structural equation models (SEMs) (multiple-pollutant analyses using latent constructs of OCs, PFASs and mercury) to estimate the associations with GDM and birth size measures, accounting for mediation and/or effect modification by GDM. RESULTS: Serum-DDE and hair-mercury concentrations were associated with GDM (adjusted OR per concentration doubling: 1.29; 95% CI: 0.94, 1.77 for DDE, and 0.79; 95% CI: 0.62, 0.99 for mercury), but in multiple pollutant-adjusted SEMs only a positive association between OC exposure and GDM remained significant (change in GDM odds per OC doubling: 0.45; 95% CI: 0.05, 0.86). PCB and overall OC exposure were positively associated with head circumference (SEM; mean change per OC doubling: 0.13cm; 95% CI, 0.01. 0.25). Overall PFAS exposure was inversely associated with birth weight (SEM; mean change per PFAS doubling: -169g; 95% CI: -359, 21), and for many single-PFASs we found a pattern of inverse associations with birth weight and head circumference in boys, and positive or null associations in girls. None of the environmental pollutants was associated with offspring length. GDM neither modified nor mediated the associations with birth size measures. CONCLUSIONS: We found associations with GDM and offspring birth size to be specific to the environmental pollutant or pollutant group. Associations with birth size measures appear to be independent of GDM occurrence.

Plasma Levels of Marine n-3 Fatty Acids Are Inversely Correlated With Proinflammatory Markers sTNFR1 and IL-6 in Renal Transplant Recipients.

OBJECTIVE: Marine n-3 polyunsaturated fatty acids (PUFAs) exert potential anti-inflammatory effects and might improve long-term outcomes after renal transplantation. We assessed associations between plasma phospholipid levels of marine n-3 PUFAs and plasma inflammatory biomarkers 10 weeks after renal transplantation. DESIGN: Cross-sectional single-center study. SUBJECTS: A study population of 861 renal transplant recipients transplanted at Oslo University Hospital between 2007 and 2011. METHODS AND MAIN OUTCOME MEASURE: Plasma phospholipid fatty acids were determined by gas chromatography. Marine n-3 PUFA levels were defined as the sum of eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid levels in weight percentage of total plasma phospholipid fatty acids. Plasma inflammatory biomarkers were measured by enzyme immunoassays. We used multivariable linear regression analysis to assess associations between levels of marine n-3 PUFAs and inflammatory biomarkers in plasma. RESULTS: Plasma marine n-3 PUFA levels were inversely associated with plasma levels of proinflammatory biomarkers soluble tumor necrosis factor receptor 1 (standardized regression coefficient -0.11, P < .001) and interleukin-6 (standardized regression coefficient -0.09, P = .01). In contrast, there was no association between plasma levels of marine n-3 PUFAs and the anti-inflammatory mediator interleukin-10. CONCLUSIONS: In this renal transplant cohort, inverse associations between plasma levels of marine n-3 PUFAs and markers of inflammation were demonstrated.

No association of tobacco use and disease activity in multiple sclerosis.

OBJECTIVE: To study whether tobacco use is associated with MRI and clinical disease activity in patients with multiple sclerosis (MS). METHODS: Prospective cohort study of 87 patients with relapsing-remitting MS originally included in a randomized placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS Study). Serum levels of cotinine (biomarker of tobacco use) were analyzed at baseline and every 6 months for 2 years. MRI activity was assessed at baseline and monthly for 9 months and after 12 and 24 months. RESULTS: Fifty-three patients (61%) had serum cotinine levels ≥85 nmol/L on ≥60% of the measurements and were considered tobacco users and 34 (39%) had cotinine levels <85 nmol/L, consistent with non-tobacco use. There was no association between tobacco use and the occurrence of new gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, or their aggregate (combined unique activity). Furthermore, there was no association between cotinine levels and MRI activity for the tobacco users, and tobacco users did not have more relapses or Expanded Disability Status Scale progression. CONCLUSION: Our results indicate that tobacco use does not directly influence MRI activity or relapse rate in MS. This may implicate that the reported association between smoking and MS disease progression could be mediated through other mechanisms.

Plasma levels of marine n-3 polyunsaturated fatty acids and renal allograft survival.

BACKGROUND: Marine n-3 polyunsaturated fatty acids (PUFAs) may exert beneficial effects on inflammation, fibrosis, endothelial function, lipid profile and blood pressure that may prevent graft loss. METHODS: In this observational cohort study in Norwegian renal transplant recipients (n = 1990), transplanted between 1999 and 2011, associations between plasma marine n-3 PUFA levels and graft loss were assessed by multivariable Cox proportional hazard regression analysis. Plasma phospholipid fatty acid composition was determined by gas chromatography and individual fatty acids recorded as weight percentage (wt%) of total fatty acids in a stable phase 10 weeks after transplantation. RESULTS: During a median follow-up time of 6.8 years, 569 (28.6%) renal allografts were lost, either due to patient death (n = 340, 59.8% of graft loss) or graft loss in surviving patients (n = 229, 40.2%). Plasma marine n-3 PUFA levels ranged from 1.35 to 23.87 wt%, with a median level of 7.95 wt% (interquartile range 6.20-10.03 wt%). When adjusting for established graft loss risk factors, there was a 11% reduced risk of graft loss for every 1.0 wt% increase in marine n-3 PUFA level [adjusted hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.84-0.93], and a 10% reduced risk of graft loss in surviving patients (adjusted HR 0.90; 95% CI 0.84-0.97). CONCLUSION: High levels of plasma marine n-3 PUFAs were associated with better renal allograft survival.

Body mass index influence interferon-beta treatment response in multiple sclerosis.

Obesity is a possible risk factor of multiple sclerosis (MS), but the association between obesity and MS disease activity has not been explored. In a cohort of 86 MS patients, 80% of overweight or obese patients (BMI≥25kg/m(2)) had MRI activity compared to 48% of the normal-weight patients (BMI<25kg/m(2)) (p=0.001) during interferon-beta treatment. NEDA-status (no evidence of disease activity) was defined as a composite that consisted of absence of any relapses, sustained disability-progression and MRI-activity. Among normal-weight patients 26% obtained NEDA-status compared to only 13% of patients with BMI >25 (p=0.05). This may indicate that BMI affects interferon-beta treatment response.

Effect of seafood mediated PCB exposure on desaturase activity and PUFA profile in Faroese septuagenarians.

Polychlorinated biphenyl (PCB) exposure may affect serum concentrations of polyunsaturated fatty acids (PUFAs) by inhibiting desaturases ∆5 and ∆6 that drive their synthesis from precursor fatty acids. Such changes in the composition of fatty acids may affect cardiovascular disease risk, which is thought to increase at elevated PCB exposures. This population-based cross-sectional study examined 712 Faroese men and women aged 70-74 years. The serum phospholipid fraction of fasting blood samples was used to determine the PUFA profile, including linoleic acid, dihomo-γ-linolenic acid, arachidonic acid, eicosatrienoic acid, and other relevant fatty acids. Ratios between precursor and metabolite fatty acids were used as proxies for ∆5 and ∆6 desaturase activity. Tertiles of serum-PCB concentrations were used in multiple regression analyses to determine the association between the exposure and desaturase activity. In multiple regression models, PCB exposure was inversely related to the estimated Δ6 desaturase activity resulting in accumulation of precursor fatty acids and decrease in the corresponding product PUFAs. A positive association between PCB and Δ5 desaturation was also found. A relative increase in EA was also observed, though only in the third tertile of PCB exposure. Non-linear relationships between the exposure and the desaturase activity were not found. Consuming fish and seafood may not be translated into beneficial fatty acid profiles if the diet simultaneously causes exposure to PCBs. Although the desaturase estimates were likely influenced by dietary intakes of product PUFAs, the association between PCB exposure and ∆6 desaturase activity is plausible and may affect cardiovascular disease risk.

The association between marine n-3 polyunsaturated fatty acid levels and survival after renal transplantation.

BACKGROUND AND OBJECTIVES: Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation. RESULTS: There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with low levels (<7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality. CONCLUSIONS: Higher plasma phospholipid marine n-3 polyunsaturated fatty acid levels were independently associated with better patient survival.

Vitamin D status and effect of interferon-ß1a treatment on MRI activity and serum inflammation markers in relapsing-remitting multiple sclerosis.

To explore if vitamin D modulates interferon-ß1a treatment effects in relapsing-remitting multiple sclerosis, we examined relationships between serum vitamin D and magnetic resonance imaging (MRI) activity and ten systemic inflammation markers in 88 patients, before and during treatment. Odds ratios for all MRI parameters were negatively associated with vitamin D levels before therapy, but converged to equally low values irrespective of vitamin D status during treatment. During therapy, similar alterations of MRI activity and inflammation markers were found across patients categorized by mean vitamin D values. This suggests that vitamin D status has no major influence on interferon-ß1a treatment effects.

Antibodies to Epstein-Barr virus and MRI disease activity in multiple sclerosis.

BACKGROUND: Previous reports indicate an association between Epstein-Barr virus (EBV) antibody levels and multiple sclerosis (MS) disease activity, but the results have been conflicting. OBJECTIVES: The objective of this paper is to study if EBV antibody levels reflect MRI disease activity in MS and examine the potential for EBV antibody levels as biomarkers for treatment response. METHODS: A total of 87 MS patients were followed for two years prior to and during interferon beta (IFNB) treatment, with MRI examinations and serum measurement of IgM and IgG antibodies to viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA-1) and early antigen (EA). Associations between EBV antibody levels and MRI activity were assessed by a logistic regression model. RESULTS: Higher anti-EBNA-1 IgG levels were associated with increased MRI activity, OR = 2.95 (95% CI 1.07-8.10; p = 0.036) for combined unique activity (CUA; the sum of T1Gd+ lesions and new or enlarging T2 lesions). Although most patients were anti-VCA IgM negative, there was an inverse association, OR = 0.32 (95% CI 0.12-0.84; p = 0.021) with CUA during IFNB treatment. CONCLUSIONS: This study supports an association between anti-EBNA-1 IgG levels and MS disease activity. We also found an inverse association with anti-VCA IgM levels during IFNB treatment not previously described, indicating anti-VCA IgM as a possible biomarker for IFNB treatment response.

Increasing serum levels of vitamin A, D and E are associated with alterations of different inflammation markers in patients with multiple sclerosis.

To explore the relationships between vitamin A, D and E and inflammation in relapsing remitting multiple sclerosis, we assessed their associations with 11 inflammation markers in 9 serial serum samples from 85 patients, before and during interferon-ß1a treatment. A negative association was found between vitamin A and pentraxin 3 independent of interferon-ß1a use, whereas positive associations between vitamin D and interleukin-1 receptor antagonist and secreted frizzled-related protein 3 were seen before, and between vitamin E and chemokine (C-X-C motif) ligand 16 during interferon-ß1a treatment. These findings suggest associations with diverse inflammatory pathways, which may be differentially influenced by interferon-ß1a treatment.

Negative confounding by essential fatty acids in methylmercury neurotoxicity associations.

BACKGROUND: Methylmercury, a worldwide contaminant of fish and seafood, can cause adverse effects on the developing nervous system. However, long-chain n-3 polyunsaturated fatty acids in seafood provide beneficial effects on brain development. Negative confounding will likely result in underestimation of both mercury toxicity and nutrient benefits unless mutual adjustment is included in the analysis. METHODS: We examined these associations in 176 Faroese children, in whom prenatal methylmercury exposure was assessed from mercury concentrations in cord blood and maternal hair. The relative concentrations of fatty acids were determined in cord serum phospholipids. Neuropsychological performance in verbal, motor, attention, spatial, and memory functions was assessed at 7 years of age. Multiple regression and structural equation models (SEMs) were carried out to determine the confounder-adjusted associations with methylmercury exposure. RESULTS: A short delay recall (in percent change) in the California Verbal Learning Test (CVLT) was associated with a doubling of cord blood methylmercury (-18.9, 95% confidence interval [CI]=-36.3, -1.51). The association became stronger after the inclusion of fatty acid concentrations in the analysis (-22.0, 95% confidence interval [CI]=-39.4, -4.62). In structural equation models, poorer memory function (corresponding to a lower score in the learning trials and short delay recall in CVLT) was associated with a doubling of prenatal exposure to methylmercury after the inclusion of fatty acid concentrations in the analysis (-1.94, 95% CI=-3.39, -0.49). CONCLUSIONS: Associations between prenatal exposure to methylmercury and neurobehavioral deficits in memory function at school age were strengthened after fatty acid adjustment, thus suggesting that n-3 fatty acids need to be included in analysis of similar studies to avoid underestimation of the associations with methylmercury exposure.

Inflammation markers in multiple sclerosis: CXCL16 reflects and may also predict disease activity.

BACKGROUND: Serum markers of inflammation are candidate biomarkers in multiple sclerosis (MS). ω-3 fatty acids are suggested to have anti-inflammatory properties that might be beneficial in MS. We aimed to explore the relationship between serum levels of inflammation markers and MRI activity in patients with relapsing remitting MS, as well as the effect of ω-3 fatty acids on these markers. METHODS: We performed a prospective cohort study in 85 relapsing remitting MS patients who participated in a randomized clinical trial of ω-3 fatty acids versus placebo (the OFAMS study). During a period of 24 months 12 repeated magnetic resonance imaging (MRI) scans and nine serum samples were obtained. We measured 10 inflammation markers, including general down-stream markers of inflammation, specific markers of up-stream inflammatory pathways, endothelial action, and matrix regulation. RESULTS: After Bonferroni correction, increasing serum levels of CXCL16 and osteoprotegerin were associated with low odds ratio for simultaneous MRI activity, whereas a positive association was observed for matrix metalloproteinase (MMP) 9. CXCL16 were also associated with low MRI activity the next month, but this was not significant after Bonferroni correction. In agreement with previously reported MRI and clinical results, ω-3 fatty acid treatment did not induce any change in the inflammation markers. CONCLUSIONS: Serum levels of CXCL16, MMP-9, and osteoprotegerin reflect disease activity in MS, but are not affected by ω-3 fatty acid treatment. CXCL16 could be a novel biomarker and potential predictor of disease activity in MS.

Visual evoked potentials in children prenatally exposed to methylmercury.

Prenatal exposure to methylmercury can cause both neurobehavioral deficits and neurophysiological changes. However, evidence of neurotoxic effects within the visual nervous system is inconsistent, possibly due to incomplete statistical adjustment for beneficial nutritional factors. We evaluated the effect of prenatal methylmercury exposure on visual evoked potential (VEP) latencies in Faroese children with elevated prenatal methylmercury exposure. A cohort of 182 singleton term births was assembled in the Faroe Islands during 1994-1995. At age 7 years, VEP tracings were obtained from 139 cohort subjects after exclusion of subjects with abnormal vision conditions. We used multiple regression analysis to evaluate the association of mercury concentrations in cord blood and maternal hair at parturition with VEP latencies after adjustment for potential confounders that included the cord-serum phospholipid concentration of n-3 polyunsaturated fatty acids (PUFAs) and the duration of breastfeeding. Unadjusted correlations between mercury exposure and VEP latencies were equivocal. Multiple regression models showed that increased mercury concentrations, especially in maternal hair, were associated with delayed latencies for VEP peak N145. After covariate adjustment, a delay of 2.22 ms (p=0.02) was seen for each doubling of the mercury concentration in maternal hair. In agreement with neuropsychological findings, the present study suggests that prenatal methylmercury exposure may have an adverse effect on VEP findings despite the absence of clinical toxicity to the visual system. However, this association was apparent only after adjustment for n-3 PUFA status.

Alpha-tocopherol and MRI outcomes in multiple sclerosis--association and prediction.

OBJECTIVE: Alpha-tocopherol is the main vitamin E compound in humans, and has important antioxidative and immunomodulatory properties. The aim of this study was to study alpha-tocopherol concentrations and their relationship to disease activity in Norwegian multiple sclerosis (MS) patients. METHODS: Prospective cohort study in 88 relapsing-remitting MS (RRMS) patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids (the OFAMS study), before and during treatment with interferon beta. The patients were followed for two years with repeated 12 magnetic resonance imaging (MRI) scans and nine serum measurements of alpha-tocopherol. RESULTS: During interferon beta (IFNB) treatment, each 10 µmol/L increase in alpha-tocopherol reduced the odds (CI 95%) for simultaneous new T2 lesions by 36.8 (0.5-59.8) %, p = 0.048, and for combined unique activity by 35.4 (1.6-57.7) %, p = 0.042, in a hierarchical regression model. These associations were not significant prior to IFNB treatment, and were not noticeably changed by gender, age, body mass index, HLA-DRB1*15, treatment group, compliance, or the concentrations of 25-hydroxyvitamin D, retinol, neutralising antibodies against IFNB, or the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. The corresponding odds for having new T1 gadolinium enhancing lesions two months later was reduced by 65.4 (16.5-85.7) %, p = 0.019, and for new T2 lesions by 61.0 (12.4-82.6) %, p = 0.023. CONCLUSION: During treatment with IFNB, increasing serum concentrations of alpha-tocopherol were associated with reduced odds for simultaneous and subsequent MRI disease activity in RRMS patients.

Long-term tracking of plasma phospholipid fatty acid concentrations and their correlation with the dietary intake of marine foods in newly diagnosed diabetic patients: results from a follow-up of the HUNT Study, Norway.

Analysis of long-chain n-3 and n-6 fatty acid (FA) concentrations is used to evaluate their potential health effects in epidemiological studies, and, recently, also to counsel patients with a suboptimal intake of n-3 FA. Data on the method's ability to track and detect differences within and between individuals in appropriate populations are, however, lacking. The present study provides such data for twenty-nine plasma phospholipid (PL) FA concentrations and indices measured in 214 newly diagnosed type 2 diabetic patients at baseline and after 3 years. 20 : 3n-6 and the 20 : 4n-6:20 : 3n-6 ratio showed the highest tracking coefficients (Spearman's r 0.68), while DHA, EPA and PLN3-index (EPA+DHA) coefficients were 0.60, 0.47 and 0.55, respectively. Fish consumption measured simultaneously with EPA, DHA, sum n-3 and PLN3 index showed Spearman's correlation coefficients of 0.47, 0.44, 0.48 and 0.49, respectively, decreasing to 0.20, 0.19, 0.22 and 0.21 when measured 3 years apart. The within-subject CV of EPA, DHA and PLN3 index were 39.9, 14.3 and 18.0 %, respectively. The corresponding between-subject CV were 33.6, 16.5 and 18.7 %, while the reference change values were 112, 41 and 52 %. In conclusion, PL n-3 FA concentrations showed a significant long-term tracking and were positively correlated with marine food intake. Analytical precision, biological variability, reference change value and the index of individuality of EPA, DHA and PLN3 index are similar to commonly used clinical biomarkers, supporting their validity as dietary markers in clinical and epidemiological work.