Vitamin D, HLA-DRB1 and Epstein-Barr virus antibody levels in a prospective cohort of multiple sclerosis patients.

BACKGROUND AND PURPOSE: Our objective was to study the association between serum levels of anti Epstein-Barr virus nuclear antigen 1 (EBNA-1) antibody and 25-hydroxyvitamin D (25(OH)D) in a prospective cohort of patients with relapsing-remitting multiple sclerosis. METHOD: The study comprised 90 patients with relapsing-remitting multiple sclerosis, all participants in a randomized clinical trial of ω-3 fatty acids (the OFAMS study). Repeated, paired measurements of serum 25(OH)D and serum EBNA-1 immunoglobulin G (IgG) levels were obtained at baseline and every 6 months for 24 months. The association between serum EBNA-1 IgG and serum 25(OH)D levels was analysed using generalized linear models for hierarchical data. RESULTS: There was a significant variation in EBNA-1 IgG antibody level between sampling months (Fdf 11 = 1.8, P = 0.043, one-way anova). There was a negative association between EBNA-1 IgG and 25(OH)D [B = -0.230, 95% confidence interval (CI) (-0.440, -0.023), P = 0.030] and a positive association between EBNA-1 IgG and HLA-DRB1*15 positive status [B = 94.7, 95% CI (2.423, 186.9), P = 0.044]. The association between 25(OH)D and EBNA-1 IgG remained significant after adjusting for the patient's age, gender, HLA-DRB1*15, retinol levels and interferon ß-1a treatment. CONCLUSION: Our study demonstrates monthly differences in EBNA-1 IgG levels and an association between EBNA-1 IgG, 25(OH)D levels and HLA-DRB1*15. These results indicate that EBNA-1 IgG serum levels are affected by genetic and environmental factors that also modulate multiple sclerosis risk.

Plasma levels of marine n-3 fatty acids and cardiovascular risk markers in renal transplant recipients.

BACKGROUND/OBJECTIVES: Cardiovascular (CV) disease is the leading cause of death after renal transplantation. Marine n-3 polyunsaturated fatty acids (PUFAs) exert potential cardio-protective metabolic effects and might reduce CV morbidity and mortality in renal transplant recipients (RTRs). SUBJECTS/METHODS: In this cross-sectional study of 1990 Norwegian RTRs, transplanted between 1999 and 2011, associations between plasma phospholipid marine n-3 PUFA levels and various CV risk markers at 10 weeks after transplant were evaluated. RESULTS: Higher plasma marine n-3 PUFA levels were associated with lower resting heart rate (rHR), lower fasting plasma glucose (fPG) levels, lower plasma triglyceride levels and higher plasma high-density lipoprotein (HDL) cholesterol levels. Plasma levels of eicosapentaenoic acid, but not docosahexaenoic acid, showed a positive association with plasma HDL cholesterol levels. Plasma marine n-3 PUFA levels were not associated with plasma low-density lipoprotein cholesterol levels, pulse wave velocity or systolic and diastolic blood pressure. A negative association between plasma marine n-3 PUFA levels and CV mortality was weakened by additional adjustment for plasma triglyceride levels and rHR. The ratio of n-6 to n-3 PUFAs showed similar associations with CV risk markers as absolute plasma marine n-3 PUFA levels. CONCLUSIONS: This is the first study in RTRs showing that marine n-3 PUFAs are negatively associated with rHR and fPG in addition to beneficial effects on plasma HDL cholesterol and triglyceride levels. Especially, effects on autonomic nervous function and triglyceride metabolism might contribute to explain the lower CV mortality risk with higher plasma marine n-3 PUFA levels previously shown in this cohort.

WT1 and interferon-ß-vitamin D association in MS: a longitudinal study.

BACKGROUND: It has been suggested that polymorphisms in the WT1 gene modulate the effect of IFN-ß treatment in multiple sclerosis (MS) through regulation of the relationship between IFN-ß and vitamin D. OBJECTIVE: To examine whether WT1 modulates the relationship between IFN-ß and vitamin D in a longitudinal study with repeated assessment of vitamin D before and after initiation of IFN-ß. METHODS: In a prospective study of 85 patients with relapsing remitting MS, 25-hydroxyvitamin D was measured at month 0, 1, 3, 6, 7, 9, 12, 18 and 24. None of the patients used any immunomodulatory treatment at inclusion, and all started IFN-ß treatment at month 6. RESULTS: The mean concentrations of seasonally adjusted 25-hydroxyvitamin increased slightly (3.1 ± 1.2 nmol/l, P = 0.008) after initiation of IFN-ß. The association between IFN-ß treatment and 25-hydroxyvitamin D was similar in patients carrying any of the two alleles in the WT1 SNPs (rs10767935 and rs5030244) recently reported to modulate this relationship. CONCLUSIONS: In this prospective study with repeated measurements of 25-hydroxyvitamin D before and during treatment with IFN-ß, we did not find that genetic variation in WT1 plays any role in regulating the relationship between IFN-ß and serum 25-hydroxyvitamin D.

Modelling and prediction of 25-hydroxyvitamin D levels in Norwegian relapsing-remitting multiple sclerosis patients.

BACKGROUND/AIM: 25-Hydroxyvitamin D (25(OH)D) levels are suggested to influence the susceptibility and risk of disease progression in multiple sclerosis (MS). Seasonal fluctuation of 25(OH)D levels may differ in magnitude between individuals. The purpose of this paper was to model the seasonal fluctuation of vitamin D in Norwegian MS patients and to examine to which extent one single 25(OH)D measurement predicts the level at other time points throughout the year. METHODS: During December 2004 and July 2008, 762 serum samples were collected from 92 Norwegian relapsing-remitting MS patients. Time series analysis and multivariate modelling techniques were used to model seasonal fluctuations and intra- and inter-individual variations in 25(OH)D values. RESULTS: Most patients reached their lowest 25(OH)D level in March/April and the highest in July/August. There were substantial intra-individual variations in the extent of seasonal fluctuation, with 36.6% of explainable variation in seasonally adjusted 25(OH)D levels (on a logarithmic scale) attributable to the patient level. The remaining 63.4% could be accounted for by sources of inter-individual variation. Both the total and inter-individual variabilities were lowest in February, and the prediction interval in this month was up to 26% narrower compared to other months. The prediction intervals would be at least 21% wider with only one observation available per patient. CONCLUSIONS: The seasonal fluctuations of 25(OH)D levels in Norwegian relapsing-remitting MS patients are subject to pronounced intra- and inter-individual variation. The most representative measurements of 25(OH)D levels are taken in February.

Effects of marine n-3 fatty acid supplementation on lipoprotein subclasses measured by nuclear magnetic resonance in subjects with type II diabetes.

OBJECTIVE: To measure effects of fish oil supplements on lipoprotein subclasses by nuclear magnetic resonance (NMR) in subjects with type II diabetes and relate them to insulin sensitivity. DESIGN: Two-armed, parallel, placebo-controlled, randomized. SUBJECTS: Normotriglyceridemic subjects with type II diabetes without insulin treatment were given either fish oil (n=12, median intake 5.9 g/day total n-3 fatty acids (FA) (1.8 g 20:5n-3, 3.0 g 22:6n-3)) or corn oil (n=14, 8.5 g/day 18:2n-6 FA). METHODS: Size and concentration of lipoproteins subclasses were measured by NMR, insulin sensitivity by hyperinsulinemic, isoglycemic clamps. RESULTS: After 9 weeks, there were differences between those treated with fish and corn oil with respect to very low-density lipoprotein (VLDL) size (median -15 vs +0.6%, P=0.001), particle concentrations of large VLDL (-99 vs -4.1%, P=0.041) and small high-density lipoprotein (HDL) (-12 vs +10%, P=0.051). Compared with corn oil fish oil tended to increase HDL size and small low-density lipoprotein (LDL) concentration (P=0.063 and 0.068, respectively, for differences between groups). There was no effect on oxidized LDL. Insulin sensitivity (glucose utilization) decreased in the fish oil group compared with the corn oil group (P=0.049). The decrease in insulin sensitivity did not correlate with the effects on lipoprotein subclasses. CONCLUSIONS: A high intake of n-3 FA exerts effects on several lipoprotein subclasses without obvious influence from changes in insulin sensitivity.

Regulation of desaturase expression in HL60 cells.

The expression of delta 5 desaturase (D5D), delta 6 desaturase (D6D) and delta 9 desaturase (D9D) was determined by RT-PCR in the human promyelocytic cell line HL60. During 72 h of culture with 10% FBS, D5D and D6D were upregulated 5 to 6-fold, whereas D9D approximately doubled. The addition of fatty acids (FAs) to the culture medium suppressed upregulation of all desaturases. N-3 and n-6 FA appeared to be more effective than n-9 or saturated FA. When FAs were added after 72 h, further upregulation during the next 24 h was suppressed for nearly all desaturases and FAs tested, except for D5D when oleic acid (OA) or stearic acid (SA) was added. In cells cultured with restricted amounts of FBS, desaturase expression increased with decreasing concentrations of FBS. Cellular FA content decreased by 60% in the neutral lipid fraction, whereas that of the phospholipid fraction decreased by 10% during 72 h of culture. The largest decrease occurred in the sum of n-3 and n-6 FA of the neutral lipid fraction, which was reduced by 83%, whereas the content of these FAs in the phospholipid fraction decreased by 32%. The results indicate that when the supply of FA to HL60 cells is limited, the intracellular content of n-3 and n-6 FA decreases and this leads to upregulation of the desaturases, particularly D5D and D6D. Since HL60 cells resemble human leukocytes, the results suggest that desaturase expression in leukocytes may be exploited as a biomarker for FA status.

Effects of a 3-day low-fat diet on metabolic control, insulin sensitivity, lipids and adipocyte hormones in Norwegian subjects with hypertriacylglycerolaemia and type 2 diabetes.

The metabolic and hormonal impact of rapid dietary changes in type 2 diabetes has not been clarified. The objective of this study was to test whether a short-term, low-fat diet affected metabolic control, insulin sensitivity, lipids and adipocyte hormones in patients with type 2 diabetes with hypertriacylglycerolaemia. Nineteen outpatient subjects (10 M, 9 F) with type 2 diabetes and triacylglycerols >2.2 mmol/L at screening were included in the study. Dietary intake was assessed by weighing during two periods of 3-day baseline diet followed by a 3-day low-fat dietary intervention. The two periods of baseline diet did not differ with respect to relevant variables during intervention. Subjects were advised to increase fibre-rich and low-fat foods and to decrease intake of visible fat in an isoenergetic manner. The percentage of energy from fat was reduced from 39 to 22 (p < 0.0001), median values. Daytime blood glucose did not change and fasting insulin and fasting glucose to insulin ratios were unaffected. Total cholesterol decreased from 6.3 to 6.2 mmol/L (p < 0.005), high-density lipoprotein cholesterol from 1.13 to 1.10 mmol/L (p < 0.048) and the ratio of n-6 to n-3 fatty acids in phospholipids from 2.5 to 1.9 (p < 0.003). Concentrations of leptin decreased from 12.1 to 9.9 ng/mL (p < 0.005) and adiponectin increased from 8.6 to 10.5 microg/mL (p < 0.024). The effect on leptin was confined to women. A low-fat diet intervention for 3 days in insulin-resistant type 2 diabetes affects lipid, adiponectin and leptin levels but fails to improve insulin sensitivity and metabolic control.

Menometrorrhagia in the perimenopause is associated with increased serum estradiol.

OBJECTIVE: The purpose of this study was to evaluate the possible association between menometrorrhagia and the level of endogenous estrogen in perimenopausal women. METHODS: A prospective controlled study in which 28 perimenopausal women > 40 years presenting with menometrorrhagia were compared with 28 age-matched (+/- 2 years) women with normal cyclical menstrual periods concerning levels of estradiol and follicle-stimulating hormone (FSH). Neither of the two groups had received sexual hormone treatment at least in 2 weeks preceding the hormonal assessment. RESULTS: The serum level estradiol in the patients was significantly higher than in the controls (0.55 nmol/l versus 0.24 nmol/l), whereas FSH was not significantly different between the two groups (21.2 IU/l versus 11.8 IU/l). Twenty of the 28 patients had performed at histologic examination of the endometrium, and 10 of these (50%) had signs of endometrial hyperplasia. No relationship was found between the endometrial histology and the estradiol level. CONCLUSIONS: An association between a high endogenous estradiol level and menometrorrhagia in the perimenopause was demonstrated. This may have implications for the choice of treatment in this group of women. It is proposed that this type of bleeding disturbances should be controlled by progestins only, and not with combined estrogen-progestin treatment. Suppression of the associated hyperestrogenism could be achieved by use of oral contraceptives or GnRH agonists.

Androgen levels in pregnant women decrease with increasing maternal age.

BACKGROUND: To investigate a possible effect of age on maternal androgen levels in uncomplicated pregnancies. METHODS: A study of 134 parous women with uncomplicated pregnancies was carried out at three university hospitals in Norway and Sweden. Maternal levels of androstenedione, dehydroepiandrosterone sulphate, testosterone and the free testosterone index were measured during weeks 17 and 33 of pregnancy. RESULTS: Maternal levels of androstenedione and testosterone had a negative association with maternal age in weeks 17 and 33 of pregnancy, while dehydroepiandrosterone sulphate and the free testosterone index were associated negatively in week 33 only. Adjustment for maternal parity, pre-pregnancy body mass index, smoking and fetal gender did not affect the results. CONCLUSIONS: Maternal androgen levels decrease with increasing maternal age. The cause and possible implication of this finding remain unknown.

Effects of long-term fasting on insulin responses to fatty acids in man.

OBJECTIVE: To investigate whether the prolonged physiological elevation of nonesterified fatty acids (NEFA) seen in man during fasting associates with an altered acute insulin response to NEFA. SUBJECTS AND METHODS: Fourteen non-diabetic subjects, age 18-25 years, BMI 23.2 +/- 0.8 kg/m2 underwent hyperglycemic clamps (blood glucose 11 mM) for 120 min, during which either saline or Intralipid was administered in the last 60 min. Subjects were tested after an overnight as well as after a 58 h fast. RESULTS: After the overnight fast, insulin levels increased during Intralipid infusion, at min 120 reaching an increment of 33.0 +/- 8.5 microU/ml vs. 9.5 +/- 4.4 microU/ml during saline; p<0.05 for difference. Conversely, after the 58 h fast. Intralipid failed to promote a successive increase of insulin levels (increment during Intralipid at min 120: 0.5 +/- 5.8 microU/ml vs. -4.3 +/- 2.5 microU/ml during saline, NS). Insulin sensitivity as assessed by the amount of infused glucose and its ratio to insulin was enhanced by Intralipid after an overnight fast, but was decreased after a 58 h fast. CONCLUSION: Long-term elevated NEFA during fasting associates with diminished beta cell responsiveness to an acute elevation of fatty acids in conjunction with negative effects on insulin sensitivity.

Benefit of population-based screening for phenotypic hemochromatosis in young men.

BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in the body, most notably in the liver. More men than women become clinically ill. The prognosis is excellent if phlebotomy treatment is started before liver cirrhosis develops. Screening has been recommended, but the benefit of population-based screening has never been shown in a randomized clinical trial. In this article, we estimate the benefit of screening young men, using a theoretical model. METHODS: A phenotypic screening scenario was modelled using a decision tree. Gain of quality-adjusted life-years was used as a measure of benefit, and estimated using Markov processes. Data on the accuracy of the screening tests, the prevalence of HH and the risk of liver cirrhosis were mainly derived from a cross-sectional study on the prevalence and morbidity of HH in 30509 men. Data on the excess mortality of cirrhosis were taken from relevant literature. Sensitivity analysis was done for important variables. RESULTS: Assuming basal case values for variables, screening a cohort of 1000 men aged 30 years for phenotypic HH would gain about 8 quality-adjusted life-years, compared to awaiting symptomatic disease. Based on actual costs of our cross-sectional study, the screening cost was US$250 per quality-adjusted life-year gained. The prevalence of phenotypic HH, the excess mortality of liver cirrhosis, the quality of life in non-cirrhotic HH patients, and the fractions of patients compliant with treatment were the most important variables in the sensitivity analysis. CONCLUSION: Incorporating screening for phenotypic HH in health survey programmes for young men may be worthwhile.

Hereditary haemochromatosis in two cousins with cluster headache.

A 60-year-old woman with secondary chronic cluster headache had increased serum ferritin and serum transferrin saturation and was homozygous for the C282Y mutation in the HFE gene, which is indicative of hereditary haemochromatosis. Treatment with venesection that normalized her iron stores led to a radical improvement of her headache complaints that had been daily for several years. Later, the headache returned to some degree in spite of normal serum ferritin levels. Her cousin, a 33-year-old man who had had episodic cluster headache for several years, also had increased transferrin saturation and was compound heterozygous for two mutations, a genotype known to be associated with a slightly increased frequency of haemochromatosis. This is the first report of a headache disorder in a patient with hereditary haemochromatosis. The coexistence of the two disorders may be a mere coincidence, but the temporary improvement of headache from depletion of iron stores may indicate a causal relation, possibly mediated by iron deposits in pain-modulating centres in the brainstem.

Persons with screening-detected haemochromatosis: as healthy as the general population?

BACKGROUND: Hereditary haemochromatosis (HH) is a common genetic disease leading to iron deposition in the liver and other organs. Early treatment will prevent clinical disease and population-based screening for HH has been advocated. However, the benefit of screening depends on the morbidity of HH. We have compared the morbidity in HH persons detected by screening with the morbidity in the rest of the population. METHODS: All inhabitants 20 years or older in a Norwegian county (94,191 persons) were invited to participate in a health survey programme. Of 65,717 participating persons, a blood specimen for transferrin saturation was obtained from 65,238. After repeated laboratory testing and clinical examination, 269 persons were found to have phenotypic HH, while 297 had genotypic HH (the C282/C282Y mutation). Using self-reported data, clinical examinations and analysis of non-fasting blood samples, the morbidity in phenotypic and genotypic HH persons was compared with the morbidity in the rest of the population. All data were collected before subjects were diagnosed with HH, and all comparisons were corrected for age and gender. RESULTS: Compared to control persons, phenotypic and genotypic HH men and women had a higher score on 1 of 17 questions dealing with joint complaints. Phenotypic and genotypic HH women below 50 years of age had a higher prevalence of hypothyroidism (15.2% and 12.5%, respectively, compared to 3.0% in the control population). Phenotypic HH women below 50 years of age had higher diastolic blood pressure than control women. Phenotypic HH men above 50 years of age and genotypic HH men scored lower than control men on a compound myocardial infarction risk score variable, in part due to lower serum cholesterol concentration. Fewer phenotypic HH men above 50 years of age reported having angina pectoris. Otherwise, the health of phenotypic and genotypic HH persons was not different from the health of control persons. CONCLUSION: When corrected for age and gender, the morbidity in persons with screening-detected HH was not very different from the morbidity in the control group, indicating that population-based screening may not be as beneficial as anticipated.

Reference intervals for procalcitonin and C-reactive protein after major abdominal surgery.

Procalcitonin (PCT). a new marker proposed as a diagnostic tool for bacterial infections, triggers a systemic-inflammatory reaction in the body (sepsis, septic shock) and has potential use in a wide range of patient settings. To interpret the results from PCT measurements, we depend on reference intervals established from relevant populations. PCT and C-reactive protein (CRP) concentrations were analysed in 47 patients with a normal postoperative course after major abdominal surgery. The mean concentration of PCT declines from the first day and reaches half its initial values on the second day after the operation. whereas the mean concentration of CRP increases in the first 48 h and reaches half its maximum value on the fifth day after the operation. We present a continuous reference interval for plasma PCT and CRP concentrations in the first week following major abdominal surgery. For PCT we also present a graphic display of expected mean and expected upper reference limits predicted from the value measured on the first postoperative day.

Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons.

BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in several organs, most notably the liver. The C282Y/C282Y mutation in the HFE gene is found in most cases. In order to prevent clinical disease and to study the cost and feasibility of screening, a large population was screened. METHODS: In a Norwegian county, all inhabitants 20 years or older were invited to participate in a population-based health survey programme. Screening for HH was one of several subprojects. Blood samples were obtained from 65,238 persons. Subjects with high serum transferrin saturation in two tests and high serum ferritin were clinically evaluated for HH. All subjects with high serum transferrin saturation in two tests were offered genotyping. RESULTS: HH was newly diagnosed in 92 women and 177 men. Phlebotomy treatment was performed in 64 women and 152 men. Severe organ damage (liver cirrhosis) was ascertained in only 4 men. We found no correlation between serum ferritin and age. The estimated cost was US$ 1.6 per subject screened and US$ 390 per newly discovered HH subject. The estimated prevalence of phenotypical HH not previously known was 0.34% in women and 0.68% in men. The prevalence of the C282Y/C282Y mutation was at least 0.68%. CONCLUSION: Large-scale screening for HH can be performed at a relatively low cost if combined with a health survey programme. The yield in terms of newly discovered cases is considerable, but few cases were found seriously ill. Better knowledge of the natural course of HH is necessary if we are to be able to estimate the cost-effectiveness of large-scale screening.

Detection of alcohol abuse in neurological patients: variables of clinical relevance to the accuracy of the %CDT-TIA and CDTect methods.

OBJECTIVES: Alcohol-related neurological diseases are encountered frequently. Early diagnosis is essential, because minimal intervention effectively reduces hazardous alcohol consumption and may prevent permanent neurological damage. Carbohydrate-deficient transferrin (CDT) is a valuable tool for the identification of alcohol abuse, but for unselected patient populations, reduced test accuracy has been reported. Recently, factors other than alcohol use have been shown to influence CDT levels. Our aim was to identify clinically relevant factors that might reduce test accuracy. MATERIAL AND METHODS: We included 397 neurological patients consecutively hospitalized for seizures, ischemic stroke, or sciatica and 87 patients who attended routine outpatient controls for epilepsy. Blood samples were analyzed for CDT by using two commercially available tests, %CDT-TIA and CDTect. All patients underwent a semistructured clinical interview that included a record of the reported ethanol consumption during the last 8 days, and all completed the Alcohol Use Disorders Identification Test (AUDIT). Current medication, medical history, and demographic information also were obtained. RESULTS: Both tests were elevated in female antiepileptic drug users, compared with others who reported no recent ethanol intake. A higher number of false-positive cases was seen for CDTect than for %CDT. Various combinations of CDT and gamma-glutamyltransferase improved sensitivity, but at the cost of reduced specificity. Variables that predicted the variation of CDT included antiepileptic drug use, sex, body mass index, and smoking. Total transferrin levels were reduced significantly in postmenopausal women, whereas a falling trend was seen for CDTect. Transferrin alterations caused a higher number of false-positive results for CDTect than for %CDT. The area under the receiver operating characteristics curve for women was higher for CDTect than for %CDT, and for %CDT, the area under the receiver operating characteristics curve was higher for men than for women. CONCLUSION: The accuracy of CDT for detection of alcohol abuse in neurological patients was generally low, particularly for women. Combination variables of CDT and gamma-glutamyltransferase did not increase test accuracy. Variables that were associated with higher CDT levels included female sex, antiepileptic drug use, transferrin alterations, and possibly low body mass index. When factors known to cause poor accuracy in particular patient groups are appreciated, CDT may be a good adjunct to the clinical examination.

Birthweight in a fishing community: significance of essential fatty acids and marine food contaminants.

BACKGROUND: Marine food provides essential fatty acids that are important during pregnancy, but the benefits may be limited at high intakes and by seafood contaminants. METHODS: In the fishing community of the Faroe Islands, 182 pregnant women with spontaneous singleton births were consecutively recruited for a cohort in 1994- 1995. Concentrations of fatty acids and seafood contaminants in blood samples were analysed as predictors of gestational length and birthweight. RESULTS: Serum concentrations of eicosapentaenoic acid (EPA) increased with maternal marine food intake, while the tendency was less clear for docosahexaenoic acid (DHA). An increase in the relative concentration of DHA in cord serum phospholipids by 1% was associated with an increased duration of gestation by 1.5 days (95% CI : 0.7-2.2). However, birthweight adjusted for gestational length decreased by 246 g (95% CI : 16-476) for each increase by 1% of the EPA concentration in cord serum. Concentrations of the seafood pollutants mercury and polychlorinated biphenyls (PCB) were associated with fatty acids levels, but the contaminants did not appear to affect any of the outcome parameters. CONCLUSION: An increased intake of marine fats appears to prolong the duration of gestation, but birthweight adjusted for gestational age may decrease at high intake levels. This effect does not seem to be due to increased exposures to seafood contaminants.

Fatty acid chain length and degree of unsaturation are inversely associated with serum triglycerides.

Little is known about the association between dietary fatty acids and serum triglycericle concentrations. Plasma fatty acids may reflect dietary intake and can be used to study the relationship between concentrations of individual fatty acids and serum lipids. We examined the cross-sectional relationship of plasma fatty acids with serum nonfasting triglyceride and total cholesterol concentrations. Relative concentrations of individual plasma phospholipid fatty acids were determined by gas liquid chromatography among 4,158 men aged 40-42 yr, who participated in a population study. The pattern of associations between individual fatty acids and cholesterol was different from that between individual fatty acids and triglyceride concentrations. All fatty acids displayed positive associations with total cholesterol concentration except linoleic acid, which was inversely related to cholesterol. In contrast, associations between individual fatty acids and triglyceride concentrations differed in strength and direction depending on both carbon chain length and the degree of unsaturation. Concentrations of very long chain (20 carbon atoms or more) saturated, monounsaturated, and n-3 polyunsaturated fatty acids showed significant inverse associations with triglycerides, whereas shorter fatty acids within these classes were positively associated with triglyceride concentrations. The present data suggest that the associations between concentrations of serum triglycerides and plasma phospholipid fatty acids depend on both fatty acid chain length and the degree of unsaturation.

Effect of dietary advice and n-3 supplementation in newly diagnosed MS patients.

OBJECTIVE: To investigate whether supplementation with fish oil given together with dietary advice and vitamin supplementation influenced the clinical outcome in newly diagnosed multiple sclerosis (MS) patients. MATERIAL AND METHODS: Sixteen consecutive, newly diagnosed patients with multiple sclerosis were recruited to an open intervention study. They were given dietary advice and supplemented with 0.9 g/day of long-chain marine fatty acids and vitamins. The patients were followed for 2 years with respect to dietary habits, blood parameters and neurological assessment including exacerbation rate. RESULTS: There was a significant reduction in the mean annual exacerbation rate and the mean Expanded Disability Status Scale (EDSS) as compared to pre-study values. The plasma total phospholipid n-3 fatty acids increased and n-6 fatty acids decreased significantly. CONCLUSIONS: The results suggest that fish oil supplementation given together with vitamins and dietary advice can improve clinical outcome in patients with newly diagnosed MS.

Quantification of plasma lipids and apolipoproteins by use of proton NMR spectroscopy, multivariate and neural network analysis.

New approaches for quantification of human blood plasma lipids and apolipoproteins are presented. One method is based on multivariate analysis of proton nuclear magnetic resonance spectra of human blood plasma. Although similar approaches have been developed previously, this is the first time principal component analysis (PCA) and partial least squares regression (PLS) have been applied to this particular task. Further, a large proportion of the subjects in this study were cancer patients undergoing treatment, which introduced a new dimension to the quantification of lipoprotein distributions. Calibration models for prediction of lipids and apolipoproteins were constructed by use of PLS, and blind samples were used to test the predictive ability. Comparison of the predicted vs observed data obtained by standard clinical chemical procedures gave good agreement; the correlation coefficient for total plasma triglyceride was 0.99, for total plasma cholesterol 0.98, for LDL cholesterol 0. 97, and for HDL cholesterol 0.88. These results are comparable with those obtained with other methods. The quantitative analysis of 14 components (including total cholesterol and total triglyceride) of human blood plasma was also undertaken using various neural network (NN) analyses of selected portions of the spectra. Conventional fully connected backpropagation neural network topologies were capable of providing excellent predictions for the majority of the variables, confirming and reinforcing literature related to this approach. However HDL triglycerides were poorly predicted, while intermediate-quality results were obtained for the LDL cholesterol, plasma apoA1 and LDL apoB variables. In these instances, applying significantly different neural network algorithms involving either general regression or polynomial neural networks in combination with genetic adaptive components for parameter optimisation made improved predictions.