Fatty acid composition of serum phospholipids in cystic fibrosis (CF) patients with or without CF related liver disease.

BACKGROUND: In cystic fibrosis (CF), changes in fatty acid (FA) composition of serum phospholipids (PL) and cell membranes can account, in part, for the inflammatory state of the disease. The severity of the genotype is known to correlate with the degree of FA changes. Liver diseases, such as cholestasis and cirrhosis are also known to influence FA status. Until now, there is no data on the influence of CF related liver disease (CFRLD) on the FA status of CF patients. The aim of this study was to evaluate, whether the presence of CFRLD influences FA status. METHODS: A fasting blood sample for the determination of serum vitamin E and PL-FA composition was collected from 79 CF patients with stable pulmonary disease and under good control in our CF centre. Patients with CFRLD (n=13) were compared to CF patients with the same severity of genotype (n=66) but without CFRLD. RESULTS: The CF patients with CFRLD had lower docosahexaenoic acid (DHA, 22:6n-3) and increased docosatetraenoic acid (22:4n-6). There were no significant differences in the precursors of these FAs. CONCLUSIONS: DHA concentration in patients with CFRLD is decreased more substantially compared with their genotype controls. The presence of CFRLD should be taken into account in future FA studies in CF patients.

Investigation of the potential association of vitamin D binding protein with lipoproteins.

BACKGROUND: Vitamin D binding protein (DBP) acts as a vitamin D carrier and an actin scavenger. We have previously reported a correlation between serum DBP and lipid parameters in a cystic fibrosis population. In the present study, the relationship between serum DBP, lipoprotein fractions and vitamin D is investigated. METHODS: The presence of DBP in lipoprotein fractions was examined using precipitation, gel permeation chromatography and ultracentrifugation. The association between DBP and lipids was investigated in a cohort study of 211 men. Total and actin-free DBP concentrations were assessed by immunonephelometry and enzyme-linked immunosorbent assay. Serum 25(OH)- and 1.25(OH)(2)-vitamin D(3) were assayed by radioimmunoassay. Total cholesterol, high-density lipoprotein cholesterol (HDL), triglycerides and insulin were measured using routine methods. Low-density lipoprotein-cholesterol (LDL) was calculated according to Friedewald's formula. RESULTS: DBP was found to be present in very-low-density lipoprotein (VLDL). Gel permeation chromatography revealed a bimodal DBP distribution with a lipid-bound fraction besides the known free fraction. Ultracentrifugation confirmed the presence of DBP and 25(OH)-vitamin D(3) in the VLDL particle. Total serum DBP concentration and the actin-bound DBP/DBP ratio correlated significantly with total cholesterol, LDL-cholesterol, triglycerides and albumin. The 25(OH)-vitamin D(3)/DBP ratio correlated negatively with serum triglyceride concentration and body mass index (BMI). The actin-bound DBP complex was identified with Western blot. CONCLUSIONS: The lipid-bound DBP fraction may be of greater importance than initially thought. The present findings may have clinical consequences in view of the important physiological role of DBP.

Lowered omega-3 PUFAs are related to major depression, but not to somatization syndrome.

BACKGROUND: Studies indicated a depletion of omega-3 fatty acid levels and an imbalance between omega-3 and omega-6 PUFAs in depressive patients. Depletion of omega-3 PUFAs may be related to the immune and serotonergic pathophysiologies of depression by alterations in membrane fluidity and modulation of membrane receptors, enzyme activities and carriers. Previous studies also found serotonergic and immunological disturbances in subjects with somatoform symptoms. Based on these findings we aimed to investigate PUFA concentrations and its relations to other biological systems in depressed patients and in patients with somatoform symptoms. METHODS: We examined 150 subjects divided in 4 groups, i.e. somatization syndrome; depression; depression and somatization syndrome; controls. Blood samples were analyzed for fatty acids, markers of the serotonergic system and the immune system. RESULTS: The study was able to replicate earlier findings in patients with depression (lowered omega-3 PUFAs, increased omega-6/omega-3 ratios in serum cholesteryl esters). The somatization syndrome group showed no abnormalities in the mentioned fatty acid levels. Only depressive patients revealed associations between fatty acids with serotonergic and immunological markers. LIMITATIONS: We used current state diagnoses, and the consideration of lifetime diagnoses and longitudinal studies could highlight further aspects of the reported results. CONCLUSIONS: The findings are further confirming that the concepts of depression and somatoform disorders should not be merged indiscriminately together, even though they often occur together. We conclude that in depression and somatoform syndrome different biological mechanisms seem to be involved.

Improvement in the plasma omega-3 index by the use of a fish oil-enriched spread.

BACKGROUND: The main aim of this pilot study was to determine whether the omega-3 status can be improved by the use of a fish oil-enriched spread in a regular diet. METHODS: The study started with an open arm where the participants consumed their regular diets followed by a randomized placebo-controlled arm with the inclusion of a spread which was either fish oil enriched or not (control). After each period,the fatty acid composition of red blood cell (RBC) and plasma phospholipids was determined by standard procedures and the sum of eicosapentaenoic and docosahexaenoic acid calculated. t tests were performed to calculate the significance. The first-order linear model was used to calculate correlations between selected parameters. RESULTS: When the patients were on their usual diets, a strong correlation was found between the omega-3 index based on RBCs and plasma.In the group consuming the fish oil-enriched spread, the omega-3 index based on both RBCs and plasma was significantly higher after 3 weeks of intervention. This was not the case after intervention with the control spread. CONCLUSION: Inclusion of reasonable amounts of a fish oil-enriched spread in an otherwise regular diet can be sufficient for obtaining a significant increase in omega-3 index.

Relation between fatty acid composition and clinical status or genotype in cystic fibrosis patients.

OBJECTIVE: To evaluate the relation of clinical parameters and genotype with the serum phospholipid fatty acid (FA) composition in cystic fibrosis (CF) patients. METHODS: A blood sample was taken from CF patients with stable pulmonary disease for the determination of phospholipid FA composition and vitamin E concentration who had been followed for at least 6 months at our Cystic Fibrosis Centre. Genotype, age, pancreatic function, nutritional status, caloric intake, pulmonary function and presence of Pseudomonas colonization, liver disease or diabetes mellitus were recorded. Patients were divided into two groups according to their genotype (group A: mutation class I, II, or III, group B: mutation class IV, V). RESULTS: CF patients (group A and B together) have significantly lower docosahexaenoic acid (DHA) (p < 0.007) and linoleic acid (LA) (p < 0.0001) and higher dihomogammalinolenic acid (DHGLA) (p < 0.0001), oleic acid (OA) (p < 0.0001) and Mead acid (MA) (p < 0.0001), resulting in an increased ratio of arachidonic acid (AA)/DHA (p < 0.004), MA/AA (p < 0.0001) and OA/LA (p < 0.0001). Compared to group B, group A had a lower LA (p < 0.002) and a higher DHGLA (p < 0.002), 22:4omega-6 (p < 0.03), 22:5omega-6 (p < 0.03) and 20:3omega-9 (p < 0.04). There was however no significant difference between the groups for age, pulmonary function, nutritional status and vitamin E concentration. There was no relation of serum FA composition with nutritional status, caloric intake, pancreatic function, gender, pulmonary function, Pseudomonas colonization or diabetes mellitus. In CF with liver disease the DHA was lower than in the patients of the same genotype. CONCLUSION: FA disturbances are more pronounced in the severe CF genotypes and the presence of CF-related liver disease. Future studies on supplementation should take these parameters into account.

Lower omega-3 polyunsaturated fatty acids and lower docosahexaenoic acid in men with pedophilia.

BACKGROUND: Previous studies have suggested that abnormalities in plasma phospholipid fatty acids may play a role in aggressive behavior. Recently, it was suggested that a dysfunctional serotonergic turnover in the brain may be involved in the etiopathology of pedophilia. Depletion of n-3 polyunsaturated fatty acids (PUFA) may cause alterations in the serotonergic system that may be related to pedophilia and aggression. METHODS: This study examines the serum phospholipid n-3 and n-6 PUFA fractions in pedophilia. Twenty-seven pedophilic men and eighteen healthy volunteers participated in this study. RESULTS: In pedophilia there was a significant depletion of the C22:6n-3 (docosahexaenoic acid, DHA), total n-3 fractions and an increase in the total n-6/n-3 and C20:4n-6/C20:5n-3 (arachidonic acid/eicosapentaenoic acid) ratios. Using the NEO Personality Inventory, lower DHA in pedophiles is related to more impulsiveness and lower agreeableness (trust, altruism, straightforwardness, compliance) and conscientiousness (self-discipline). CONCLUSIONS: The results of this study suggest that a depletion of the serum phospholipid n-3 higher unsaturated fatty acids (HUFAs) and, in particular, of DHA may take part in the pathophysiology of pedophilia. One hypothesis is that a depletion of n-3 HUFAs and DHA may cause alterations in the serotonergic turnover, which are related to impulse discontrol and aggression-hostility, behaviors which are associated with pedophilia.

Polyunsaturated fatty acids: do they have a role in the pathophysiology of autism?

OBJECTIVES: There is now some evidence that alterations in fatty acids may play a role in the pathophysiology of autism. The aim of the present study was to examine whether autism is accompanied by abnormalities in the composition of the polyunsaturated fatty acids (PUFAs) in plasma phospholipids. METHODS: The plasma phospholipid omega-3 (3) and omega-6 (6) PUFA fractions and the 3/6 ratio were measured in 16 high-functioning male youngsters with autism (age 12-18) and 22 healthy volunteers. Group mean differences were assessed by means of analysis of variance (ANOVA). RESULTS: In autism there was a significant increase in the fraction of C22:6-3 (docosahexaenoic acid, DHA) and an increase in the total 3/6 ratio. DISCUSSION: The results of this study suggest that an increase of the plasma phospholipid 3 PUFAs, in particular DHA, and of the total 3/6 ratio may take part in the pathophysiology of autism. One hypothesis is that an increase of 3 PUFAs may cause alterations in the serotonergic turnover and the immune response system, both known to be associated with autism. Caution must be exercised against highly concentrated 3 PUFAs supplementation.

Comparison of triglyceride concentration with lipemic index in disorders of triglyceride and glycerol metabolism.

BACKGROUND: In plasma, triglycerides (TG) are transported in lipoprotein particles (mainly chylomicrons, very low-density and low-density lipoprotein). Turbidimetry (bichromatically at 660 and 700 nm) allows measurement of the lipemic (L) index. We explored the use of this index, in combination with a TG assay, to detect errors due to non-fasting, to assess abnormalities in TG metabolism and to detect patients with glycerol kinase deficiency (GKD). METHODS: We collected 2441 patient samples. Normolipidemic (n=2347), type IV hyperlipidemic (n=80), postprandial samples (n=22) and serial dilutions of Intralipid with saline (n=6) were selected. One patient presenting with GKD was included, as well as two patients with type I and type V hyperlipoproteinemia, respectively. RESULTS: We introduced the use of the ratio between the logarithm of serum triglycerides and that of the L-index (TG/L ratio). CONCLUSION: Although the proposed TG/L-index ratio cannot be regarded as an alternative for the accurate diagnosis of lipid disorders, it provides additional information about TG-containing particles.

Long-chain omega6 polyunsaturated fatty acids in erythrocyte phospholipids are associated with insulin resistance in non-obese type 2 diabetics.

BACKGROUND: Associations have been described between insulin action and long-chain omega6 polyunsaturated fatty acids in skeletal muscle and erythrocytes of healthy individuals. We evaluated whether there was an association between insulin resistance and long-chain omega6 polyunsaturated fatty acids in erythrocyte phospholipids of type 2 diabetics. METHODS: Erythrocyte phospholipid fatty acid composition was determined in 43 adult non-obese type 2 diabetics. Insulin resistance was estimated by the HOMA mathematical approximations. Individual omega6 fatty acids and the sum of long-chain omega6 polyunsaturated fatty acids were correlated with insulin resistance. The same association was assessed for fatty acid product/precursor ratios taken as measures of Delta5 desaturase, Delta6 desaturase and their combined action. RESULTS: Except for 18:2omega6, 20:2omega6 and 20:3omega6, the individual omega6 fatty acids tested and the sum of long-chain omega6 polyunsaturated fatty acids correlated negatively with insulin resistance at p<0.005. Likewise, a negative correlation was found for the combined action of Delta5 and Delta6 desaturases (p<0.005). CONCLUSIONS: Our results indicate that formation of long-chain omega6 fatty acids from 18:2omega6 by desaturation-elongation is impaired under insulin resistant conditions and reduced desaturase activities may be involved. In view of our results, we hypothesize that in insulin resistant conditions, insulin-mediated activation of Delta5 and Delta6 desaturases may not occur.

La ingestión de nutrientes de diabéticos tipo 2 cubanos difiere de las recomendaciones / Nutrition intake of Cuban type 2 diabetics differs from recommendations

Fundamentos: Múltiples estudios han demostrado laeficacia de intervenciones en el estilo de vida (dirigidoshacia la dieta y el ejercicio) en la reducción del riesgo desufrir diabetes mellitus tipo 2.Objetivo: Documentar la ingestión diaria de energía,macronutrientes y micronutrientes antioxidantes seleccionadosde diabéticos tipo 2 cubanos y compararlascon las recomendaciones cubanas y de la ADA.Métodos: Se aplicaron encuestas dietéticas de 3 días a56 diabéticos tipo 2 no obesos. Las mismas fueronanalizadas a través del programa CERES, basado en laTabla Cubana de Composición de Alimentos. Se calculóy graficó la contribución relativa de 10 grupos de alimentosa la energía total, las grasas totales, saturadas,poliinsaturadas y esenciales.Resultados: Una gran proporción de los diabéticos excediólas recomendaciones para las grasas totales y saturadaspero no las alcanzó para los carbohidratos, fibra,vitamina E y cinc.Conclusiones: Aconsejamos disminuir la ingestión degrasas totales y saturadas reduciendo el consumo depollo con piel, carne de cerdo y sus derivados. Debeaconsejarse el consumo de pescados y huevos al serfuentes ricas en cinc y vitamina E. Las dietas ricas engrasas deben ser sustituidas por dietas con baja cargaglicémica ricas en carbohidratos complejos y fibra

Background: Several studies have demonstrated theefficacy of lifestyle interventions (targeting diet andexercise) in reduction of risk of type 2 diabetes.Objective: To document the daily intake of energy,macronutrients and selected antioxidant micronutrientsof Cuban type 2 diabetics and compare them with theCuban and the ADA recommendations.Methods: 3-day food diaries from 56 non-obese type 2diabetics were obtained. Nutrient analysis was performedby the nutritional software CERES based on the CubanFood Composition Table. The contribution of 10 foodgroups to total energy intake, total fats, saturated, polyunsaturatedand essential fatty acids were calculated andgraphically represented.Results: A high proportion of diabetics exceeded therecommendations for total and saturated fats and did notreach the recommendations for carbohydrates, fiber,vitamin E and zinc.Conclusions: We advise to decrease total and saturatedfat intakes by reducing the intake of chicken with skin,pork and its derivatives. Fish consumption should beadvised as it is a good source of zinc. Since eggs are richin vitamin E and zinc, their consumption should beincreased under certain limits. Fat rich diets should bereplaced by low glycaemic load diets rich in complexcarbohydrates and fiber

Effect of diabetes mellitus and different treatments on plasma and erythrocyte phospholipid fatty acid composition in type 2 diabetics.

AIM: The aim of the present study was to determine how the fatty acid composition of plasma and erythrocyte phospholipids is influenced by the diabetic condition and by dietary or glibenclamide treatment in type 2 diabetes. METHODS: The fatty acid composition of plasma and erythrocyte phospholipids is assessed in 3 nonobese groups of Cuban diabetics with comparable age and BMI: 13 newly diagnosed, 15 on diet alone and 15 on diet/glibenclamide. Thirteen healthy individuals were used as controls. Fasting serum glucose, insulin and glycosylated hemoglobin and dietary fat intake were assessed. RESULTS: In plasma phospholipids, significant lower values were found for 14:0, 15:0 and 17:0 in newly diagnosed patients than in controls. In red blood cell phospholipids, 14:1, 20:0 and 24:1 of newly diagnosed patients were significantly lower than of controls, and 16:1omega7 and 18:4omega3 were significantly higher. The different treatments had an effect on 18:0, 18:1t, 20:0 and total trans fatty acids in erythrocyte, but not in plasma phospholipids. CONCLUSIONS: Changes in plasma phospholipid fatty acids found in type 2 diabetics may be due to an 'adapted' dietary pattern, whereas those in erythrocyte phospholipids may be attributed to effects of the disease itself and may be susceptible to normalization by diet or glibenclamide.

Fatty acid composition of erythrocyte phospholipids is related to insulin levels, secretion and resistance in obese type 2 diabetics on Metformin.

BACKGROUND: Relationships between fatty acids in erythrocyte phospholipids and insulin parameters have been described in healthy and overweight individuals, but not in obese diabetics. We assessed whether erythrocyte phospholipid fatty acids are related to insulin parameters in obese type 2 diabetics on Metformin. METHODS: In 23 diabetics, the fractions of the different fatty acids in erythrocyte phospholipids were correlated with insulin levels, secretion, sensitivity, resistance and insulinemic response following a standardised breakfast. RESULTS: Fasting insulin levels and insulin resistance correlated positively with the fraction of alpha-linolenic and dihomo-gamma-linolenic acid and with the ratios of stearic to palmitic and dihomo-gamma-linolenic to linoleic acid and negatively with the fraction of palmitic acid in erythrocyte phospholipids. Insulin secretion correlated negatively with the fraction of palmitic acid. For this parameter, a positive correlation was also found with the sum of uneven fatty acids. Insulinemic response following a meal was negatively associated with the fraction of oleic acid in erythrocyte phospholipids. Insulin sensitivity did not correlate with erythrocyte fatty acids. CONCLUSIONS: The relationships found differ from those described in healthy and overweight individuals and may be characteristic for type 2 diabetics. They concur with the recommendations that saturated fat intake should be reduced and monounsaturated increased.

What exactly was wrong with the Trilucent breast implants? A unifying hypothesis.

Trilucent soybean oil-filled breast implants were initially announced as the ultimate prostheses for breast augmentation. However, after an increasing number of reports of local complications and hazardous metabolites attributable to lipid oxidation, first the United Kingdom Medical Devices Agency and later the Belgian National Ministry of Health urged all plastic surgeons to contact their patients and advise them to have the implants removed and, if desired, replaced with another type of prosthesis. In our plastic surgery department, 13 patients received bilateral implants with triglyceride-filled prostheses between February and July of 1996, for primary breast augmentation or replacement of previously implanted prostheses. For 12 of those 13 patients, the prostheses have been explanted, because of unilateral breast enlargement attributable to a ruptured prosthesis for five patients and following the recommendation of the Belgian National Ministry of Health for the other seven patients. Before explantation, all patients underwent standard clinical examinations, with assessments of breast shape, volume, and firmness. Blood analyses were performed, with a special focus on liver enzymes, as were urinalyses. Magnetic resonance imaging scans were obtained before explantation; for two patients, the scans revealed a fluid level separating two liquid layers in an intact prosthesis. This is the first report of such a finding. The removed implants were examined for any damage or shell deterioration and for changes in color and viscosity, the weights and volumes were measured and compared with the initial values for the implanted prostheses, and complete biochemical analyses of the accumulated fluid in cases of ruptured prostheses and of the filler material in cases of intact prostheses were performed. This small but well-documented series illustrates the multitude of problems associated with triglyceride-filled implants, including bleeding of the triglyceride filler; shell deterioration, as indicated by a loss of texture and extreme fragility of the implant (with rupture or delamination with a simple finger touch); an increase in osmotic pressure exerted by the degraded filler material; progressive weakening of the outer silicone shell, with influx of plasma proteins of up to 750 kDa, eventually resulting in rupture of the prosthesis; a lack of oxidative stability and the formation of toxic oxidation products; a lack of biocompatibility, with the formation of insoluble organic soap-like material; and a pronounced inflammatory reaction. It is concluded that the sequential and/or simultaneous occurrence of (1) implant bleeding, (2) lipid infiltration of the silicone elastomer, and (3) inflammation attributable to oxidation products provides an overall explanation or unifying hypothesis for the wide variety of adverse events related to soybean oil-filled implants.

The effect of supplementation with an antioxidant preparation on LDL-oxidation is determined by haptoglobin polymorphism.

The genetic polymorphism of haptoglobin (Hp) is an independent risk factor in the pathogenesis of atherosclerosis, a condition in which decreased resistance to in vitro oxidation of LDL-cholesterol is observed. We hypothesised that the Hp polymorphism is one of the factors modulating the resistance to Cu(2+)-induced oxidation of LDL during antioxidant supplementation. In this study, 74 middle-aged subjects with increased oxidative stress were allocated to either matched placebo or oral antioxidative treatment (Quatral) once daily for 16 weeks. Study parameters were increase of lag phase (DeltaLAG) and the ratio of lag phase during treatment period versus baseline (relative oxidation resistance, ROR), measured by Cu(2+)-induced oxidation of isolated LDL. Hp phenotypes were determined by starch gel electrophoresis. A significant and persistent increase of DeltaLAG (P < 0.05) and ROR (P < 0.01) were observed after 16 weeks of active treatment versus placebo. Interindividual differences in both parameters were significantly associated with the Hp polymorphism: in the active treatment group, DeltaLAG and ROR were significantly higher in Hp 1-1 subjects (P < 0.01) compared to Hp 2-1 and 2-2. Our data demonstrate that Hp phenotype is one of the modulating factors determining the increased resistance to Cu(2+)-induced oxidation of LDL during antioxidative treatment.