Prenatal omega 3 fatty acid supplementation to a micronutrient imbalanced diet protects brain neurotrophins in both the cortex and hippocampus in the adult rat offspring

ObjectiveOur earlier studies show that maternal diets imbalanced in micronutrients like folic acid and vitamin B₁₂ reduced brain docosahexaenoic acid (DHA) and brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the offspring at birth and postnatal d21. This study followed the offspring till 3 months to examine the hypothesis that impaired brain neurotrophins at birth and d21 due to altered maternal micronutrients can be reversed by prenatal omega 3 fatty acid but not a postnatal control diet leading to altered cognition in adult life.Materials and MethodsPregnant rats were divided into control and five treatment groups at two levels of folic acid (normal and excess folate) in the presence and absence of vitamin B₁₂ (NFBD, EFB and EFBD). Omega 3 fatty acid supplementation was given to the vitamin B₁₂ deficient groups (NFBDO and EFBDO). Following delivery, 8 dams from each group were shifted to control and remaining continued on same diet.ResultsImbalance in maternal micronutrients up to 3 months decreased DHA, BDNF and NGF in cortex and only BDNF in the hippocampus and impaired cognitive performance. Postnatal control diet normalized BDNF in the cortex but not the hippocampus and also altered cognitive performance. Prenatal omega 3 fatty acid supplementation normalized DHA, BDNF and NGF while long term supplementation was not beneficial only when micronutrients were imbalanced.ConclusionPatterns established at birth are not totally reversible by postnatal diets and give clues for planning intervention studies for improving brain functioning and cognitive abilities.     

Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring

Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.     

Plasma total odd-chain fatty acids in the monitoring of disorders of propionate,methylmalonate and biotin metabolism

Summary Total plasma odd-numbered long-chain fatty acids were analysed in patients with methylmalonic acidaemia (vitamin B₁₂-responsive and unresponsive), combined methylmalonic acidaemia/homocystinuria (CblC), propionic acidaemia (both neonatal-onset and late-onset), biotinidase deficiency and holocarboxylase synthase deficiency, as well as in hospital controls. Total odd-numbered long-chain fatty acids (C_15:0, C_17:1 and C_17:0) were expressed as a percentage of total C₁₂–C₂₀ fatty acids. Control values were 0.72%±0.31% (n=12). Normalization of the percentage of odd-chain fatty acids occurred in all vitamin-responsive patients, following the institution of vitamin treatment. In general the neonatal-onset propionic acidaemia and B₁₂-unresponsive methylmalonic acidaemia patients had the highest plasma odd-chain fatty acid concentrations, which correlated with the clinical condition but not with the urinary excretion of methylcitrate or methylmalonate. Plasma odd-chain fatty acid concentrations and methylmalonate excretions in CblC patients reacted very well to vitamin B₁₂ treatment, but with no clinical response. Measurement of plasma odd-chain fatty acids is of no value for the monitoring of defects of biotin metabolism.     

Blood pressure in 12-year-old children is associated with Fatty Acid composition of human milk: the prevention and incidence of asthma and mite allergy birth cohort

Breastfed individuals have a lower blood pressure than formula-fed individuals. Supplementation with n-3 long-chain polyunsaturated fatty acids in adults is also associated with a lower blood pressure. We studied whether children receiving human milk with a relatively high content of n-3 long-chain polyunsaturated fatty acids have a lower blood pressure at age 12 years, and, if so, whether this association is explained by the n-3 long-chain polyunsaturated fatty acids content in erythrocyte membranes at age 12 years. Within a 12-year follow-up of a population-based birth cohort, we compared blood pressure of 205 never-breastfed children and 109 children who had fatty acid composition of their mothers' breast milk measured during lactation. In addition, 973 children had information on erythrocyte fatty acid composition and blood pressure at age 12 years. Children who received human milk with an n-3 long-chain polyunsaturated fatty acids content above the median (ie, 0.51 weight percentage) had a 4.79-mm Hg lower systolic (95% CI, -7.64 to -1.94) and a 2.47-mm Hg lower diastolic (95% CI, -4.45 to -0.49) blood pressure at age 12 years than never-breastfed children. N-3 long-chain polyunsaturated fatty acids levels in human milk below the median value and current n-3 long-chain polyunsaturated fatty acid status were not associated with blood pressure at age 12 years. Thus, a relatively high content of n-3 long-chain polyunsaturated fatty acids in human milk is associated with a lower blood pressure in children at age 12 years, a finding not explained by current n-3 long-chain polyunsaturated fatty acids status.     

Vitamin and mineral status in elderly patients with chronic obstructive pulmonary disease

Introduction: Eating problems are common in patients with chronic obstructive pulmonary disease (COPD), and intake of micronutrients might be lower than recommended. Objective: To study dietary intake, serum and urinary concentration of trace elements and vitamins in elderly underweight patients with established severe COPD. Methods: Outpatients at a university clinic for lung medicine, with COPD, 70–85 years old, with no other serious disease, and with a body mass index (BMI) of ≤20 kg/m² and an FEV₁of <50 % predicted were recruited. Body composition and bone density were evaluated with dual energy X‐ray absorptiometry. Dietary intake was studied by a trained dietitian using diet‐history interview. Blood and urine samples were analysed for various vitamins and trace elements. Results: Seventeen of 30 recruited patients took part. Osteoporosis or osteopaenia was found in 16 patients. Dietary intake of energy and macronutrients was in line with recommendations for healthy individuals. Intake of protein did not meet recommendations for COPD patients. Intake of polyunsaturated fatty acids was lower than recommended and intake of saturated fatty acids was higher than recommended. Mean intake of vitamin D and folic acid was far below recommendations. Serum concentrations for folic acid and methylmalonate and plasma concentrations for homocysteine were below normal in several patients. Conclusion: Intake of vitamin D and calcium is often low in older COPD patients, which might contribute to osteoporosis. Low intake of folic acid might also be a problem. The results support prophylaxis with calcium, vitamin D and folic acid. Please cite this paper as: Andersson I, Grönberg A, Slinde F, Bosaeus I and Larsson S. Vitamin and mineral status in elderly patients with chronic obstructive pulmonary disease. The Clinical Respiratory Journal 2007;1:23–29.     

Daily consumption of milk enriched with fish oil, oleic acid, minerals and vitamins reduces cell adhesion molecules in healthy children

Background and aims

Several studies have suggested that polyunsaturated fatty acids, vitamins and minerals have beneficial effects on lipid profile and systemic inflammation in adults.

Methods and results

We examined the effects of a daily intake of milk enriched with long-chain polyunsaturated fatty acids, oleic acid, carbohydrates, vitamins, minerals and low in saturated fatty acids (SFAs) for 5 months, on several cardiovascular (CVD) risk biomarkers in healthy children aged 8-14 years. In a randomized double-blind placebo-controlled trial, a total of 107 children of both genders were assigned to two study groups: 1) a supplemented group (SG, n = 53) who consumed 0.6 L/day of an enriched dairy product, and 2) a control group (CG, n = 54) who consumed 0.6 L/day of standard whole milk. Both groups consumed the dairy drinks for 5 months, in addition to their usual diet. Serum levels of adhesion molecules as indices of vascular endothelial cell activation were assessed in both groups at 0 and 5 months as well as white blood cell counts, lipid profile, serum proteins, total serum calcium, 25-OH vitamin D, glucose, insulin and adiponectin. In the enriched dairy drink supplemented group, adhesion molecules E-selectin and ICAM-1 as well as lymphocyte levels decreased while plasma docosahexaenoic acid (DHA) and serum calcium concentrations increased. In the control group, serum total protein, transferrin, total cholesterol, HDL-cholesterol and adiponectin concentrations decreased.

Conclusion

The consumption of a milk enriched with fish oil, oleic acid, minerals and vitamins reduced indices of endothelial cell activation in the studied group of healthy children.     

Polyunsaturated fatty acids in the diet and breast milk of lactating icelandic women with traditional fish and cod liver oil consumption

BACKGROUND/AIMS: The proportion of polyunsaturated fatty acids (PUFA) in the diet and breast milk of lactating women with traditional fish and cod liver oil consumption was investigated under free-living conditions. METHODS: Dietary intake of 77 lactating women was investigated by 24-hour recalls and breast milk samples were taken at the same occasions. Maternal intake data was calculated and fatty acid pattern from breast milk samples analyzed with gas chromatography. RESULTS: Women using cod liver oil (n = 18) had a significantly higher total PUFA intake (14 +/- 10 vs. 9 +/- 7 g/day; 5.0 +/- 3.4 vs. 3.9 +/- 3.0 Energy%; p < 0.05) than women who did not use it (n = 59). In particular, mothers consuming cod liver oil had higher breast milk proportion of docosahexaenoic acid (DHA, 0.54 vs. 0.30%, p < 0.05). They also had higher breast milk proportions of eicosapentaenoic acid (EPA; 0.16 vs.0.07%; p < 0.05) and docosapentaenoic acid (DPA; 0.22 vs. 0.17%; p < 0.05). CONCLUSION: The proportion of PUFA in the diet is significantly higher among women consuming cod liver oil. Its use also gives higher proportion of EPA,DPA and DHA in breast milk without decreasing other important fatty acids. As this may have an impact on the health and development of breast-fed infants in later life, regular maternal cod liver oil intake could be relevant for the infant as well as for the nutritional adequacy of the maternal diet.     

Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids.

A specially prepared dog model of myocardial infarction was used to test the efficacy of the long-chain polyunsaturated fish oil omega 3 fatty acids eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n-3) acids to prevent ischemia-induced malignant cardiac arrhythmias. The dogs had sustained a prior experimental myocardial infarction from ligation of the left anterior descending coronary artery, and a hydraulic cuff was implanted around the left circumflex artery at that operation. After recovery from that procedure the animals were tested during a treadmill exercise test. With compression of the left circumflex artery sensitive animals will predictably develop ventricular fibrillation (VF). In such prepared dogs an emulsion of fish oil fatty acids was infused i.v. over a 50- to 60-min period just before the exercise-plus-ischemia test, and the effect on development of VF was recorded. The infusion was 100 ml of a 10% (vol/vol) emulsion of a fish oil concentrate containing 70% omega 3 fatty acids with free eicosapentaenoic acid and docosahexaenoic acid composing 33.9% and 25.0% of that total, respectively. Alternatively, some animals similarly received an emulsion containing 5 ml of the free fatty acid concentrate plus 5 ml of a triacylglyerol concentrate containing 65% omega 3 fatty acids with eicosapentaenoic acid and docosahexaenoic acid composing 34.0% and 23.6% of that total, respectively. In seven of eight animals the infusion of the fish oil emulsion completely prevented the acute occurrence of VF in the susceptible animals (P < 0.005). In five of five of these animals the subsequent exercise-plus-ischemia test after a similar infusion of an emulsion in which soy bean oil replaced the fish oil fatty acid concentrates resulted in prompt development of VF. Possible mechanisms for this protective effect of omega 3 fatty acids against exercise and ischemia-induced malignant arrhythmias are considered.     

Hypertension prevention: from nutrients to (fortified) foods to dietary patterns. Focus on fatty acids

Diet affects significantly the incidence and severity of cardiovascular diseases and fatty acid intake, in its qualitative as well as quantitative aspects, and influences several risk factors including cholesterol (total, LDL and HDL), triglycerides, platelet aggregation and blood pressure, as evidenced in the 2001 WHO report. This review focuses on the qualitative concern of lipid intake, the various classes of fatty acids of the lipid fraction of the diet, saturated, monounsaturated and polyunsaturated, and their effects on blood pressure. Saturated fat have a bad file and several experimental studies in the rat showed a progressive increase in blood pressure in response to a highly saturated diet. Moreover, a highly saturated diet during gestation led to offspring which, when adults, presented a gender-related hypertension. The mechanism of this effect may be related to the polyunsaturated/saturated ratio (p/s). During the past 20 years, trans fatty acids have been suspected of deleterious health effects, but the investigations have shown that these fatty acids display a biological behaviour close to that of saturated fatty acids (SFA). Moreover, epidemiological investigations did not confirm the relationship between trans fatty acids and cardiovascular pathology. Polyunsaturated fatty acids have been shown to exert a positive action on hypertension. This effect could be attributed to the alteration of the p/s, but mainly to the omega3 polyunsaturated fatty acids (PUFAs). The comparison of several animal models led to the conclusion that long-chain omega3 PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) can prevent the increase in blood pressure and reduce established hypertension, but the efficient dose remains an object of discussion. Moreover, the two long-chain omega3 PUFAs, EPA and DHA, display specific effects, which vary with the aetiology of hypertension, because their mechanism of action is different. DHA acts on both blood pressure and heart function (heart rate and ECG) and interferes with the adrenergic function. Conversely, EPA, which is not incorporated in cardiac phospholipids, has no effect on the heart and its mechanism of action is largely unknown. Although it is accepted by the scientific community that the intake of EPA and DHA needs to be increased, we will have to discover new ways to do it, since marine products are the main source of these fatty acids, and this source is not inexhaustible.     

High vitamin intake by Wistar rats during pregnancy alters tissue fatty acid concentration in the offspring fed an obesogenic diet

Diet during pregnancy affects the long-term health of the offspring. Vitamins are known to modulate lipid metabolism, which may be reflected in tissue fatty acid (FA) concentrations. The objective of this study was to investigate the effect of high vitamin intake during pregnancy on tissue FA concentration of the offspring. Wistar rats were fed an AIN-93G diet with either the recommended vitamin or 10-fold higher amounts (HV) during pregnancy. Afterward, offspring were weaned onto an obesogenic diet. Liver, quadriceps, adipose, and brain were collected over 48 weeks. Fatty acid concentration of tissue total lipids was analyzed by gas chromatography. At birth, the liver from HV offspring was higher in monounsaturated, stearic, and arachidonic acids. At weaning, the liver from HV offspring was higher in stearic and oleic acids; and in adipose tissue, n-6 and n-3 FAs were lower only in the male HV offspring (P < .05). At 12 weeks, HV offspring had higher concentrations of total fat, saturates, monounsaturates, and n-6 FA in muscle (P < .05), but not in other tissues. At 48 weeks, gestational diet did not affect tissue total lipid FA concentrations; but differences remained in specific tissue phospholipids species. Liver phospholipids from HV offspring were lower in monounsaturates and n-6 FA. Brain phosphatidylethanolamine was higher in oleic, n-6 FA, and docosahexaenoic acid in the HV offspring. Phosphatidylinositol was lower in saturates, monounsaturates, arachidonic, and docosahexaenoic acids only in HV female offspring. These observations demonstrate that high vitamin intake during pregnancy has short- and long-term effects on tissue FA concentration in the offspring.     

Identification of bifunctional delta12/omega3 fatty acid desaturases for improving the ratio of omega3 to omega6 fatty acids in microbes and plants

We report the identification of bifunctional Delta12/omega3 desaturases from Fusarium moniliforme, Fusarium graminearum, and Magnaporthe grisea. The bifunctional activity of these desaturases distinguishes them from all known Delta12 or omega3 fatty acid desaturases. The omega3 desaturase activity of these enzymes also shows a broad omega6 fatty acid substrate specificity by their ability to convert linoleic acid (LA), gamma-linolenic acid, di-homo-gamma-linolenic acid, and arachidonic acid to the omega3 fatty acids, alpha-linolenic acid (ALA), stearidonic acid, eicosatetraenoic acid, and eicosapentaenoic acid (EPA), respectively. Phylogenetic analysis suggests that omega3 desaturases arose by independent gene duplication events from a Delta12 desaturase ancestor. Expression of F. moniliforme Delta12/omega3 desaturase resulted in high ALA content in both Yarrowia lipolytica, an oleaginous yeast naturally deficient in omega3 desaturation, and soybean. In soybean, seed-specific expression resulted in 70.9 weight percent of total fatty acid (%TFA) ALA in a transformed seed compared with 10.9%TFA in a null segregant seed and 53.2%TFA in the current best source of ALA, linseed oil. The ALA/LA ratio in transformed seed was 22.3, a 110- and 7-fold improvement over the null segregant seed and linseed oil, respectively. Thus, these desaturases have potential for producing nutritionally desirable omega3 long-chain polyunsaturated fatty acids, such as EPA, with a significantly improved ratio of omega3/omega6 long-chain polyunsaturated fatty acids in both oilseeds and oleaginous microbes.     

Randomized, placebo-controlled trial of intramuscular vitamin B12 for the treatment of hyperhomocysteinaemia in dialysis patients

Abstract Background: Plasma homocysteine is elevated in patients with end‐stage renal disease (ESRD) and is a risk factor for cardiovascular disease. Folic acid has been shown to partially reduce homocysteine levels in dialysis patients. It is not known whether vitamin B₁₂ reduces homocysteine independent of folic acid in patients who are not vitamin B₁₂ deficient. Aim: To determine whether 1 mg vitamin B₁₂ lowers homocysteine in stable, chronic, haemodialysis patients independent of folic acid. Methods: Twenty‐eight haemodialysis patients were randomized to receive three doses of 1 mg vitamin B₁₂ or 1 mL saline placebo in a double‐blind fashion at 1‐month intervals. Fasting plasma total homocysteine, folic acid, red‐cell folate, vitamin B₁₂ and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection. The study was powered to detect a 30% reduction in homocysteine over the 3 months. Results: Both the two groups were well matched with respect to total homocysteine levels, folic acid, red‐cell folate and vitamin B₁₂ levels. Serum vitamin B₁₂ levels were significantly higher in the treatment group compared to placebo (217.7 pmol/L; 95% confidence interval (CI) 103.0?332.5; P < 0.001) at the end of the trial but homocysteine levels were not significantly different (3.08 µmol/L; 95% CI ?4.44?10.61; P= 0.406). Conclusions: The administration of intramuscular vitamin B₁₂ over a 3‐month period does not result in any reduction of plasma homocysteine levels in haemo­dialysis patients independent of folate status, however reductions of <30% cannot be excluded by the present study. High‐dose folic acid remains the treatment of choice in reducing homocysteine, but whether this results in a reduction in cardiovascular events remains to be determined. (Intern Med J 2003; 33: 489?494)     

Prevention of Hypertensive Disorders of Pregnancy: a Novel Application of the Polypill Concept

Nearly all of the annual 287,000 global maternal deaths are preventable. Hypertensive disorders of pregnancy (HDP) are among the major causes. A novel fixed-dose combination pill or polypill to prevent cardiovascular disease is a promising strategy for prevention of HDP. The aim of this study was to identify eligible candidates for a polypill for the prevention of HDP. A comprehensive review of systematic reviews on drug and dietary interventions to prevent HDP was conducted. Interventions were evaluated based on efficacy, dose, route of administration, and side effects. Fourteen interventions were assessed. Low-dose aspirin and calcium were identified as candidates for a polypill, with risk reduction estimations for pregnancy-induced hypertension and preeclampsia ranging between 10 and 62 %, depending on patient population characteristics including a priori risk, and gestation age at start of intervention. Their effect may be augmented through the addition of vitamin D, vitamin B₁₂, and folic acid. The effect and optimal composition needs to be evaluated in future trials. Given the persistent burden of maternal and perinatal mortality associated with HDP, prevention of these disorders is key—especially in low-resource settings. The polypill approach with a combination of aspirin, calcium, vitamin D, vitamin B₁₂, and folic acid is a promising strategy to improve maternal and perinatal health outcomes.     

Fatty Acid Composition of Plasma Lipid Classes in Chronic Alcoholic Pancreatitis

Background/Aims: Supplementation of n-3 long-chain polyunsaturated fatty acids (LCPUFA) is considered as adjuvant therapy in acute pancreatitis. We investigated plasma fatty acid status in chronic pancreatitis (CP). Methods: Patients with alcoholic CP (n = 56, gender: 33/23 male/female, age: 60.0 [14.0] years (median [IQR]), who reported giving up alcohol consumption several years ago and 51 control subjects were included into the study. The fatty acid composition of plasma phospholipids (PL), triacylglycerols (TG) and sterol esters (STE) was analyzed. Results: The sum of monounsaturated fatty acids was significantly higher in patients with CP than in controls (PL; 12.83 [3.35] vs. 12.20 [1.95], TG; 40.51 [6.02] vs. 37.52 [5.80], STE; 20.58 [7.22] vs. 17.54 [3.48], CP vs. control, % weight/weight, median [IQR], p < 0.05). Values of arachidonic acid were significantly lower in patients with CPthan in controls (PL; 10.57 [3.56] vs. 11.66 [3.25], STE; 8.14 [2.63] vs. 9.24 [2.86], p ! 0.05). Values of eicosapentaenoic acid and docosahexaenoic acid did not differ and there was no difference in the ratio of n-3 to n-6 LCPUFA. Conclusion: Our present data do not furnish evidence for the supplementation of n-3 LCPUFA to the diet of CP patients in relatively good clinical condition.     

The comparative reductions of the plasma lipids and lipoproteins by dietary polyunsaturated fats: Salmon oil versus vegetable oils

The lower plasma lipid levels and lower incidence of atherosclerotic diseases in Greenland Eskimos suggested that the unusual fatty acids present in their diet of seal and fish may be anti-atherogenic. These fatty acids are eicosapentaenoic (C20:5) and docosahexaenoic (C22:6) acids and are of the omega-3 fatty acid family. We have compared a salmon oil diet containing high levels of these unique fatty acids to a control diet high in saturated fat and to a vegetable oil diet high in linoleic acid (C18:2). All diets contained 40% of the total calories as fat and 500 mg of cholesterol; they differed only in fatty acid composition. In 4 wk the salmon oil diet reduced plasma cholesterol levels from 188 to 162 mg/dl (p < 0.001) and triglyceride levels from 77 to 48 mg/dl (p < 0.005). LDL and VLDL cholesterol levels changed from 128 to 108 and 13 to 8 mg/dl (p < 0.005), respectively. HDL cholesterol levels did not change. The vegetable oil diet caused similar decreases in cholesterol levels but did not lower triglyceride levels. The omega-3 fatty acids comprised up to 30% of the total fatty acids in each plasma lipid class after the salmon diet. Fish oils contain fatty acids which may be metabolically unique and potentially useful in the control of both hypercholesterolemia and hypertriglyceridemia.     

Fatty acid status in infancy is associated with the risk of type 1 diabetes-associated autoimmunity

Aims/hypothesis

We investigated the association of early serum fatty acid composition with the risk of type 1 diabetes-associated autoimmunity. Our hypothesis was that fatty acid status during infancy is related to type 1 diabetes-associated autoimmunity and that long-chain n-3 fatty acids, in particular, are associated with decreased risk.

Methods

We performed a nested case–control analysis within the Finnish Type 1 Diabetes Prediction and Prevention Study birth cohort, carrying HLA-conferred susceptibility to type 1 diabetes (n = 7782). Serum total fatty acid composition was analysed by gas chromatography in 240 infants with islet autoimmunity and 480 control infants at the age of 3 and 6 months. Islet autoimmunity was defined as repeated positivity for islet cell autoantibodies in combination with at least one of three selected autoantibodies. In addition, a subset of 43 infants with primary insulin autoimmunity (i.e. those with insulin autoantibodies as the first autoantibody with no concomitant other autoantibodies) and a control group (n = 86) were analysed. A third endpoint was primary GAD autoimmunity defined as GAD autoantibody appearing as the first antibody without other concomitant autoantibodies (22 infants with GAD autoimmunity; 42 infants in control group). Conditional logistic regression was applied, considering multiple comparisons by false discovery rate <0.05.

Results

Serum fatty acid composition differed between breastfed and non-breastfed infants, reflecting differences in the fatty acid composition of the milk. Fatty acids were associated with islet autoimmunity (higher serum pentadecanoic, palmitic, palmitoleic and docosahexaenoic acids decreased risk; higher arachidonic:docosahexaenoic and n-6:n-3 acid ratios increased risk). Furthermore, fatty acids were associated with primary insulin autoimmunity, these associations being stronger (higher palmitoleic acid, cis-vaccenic, arachidonic, docosapentaenoic and docosahexaenoic acids decreased risk; higher α-linoleic acid and arachidonic:docosahexaenoic and n-6:n-3 acid ratios increased risk). Moreover, the quantity of breast milk consumed per day was inversely associated with primary insulin autoimmunity, while the quantity of cow’s milk consumed per day was directly associated.

Conclusions/interpretation

Fatty acid status may play a role in the development of type 1 diabetes-associated autoimmunity. Fish-derived fatty acids may be protective, particularly during infancy. Furthermore, fatty acids consumed during breastfeeding may provide protection against type 1 diabetes-associated autoimmunity. Further studies are warranted to clarify the independent role of fatty acids in the development of type 1 diabetes.

     

Diets rich in saturated n-9 and n-3 fatty acids differentially affect the fatty acid composition of phospholipids and function of rat platelets

The aim of the present study was to determine whether dietary intake of monounsaturated or long chain n-3 fatty acids could be effective in lowering platelet responsiveness through modulation of platelet phospholipid composition. Rats were fed diets containing 20% fat with equal cholesterol and 13a-tocopherol contents. These diets were supplemented with saturated, oleic or n-3 fatty acids, n-3 polyunsaturated fatty acids being added either pure, as eicosapentaenoic and docosahexaenoic ethyl esters, or as MaxEPA oil. Dietary n-3 fatty acids did not affect the oxidation status of plasma lipids. Oleic acid- and saturated fatty acid-rich diets led to similar enrichment of platelet phospholipids in arachidonic acid and to comparable thromboxane A₂ generation on stimulation with collagen or thrombin. Platelets of n-3-fed groups were differently enriched in eicosapentaenoic and docosahexaenoic acids at the expense of arachidonic acid. These groups displayed similar thromboxane A₂ production, although levels were lower than those for groups fed with oleic- or saturated fatty acid-rich diets. Only the MaxEPA diet led to a reduction in platelet reactivity, measurable as a small decrease in the aggregation induced by collagen. This diet was also responsible for a high cholesteroUphospholipid ratio and low a-tocopherol content in platelets. Overall results indicated that (i) only MaxEPA reduced platelet reactivity and (ii) this effect was moderate and apparently unrelated to platelet arachidonic acid content, membrane cholesterol to phospholipid ratio or thromboxane A₂ production.     

Homocysteine levels in patients with Beh?et’s disease and patients with recurrent aphthous stomatitis

The mechanism for vascular involvement of Behçet disease (BD) includes arterial and venous thrombosis. Although the exact etiology of systemic vasculitis and thrombosis is still unknown, many hypotheses have been suggested. One of these hypotheses is that hyperhomocysteinemia causes vascular disease and thrombosis. The aim of this study was to compare the levels of homocysteine, vitamin B₁₂, and folic acid of BD patients with those of recurrent aphthous stomatitis (RAS) patients and healthy controls. Forty-five BD patients, 47 RAS patients, and 69 healty control subjects were included in this study. Vitamin B₁₂, folic acid, and homocysteine levels of the patients and controls were measured, and statistical differences among the groups were determined. BD patients had mostly cutaneous symptoms. Arthritis and ocular and vascular involvement were seen in 24.4%, 22%, and 11% of BD patients, respectively. No significant difference was detected among the groups in the levels of vitamin B₁₂, folic acid, and homocysteine. There was no significant difference in any parameters according to sex and age of the patients and activity of BD and if the patients with BD were treated or not. Homocysteine level inversely correlated with vitamin B₁₂ and folic acid levels in the BD group. We could not find any differences in homocysteine, vitamin B₁₂, and folic acid levels between BD and RAS patients and controls. This may be due to the fact that our patients mostly had cutaneous symptoms rather than vascular involvement.     

Some aspects of the metabolism of antimegaloblastic substances in man

1. When the sera of pernicious anemia patients or controls were heated at100 C. for 30 minutes, they developed the ability to support the growth of L.leichmannii by virtue of some substance other than vitamin B₁₂. It seemedlikely, however, that following the administration of the vitamin, such heatingalso liberated free B₁₂ in the serum from a combined form.

2. The L. leichmannii assay did not appear to be satisfactory for showingpossible difference in the levels of vitamin B₁₂ in the urines or sera of perniciousanemia patients and controls.

3. Parenterally administered vitamin B₁₂ did not cause any measurable risein the serum level of folic acid or citrovorum factor in pernicious anemia patientsor controls.

4. The synthetic folic acid conjugates pteroyldiglutamic acid and pteroyltriglutamic acid appeared in the sera and urines of pernicious anemia patientsas pteroylglutamic acid or some related substance with folic acid activity forS. faecalis.

5. Orally administered citrovorum factor appeared to be largely converted bythe gastric juice to folic acid if free hydrochloric acid was present. When administered parenterally, however, citrovorum factor was excreted in the urinelargely unchanged.

Submitted on October 19, 1952 Accepted on January 6, 1953     

Evidence that folic acid deficiency is a major determinant of hyperhomocysteinemia in Parkinson′s disease

In the present work we measured blood levels of total homocysteine (_tHcy), vitamin B₁₂ and folic acid in patients with Parkinson′s disease (PD) and in age-matched controls and searched for possible associations between these levels with smoking, alcohol consumption, L-DOPA treatment and disease duration in PD patients. We initially observed that plasma _tHcy levels were increased by around 30 % in patients affected by PD compared to controls. Linear correlation, multiple regression and comparative analyses revealed that the major determinant of the increased plasma concentrations of _tHcy in PD patients was folic acid deficiency, whereas in controls _tHcy levels were mainly determined by plasma vitamin B₁₂ concentrations. We also observed that alcohol consumption, gender and L-DOPA treatment did not significantly alter plasma _tHcy, folic acid and vitamin B₁₂ levels in parkinsonians. Furthermore, disease duration was positively associated with _tHcy levels and smoking was linked with a deficit of folic acid in PD patients. Considering the potential synergistic deleterious effects of Hcy increase and folate deficiency on the central nervous system, we postulate that folic acid should be supplemented to patients affected by PD in order to normalize blood Hcy and folate levels, therefore potentially avoiding these risk factors for neurologic deterioration in this disorder.