Plasma Arachidonic Acid Research Articles

Chronic lamotrigine does not alter the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat: implications for the treatment of bipolar disorder

Drugs that are effective in treating the manic phase of bipolar disorder (lithium, carbamazepine, and valproate) upon chronic administration to rats decrease the turnover of arachidonic acid in their brain phospholipids. Lamotrigine may not be effective in the manic phase, but is effective in delaying the depressive phase and for treating rapid cycling bipolar disorder. Thus, lamotrigine provides a pharmacological tool to differentiate if downregulation of arachidonic acid turnover is specific to drugs effective in the manic phase of bipolar disorder. To test this hypothesis, rats were administered lamotrigine (10 mg kg(-1) day(-1)) or vehicle intragastrically once daily for 42 days. In the unanesthetized rat, [1-(14)C]arachidonic acid was infused intravenously and arterial blood plasma was sampled until the animal was killed at 5 min, and its microwaved brain was subjected to chemical and radiotracer analysis. Using equations from our fatty acid model, we found that chronic lamotrigine compared with vehicle did not alter the net incorporation rate of plasma arachidonic acid into brain phospholipids, nor did it alter the turnover of arachidonic acid within brain phospholipids. Chronic lamotrigine, which is effective in the depressive phase or rapid cycling bipolar disorder does not alter brain arachidonic acid turnover in the unanesthetized rat. These results are consistent with the hypothesis that drugs effective in treating the manic phase of bipolar disorder decrease brain arachidonic acid turnover.

Essential fatty acid deficiency profile in patients with nephrotic-range proteinuria

Plasma free fatty acids are bound to albumin, filtered through the glomeruli, and reabsorbed at the proximal nephron. The aim of the present investigation was to determine if urinary loss of fatty acids results in essential fatty acid (EFA) deficiency in patients with nephrotic-range proteinuria. We studied 12 patients aged 9 months to 23 years (eight male, four female) four suffering from congenital nephrotic syndrome (NS) and eight from different renal diseases. Six patients were studied postrenal transplantation. Proteinuria ranged between 41 and 829 mg/m2/h. Results were compared with data obtained in 83 healthy children. The patients had significantly lower values for plasma arachidonic acid content and EFA index (omega3 + omega6/omega7 + omega9). Deficiency in polyunsaturated fatty acids (PUFA) was especially manifest in infants with congenital NS. Plasma content of arachidonic and docosahexaenoic acids related negatively with the degree of proteinuria. In the lineal regression model, the degree of proteinuria explained 60% of the variability of plasma values of those fatty acids. We conclude that plasma fatty acid status should be regularly monitored in patients with nephrotic-range proteinuria, especially in young infants with congenital NS, who represent a population at special risk with regard to neurological development.

Linoleic and arachidonic acid in perinatal asphyxia and prematurity

Objectives. Long-chain polyunsaturated fatty acids (LC-PUFA) are important for fetal and infant growth and development. The effects of prematurity and perinatal asphyxia on the levels of linoleic acid (LA) and arachidonic acid (AA) in plasma and red blood cell (RBC) membranes were investigated.Methods. Fifty-five neonates were studied: 18 full term neonates with perinatal asphyxia (group A), nine preterm neonates (group B), and 28 healthy term neonates (group C). Non-esterified and total levels of LA and AA in plasma and RBC membranes were estimated using gas chromatography within the first day of life. Malondialdehyde (MDA) levels were measured using the thiobarbituric acid (TBA) reactivity method.Results. Compared to group C, statistically significant lower levels of plasma free and total AA and free LA were observed in group A, whereas statistically significant higher levels of RBC total LA and AA were observed in RBC membranes of group B. A negative correlation between MDA and LC-PUFA levels was found.Conclusion. Perinatal asphyxia is associated with a reduction in LC-PUFA levels, most likely as a result of increased oxidative stress. Premature infants soon after birth have higher LC-PUFA levels than term neonates, probably reflecting the overall metabolic activity and/or intrauterine transport of LC-PUFA.

Distribution, interconversion, and dose response of n−3 fatty acids in humans

n-3 Fatty acids have important visual, mental, and cardiovascular health benefits throughout the life cycle. Biodistribution, interconversion, and dose response data are reviewed herein to provide a basis for more rational n-3 dose selections. Docosahexaenoic acid (DHA) is the principal n-3 fatty acid in tissues and is particularly abundant in neural and retinal tissue. Limited storage of the n-3 fatty acids in adipose tissue suggests that a continued dietary supply is needed. A large proportion of dietary alpha-linolenic acid (ALA) is oxidized, and because of limited interconversion of n-3 fatty acids in humans, ALA supplementation does not result in appreciable accumulation of long-chain n-3 fatty acids in plasma. Eicosapentaenoic acid (EPA) but not DHA concentrations in plasma increase in response to dietary EPA. Dietary DHA results in a dose-dependent, saturable increase in plasma DHA concentrations and modest increases in EPA concentrations. Plasma DHA concentrations equilibrate in approximately 1 mo and then remain at steady state throughout supplementation. DHA doses of approximately 2 g/d result in a near maximal plasma response. Both dietary DHA and EPA reduce plasma arachidonic acid concentrations. Tissue contents of DHA and EPA also increase in response to supplementation with these fatty acids. Human milk contents of DHA are dependent on diet, and infant DHA concentrations are determined by their dietary intake of this fatty acid. We conclude that the most predictable way to increase a specific long-chain n-3 fatty acid in plasma, tissues, or human milk is to supplement with the fatty acid of interest.

Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism

Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because their diet is low in EFAs and LCPUFAs. We have investigated the EFA and LCPUFA status of children with various amino acid metabolism disorders (not PKU) under treatment. Fatty acid profiles of plasma and erythrocyte phospholipids of 33 patients (aged 0–18 years) and 38 matched controls were determined by gas–liquid chromatography. Food-frequency questionnaires were used to assess the mean fatty acid intake. The dietary intake of the EFAs linoleic acid (LA) and α-linolenic acid (ALA) was comparable in both groups, while the LCPUFA intake was much lower in patients. This was associated with lower relative concentrations (% of total fatty acids) of n-3 docosahexaenoic acid (DHA) in plasma and erythrocyte phospholipids. Concentrations of arachidonic acid (AA) did not differ. The same was observed for the two EFAs LA and ALA. Thus, as compared to healthy controls, children with amino acid metabolism disorders have a lower intake of LCPUFAs and have lower concentrations of DHA but not of AA in plasma and erythrocyte phospholipids. This suggests that endogenous AA synthesis might guarantee an adequate AA status. The lower DHA status, however, warrants further investigations regarding the impact of DHA supplementation on growth and development of these children.

Thr-encoding Allele Homozygosity at Codon 54 of FABP 2 Gene May be Associated with Impaired Delta 6 Desatruase Activity and Reduced Plasma Arachidonic Acid in Obese Children

Alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Impairment in the activity of delta 6 and 5 desaturases is also supposed to be a factor predisposing the development of insulin resistance syndrome. We investigated the relationship between A54T polymorphism in FABP2 and the impairment of long-chain polyunsaturated fatty acid metabolism in obese children. Thirty-two obese children participated. During the study, the children continued their habitual diet, which was documented in a 3-day food record using household measures. Anthropometry was performed, and serum lipid and fatty acid composition in plasma were analyzed. The polymorphism of codon 54 in the FABP 2 gene was analyzed. The allele frequency was 0.66 and 0.34 for Ala54 and Thr54, respectively. There were no significant differences in age, body mass index, fasting serum glucose, insulin or serum lipoproteins among the three polymorphism groups. These were also no significant differences in the intake of energy, the percentage of energy nutrients or in the dietary lipid composition. The content of arachidonic acid (AA) in plasma was lowest in Thr/Thr54 (p < 0.05). The indices of delta-6 desaturase (D6D) activity in Thr/Thr54 were significantly lower than in Thr/Ala54 or Ala/Ala54 (p < 0.05, p < 0.01, respectively). In obese children, Thr/Thr54 of the FABP 2 gene is associated with impaired activation of D6D and reduced AA content. The results in the LCPUFA profile suggest that Thr/Thr54 may predispose the to development of insulin resistance.

P‐76 The effect of omega‐3 fatty acid supplementation on cutaneous and plasma fatty acid concentrations in dogs with atopic dermatitis

The purpose of this study was to evaluate the influence of a fatty acid supplement on the concentration of essential fatty acids in the skin and plasma of dogs with atopic dermatitis. Twenty‐nine dogs with nonseasonal atopic dermatitis were supplemented with 1000 mg flax oil capsules, 3V Caps containing 180 mg of eicosapentaenoic acid (EPA) and 120 mg of docosahexaenoic acid (DHA)/capsule, or mineral oil as placebo at 1 capsule/5 kg once daily for 10 weeks in a randomized, double‐blinded trial. Dogs were evaluated by owners and clinicians before and after supplementation using a clinical scoring system. Blood samples and skin biopsies from the lateral chest were taken before and after 10 weeks of supplementation. Overall, daily intake of omega‐3 and ‐6 fatty acids was calculated for each patient before and after supplementation. Linoleic acid (LA), α‐linolenic acid (α‐LA), arachidonic acid (AA), EPA and DHA were determined in plasma and skin using gas chromatography. α‐Linolenic acid and EPA were significantly increased in plasma (P = 0.0165 and 0.0042, respectively), but not in skin after supplementation with 3V Caps. The concentration of α‐LA was increased after flax oil supplementation (P = 0.0226). Plasma AA decreased in dogs supplemented with 3V Caps (P = 0.0029). Supplements changed the plasma and skin fatty acid concentrations significantly. A significant correlation between clinical outcome and cutaneous or plasma concentration was not present for any of the fatty acids. Based on these results, supplementation with fatty acids changes the plasma, but not skin concentrations of fatty acids in dogs with atopic dermatitis. Funding: Shipley Foundation.

Dose response of bone mass to dietary arachidonic acid in piglets fed cow milk-based formula

The addition of arachidonic acid (AA) and docosahexaenoic acid (DHA) to infant formula was recently approved in North America. In piglets, dietary AA is linked to elevations in bone mass. The objective was to investigate the effects of varied amounts of dietary AA on bone modeling and bone mass with the use of the piglet model for infant nutrition. Male piglets (n = 32) were randomly assigned to receive 1 of 4 formulas supplemented with AA (0.30%, 0.45%, 0.60%, or 0.75% of fat) plus DHA (0.1% of fat) from days 5 to 20 of life. Measurements included biomarkers of bone modeling, fatty acid status, and whole-body and femur bone mineral content; bone area was measured by dual-energy X-ray absorptiometry. Differences among groups were detected with two-factor analysis of variance. Regression analyses were used to determine factors responsible for bone mineral content after dietary AA was accounted for. Proportions of AA in plasma, liver, and adipose were modified by the dietary treatments, but bone modeling was not affected. Liver AA was positively related to plasma insulin-like growth factor 1 and calcitriol and urinary N-telopeptide. Whole-body bone mineral content was elevated in the piglets fed 0.60% and 0.75% AA and was best predicted by dietary AA and bone resorption. This study confirms that dietary AA alters bone mass and clarifies the best amount of AA to add to the diet of pigs born at term. Because the amount of dietary DHA was held constant, whether other amounts of DHA are related to bone mass requires investigation.

Relationship of arachidonic acid concentration to cyclooxygenase-dependent human platelet aggregation.

Inhibition of ex vivo arachidonic acid (AA)-induced aggregation is a biomarker for the isotype selectivity of cyclooxygenase (COX) inhibitors since platelets express COX-1 but not COX-2. At low concentrations, there is broad inter- and intrasubject variability in AA-induced aggregation of platelets ex vivo. This study defined a concentration that reliably induces aggregation without overcoming inhibition by therapeutic aspirin therapy (ASA, 81-mg) treatment. Logistic regression analysis of ex vivo aggregation, induced with increasing concentrations of AA in platelet-rich plasma (PRP), estimated that platelets from > or = 90% of subjects would aggregate at > or = 1.5 mM AA (95% confidence interval [CI], 1.1, 2.1). A concentration of 1.6 mM AA failed to aggregate platelets from 26 healthy volunteers, who had previously aggregated at this concentration, following six daily oral doses of 81 mg of ASA. These data demonstrate that 1.6 mM AA reproducibly induces platelet aggregation in PRP from healthy volunteers without overcoming the antiplatelet effect of daily low-dose aspirin therapy.

Inhibition of leukotriene synthesis, pharmacokinetics, and tolerability of a novel dietary fatty acid formulation in healthy adult subjects

Background: Numerous studies have explored dietary-management strategies for decreasing leukotriene synthesis by inflammatory cells through supplementation with polyunsaturated fatty acids such as gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA). Objectives: This study sought to determine the optimal daily intake, ratios, and formulation of dietary GLA and EPA required to safely reduce leukotriene biosynthesis in healthy individuals, and to evaluate the pharmacokinetics and safety profile of such a formulation. Methods: Two preliminary trials were conducted to determine the minimum effective levels of GLA and EPA intake needed to reduce leukotriene biosynthesis and prevent increases in plasma arachidonic acid (AA) concentrations. These preliminary trials were followed by a single-center, randomized, double-blind, placebo-controlled, parallel-group, escalating-intake inpatient trial of a dietary GLA/EPA emulsion (PLT 3514) in healthy adult subjects. Subjects consumed either 10, 20, or 100 g of the PLT 3514 emulsion (respectively containing 0.75 g GLA + 0.5 g EPA, 1.5 g GLA + 1 g EPA, and 7.5 g GLA + 5 g EPA), or a placebo emulsion containing olive oil daily for 14 days. Plasma fatty acids were measured by gas chromatography. Stimulated whole blood leukotrienes were measured by high-performance liquid chromatography with ultraviolet detection. Results: Thirty subjects were included in the preliminary trials; 47 subjects were enrolled in the escalating-intake trial, of whom 42 completed the study. In the preliminary trials, intake of GLA 1.5 g/d in gelatin capsules decreased the capacity to synthesize leukotrienes but increased plasma levels of AA (both, P < 0.05). Inclusion of 0.25 or 1 g of dietary EPA prevented the increase in plasma AA concentrations. Dietary GLA and EPA showed significantly enhanced bioavailability when consumed in 20 g PLT 3514 emulsion compared with consumption in gelatin capsules ( P < 0.05), resulting in a reduction in the amount of intake required to block leukotriene biosynthesis. Pharmacokinetic analyses indicated that fasting plasma GLA and EPA levels plateaued within 7 days' daily consumption at all levels of intake, whereas the time to maximum plasma concentration (T max) was shorter for GLA than for EPA. The T max was similar on days 1 and 14 for both GLA and EPA. There were no clinically significant between-group differences in changes in vital signs, mean clinical laboratory values, or abbreviated hematology laboratory tests, or significant differences in the occurrence of treatment-emergent adverse events between the group consuming up to 20 g/d of the GLA/EPA emulsion and the group consuming placebo. Conclusion: Consumption of specific proportions and intake levels of dietary GLA and EPA in a novel emulsion formulation inhibited leukotriene biosynthesis and appeared to be well tolerated in this population of healthy adult subjects.

Influence of Dietary Linoleic Acid Intake with Different Fat Intakes on Arachidonic Acid Concentrations in Plasma and Platelet Lipids and Eicosanoid Biosynthesis in Female Volunteers

Background/Aim: N-6 fatty acids are considered to promote diseases prevalent in industrialized countries and characterized by an increased eicosanoid biosynthesis from arachidonic acid (AA). We investigated the impact of the linoleic acid (LA) intake on AA levels in humans. Methods: Six healthy female volunteers (age range 23–34 years) were given liquid formula diets (LFD) devoid of AA for 6 weeks, providing a constant intake of zero energy% (LFD 0: protein 15%, carbohydrates 85%) or 20 energy% (LFD 20: protein 15%, carbohydrates 55%, fat 30%) LA, for 3 weeks each. Fatty acids of plasma cholesteryl esters and platelet lipids were determined each week, and the prostaglandin biosynthesis was measured in 24-hour urine samples. Results: LFD 0 increased (+31% of initial value) and LFD 20 lowered (–30% of initial value) the percentage of AA in plasma cholesteryl esters and platelet lipids. Moreover, absence of dietary AA lowered the percentages of AA in plasma (–31% week 0 vs. week 6) and platelet (–11%) lipids, indicating a low transformation of LA. LFD 0 reduced urinary metabolite levels of prostaglandins D, E, and F in 24-hour urine samples (–48%, p < 0.001) within 24 h, but did not significantly affect platelet aggregation (–10%) and thromboxane formation (–25%). LFD 20 significantly lowered platelet aggregation (–25%) and thromboxane formation (–43%). The prostaglandin metabolite levels increased during the first 10 days, declined thereafter, and were lower than the preexperimental values at the end of the 3-week period. Conclusions: The results show that dietary LA does not increase the AA levels in plasma or platelet lipids and does not persistently contribute to prostaglandin biosynthesis which is increased by AA intake with Western diets.

Comparison of Triglycerides and Phospholipids as Supplemental Sources of Dietary Long-Chain Polyunsaturated Fatty Acids in Piglets

Addition of arachidonic acid (AA) and docosahexaenoic acid (DHA) to infant formula promotes visual and neural development. This study was designed to determine whether the source of dietary long-chain polyunsaturated fatty acids (LCPUFA) affected overall animal health and safety. Piglets consumed ad libitum from 1 to 16 d of age a skim milk-based formula with different fat sources added to provide 50% of the metabolizable energy. Treatment groups were as follows: control (CNTL; no added LCPUFA), egg phospholipid (PL), algal/fungal triglyceride (TG) oils, TG plus PL (soy lecithin source) added to match phospholipid treatment (TG + PL) and essential fatty acid deficient (EFAD). Formulas with LCPUFA provided 0.6 and 0.3 g/100 g total fatty acids as AA and DHA, respectively. CNTL piglets had 40% longer ileal villi than PL piglets (P < 0.03), but the TG group was not different from the CNTL group. Gross liver histology did not differ among any of the formula-fed groups (P > 0.1). Apparent dry matter digestibility was 10% greater in CNTL, TG and TG + PL groups compared with PL piglets (P < 0.002). No differences in alanine aminotransferase were detected among treatments, but aspartate aminotransferase was elevated (P < 0.03) in PL piglets compared with TG + PL piglets. Total plasma AA concentration was greater in the TG group compared with CNTL piglets (P < 0.05). Total plasma DHA concentrations were greater in TG piglets compared with PL (P < 0.06) or CNTL (P < 0.02) piglets. These data demonstrate that the algal/fungal TG sources of DHA and AA may be a more appropriate supplement for infant formulas than the egg PL source based on piglet plasma fatty acid profiles and apparent dry matter digestibilities.

Visual acuity and retinal function in infant monkeys fed long-chain PUFA.

Previous randomized clinical trials suggest that supplementation of the human infant diet with up to 0.35% DHA may benefit visual development. The aim of the current study was to assess the impact of including arachidonic acid (AA) and a higher level of DHA in the postnatal monkey diet on visual development. Infant rhesus monkeys were fed either a control diet (2.0% alpha-linolenic acid as the sole n-3 FA) or a supplemented diet (1.0% DHA and 1.0% AA) from birth. Visual evoked potential acuity was measured at 3 mon of age. Rod and cone function were assessed in terms of parameters describing phototransduction. Electroretinogram (ERG) amplitudes and implicit times were recorded over a wide intensity range (-2.2 to 4.0 log scot td-sec) and assessed in terms of intensity response functions. Plasma DHA and AA were significantly increased (P < 0.001) in the diet-supplemented monkeys compared with the control monkeys. There was an approximately equal effect of diet for the rod phototransduction parameters, sensitivity, and capacitance but in the opposite directions. Diet-supplemented monkeys had significantly shorter b-wave implicit times at low retinal illuminances (<-0.6 log scot td-sec). There were no significant effects of diet for visual acuity or the other 23 ERG parameters measured. The results suggest that supplementation of the infant monkey diet with 1.0% DHA and 1.0% AA neither harms nor provides substantial benefit to the development of visual acuity or retinal function in the first four postnatal months.

Red blood cell and plasma phospholipid arachidonic and docosahexaenoic acid levels at birth and cognitive development at 4 years of age.

The long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) have biophysical properties that may mediate behavioral outcome, especially cognitive development. This study examined the relationship between the LCPUFA-status at birth and cognitive development at 4 years of age. Cognitive development of 128 full-term neonates, whose umbilical venous plasma and/or red blood cell phospholipid DHA and AA levels were known, was assessed at 4 years of age. Pearson correlation coefficients were calculated between cognitive development and DHA, AA, maternal intelligence, birth weight, duration of breast-feeding and paternal educational attainment. Multiple linear regressions were employed with cognitive development as the dependent variable and whereby the above-mentioned covariables were entered in step one while each of the four LCPUFAs was entered in step two. In bivariate analysis, maternal intelligence, birth weight, maternal smoking habits during pregnancy, paternal education and duration of breast-feeding showed significant correlations with cognitive development (p<0.01). The association of cognitive development with DHA and AA measured zero in bivariate analysis (plasma levels: r=0.03 and r=-0.03, respectively; erythrocyte levels: r=0.01 and r=0.05) and in multiple regression analysis (plasma DHA r=0.01, p=0.88; plasma AA r=0.02, p=0.80; erythrocyte DHA r=-0.01, p=0.95) except for erythrocyte AA (r=0.15, p=0.09). No evidence was found for an association of the DHA or AA-status at birth with cognitive development at 4 years of age.

A double‐blind, randomized, placebo‐controlled trial of n‐3 versus n‐6 fatty acid‐based lipid infusion in atopic dermatitis

In the involved epidermis of patients with atopic dermatitis, changes in the metabolism of eicosanoids with increased quantities of the arachidonic acid (AA)-derived lipoxygenase products have been observed. Free eicosapentaenoic acid (EPA), a fish oil-derived alternative (n-3) fatty acid, may compete with AA, resulting in an anti-inflammatory effect. In a 10-day double-blind, randomized, placebo-controlled trial, 22 patients hospitalized for moderate-to-severe atopic dermatitis were randomly assigned to receive daily infusions of either a n-3 fatty acid-based lipid emulsion (fish oil, 10%; 200 mL/d) or a conventional n-6-lipid emulsion (soybean oil, 10%; 200 mL/d). Topical treatment was restricted to emollients. The severity of disease was evaluated daily with scoring of erythema, infiltration, and desquamation and by subjective patient scoring of clinical manifestations. In addition, plasma-free and total-bound fatty acids and the composition of membrane fatty acids in blood cells (thrombocytes, granulocytes, and erythrocytes), lipid mediators from isolated neutrophils and platelets, and lymphocyte-activation parameters were determined. Twenty patients completed the trial. Marked improvement from baseline was seen in both groups. On days 6, 7, 8, and 10, disease severity score-defined as the sum of all scores-was more pronounced (p < .05) in the n-3 group compared with the n-6 group. Free arachidonic acid in plasma did not change substantially in both groups, whereas plasma-free EPA, total-bound EPA, and the membrane EPA/AA ratio markedly increased in response to n-3-lipid infusion. In parallel, EPA-derived lipid mediators appeared, whereas lymphocyte functions were unaffected. In the post-treatment period (2/4 weeks), relapse was observed in some patients after n-3 psoralene-ultraviolet A (PUVA) infusion, whereas there was a marked long-term improvement in the n-6 group. IV n-3-fatty acid administration is effective in acutely improving the severity of atopic dermatitis, paralleled by changes in plasma and membrane fatty acid composition and lipid mediator synthesis. The long-term beneficial effects of IV n-6 fatty acids should be evaluated further.

Habitual food intake and polyunsaturated fatty acid deficiency in liver cirrhosis

OBJECTIVE: We compared the habitual food intake and plasma fatty acid composition in cirrhotic patients living in two different regions in Japan, Okayama and Toyama, and evaluated the effects of dietary polyunsaturated fatty acid and α-tocopherol intake on serum alanine aminotransferase (ALT) activity. METHOD: A quantitative food-frequency questionnaire method was used. RESULTS: The significantly higher intake of fish in the patients living in Toyama resulted in higher plasma levels of docosahexaenoic acid and lower levels of arachidonic acid. Serum ALT activity correlated negatively with plasma arachidonic acid ( r = −0.456, P < 0.05) and α-tocopherol ( r = −0.505, P < 0.05) levels. Dietary intakes of vitamin E and polyunsaturated fatty acids (mg/g) correlated negatively with serum ALT ( r = −0.377, P < 0.05). Dietary intake of linoleic acid and the ratio of polyunsaturated to saturated fatty acid in dietary fat correlated significantly with serum ALT ( r = 0.604, P < 0.01, and r = 0.622, P < 0.01, respectively). The amount of vegetable intake correlated with intake of vitamin E and polyunsaturated fatty acid ( r = 0.527, P < 0.02). CONCLUSIONS: These findings suggest that habitual food intake affects the plasma fatty acid profile and that elevated serum ALT may be related to arachidonic acid deficiency and vulnerability to lipid peroxidation in cirrhotic patients with hepatitis B and C viruses.

Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet.

Blood lipid studies are reported in 25 adults and 2 adolescents with PKU who had been on phenylalanine-restricted diets for a mean period of 22.6 years (range 7-39 years). Measurements included plasma concentrations of phenylalanine, cholesterol, lipoproteins, triglycerides and fatty acid profiles, including the analysis of seven fatty acids in plasma and red blood cells. Lipid screening identified 7 subjects with significantly elevated cholesterol/HDL ratios ranging from 5.6 to 10.3. Triglyceridaemia was documented in 5 of these 7, with concentrations ranging between 0.24 and 4.5 mmol/L (219-402 mg/dl) with a mean of 3.5 mmol/L (310 mg/dl). The fatty acid analyses demonstrated slight but statistically significant reductions in the concentrations of long-chain polyunsaturated fatty acids (LCPUFA), including plasma docosahexaenoic (DHA) and arachidonic acid (AA), and red blood cell DHA concentrations. The pattern resembles that reported previously in children, but alterations in the mean levels are less severe. In six of the adult patients plasma DHA or AA concentrations were less than 50% of controls. Since DHA and AA have important physiological roles, including brain and retinal function, it is recommended that blood lipid concentrations be monitored in all patients with PKU, including adults, and that DHA and AA supplementation be provided, particularly in those patients in whom the blood concentrations of these substances are reduced significantly.

Different quantities and quality of fat in milk products given to young children: effects on long chain polyunsaturated fatty acids and trans fatty acids in plasma

In this study we compared plasma contents of long‐chain polyunsaturated fatty acids (LC‐PUFAs) and trans fatty acids in triglycerides (TG), phospholipids (PL) and cholesterolesters (CE) in young children fed milk diets containing different amounts of linoleic (LA) and α‐linolenic acid (ALA). Because the diets differed in vitamin A and E content, plasma concentrations of vitamin A and E were also studied. Thirty‐seven 1‐y‐old children were randomly assigned to one of four feeding groups: (1) low‐fat milk (LF) (1.0 g cow's milk fat/dL); (2) standard‐fat milk (SF) (3.5 g cow's milk fat/dL); (3) partially vegetable fat milk (PVF) (3.5 g fat/dL; 50% vegetable fat from rapeseed oil, 50% milk fat); and (4) full vegetable fat milk (FVF) (3.5 g fat/dL; 100% vegetable fat from palm‐, coconut‐ and soybean oil). We found higher amounts of plasma LA in the FVF group than in the LF and SF groups (p &lt; 0.001) and higher amounts of ALA in the PVF group than in the SF (p &lt; 0.001 in TGs, p &lt; 0.05 in CEs) and LF (p &lt; 0.01 in PLs and CEs, p &lt; 0.05 in TGs) groups. However, amounts of plasma arachidonic acid (AA) were similar between groups as well as the amounts of docosahexaenoic acid (DHA) in CEs and PLs. Total trans FAs were lower in CEs in the PVF and FVF groups than in the SF group (p &lt; 0.05 SF vs PVF; p &lt; 0.01 SF vs FVF). Plasma concentrations of α‐tocopherol were higher in the FVF group than in the other groups (p &lt; 0.05 FVF vs SF, p &lt; 0.01 FVF vs SF and PVF). Conclusion: Children consuming milk diets containing high amounts of vegetable fat present with higher plasma LA and ALA without any effects on amounts of plasma LC‐PUFA. The plasma LC‐PUFA status is not adversely affected by a low‐fat milk diet. AHA and DHA in plasma are not affected by the diets studied, presumably because 15‐mo‐old children may be able to compensate for dietary influences through endogenous LC‐PUFA metabolism.

Maternal-Fetal N-6 and N-3 Polyunsaturated Fatty Acids Gradient in Plasma and Red Cell Phospholipids

Fatty acid distribution was investigated in ethnically and economically homogenous Korean mothers (n = 40) and neonates. Venous blood, maternal before delivery and cord, was obtained. Choline (CPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SM) were assayed. Mean arachidonic acid (AA) level was higher in plasma CPG and SM (p < 0.0001), and red cell CPG (p < 0.0001), EPG (p < 0.0001) and SM (p = 0.005) of the neonates. Similarly, the neonates had higher proportions of docosahexaenoic acid (DHA) in plasma CPG (p < 0.0001) and red cell CPG (p = 0.001) and EPG (p = 0.036). In contrast, linoleic and alpha-linolenic acids were significantly higher in maternal blood. Mead acid was elevated in plasma CPG (p < 0.0001) and red cell CPG and EPG (p < 0.0001) of the neonates. Consistent with data from high-fat-intake populations, our subjects, whose traditional diet is low in fat, exhibited maternal-fetal gradient in AA and DHA in plasma and red cell phospholipids. This may be due to an imbalance between supply and maternal and fetal requirements, and/or a physiological response to pregnancy. Prenatal nutritional constraint is associated with impaired development and a risk of chronic diseases in adults. AA and DHA are vital nutrients. Hence, there is a need to investigate whether the discrepancy between maternal and neonatal AA and DHA is a manifestation of nutritional insufficiency.

Growth and Development in Term Infants Fed Long-Chain Polyunsaturated Fatty Acids: A Double-Masked, Randomized, Parallel, Prospective, Multivariate Study

To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids, arachidonic acid (AA), and docosahexaenoic acid (DHA) on multiple indices of infant growth and development. A double-masked, randomized, parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year (N = 239). Reference groups of breastfed infants (N = 165) weaned to formulas with and without AA+DHA were also studied. Infants in the formula groups were randomized at </=9 days of age to a control formula with no AA or DHA (n = 77) or 1 of 2 otherwise identical formulas containing AA+DHA (AA, 0.46% and DHA, 0.14% of total fatty acids) from either egg-derived triglyceride (egg-DTG [n=80]) or fish oil and fungal oil (fish/fungal [n = 82]) at levels similar to the average in breast milk samples as measured in the reference group. All formulas contained 50% of energy from fat with the essential dietary fatty acids, linoleic acid (20% fatty acids) and alpha-linolenic acid (2% fatty acids). The main study outcomes were AA and DHA levels in plasma and red blood cells, and multiple measures of infant development at multiple ages from birth to 14 months: growth, visual acuity, information processing, general development, language, and temperament. AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups. No developmental test results distinguished these groups. Expected differences in family demographics associated with breastfeeding were found, but no advantages to breastfeeding on any of the developmental outcome demonstrated. These findings do not support adding AA+DHA to formulas containing 10% energy as linoleic acid and 1% energy as alpha-linolenic acid to enhance growth, visual acuity, information processing, general development, language, or temperament in healthy, term infants during the first 14 months after birth.infant development, breast feeding, infant formula, long-chain polyunsaturated fatty acids, docosahexaenoic acid.