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The present review investigates the relationship between polyunsaturated fatty acids (PUFAs) and mental health disorders, such as dementia, psychosis, schizophrenia, Alzheimer's disease, anorexia nervosa, and impairment problems in animals and human models. Data were collected from a variety of studies: randomized intervention trials, observational and interventional studies, case reports, and epidemiological studies. The evidence suggests that PUFAs are beneficial for mental health, brain function, and behavior. ALA, EPA, and DHA have very significant neuroprotective properties, particularly in inducing changes to the synaptic membrane and modulating brain cell signaling. In the case of neurodegenerative disorders, PUFAs incorporated into cellular membranes have been shown to protect against cell atrophy and death. The formal analyses of the included studies pointed to a decrease in ALA, EPA, and DHA levels in various populations (e.g., children, adolescents, adults, and seniors) presenting with different types of mental disorders. These results indicate that PUFA supplementation may be considered as an innovative therapeutic strategy to reduce the risk of neuronal degeneration.

Epidemiological studies show that circulating polyunsaturated fatty acids contribute to preserve renal function. In renal disease states there is generally a lack of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) as measured in biological samples, but despite intense research for more than 30 years, it is still unclear how and to what extent their supplementation would benefit kidney disorders. Studies evaluating the n-6 series and the kidney are less frequent. The last compilation of clinical trials with n-3 LCPUFA supplements focusing on renal function and damage dates back to 2012. We here discuss n-3 and n-6 fatty acids in relation to the kidney summarizing single- and double blind randomized controlled trials performed between 2012 and 2016. Nine were sub-studies/post-hoc analyses of previous parent trials. Twelve out of the twenty trials reported on fatty acid profile or fatty acid species. Factors that may explain inconsistent results obtained after supplementation with the n-3 LCPUFA EPA and DHA in kidney disease are discussed such as baseline levels determining response, drug interaction. The need of evaluating fatty acid status before and after intervention is emphasized, to match changes in outcome measure with changes of any fatty acid potentially involved., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: This study aimed to investigate the relationship between polyunsaturated fatty acids (PUFAs) status, cognitive, and behavioral traits of ADHD in school-aged children., Method: Seventy-three children with and without ADHD were assessed with cognitive tasks and behavioral rating scales including quality of life and global functioning at baseline of an intervention trial (clinicaltrials.gov NCT01796262). Correlation analyses were performed between the cognitive tasks/behavioral ratings and blood PUFA levels., Results: Children with ADHD had lower levels of DHA, omega-3 index, and total PUFA. PUFAs were positively associated with behavior but not consistently related to cognitive domains., Conclusion: The present study confirms that children with ADHD display abnormal fatty acid profiles within an Italian setting. Furthermore, PUFAs were associated with behavior but not with cognition. Accordingly, for the first time, lower blood levels of PUFA were associated not only with symptoms of ADHD but also with a poorer quality of life.

Long-chain polyunsaturated fatty acid (LCPUFA) status has recently been related to the pathogenesis of obesity. Our aims were to systematically review observational studies investigating LCPUFA status from different blood compartments in overweight or obese subjects and to assess the relationship between LCPUFA profile and obesity. The Ovid MEDLINE, Scopus and Cochrane Library CENTRAL databases were searched from inception to January 2014. The meta-analysis showed significant differences in the LCPUFA composition of total plasma lipids, plasma phospholipids and plasma cholesteryl esters between overweight or obese subjects and controls. Dihomo-γ-linolenic acid (DGLA) values were significantly higher in overweight or obese subjects compared with controls in all the investigated biomarkers. In addition, the DGLA/linoleic acid ratio (surrogate parameter for Δ6 desaturase activity) in plasma phospholipids was significantly elevated (mean difference [MD]: 0.05; 95% confidence interval [CI]: 0.02, 0.08; n = 280), while the arachidonic acid/DGLA ratio (surrogate parameter for Δ5 desaturase activity) was significantly decreased (MD: -0.55; 95% CI: -0.71, -0.39; n = 347) in overweight or obese subjects compared with controls. The results of the present meta-analysis confirm that LCPUFA profile is altered in obesity and suggest that the differences observed in desaturase activities may be responsible for the disturbed LCPUFA metabolism in obesity., (© 2015 World Obesity.)

Background & Aims: The biological role of fatty acids (FA) in the perinatal period is under active investigation. We here describe the application of a simplified microanalytical procedure to compare the FA profile of maternal, umbilical cord and infant whole blood, inclusive of all circulating lipid fractions and cells., Methods: The FA composition has been analyzed with a micromethod in 16 triplets, including maternal blood, cord blood at delivery and infant blood at day 4, respectively., Results: As expected, the FA composition of blood samples withdrawn from the umbilical cord is more similar to the FA composition of blood from 4-day old infants than the FA pattern of maternal blood at delivery. Nevertheless, infant blood FA profile differed from cord for lower long-chain polyunsaturated FA and higher monounsaturated FA., Conclusions: Our explorative data using whole blood microanalysis confirm the progressive increase of long-chain polyunsaturated FA levels from the mothers towards cord and then infant blood., (Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: To assess fatty acid (FA) profiles in whole blood of 90 cystic fibrosis patients (CF) and 30 control subjects (C) and to correlate FA changes to the severity of respiratory disease., Methods: Whole blood FA were assessed by GC with a micromethod-based analysis., Results: Saturated and monounsaturated FA are higher, whereas polyunsaturated FA are lower in CF versus C with reduction of total n-6 FA, 22:5n-3 and 22:6n-3 (DHA). The product of linoleic acid (LA) x DHA, proposed as a marker for the disease, is 30% lower in CF than in C. Correlations with the severity of the respiratory disease are present for different FA and for the LA x DHA product. There is a reduction of Delta5 desaturase activity in CF, greater in severe disease, suggesting a basic metabolic alteration., Conclusions: The micromethod-based analysis of blood FA facilitates the assessment of the FA status while confirming alterations of FA profiles already reported in specific blood compartments of CF.

This study examined the association of insulin resistance with single-nucleotide polymorphism (SNP) 276G>T at adiponectin gene and the plasma long-chain polyunsaturated fatty acids (LCPUFAs) profile in obese children. One hundred thirty-one normolipidaemic obese children aged 8-13 y (53 girls and 68 boys) entered the study. The prevalence of T allele carriers at SNP276 was 48.8%. Mean [SD] values of fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR) index in noncarriers versus carriers of T allele were 12.4 [6.4] versus 20.6 [6.3] muU/mL (p = 0.039) and 2.6 [1.4] versus 4.5 [1.7] (p = 0.032). Mean [SD] values of plasma C18:3n - 3, C20:5n - 3/C20:4n - 6, and n - 6/n - 3 LCPUFA in phospholipids in noncarriers versus carriers of T allele were 0.10 [0.04] versus 0.08 [0.03] % (p = 0.013), 0.04 [0.01] versus 0.03 [0.01] % (p = 0.045), and 4.4 [0.7] versus 4.9 [0.9] % (p = 0.005), respectively. Insulin resistance was independently associated with SNP 276G>T (p = 0.002) and n - 6/n - 3 LCPUFA (p = 0.042) in plasma phospholipids, and interaction was found between SNP 276G>T and n - 6/n - 3 LCPUFA (p = 0.046). These findings suggest that obese children carriers of the SNP 276G>T may be at increased risk of metabolic complications compared with noncarriers, possibly due in part to a different plasma phospholipids profile.

The 2 most abundant long-chain polyunsaturated fatty acids (LCPUFAs) in the brain are docosahexaenoic acid (DHA) and arachidonic acid (ARA), where they have a functional and structural role in infant development. DHA is concentrated in the prefrontal cortex, which is important for association and short-term memory, and in some retinal cells. Concentrations of PUFAs in human breast milk are relatively consistent during the first year of life, and studies have shown that breast-fed infants have a greater mean weight percentage of DHA and a greater proportion of DHA in their red blood cells and brain cortex than formula-fed infants. Furthermore, cortex DHA in breast-fed infants increases with age, probably due to the length of feeding. Maternal supplementation with cod liver oil, which is rich in DHA and eicosapentaenoic acid, improved children's intelligence quotient compared with corn-oil supplementation by 4 years of age. The LCPUFA content of human breast milk is affected by a number of factors, including diet, gestational age, parity, and smoking. Supplementation of formula feed with DHA and ARA results in infant development that is similar to breast-feeding, and may have benefits on blood pressure in later childhood. The beneficial effects of LCPUFA supplementation on visual acuity continue after weaning irrespective of the type of diet. The long-term effects and duration of supplementation of breast- and formula-fed infants requires further investigation.

Objective: To study the effects of maternal smoking on the status of long-chain polyunsaturated fatty acids (LCPUFA) in infants' whole-blood lipids., Design: A case-control matched study planned on the basis of preliminary observations., Setting: Maternity ward., Patients: A total of 159 healthy, term, breastfed infants with weight appropriate for gestational age, subdivided (53 per group) into those born to non-smokers (reference), smokers (> or = 5 cigarettes per day) who either stopped within the first trimester of pregnancy (early smokers) or who continued througout pregnancy (late smokers)., Interventions: The fatty acid profile of 4-day-old infants was determined on whole blood., Results: Higher levels of linoleic (LA) and alpha-linolenic acid (ALA) and lower levels of the metabolic products di-homo-gammalinolenic (DHGLA) and arachidonic (AA), of the n-6 series, and docosahexaenoic acid (DHA), of the n-3 series, were found in infants born to late smokers compared with the reference group. The DHGLA/LA and AA/DHGLA ratios in the n-6 series and DHA/ALA in the n-3 series, which are indices of the metabolic processes in LCPUFA synthesis, were lower in infants born to smokers compared with those born to non-smokers. Infants born to early smokers showed n-6 PUFA levels and ratios similar to references and n-3 parameters closer to those born to late smokers. No dietary differences were found among the three groups of mothers. All the independent associations with smoking persisted after adjustment for maternal covariates. Pre-pregnancy body weight, which is lower in late smokers compared with non-smokers, independently correlated with LCPUFA levels in both series., Conclusions: Maternal smoking is associated with a reduction in LCPUFA pools in infants, which might have structural and functional consequences.

This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations.

Objective: To assess the relationship between dietary intakes, plasma phospholipid (PL) fatty acid profile and clinical parameters in children with cystic fibrosis (CF) in comparison to healthy controls., Patients and Methods: A cross-sectional survey including 37 patients with CF (ages 8.0 +/- 2.9 yrs) and a reference group of 68 healthy children (ages 8.0 +/- 0.7 yrs) was carried out by means of a food-frequency questionnaire. At enrollment, all subjects underwent blood sampling for plasma PL fatty acids (FA). In CF patients, pulmonary function tests (forced expiratory volume in 1 second and forced vital capacity), anthropometric measurements and the Shwachman score were also determined., Results: In CF patients, mean z score for weight and height (-0.35 +/- 1.16 and -0.28 +/- 0.99) were lower than controls (0.83 +/- 1.73 and 0.55 +/- 1.11, respectively). Patients with CF showed higher energy intakes (110 +/- 43 kcal/d) compared with controls (75 +/- 22 kcal/d; P < 0.0001), with higher intake of total (saturated and monounsaturated) fats and lower intake of polyunsaturated FA (3.9 +/- 1.0% of total macronutrient intake vs 4.3 +/- 1.2%, P = 0.05). In CF patients, plasma and PL levels of linoleic and docosahexaenoic acids were lower, whereas those of arachidonic acid were similar compared with controls. The Shwachman score showed significant positive associations with plasma PL levels of arachidonic acid and total n-6 long-chain FA (r = 0.32, P = 0.05, and r = 0.35, P = 0.03, respectively)., Conclusions: The data give suggestions that fat intake and CF-associated biomechanisms are bound in a vicious circle, concurring to create the clinical and biochemical picture of CF. The quantity and quality of fat supplementation in CF need careful attention to balance the fat supply with polyunsaturated FA.

Pro12Ala variant of peroxisome-proliferator-activated receptor-gamma2 (PPAR-gamma2) may be linked to insulin sensitivity. This study examined whether an association of PPAR-gamma2 Pro12Ala with insulin resistance and plasma LCPUFAs may exist in obese children. One hundred and forty Italian normolipidemic obese children (58 girls and 82 boys, mean age [SD], 10.2 [2.7] y) entered the study. Obesity was defined according to International Obesity Task Force. BMI Z-scores were calculated. Fasting blood glucose, insulin, lipids and plasma fatty acids were measured. Insulin resistance was estimated by the homeostatic model assessment (HOMA-IR). The frequency of Ala allele was 9%. Mean [SD] values of fasting insulin and HOMA-IR in Pro/Pro versus Pro12Ala groups were: 19.3 [10.6] versus 14.1 [10.4] microU/mL (p = 0.017) and 4.2 [2.3] versus 3.0 [2.3] (p = 0.022). Mean [SD] values of plasma C20:3n-9 and of C20:4n-6, C20:5n-3, C22:6n-3 and n-6/n-3 LCPUFA in phospholipds in Pro/Pro versus Pro12Ala groups were: 0.15 [0.07] versus 0.12 [0.08] % (p = 0.014), 8.9 [1.9] versus 10.2 [2.6] % (p = 0.023), 0.34 [0.15] versus 0.42 [0.11] % (p = 0.005), 2.1 [0.9] versus 2.6 [0.9] % (p = 0.032) and 4.8 [1.2] versus 4.2 [0.7] (p = 0.017). Pro12Ala may be associated with higher insulin sensitivity and higher LCPUFAs, particularly n-3, levels in plasma phosholipids of obese children.

Aim: To examine whether the plasma levels of long-chain polyunsaturated fatty acids (LC-PUFAs) are associated with the degree of obesity in children., Methods: Sixty-seven normolipidaemic obese children, aged 8-12 y, and 67 age- and sex-matched normal-weight children were included in the study. Obesity was defined in accordance with the International Obesity Task Force. BMI z-scores were calculated. Fasting blood samples were analysed for insulin, glucose, lipid profile and fatty acid (FA) levels (expressed as % total FA). Insulin resistance was estimated by homeostatic model assessment (HOMA)., Results: Compared with normal-weight children, obese children exhibited lower mean plasma total PUFA (37.8% vs 39.7%), omega-6 PUFAs (35.0% vs 36.8%) and C22:6omega-3-to-C18:3omega-3 ratio (5.52 vs 7.61), and higher total monounsaturated FA (26.6% vs 25.0%), C18:3omega-3 (0.28% vs 0.25%) and C20:5omega-3 (0.45% vs 0.39%). In obese children, the BMI z-score was negatively related to plasma PUFA, omega-3 PUFAs, C22:6omega-3, and the C22:6omega-3-to-C20:6omega-6 and C22:6omega-3-to-C18:3omega-3 ratios, and positively with total saturated FA and C20:3omega-9., Conclusion: In obese children, plasma LC-PUFA profile may be associated with the degree of obesity.

Forty-two infants (20 males, 22 females) with classical phenylketonuria (PKU) entered a prospective, double-blind, randomized study to investigate the effects on biochemical and physiological outcomes of a phenylalanine-free infant formula containing a fat blend supplemented with the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6 n-3), and arachidonic acid (AA, C20:4 n-6). Between entry and 20 weeks (entry and 1y) of age, median DHA levels in erythrocyte membrane phospholipids decreased by 15% (22%) in the LC-PUFA supplemented group (n=21) and by 61% (64%) in the control group (p<0.001; n=18). A dietary supply of LC-PUFA in infants with PKU prevents the decline in DHA levels associated with a diet supplying minimal sources of LC-PUFA. DHA status in turn, independent of diet, may influence the maturation of the visual system in infants with PKU.

Unlabelled: The content of long-chain polyunsaturated fatty acids (LC-PUFAs) in human milk has been connected with infant growth and developmental indices. The LC-PUFA content of human milk usually reflects the dietary habits of mothers, so questions have been raised regarding the possibility of enriching maternal diet with LC-PUFAs during lactation (or even before) in order to improve infant outcome. Nevertheless, environmental and genetic factors have independent roles in affecting both maternal milk composition and infant development., Conclusion: Diet-related differences in the LC-PUFA composition of human milk are under active investigation for their possible contribution to infant development, but environment- and gene-related differences in both human milk composition and maternal diet should be considered in evaluating the adaptive mechanisms of infants and the effects of specific LC-PUFA dietary supplementations.

Background and Aims: Environmental contaminants such as persistent organic chlorines and heavy metals, which are supplied to the foetus by transplacental transfer and to breastfed infants by the milk, may impair cognitive functions. Long-chain polyunsaturated fatty acids, which are known to enhance development during foetal life and early infancy, may counteract the toxic effect of environmental contaminants. In this study, we have investigated whether polychlorinated biphenyls (PCBs) impair early development of vision, and whether such impairment can be modulated by essential long-chain polyunsaturated fatty acids., Material: Healthy term infants born in Milan and its surroundings, and who were exclusively breastfed for at least 4 mo, were prospectively examined up to the age of 12 mo., Methods: Samples from colostrums, the first 2 d after delivery, and of mature breast-milk after 1 and 3 mo were collected. The samples were analyzed for PCB 105, 118, 138, 153, 156 and 180 and for DDT and DDE. In all infants, the plasma levels of the long-chain polyunsaturated fatty acids (LC-PUFAs), C18:2 n-6, C18:3 n-3, C20:4 n-6, C20:5 n-3 and C22:6 n-3 were analysed within the first three postnatal days. The PCB levels in colostral milk, as well as of LC-PUFAs in plasma, were considered to mirror perinatal supply. Visual function was evaluated by P100 with latency evoked potentials (VEPs) at 12 mo of age. Statistical analysis was based on simple and partial correlation coefficients (p < 0.05)., Results: On bivariate analysis, wave latency VEP at 15 min was significantly related to the colostral levels of DDT, DDE and all examined PCBs except PCB 105 (with correlation coefficient r = 0.401 to 0.618), whereas P100 wave latency VEP at 60 min was related to DDT (r = 0.513) and PCB 180 (r = 0.504). Infant plasma levels of C22:6 n-3 were inversely associated with P100 wave latency at 60 min (r = -0.418) and at 1Hz-2J (r = -0.466). After controlling for C22:6 n-3, the partial correlation coefficient of P100 wave latency VEP at 15 min to the colostral level of PCB 180 was 0.403 (p = 0.07)., Conclusion: Within the population of this study, a weak relation was found between impaired visual function at 12 mo of age of healthy infants and the levels of PCBs, DDT and DDE in colostral milk. The effect of impairment was no longer evident after controlling for the plasma level of LC-PUFAs as found in the infant a few days after birth.

Unlabelled: The evidence emerging from developing countries indicates a wide variability in the fat composition of human milk. The linoleic:alpha linolenic acid ratios, suggested to be included within the range of 5:1 and 15[20]:1, tend to fluctuate, and could indicate the capability of humans to self-adapt according to different dietary and environmental conditions., Conclusion: When referring to optimal "standard" dietary intakes for infants, the complex interactions between genetics and environment should be considered in interpreting observations from different settings.

Objective: To investigate the relation between maternal smoking habits, plasma lipids and milk fatty acid (FA) content and composition., Design: Breastfeeding mothers who gave birth to healthy, full-term infants were recruited. Mothers were interviewed on smoking habits, being defined smokers (S) when usually smoking at least five cigarettes per day before pregnancy., Setting: Department of Pediatrics, San Paolo Hospital, Milan, Italy., Subjects: In total, 92 mothers: 61 non-S (NS) and 31 S., Interventions: Pooled hindmilk was collected at the first raise of milk (colostrum stage), 1, 3 and 6 months, and total lipid (TL) content and fatty acid (FA) composition were evaluated. Maternal dietary habits were assessed by a food-frequency questionnaire. Two subsamples (16 NS, 6 S) were investigated after delivery and at 3 months for serum lipids and FA status. At 6 months after delivery, the number of mothers still breastfeeding decreased to 30. Variables were compared using nonparametric tests., Results: In smoking mothers serum levels of triglycerides, cholesterol and low-density lipoproteins were higher, while those of high-density lipoproteins were lower. TL content in breast milk was similar in the two groups just after delivery but higher in milk from NS at 1 month. TL content and FA absolute amounts of linoleic, arachidonic, alpha-linolenic and docosahexaenoic (DHA) acid in breast milk were lower in S vs NS 1 month after delivery. Also 3 months after delivery, the breast milk of smoking mothers contained less DHA than the breast milk of nonsmoking mothers., Conclusions: Maternal cigarette smoking in early pregnancy is associated with higher plasma lipid levels and lower milk TL and DHA content in the first months of lactation.

Blood fatty acid status and visual function of 20 treated hyperphenylalaninemic (HPA) children, randomly allocated into two groups to receive supplementation of either long chain polyunsaturated fatty acids (LCPUFA), including docosahexaenoic acid (DHA), or placebo for 12 months, have been investigated three years after the end of the treatment. Although in the LCPUFA group blood DHA levels and P100 wave latency improved at the end of supplementation, they had returned to baseline after three years.

Objective: To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids (LCPUFAs) influences blood pressure in later childhood., Design: Follow up of a multicentre, randomised controlled trial., Setting: Four study centres in Europe., Participants: 147 formula fed children, with a reference group of 88 breastfed children., Intervention: In the original trial newborn infants were randomised to be fed with a formula supplemented with LCPUFAs (n=111) or a formula without LCPUFAs but otherwise nutritionally similar (n=126). In the present follow up study the blood pressure of the children at age 6 years was measured., Main Outcome Measures: Systolic, diastolic, and mean blood pressure., Results: 71 children in the LCPUFA supplementation group (64% of the original group) and 76 children in the non-supplementation group (60%) were enrolled into the follow up study. The LCPUFA group had significantly lower mean blood pressure (mean difference -3.0 mm Hg (95% confidence interval -5.4 mm Hg to -0.5 mm Hg)) and diastolic blood pressure (mean difference -3.6 mm Hg (-6.5 mm Hg to -0.6 mm Hg)) than the non-supplementation group. The diastolic pressure of the breastfed children (n=88 (63%)) was significantly lower than that of the non-supplemented formula group but did not differ from the LCPUFA formula group., Conclusions: Dietary supplementation with LCPUFAs during infancy is associated with lower blood pressure in later childhood. Blood pressure tends to track from childhood into adult life, so early exposure to dietary LCPUFAs may reduce cardiovascular risk in adulthood.

The aims of the study were to examine the relationship between long-chain polyunsaturated fatty acid (LCPUFA) status at diagnosis of phenylketonuria (PKU) and neurodevelopment through the first 12 months of life, and to assess whether any difference exists between infants breastfed and bottlefed in the first days of life on the basis of LCPUFA status. Twenty infants with PKU were prospectively examined through the first year of life. Plasma fatty acids were measured in infants at diagnosis. Plasma phenylalanine levels were determined monthly. Main outcome measures were the Bayley Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 5 and 12 months of age, and the visual function at 12 months, evaluated by P100 wave latencies with visual evoked potentials. A higher PDI score was associated with higher plasma arachidonic acid at diagnosis (adjusted correlation coefficient of PDI at 5 months, r=0.38, p=0.05). P100 wave latency at 15 minutes of arc (15') was associated with the early plasma arachidonic acid (adjusted r=-0.56, p=0.02) and phenylalanine levels at 12 months (adjusted r=0.22, p=0.05). No association was found between MDI score and any essential fatty acids. Breastfed infants exhibited higher plasma arachidonic acid (mean difference, delta, =3.4%; 95% confidence interval [CI]=1.2-5.6%) and shorter P100 wave latency at 15' (delta=-21 ms, 95%CI=-30 to -12) than bottlefed infants. Within the population of this study, a weak positive association has been found between plasma LCPUFAs at diagnosis (higher in breastfed infants) and neurodevelopmental indices through the first year of life.

Fetuses with intrauterine growth restriction (IUGR) are at increased risk of death and disease during neonatal, pediatric, and adult life. Postnatal deficits in essential fatty acids have been associated with the neural and vascular complications of premature neonates. We studied whether fetal-maternal fatty acid relationships are already impaired in utero in IUGR fetuses. Fetal (F) and maternal (M) fatty acid profiles were determined in utero in 11 normal [appropriate for gestational age (AGA)] and in 10 IUGR fetuses by fetal blood sampling (FBS) between 19 and 39 wk. Total plasma fatty acid concentrations were significantly higher in M than in F of both AGA (M: 2.03 +/- 0.53 mg/mL; F: 0.64 +/- 0.29 mg/mL; p < 0.001) and IUGR (M: 2.16 +/- 0.59 mg/mL; F: 0.73 +/- 0.17 mg/mL; p < 0.001). The F/M ratio was significantly higher for linoleic acid (AGA: 0.36 +/- 0.09; IUGR: 0.52 +/- 0.12; p < 0.01) and significantly lower for the long-chain polyunsaturated fatty acid docosahexaenoic acid (AGA: 1.94 +/- 0.32; IUGR: 1.25 +/- 0.19; p < 0.05) and arachidonic acid (AGA: 2.35 +/- 0.35%; IUGR: 2.04 +/- 0.3%; p < 0.05) in IUGR compared with AGA pregnancies. The differences observed in the relative amounts but not in total plasma concentrations of fatty acid fetal-maternal relationships in pregnancies associated with IUGR could be related to inadequate transplacental supply as well as to a fetal lack of the enzymes necessary for elaboration of these metabolically relevant conditionally essential fatty acids. These differences might have a role in determining the biochemical environment leading to the neural and vascular complications associated with IUGR.

In order to explain processes underlying the transfer of fatty acids from the maternal compartment into human milk, the lipid content and the fatty acid composition of maternal plasma and milk have been analyzed in breastfeeding mothers at 1 day and 3 months of lactation. The rise in milk lipids occurring during the study period was concomitant with a fall in plasma total fat content, mainly due to the decrease of triglycerides. Significant correlations between plasma and milk fatty acids at the two time points were observed only for linoleic (LA, 18:2 n-6) and (alpha;-linolenic acid (alpha LNA, 18:3 n-3), while for arachidonic (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) correlations were found only at one day and 3 months, respectively. These data suggest that levels of the n-6 and n-3 18C polyunsaturated fatty acids in milk are closely dependent on their concentrations in maternal plasma, in turn related with the dietary intake, while the accumulation of AA and DHA in milk is the result of a sequence of transfer and metabolic processes.

Unlabelled: This paper reports on the conclusions of a workshop on the role of long chain polyunsaturated fatty acids (LC-PUFA) in maternal and child health. The attending investigators involved in the majority of randomized trials examining LC-PUFA status and functional outcomes summarize the current knowledge in the field and make recommendations for dietary practice. Only studies published in full or in abstract form were used as our working knowledge base., Conclusions: For healthy infants we recommend and strongly support breastfeeding as the preferred method of feeding, which supplies preformed LC-PUFA. Infant formulas for term infants should contain at least 0.2% of total fatty acids as docosahexaenoic acid (DHA) and 0.35% as arachidonic acid (AA). Since preterm infants are born with much less total body DHA and AA, we suggest that preterm infant formulas should include at least 0.35% DHA and 0.4% AA. Higher levels might confer additional benefits and should be further investigated because optimal dietary intakes for term and preterm infants remain to be defined. For pregnant and lactating women we consider it premature to recommend specific LC-PUFA intakes. However, it seems prudent for pregnant and lactating women to include some food sources of DHA in their diet in view of their assumed increase in LC-PUFA demand and the relationship between maternal and foetal DHA status.

Hyperphenylalaninemic (HPA) children display low levels of long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), in circulating lipids and erythrocytes. We have investigated the effects on the blood fatty acid status and lipid picture of a balanced supplementation with LCPUFA in HPA children through a double-blind, placebo-controlled trial. A total of 20 well-controlled HPA, school-age children were randomized to receive through a 12-month trial fat capsules supplying either 26% fatty acid as LCPUFA (including 4.6%gamma -linolenic acid, 7.4% arachidonic acid, AA, 5.5% eicosapentaenoic acid and 8% DHA) or placebo (olive oil). The study supplementation was administered in order to provide 0.3-0.5% of the individual daily energy requirements as LCPUFA. Reference data were obtained from healthy children of comparable age. Among HPA children (whose DHA status was poor at baseline), those supplemented with LCPUFA showed an increase of around 100% in the baseline DHA levels in plasma phospholipids and erythrocytes. No changes of AA levels were observed. Blood lipid levels did not significantly change. A balanced supplementation with LCPUFA in treated HPA children may improve the DHA status without adversely affecting the AA status.

We assessed the total fat content and fatty acid concentrations in colostrum and throughout a nursing period of 12 months in a group of mothers recruited after delivery of full-term infants. Pooled human milk (hindmilk) was collected from all feedings over 24 hours at the following times: 1st day of nursing (colostrum), and at 1, 3, 6, 9, and 12 months. Total fat was quantified by a microgravimetric method. Fatty acids were analyzed by means of capillary gas chromatography. Comparisons were made with analysis of variance for repeated measures. Ten mothers completed the follow-up 12-month nursing period. We found that the total lipid content of hindmilk (mg/dL) rises more than 3-fold from the colostrum up to the 3rd month, and then more slowly up to the 12th month. Total saturated fatty acids progressively increase and total monounsaturated FA progressively decrease. Among long-chain polyunsaturated fatty acids, we found that the concentrations (mg/dL) of C20:4 and C22:6 remain stable from colostrum up to the 12th month of nursing, while their percentage levels are highest in colostrum and decrease afterwards in association with the increase in total fats. The C18:2n6 and C18:3n3 amounts progressively increase, following the trend of total fats. These data indicate that the secretion of arachidonic acid and docosahexaenoic acid during lactation remains constant, in spite of changes in total fat and in the linoleic acid and alpha-linolenic acid contents of milk.

Background: Children with phenylalanine-hydroxylase deficiency (type-I hyperphenylalaninemia, HPA) follow a low-phenylalanine diet, severely restricted in animal foods and long-chain polyunsaturated fatty acids (LCPUFA). Consequently, they have a poor LCPUFA status, particularly for docosahexaenoic acid (DHA). DHA is relevant to visual and neural development., Objective: To investigate the effects of a 12-month supplementation with LCPUFA in a double-blind, placebo-controlled trial in treated children with HPA., Study Design: Twenty children with well-controlled HPA were randomly allocated to receive either a fat supplement (supplying 26% as fatty acids including DHA, 8%) or a placebo. The fatty acid composition of erythrocyte lipids and the visual evoked potentials were measured at baseline and after 12 months of supplementation. Reference data were obtained from healthy children of comparable age., Results: At baseline children with HPA had a poorer DHA status and prolonged P100 wave latencies than the reference group. At the end of the trial the LCPUFA group showed a significant increase in DHA levels of erythrocyte lipids. In the LCPUFA group P100 wave latency decreased and was negatively associated with the DHA changes., Conclusions: A balanced dietary supplementation with LCPUFA in children with HPA is associated with an increase of the DHA pool and improved visual function.

While a wealth of data on the fatty acid composition of mature human milk has been published, limited information is available on the quantities of individual fatty acids supplied to the suckling infant with maternal milk, through the whole first year of life. Our aim was to qualitatively and quantitatively evaluate the fatty acid composition of human milk from Italian mothers, throughout extended lactation with particular emphasis on the long-chain polyunsaturated fatty acids. We have thus measured the total fat content and the concentrations of major fatty acids by quantitative GLC in pooled breast hindmilk collected from all feedings over 24 h at colostrum, 1, 3, 6, 9 and 12 months in ten mothers recruited after delivery of full-term infants. Total saturated fatty acids progressively increase and total monounsaturated progressively decrease as percentage levels, while among long-chain polyunsaturated fatty acids, percentages of arachidonic acid and docosahexaenoic acid decrease from colostrum up to the third month. Hindmilk total lipids (mg/dl) rise more than twofold up to 3 months, and then remain stable. The amounts (mg/dl) of linoleic acid and alpha-linolenic acid progressively increase, following the trend of total fat, while arachidonic and docosahexaenoic concentrations (mg/dl) remain stable throughout the whole nursing period. Assessment of the intakes per kg body weight shows different trends for the individual major long-chain polyunsaturated fatty acids supplied to the infant from hindmilk during exclusive breast-feeding (3 months). This information may be useful for the evaluation of infant intakes during extended lactation.

Children infected with the type-1 human immunodeficiency virus (HIV) are at risk of nutritional deficiencies leading to an impaired polyunsaturated fatty acid (PUFA) status. The aim of the present study was to compare the PUFA composition of plasma lipid classes (total lipids, phospholipids (PL), cholesteryl esters (CE) and triglycerides) in well-growing HIV-infected children with an age-matched group of HIV-seroreverter children born to infected mothers. Eighteen HIV children, of both sexes, mean age 4.6 y, most of whom under combined antiretroviral regimen, were compared with 18 seroreverters, mean age 5.4 y, comparable for demographic, anthropometric and dietary characteristics. All children had adequate growth parameters (weight and height > 3rd percentile). The plasma fatty acid content was similar in the two groups. HIV seropositive subjects showed lower linoleic acid (LA) levels in all the plasma lipid fractions, with higher 20:3n-9 and 20:5n-3 levels in PL and CE. The plasma PL triene/tetraene ratio (marker of relative LA deficiency) related positively to the viral load and negatively to the blood CD4+ lymphocyte count. Compared to age-matched seroreverter subjects, HIV-seropositive children show a lipid fatty acid status suggestive of relative LA deficiency and increased turnover of the PUFA series.

Arachidonic acid and docosahexaenoic acid are the most representative long-chain polyunsaturated fatty acids (LCPUFA) since they may affect infants' growth and development. LCPUFA are present in the milk of all lactating women throughout lactation. The mothers' dietary habits may affect the levels of these fatty acids in maternal blood lipids and then in milk. LCPUFA show marked differences in levels as wt%, particularly from colostrum to mature human milk, but only mild differences in absolute content. Both the major presence of LCPUFA in human milk phospholipids and some regulatory mechanisms in the mammary gland cells could contribute to the LCPUFA levels in milk beyond those in maternal plasma.

The early dietary supply of long-chain polyunsaturated fatty acids (LCPUFA) might contribute to the higher developmental scores of children breast-fed as infants. Preterm infants' improved visual acuity and neurodevelopmental performance correlate with dietary supplementation of LCPUFA in amounts similar to those that breast-fed infants receive and studies of term infants report similar effects with LCPUFA supplementation. Whether term infants may benefit from LCPUFA-unsupplemented formulas with higher amounts of alpha-linolenic acid (n - 3 LCPUFA precursor) is controversial. With the onset of weaning, the question of the exact quantity and quality of which dietary lipids to give for prevention purposes is still open. Early dietary intervention studies of weaned children under 2 years are in progress in populations at high risk for early cardiovascular disorders. Preliminary results indicate that these interventions, while preventing an age-dependent increase in blood lipid levels, are safe for growth, but the balance of all the macronutrients should be carefully considered before general recommendations can be made.

Both long-chain polyunsaturated (LCP) fatty acids and cholesterol are supplied by human milk. Dietary long-chain polyunsaturated fatty acids in the first 2 years of life have been associated with growth and developmental indices. Cholesterol supply does not seem relevant for structural purposes, but could have a role in the metabolism of LCP. Complex relationships between dietary fatty acids and cholesterol seem to be major determinants of blood lipid levels in the first months of life. Data from both suckling and weaned infants indicate that their blood lipid profile reacts to changes in their diet in a manner similar to adults. Early intervention trials on weaned infants (<2 years of age) have been addressed in populations at high risk for early cardiovascular disorders and seem safe for growth at short-term assessments, but the balance of all the macronutrients should be carefully considered. While the effects of plasma cholesterol concentrations in the suckling infant on the subsequent development of atheroslerosis are still unknown, both the diet composition and the way by which food is supplied to infants seem to be major determinants of their metabolic profile.

Aim: A follow up study of developmental quotient (DQ) at 24 months of toddlers whose diets in early infancy differed in fatty acid composition, and in whom an association between diet and DQ was observed at 4 months., Methods: 81 toddlers were distributed among three groups according to early type of diets standard infant formula (SFo, n = 30); long chain polyunsaturated fatty acid (LC-PUFA) enriched formula (LCPFo, n = 26); human milk (HM, n = 25). DQ at 24 months was assessed by Brunet-Léxine's psychomotor developmental test. A subgroup (n = 20; SFo 8; LCPFo 6; HM 6) was tested for erythrocyte phosphatidyicholine and phosphatidylethanolamine., Results: No DQ differences were found by analysis of variance. Neither DQ nor erythrocyte docosahexaenoic acid at 4 months were predictors of DQ scores at 24 months. Phosphatidylcholine arachidonic and docosahexaenoic acid correlated positively, and phosphatidylcholine linoleic acid and phosphatidylethanolamine eicosapentaenoic acid negatively, with DQ. Multiple regression analysis including these variables explained 52% of inter-individual DQ variance. A strong association was found between the erythrocyte phosphatidylcholine arachidonic/ linoleic acid ratio and DQ (r = 0.75; p = 0.0001)., Conclusions: The diet/DQ association found at 4 months was not predictive of DQ scores at 24 months. Irrespective of dietary or genetic factors, there appears to be a strong correlation between the LC-PUFA composition of the red cell membrane and higher neurodevelopmental performance.

Children treated for phenylketonuria (PKU) have a low intake of whole animal foods. Consequently, the dietary intake of long-chain polyunsaturated fatty acids (PUFA) is just a few milligrams per day, mostly represented by arachidonic acid (AA). In a consecutive series of studies, we assessed in treated PKU children their long-chain PUFA status, the AA-related eicosanoid synthesis and the effects of specific PUFA supplementations. We found that the good compliance with the dietary regimen negatively influences the long-chain PUFA status and serum eicosanoid release from platelets. Supplementation with either marine or blackcurrant oils modifies the long-chain PUFA status of PKU children without approaching the fatty acid pattern of a healthy control population. Good-compliant PKU patients have diet-related, low levels of circulating long-chain PUFA, whose clinical and functional consequences deserve further investigation. The effects of dietary supplementations with long-chain PUFA of both the n-6 and n-3 series should be carefully evaluated.

Dietary-treated phenylketonuric patients (PKUs) display low levels of long-chain polyunsaturated fatty acids (PUFA) in plasma lipids. In a 6-month clinical trial we observed a decrease of triglycerides and an increase of n-3 long-chain PUFA in plasma of PKUs supplemented with fish oil, while no major differences in respect to the baseline values were found in a group supplemented with blackcurrant oil. A more complete source of long-chain PUFA of both the n-6 and n-3 series should be investigated for dietary supplementation of PKU patients.

A direct influence of dietary long-chain polyunsaturated fatty acids (LC-PUFA) on the developmental quotient (DQ) of the healthy term infant remains unexplored. To test this hypothesis, we designed a prospective study of three types of diet. Twenty-nine infants received a LC-PUFA-supplemented formula, 31 received a standard infant formula, and 30 infants were breast-fed exclusively. Neurodevelopmental response was measured by the Brunet-Lézine psychomotor development test at 4 mo. The fatty acid status was also assessed among three diet subgroups (59 subjects) at 4 mo. Formula-fed infants who received LC-PUFA supplementation scored significantly higher (p < 0.01) on the Brunet-Lézine scale than infants who received the standard formula. Breast-fed infants also performed better than those fed the standard formula. Arachidonic acid and docosahexaenoic acid levels in circulating lipids and erythrocyte phospholipids were higher among breast-fed infants and among the group fed the arachidonic- and docosahexaenoic acid-supplemented formula. These findings are suggestive that formula supplementation with one or both of these fatty acids can benefit term infants in neurodevelopmental performance.

Objective: To compare the effects of the exogenous supply of long-chain polyunsaturated fatty acids (LCP) and cholesterol on the lipid and fatty acid status in full-term, 4-month old infants., Methods: Twenty-three infants received a standard infant formula while twenty-one were given a formula enriched with LCP and cholesterol in a prospective, randomized study. The composition of the two formulas differed only in fat quality. A group of fifteen breastfed infants fed was used as reference. No one was complemented with solid foods before blood sampling at 4 months of life., Results: Differences in total-cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels between feeding groups were mainly gender-related. Dietary cholesterol tended to increase LDL-C plasma levels. The breastfed and the enriched formula-fed groups had higher levels of circulating LCP than the group that received the standard formula. In the erythrocytes of infants fed the standard formula, C22:6 n-3 levels were less than 50% those of the breastfed and the enriched formula-fed ones. Higher C20:4 n-6 levels were found in the erythrocytes of the enriched formula-fed group., Conclusions: Formula-fed, full-term infants maintain a lipid and fatty acid status close to that of breastfed infants when supplied with dietary LCP and cholesterol.

The fatty acid composition of plasma and erythrocyte lipids was analyzed in 15 children with phenylketonuria (aged 3 to 12 years) during dietary treatment aimed to maintain plasma phenylalanine levels at less than 8 mg/dl (485 mumol/L), and compared with those of 12 matched control subjects. The diet of children with phenylketonuria provided less protein, with a very low proportion of animal proteins, less fat, but a higher proportion of linoleic acid as a percentage of calories, and a higher carbohydrate content versus that in the diet of control subjects. The children with phenylketonuria had higher plasma levels of oleic acid but lower levels of arachidonic (n-6) and n-3 fatty acids. Linoleic and eicosatrienoic (n-9) acid levels were the same in both groups. These changes in patients with phenylketonuria resemble those observed in vegetarians and may be due to the absence of preformed arachidonic acid and long-chain n-3 fatty acids in the phenylketonuric diet.