Role for animal models in understanding essential fatty acid deficiency in cystic fibrosis.

Essential fatty acid deficiency has been observed in most patients with Cystic Fibrosis (CF); however, pancreatic supplementation does not restore the deficiency, suggesting a different pathology independent of the pancreas. At this time, the underlying pathological mechanisms are largely unknown. Essential fatty acids are obtained from the diet and processed by organs including the liver and intestine, two organs significantly impacted by mutations in the cystic fibrosis transmembrane conductance regulator gene (Cftr). There are several CF animal models in a variety of species that have been developed to investigate molecular mechanisms associated with the CF phenotype. Specifically, global and systemic mutations in Cftr which mimic genotypic changes identified in CF patients have been generated in mice, rats, sheep, pigs and ferrets. These mutations produce CFTR proteins with a gating defect, trafficking defect, or an absent or inactive CFTR channel. Essential fatty acids are critical to CFTR function, with a bidirectional relationship between CFTR and essential fatty acids proposed. Currently, there are limited analyses on the essential fatty acid status in most of these animal models. Of interest, in the mouse model, essential fatty acid status is dependent on the genotype and resultant phenotype of the mouse. Future investigations should identify an optimal animal model that has most of the phenotypic changes associated with CF including the essential fatty acid deficiencies, which can be used in the development of therapeutics.

Complementary Foods and Milk-Based Formulas Provide Excess Protein but Suboptimal Key Micronutrients and Essential Fatty Acids in the Intakes of Infants and Toddlers from Urban Settings in Malaysia.

This study determined the intakes of complementary foods (CFs) and milk-based formulas (MFs) by a total of 119 subjects aged 6-23.9 months from urban day care centers. Dietary intakes were assessed using two-day weighed food records. Intake adequacy of energy and nutrients was compared to the Recommended Nutrient Intakes (RNI) for Malaysia. The most commonly consumed CFs were cereals (rice, noodles, bread). The subjects derived approximately half of their energy requirements (kcals) from CFs (57 ± 35%) and MFs (56 ± 31%). Protein intake was in excess of their RNI requirements, from both CFs (145 ± 72%) and MFs (133 ± 88%). Main sources of protein included meat, dairy products, and western fast food. Intake of CFs provided less than the RNI requirements for vitamin A, thiamine, riboflavin, folate, vitamin C, calcium, iron, and zinc. Neither CF nor MF intake met the Adequate Intake (AI) requirements for essential fatty acids. These findings indicate imbalances in the dietary intake of the subjects that may have adverse health implications, including increased risk of rapid weight gain from excess protein intake, and linear growth faltering and intellectual impairment from multiple micronutrient deficiencies. Interventions are needed to improve child feeding knowledge and practices among parents and child care providers.

Plasma and Red Blood Cell PUFAs in Home Parenteral Nutrition Paediatric Patients-Effects of Lipid Emulsions.

Background: Mixed lipid emulsions (LE) containing fish oil present several advantages compared to the sole soybean oil LE, but little is known about the safety of essential fatty acids (EFA) profile in paediatric patients on long-term Parenteral Nutrition (PN). Aim of the study: to assess glycerophosfolipid polyunsaturated fatty acids (PUFA) levels on plasma and red blood cell (RBC) membrane of children on long term PN with composite LE containing fish oil (SMOF), and to compare it with a group receiving olive oil LE (Clinoleic®) and to the reference range for age, previously determined on a group of healthy children. Results: A total of 38 patients were enrolled, median age 5.56 (0.9-21.86) years, 15 receiving Clinoleic®, 23 receiving SMOF. Patients on SMOF showed significantly higher levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower levels of arachidonic acid (ARA) and Mead acid (MEAD)/ARA ratio in plasma and RBC compared with patients on Clinoleic® and with healthy children. Triene:tetraene (T:T) ratio of both groups of patients did not differ from that of healthy children-median plasma (MEAD/ARA: 0.01, interquartile rage (IQR) 0.01, p = 0.61 and 0.02, IQR 0.02, p = 0.6 in SMOF and Clinoleic® patients, respectively), and was considerably lower than Holman index (>0.21). SMOF patients showed no statistically significant differences in growth parameters compared with Clinoleic® patients. Patients of both groups showed stiffness class F0-F1 of liver stiffness measure (LSM) 5.6 (IQR 0.85) in SMOF patients and 5.3 (IQR 0.90) in Clinoleic® patients, p = 0.58), indicating absence of liver fibrosis. Conclusions: Fatty acids, measured as concentrations (mg/L), revealed specific PUFA profile of PN patients and could be an accurate method to evaluate nutritional status and eventually to detect essential fatty acid deficiency (EFAD). SMOF patients showed significantly higher EPA, DHA and lower ARA concentrations compared to Clinoleic® patients. Both LEs showed similar hepatic evolution and growth.

Essential fatty acids deficient diet modulates N-Acylethanolamide profile in rat's tissues.

No data are available on whether a diet deficient of the essential fatty acids is able to modulate tissue levels of endocannabinoids and congeners. Male rats fed for 12 weeks a diet deficient of essential fatty acids, palmitic and oleic acids (EFAD), replaced with saturated fatty acids (SAFA), showed lowered n-3 and n-6 PUFAs levels in plasma, liver and adipose tissue, with concomitant steep increase of oleic and mead acids, while in hypothalamus no changes in PUFA concentration were detected and only palmitoleic acid was found increased. We found a reduction of anandamide and palmitoylethanolamide in liver and brain, while oleoylethanolamide increased significantly in liver and adipose tissue, associated to a 50 % body weight decrease. Changes in N-acylethanolamide profile may contribute to body weight reduction distinctive of EFA deficiency.

Enhanced Triacylglycerol Content and Gene Expression for Triacylglycerol Metabolism, Acyl-Ceramide Synthesis, and Corneocyte Lipid Formation in the Epidermis of Borage Oil Fed Guinea Pigs.

Triacylglycerol (TAG) metabolism is related to the acyl-ceramide (Cer) synthesis and corneocyte lipid envelope (CLE) formation involved in maintaining the epidermal barrier. Prompted by the recovery of a disrupted epidermal barrier with dietary borage oil (BO: 40.9% linoleic acid (LNA) and 24.0% γ-linolenic acid (GLA)) in essential fatty acid (EFA) deficiency, lipidomic and transcriptome analyses and subsequent quantitative RT-PCR were performed to determine the effects of borage oil (BO) on TAG content and species, and the gene expression related to overall lipid metabolism. Dietary BO for 2 weeks in EFA-deficient guinea pigs increased the total TAG content, including the TAG species esterified LNA, GLA, and their C20 metabolized fatty acids. Moreover, the expression levels of genes in the monoacylglycerol and glycerol-3-phosphate pathways, two major pathways of TAG synthesis, increased, along with those of TAG lipase, acyl-Cer synthesis, and CLE formation. Dietary BO enhanced TAG content, the gene expression of TAG metabolism, acyl-Cer synthesis, and CLE formation.

Essential Fatty Acid Requirements and Intravenous Lipid Emulsions.

Linoleic acid (LA) and α-linolenic acid (ALA) must be supplied to the human body and are therefore considered essential fatty acids. This narrative review discusses the signs, symptoms, diagnosis, prevention, and treatment of essential fatty acid deficiency (EFAD). EFAD may occur in patients with conditions that severely limit the intake, digestion, absorption, and/or metabolism of fat. EFAD may be prevented in patients requiring parenteral nutrition by inclusion of an intravenous lipid emulsion (ILE) as a source of LA and ALA. Early ILEs consisted solely of soybean oil (SO), a good source of LA and ALA, but being rich in LA may promote the production of proinflammatory fatty acids. Subsequent ILE formulations replaced part of the SO with other fat sources to decrease the amount of proinflammatory fatty acids. Although rare, EFAD is diagnosed by an elevated triene:tetraene (T:T) ratio, which reflects increased metabolism of oleic acid to Mead acid in the absence of adequate LA and ALA. Assays for measuring fatty acids have improved over the years, and therefore it is necessary to take into account the particular assay used and its reference range when determining if the T:T ratio indicates EFAD. In patients with a high degree of suspicion for EFAD, obtaining a fatty acid profile may provide additional useful information for making a diagnosis of EFAD. In patients receiving an ILE, the T:T ratio and fatty acid profile should be interpreted in light of the fatty acid composition of the ILE to ensure accurate diagnosis of EFAD.

Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure-Associated Liver Disease.

BACKGROUND: Intravenous fish oil (FO) treats pediatric intestinal failure-associated liver disease (IFALD). There are concerns that a lipid emulsion composed of ω-3 fatty acids will cause an essential fatty acid deficiency (EFAD). This study's objective was to quantify the risk for abnormal fatty acid concentrations in children treated with FO. METHODS: Inclusion criteria for this prospective study were children with intestinal failure. Intravenous soybean oil (SO) was replaced with FO for no longer than 6 months. Serum fatty acids were analyzed using linear and logistic models, and compared with age-based norms to determine the percentage of subjects with low and high concentrations. RESULTS: Subjects (n = 17) started receiving FO at a median of 3.6 months (interquartile range 2.4-9.6 months). Over time, α-linolenic, linoleic, arachidonic, and Mead acid decreased, whereas docosahexaenoic and eicosapentaenoic acid increased (P < 0.001 for all). Triene-tetraene ratios remained unchanged (P = 1). Although subjects were 1.8 times more likely to develop a low linoleic acid while receiving FO vs SO (95% CI: 1.4-2.3, P < 0.01), there was not a significant risk for low arachidonic acid. Subjects were 1.6 times more likely to develop high docosahexaenoic acid while receiving FO vs SO; however, this was not significant (95% CI: 0.9-2.6, P = 0.08). CONCLUSION: In this cohort of parenteral nutrition-dependent children, switching from SO to FO led to a decrease in essential fatty acid concentrations, but an EFAD was not evident. Low and high levels of fatty acids developed. Further investigation is needed to clarify if this is clinically significant.

Essential Fatty Acid Deficiency with SMOFlipid Reduction in an Infant with Intestinal Failure-Associated Liver Disease.

Multicomponent lipid emulsions, such as SMOFlipid, contain intermediate amounts of essential fatty acids (EFAs) compared with traditional soybean-oil based lipid emulsions and 100% fish-oil lipid emulsions. We describe the development of moderate EFA deficiency (EFAD) and slow weight gain in an infant with intestinal failure-associated liver disease managed with SMOFlipid reduction (1 g/kg/d). Once SMOFlipid dosage was increased (2-3 g/kg/d), EFA levels normalized, adequate growth resumed, and the infant's cholestasis resolved. We recommend avoiding lipid reduction of SMOFlipid, which not only increases the risk for EFAD, but also is unnecessary given that cholestasis can be reversed on conventional doses of SMOFlipid.

Essential Fatty Acid Status in Surgical Infants Receiving Parenteral Nutrition With a Composite Lipid Emulsion: A Case Series.

Infants requiring prolonged parenteral nutrition (PN) may receive intravenous (IV) lipid in the form of soybean oil, fish oil, or a composite lipid emulsion (CLE) (i.e., SMOFlipid®). Soybean oil lipid-dose restriction is a popular method of treating and reducing the risk of intestinal failure-associated liver disease (IFALD) that may influence dosing strategies of other IV fat emulsions. Here we present 4 infants receiving PN with SMOFlipid® as their IV lipid source and examine trends in essential fatty-acid status, triglycerides, and dosing strategy. The infants on restricted doses of CLE developed biochemical essential fatty-acid deficiency (EFAD) that resolved with a dosage increase or by transition to a pure fish-oil lipid emulsion. Three of the 4 infants originally prescribed CLE were diagnosed with IFALD and started a pure fish-oil lipid emulsion after treatable causes of cholestasis were excluded. One of the 4 infants presented with hypertriglyceridemia that resolved upon transition to pure fish-oil lipid emulsion. Misapplication of lipid restriction protocols to CLE regimens render infants at risk for EFAD. CLE should be dosed within recommended ranges to prevent EFAD. Restricted protocols warrant close monitoring of essential fatty-acid status in infants receiving prolonged PN, particularly in those with minimal or no enteral intake. Hypertriglyceridemia and cholestasis are known adverse effects of CLE and require monitoring.

Borage oil restores acidic skin pH by up-regulating the activity or expression of filaggrin and enzymes involved in epidermal lactate, free fatty acid, and acidic free amino acid metabolism in essential fatty acid-deficient Guinea pigs.

Borage oil (BO) reverses a disrupted epidermal lipid barrier and hyperproliferation in essential fatty acid deficiency (EFAD). However, little is known about its effect on skin pH, which is maintained by epidermal lactate, free fatty acids (FFAs), and free amino acids (FAAs) which is generated by lactate dehydrogenase (LDH), secreted phospholipase A2 (sPLA2), or filaggrin degradation with peptidylarginine deiminase-3 (PADI3). We hypothesized that BO restores skin pH by regulating epidermal lactate, FFA metabolism, or FAA metabolism in EFAD. To test this hypothesis, EFAD was induced in guinea pigs by a hydrogenated coconut oil (HCO) diet for 8 weeks, followed by 2 weeks of a BO diet (group HCO + BO). As controls, groups HCO and BO were fed HCO or BO diets for 10 weeks. In group HCO + BO, skin pH, which was less acidic in group HCO, was restored; and epidermal lactate and total FFAs, including palmitate, stearate, linoleate, arachidate, behenate, and lignocerate, were higher than in group HCO. LDH and sPLA2 (mainly the PLA2G2F isoform) activities and protein expressions were similar between groups HCO + BO and BO. Epidermal acidic FAAs, as well as filaggrin and PADI3 protein and mRNA expressions were higher in group HCO + BO than in group HCO. Oleate, total FAAs including other FAAs, and LDH and sPLA2 mRNA expressions were not altered between groups HCO and HCO + BO. Basic FAAs were not altered among groups. Dietary BO restored acidic skin pH and increased epidermal levels of lactate, most FFAs, and acidic FAAs by up-regulating LDH, sPLA2, filaggrin, and PADI3 activities as well as protein or mRNA expressions in EFAD.

Controversies in the Use of Lipid Injectable Emulsion in Hospitalized Patients.

Soybean oil-based lipid injectable emulsion (SO-based ILE) is an 18-carbon, ω-6 macronutrient providing a concentrated source of calories, which can be administered in or with parenteral nutrition to patients unable to tolerate or consume adequate enteral nutrition. Beyond the provision of energy, SO-based ILE provides linoleic and linolenic acid, 2 essential fatty acids necessary for the prevention of essential fatty acid deficiency. However, SO-based ILE with its high levels of ω-6 fatty acids, long-chain triglycerides, phospholipid emulsifiers, and glycerin has been associated with worsening clinical outcomes, including increase of infections, lengthier intensive care and hospital stay, and prolonged mechanical ventilation. Recognizing this, studies have investigated omitting SO-based ILE in the critically ill patient for the first 7 days to observe if clinical outcomes are improved. Unfortunately, there is extremely limited research, and what is available is controversial. National guidelines have analyzed the studies, and they too are challenged to define a clear, high quality of evidence recommendation. It is important for the healthcare clinician to understand the research around this controversy to make best decisions for their patients.

Erythrocyte fatty acid composition of Nepal breast-fed infants.

PURPOSE: Essential fatty acids play a critical role in the growth and development of infants, but little is known about the fatty acid status of populations in low-income countries. The objective was to describe the fatty acid composition of red blood cells (RBC) in breastfeed Nepali infants and a subsample of their mothers and to identify the main sources of fatty acids in the mother's diet, as well as the fatty acid composition of breast milk. METHODS: RBC fatty acid composition was analyzed in a random sample of 303 infants and 72 mother, along with 68 breastmilk samples. Fatty acid profiles of the most important dietary fat sources were analyzed. Information on mother's diet and intake of fat was collected by three 24-h dietary recalls. RESULTS: In infant RBC's, docosahexaenoic acid (DHA) was the main n-3 fatty acid, and arachidonic acid (AA) was the major n-6 fatty acid. Total n-6 PUFA was three times higher than total n-3 PUFA. Height-for-age (HAZ) was positively associated with DHA status and AA status in multivariable models. The concentration of all fatty acids was higher in children, compared to mothers, except Total n-6 PUFA and Linoleic acid (LA) where no differences were found. The mother's energy intake from fat was 13% and cooking oil (sesame, mustard, soybean or sunflower oil) contributed 52% of the fat intake. CONCLUSIONS: RBC-DHA levels in both infants and mother was unexpected high taking into account few dietary DHA sources and the low DHA concentrations in breastmilk.

Essential fatty acid deficiency during parenteral soybean oil lipid minimization.

OBJECTIVE: To determine if parenteral lipid minimization in infants results in essential fatty acid (EFA) deficiency. STUDY DESIGN: Prospective study of infants >30 days old and >34 weeks postmenstrual age receiving parenteral lipid minimization (<1.5 g kg-1 per day) with either soybean oil or fish oil and >90% of total nutritional intake parenterally in the 14 days before a serum EFA sample. Nonparametric tests were used for statistical analyses with significance at 0.05. RESULTS: Fifteen samples on soybean oil and nine on fish oil were included. Energy and macronutrient intakes and weight gain were similar between groups. Biochemical EFA deficiency occurred in 60% receiving soybean oil but none receiving fish oil (P<0.01). Average daily weight gain was 49% less in EFA deficient infants than EFA sufficient infants (P=0.02). CONCLUSION: Infants on lipid minimization with parenteral soybean oil, but not fish oil, are at high risk of biochemical EFA deficiency with slower weight gain.

Long-Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure-Associated Liver Disease [Formula: see text].

BACKGROUND: Fish oil lipid emulsion (FOLE) and multidisciplinary care for infants with intestinal failure (IF) have been associated with reduced morbidity and mortality due to IF-associated liver disease (IFALD). With increased survival, a greater proportion of infants with IF are now able to remain on parenteral nutrition (PN) in the long term. The purpose of this study was to examine outcomes in children with IFALD who have required long-term PN and FOLE therapy due to chronic IF. MATERIALS AND METHODS: A review of prospectively collected data was performed for children with IFALD who required at least 3 years of PN and FOLE therapy due to chronic IF. Outcomes examined include the incidence of death, transplantation, and essential fatty acid deficiency (EFAD), as well as growth parameters and the biochemical markers of liver disease. RESULTS: Of 215 patients with IFALD treated from 2004-2015, 30 required PN and FOLE therapy for at least 3 years (median, 4.6 years). To date, no patients have died, required transplantation, or developed EFAD. Biochemical markers of liver disease normalized within the first year of therapy with no recurrent elevations in the long term. Weight-for age and length-for-age z scores improved and PN dependence decreased in the first year of therapy, with a stable rate of growth in the long term. CONCLUSIONS: Children with IFALD who required long-term PN and FOLE for chronic IF had no mortality, need for transplantation, EFAD, or recurrence of liver disease in the long term, allowing for continued intestinal rehabilitation.

Omega 3 polyunsaturated fatty acids and the treatment of depression.

Depression is a common, recurrent, and debilitating illness that has become more prevalent over the past 100 years. This report reviews the etiology and pathophysiology of depression, and explores the role of omega 3 polyunsaturated fatty acids (n-3 PUFA) as a possible treatment. In seeking to understand depression, genetic factors and environmental influences have been extensively investigated. Research has led to several hypotheses for the pathophysiological basis of depression but a definitive pathogenic mechanism, or group thereof, has hitherto remained equivocal. To date, treatment has been based on the monoamine hypothesis and hence, selective serotonin reuptake inhibitors have been the most widely used class of medication. In the last decade, there has been considerable interest in n-3 PUFAs and their role in depression. These fatty acids are critical for development and function of the central nervous system. Increasing evidence from epidemiological, laboratory, and randomized placebo-controlled trials suggests deficiency of dietary n-3 PUFAs may contribute to development of mood disorders, and supplementation with n-3 PUFAs may provide a new treatment option. Conclusions based on systematic reviews and meta-analyses of published trials to date vary. Research into the effects of n-3 PUFAs on depressed mood is limited. Furthermore, results from such have led to conflicting conclusions regarding the efficacy of n-3 PUFAs in affecting reduction in symptoms of depression. PUFAs are generally well tolerated by adults and children although mild gastrointestinal effects are reported. There is mounting evidence to suggest that n-3 PUFAs play a role in depression and deserve greater research efforts.

Acrodermatitis caused by nutritional deficiency and metabolic disorders.

Both the metabolism and dietary intake of vitamins and minerals are essential to homeostatic function in the body. Dietary excess or deficiency, as well as genetic and acquired disorders in metabolism, can present dermatologically and systemically. More specifically, disorders in metabolism of zinc, biotin, essential fatty acids, and vitamin B, can appear with acrally distributed dermatoses. Recognition of the dermatologic manifestations associated with nutritional disorders is important for early diagnosis and management.

Effect of dietary docosahexaenoic acid (DHA) in phospholipids or triglycerides on brain DHA uptake and accretion.

Tracer studies suggest that phospholipid DHA (PL-DHA) more effectively targets the brain than triglyceride DHA (TAG-DHA), although the mechanism and whether this translates into higher brain DHA concentrations are not clear. Rats were gavaged with [U-(3)H]PL-DHA and [U-(3)H]TAG-DHA and blood sampled over 6h prior to collection of brain regions and other tissues. In another experiment, rats were supplemented for 4weeks with TAG-DHA (fish oil), PL-DHA (roe PL) or a mixture of both for comparison to a low-omega-3 diet. Brain regions and other tissues were collected, and blood was sampled weekly. DHA accretion rates were estimated using the balance method. [U-(3)H]PL-DHA rats had higher radioactivity in cerebellum, hippocampus and remainder of brain, with no differences in other tissues despite higher serum lipid radioactivity in [U-(3)H]TAG-DHA rats. TAG-DHA, PL-DHA or a mixture were equally effective at increasing brain DHA. There were no differences between DHA-supplemented groups in brain region, whole-body, or tissue DHA accretion rates except heart and serum TAG where the PL-DHA/TAG-DHA blend was higher than TAG-DHA. Apparent DHA ß-oxidation was not different between DHA-supplemented groups. This indicates that more labeled DHA enters the brain when consumed as PL; however, this may not translate into higher brain DHA concentrations.

Comparison of Formulas Based on Lipid Emulsions of Olive Oil, Soybean Oil, or Several Oils for Parenteral Nutrition: A Systematic Review and Meta-Analysis.

Many studies have reported that olive oil-based lipid emulsion (LE) formulas of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) may be a viable alternative for parenteral nutrition. However, some randomized controlled clinical trials (RCTs) have raised concerns regarding the nutritional benefits and safety of SMOFs. We searched principally the MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials databases from inception to March 2014 for the relevant literature and conducted a meta-analysis of 15 selected RCTs that 1) compared either olive oil- or SMOF-based LEs with soybean oil-based LEs and 2) reported plasma concentrations of α-tocopherol, oleic acid, and ω-6 (n-6) and ω-3 (n-3) long-chain polyunsaturated fatty acids (PUFAs) and liver concentrations of total bilirubin and the enzymes alanine transaminase, aspartate transaminase, alkaline phosphatase, and γ-glutamyl transferase. The meta-analysis suggested that SMOF-based LEs were associated with higher plasma concentrations of plasma α-tocopherol, oleic acid, and the ω-3 PUFAs eicosapentaenoic and docosahexaenoic acid. Olive oil- and SMOF-based LEs correlated with lower plasma concentrations of long-chain ω-6 PUFAs and were similar to soybean oil-based LEs with regard to their effects on liver function indicators. In summary, olive oil- and SMOF-based LEs have nutritional advantages over soybean oil-based LEs and are similarly safe. However, their performance in clinical settings requires further investigation.

The effect of the paraoxonase 1 (PON1) T(-107)C polymorphism on serum PON1 activity in women is dependent on fatty acid intake.

Paraoxonase 1 (PON1) is an enzyme that prevents the peroxidation of lipoprotein and cell membranes. Our hypothesis is that the effect of the PON1 T(-107)C polymorphism on serum PON1 activity in healthy adult women is dependent on their fatty acid intake profile. This study included women (n = 39) who completed a food frequency questionnaire. Fatty acid intake was estimated based on the interview and a nutrient reference table. Blood samples were collected for genotyping and to measure serum PON1 activity. Serum PON1 activity was different among genotypes and was higher for women of the CC genotype (P < .001). Women in the study were categorized in 2 groups according to the median nutrient intake. Overall, there was a difference (P < .05) in serum PON1 activity between the CC and TT genotypes in women ingesting either above or below the median total fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, omega 3 (n-3) and omega 6 (n-6; P < .05). However, genotype effects on serum PON1 activity were not observed in women ingesting below the median (15:1) ratio of n-6/n-3 (P > .05) but were observed in women ingesting above the ratio of n-6/n-3 (P < .05). This is partly because women of the CC genotype had decreased PON1 activity when ingesting a lower ratio of n-6/n-3 diet (P < .05), while women of the TT genotype had increased PON1 activity (P < .05). In conclusion, the overall presence of the C allele was associated with increased serum PON1 activity, although a diet with high saturated fatty acid or a low ratio of n-6/n-3 reduced PON1 activity in women with the CC genotype.

Long-chain polyunsaturated fatty acids and the preterm infant: a case study in developmentally sensitive nutrient needs in the United States.

The vast majority of infant formulas in the United States contain the long-chain polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6), which were first permitted by the US Food and Drug Administration in 2001. As a scientific case study, preclinical animal studies of these nutrients definitively influenced the design and interpretation of human clinical studies. Early studies were tied to the availability of test substances, and in hindsight suggest re-evaluation of the essential fatty acid concept in light of the totality of available evidence. Research in the 1950s established the essentiality of n-6 PUFAs for skin integrity; however, widespread recognition of the essentiality of n-3 PUFAs came decades later despite compelling evidence of their significance. Barriers to an understanding of the essentiality of n-3 PUFAs were as follows: 1) their role is in neural function, which is measured only with difficulty compared with skin lesions and growth faltering that are apparent for n-6 PUFAs; 2) the experimental use of vegetable oils as PUFA sources that contain the inefficiently used C18 PUFAs rather than the operative C20 and C22 PUFAs; 3) the shift from reliance on high-quality animal studies to define mechanisms that established the required nutrients in the first part of the 20th century to inherently challenging human studies. Advances in nutrition of premature infants require the best practices and opinions available, taking into account the totality of preclinical and clinical evidence.