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1.  Erythrocyte Membrane Fatty Acid Content in Infants Consuming Formulas Supplemented with Docosahexaenoic Acid (DHA) and Arachidonic Acid (ARA): an Observational Study 
Maternal & child nutrition  2010;6(4):338-346.
In this observational study, we compared erythrocyte membrane fatty acids in infants consuming formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) with those consuming other types of milks. In 110 infants who were participants in a cohort study of otherwise healthy children at risk for developing type 1 diabetes, erythrocytes were collected at approximately 9 months of age, and fatty acid content was measured as a percent of total lipids. Parents reported the type of milk the infants consumed in the month of and prior to erythrocyte collection – infant formula supplemented with ARA and DHA (supplemented formula), formula with no ARA and DHA supplements (non-supplemented formula), breast-milk, or non-supplemented formula plus breast-milk. Membrane DHA (4.42 versus 1.79, p < 0.001) and omega-3 fatty acid (5.81 versus 3.43, p < 0.001) levels were higher in infants consuming supplemented versus non-supplemented formula. Omega-6 fatty acids were lower in infants consuming supplemented versus non-supplemented formula (26.32 versus 29.68, p = 0.023); ARA did not differ between groups. Infants given supplemented formula had higher DHA (4.42 versus 2.81, p < 0.001) and omega-3 fatty acids (5.81 versus 4.45, p = 0.008) than infants drinking breast-milk. In infants whose mothers did not receive any dietary advice, use of supplemented formula is associated with higher omega-3 and lower omega-6 fatty acid status.
doi:10.1111/j.1740-8709.2009.00230.x
PMCID: PMC2992442  PMID: 21050388
Arachidonic Acid; Docosahexaenoic Acid; Breastfeeding; Infant Feeding; Infant Formula; Infant Feeding Behavior
2.  Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice 
Background
Marine derived oils are rich in long-chain polyunsaturated omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been associated with health promoting effects such as reduced plasma lipid levels and anti-inflammatory effects. Krill oil (KO) is a novel marine oil on the market and is also rich in EPA and DHA, but the fatty acids are incorporated mainly into phospholipids (PLs) rather than triacylglycerols (TAG). This study compares the effects of fish oil (FO) and KO on gene regulation that influences plasma and liver lipids in a high fat diet mouse model.
Methods
Male C57BL/6J mice were fed either a high-fat diet (HF) containing 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or the HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks. Total levels of cholesterol, TAG, PLs, and fatty acid composition were measured in plasma and liver. Gene regulation was investigated using quantitative PCR in liver and intestinal epithelium.
Results
Plasma cholesterol (esterified and unesterified), TAG and PLs were significantly decreased with FO. Analysis of the plasma lipoprotein particles indicated that the lipid lowering effect by FO is at least in part due to decreased very low density lipoprotein (VLDL) content in plasma with subsequent liver lipid accumulation. KO lowered plasma non-esterified fatty acids (NEFA) with a minor effect on fatty acid accumulation in the liver. In spite of a lower omega-3 fatty acid content in the KO supplemented diet, plasma and liver PLs omega-3 levels were similar in the two groups, indicating a higher bioavailability of omega-3 fatty acids from KO. KO more efficiently decreased arachidonic acid and its elongation/desaturation products in plasma and liver. FO mainly increased the expression of several genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in the early steps of isoprenoid/cholesterol and lipid synthesis.
Conclusions
The data show that both FO and KO promote lowering of plasma lipids and regulate lipid homeostasis, but with different efficiency and partially via different mechanisms.
doi:10.1186/1743-7075-11-20
PMCID: PMC4021563  PMID: 24834104
Omega-3 fatty acids; Plasma lipids; High-fat diet; Gene regulation; Krill oil
3.  Essential fatty acids in full term infants fed breast milk or formula. 
To determine the biochemical effects of the fatty acid composition of plasma lipids, two groups of 10 healthy full term infants who were either exclusively breast fed or received a formula with similar contents of linoleic and alpha linolenic acids, but without long chain polyunsaturated (LCP) fatty acids, were studied prospectively. Plasma phospholipid, triglyceride, and sterol ester fatty acids were determined at the age of 2, 4, and 8 weeks by high resolution capillary gas chromatography. Breast fed infants maintained stable LCP fatty acid concentrations throughout the study. Formula fed infants had significantly lower median values of arachidonic acid (AA) at the ages of 2 (6.9 v 9.5% wt/wt) and 4 weeks (5.9 v 7.9%) and docosahexaenoic acid (DHA) at the ages of 4 (1.1 v 1.7%) and 8 weeks (1.0 v 1.7%) in plasma phospholipids. Median AA values in triglycerides were also significantly lower in the infants receiving formula at the ages of 2 (0.4 v 0.6%) and 4 weeks (0.3 v 0.6%). It is concluded that formula fed full term infants are unable to match the omega-3 and omega-6 LCP status of breast fed full term infants until at least two months after birth.
PMCID: PMC2528425  PMID: 7743279
4.  Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial 
BMJ : British Medical Journal  2003;326(7396):953.
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.
What is already known on this topicBreast milk contains long chain polyunsaturated fatty acids, and breastfed children have lower blood pressure than children fed with formula milkBlood pressure differences in childhood are known to carry through into adulthoodDietary omega 3 fatty acid supplementation can lower blood pressure in adults with hypertensionWhat this paper addsSupplementation with long chain polyunsaturated fatty acids in infancy results in lower blood pressure later in childhood
PMCID: PMC153849  PMID: 12727766
5.  Plasma Phospholipid Fatty Acid Concentration and Incident Coronary Heart Disease in Men and Women: The EPIC-Norfolk Prospective Study 
PLoS Medicine  2012;9(7):e1001255.
Kay-Tee Khaw and colleagues analyze data from a prospective cohort study and show associations between plasma concentrations of saturated phospholipid fatty acids and risk of coronary heart disease, and an inverse association between omega-6 polyunsaturated phospholipid fatty acids and risk of coronary heart disease.
Background
The lack of association found in several cohort studies between dietary saturated fat and coronary heart disease (CHD) risk has renewed debate over the link between dietary fats and CHD.
Methods and Findings
We assessed the relationship between plasma phospholipid fatty acid (PFA) concentration and incident CHD using a nested case control design within a prospective study (EPIC-Norfolk) of 25,639 individuals aged 40–79 years examined in 1993–1997 and followed up to 2009. Plasma PFA concentrations were measured by gas chromatography in baseline samples retrieved from frozen storage. In 2,424 men and women with incident CHD compared with 4,930 controls alive and free of cardiovascular disease, mean follow-up 13 years, saturated PFA (14:0, 16:0,18:0) plasma concentrations were significantly associated with increased CHD risk (odds ratio [OR] 1.75, 95% CI 1.27–2.41, p<0.0001), in top compared to bottom quartiles (Q), and omega-6 polyunsaturated PFA concentrations were inversely related (OR 0.77, 0.60–0.99, p<0.05) after adjusting for age, sex, body mass index, blood pressure, smoking, alcohol intake, plasma vitamin C, social class, education, and other PFAs. Monounsaturated PFA, omega-3 PFA, and trans PFA concentrations were not significantly associated with CHD. Odd chain PFA (15:0, 17:0) concentrations were significantly inversely associated with CHD (OR 0.73, 0.59–0.91, p<0.001, Q4 versus Q1). Within families of saturated PFA or polyunsaturated PFA, significantly heterogeneous relationships with CHD were observed for individual fatty acids.
Conclusions
In this study, plasma concentrations of even chain saturated PFA were found to be positively and omega-6 polyunsaturated PFA inversely related to subsequent coronary heart disease risk. These findings are consistent with accumulating evidence suggesting a protective role of omega-6 fats substituting for saturated fats for CHD prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Coronary heart disease (CHD) is a condition caused by a build-up of fatty deposits on the inner walls of the blood vessels that supply the heart, causing the affected person to experience pain, usually on exertion (angina). A complete occlusion of the vessel by deposits causes a heart attack (myocardial infarction). Lifestyle factors, such as diet (particularly one high in fat), contribute to causing CHD. There are different types of fat, some of which are thought to increase risk of CHD, such as saturated fat, typically found in meat and dairy foods. However, others, such as unsaturated fats (polyunsaturated and monounsaturated fats) found in foods such as vegetable oils, fish, and nuts, may actually help prevent this condition.
Why Was This Study Done?
Although there have been many studies investigating the role of different types of dietary fat in coronary heart disease, it is still not clear whether coronary heart disease can be prevented by changing the type of dietary fat consumed from saturated to unsaturated fats or by lowering all types of dietary fat. Furthermore, many of these studies have relied on participants recalling their dietary intake in questionnaires, which is an unreliable method for different fats. So in this study, the researchers used an established UK cohort to measure the levels of different types of fatty acids in blood to investigate whether a diet high in saturated fatty acids and low in unsaturated fatty acids increases CHD risk.
What Did the Researchers Do and Find?
The researchers used a selection of 10,000 participants (all men and women aged 40–79 years) from the prospective European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Blood samples from the selected participants taken at the start of the study in 1993–1997 were analyzed to determine levels of specific fatty acids. Participants were followed up till 2011. The researchers identified 2,424 participants who were subsequently diagnosed with CHD using death certificates and hospital discharge data and matched these with 4,930 controls who were still alive and free of known coronary disease. The researchers grouped the type of blood fatty acids identified in the blood samples into six families (even chain saturated fatty acid, odd chain saturated fatty acid, omega-6 polyunsaturated fatty acid, omega-3 polyunsaturated fatty acid, monounsaturated fatty acid, and trans-fatty acid), which represented saturated and unsaturated fatty acids. Using statistical methods, the researchers then compared the risks of developing CHD between cases and controls by the concentration of fatty acid families after adjusting for age and sex and other factors, such as body mass index, physical activity, and smoking. Using these methods, the researchers found that there was no overall significant relationship between total blood fatty acid concentration and CHD but there was a positive association with increasing blood saturated fatty acid concentration after adjusting for other fatty acid concentrations, with an odds ratio of 1.83 comparing higher versus lower concentrations. This risk was attenuated after adjusting for cholesterol levels, indicating that much of the association between saturated fatty acid and CHD is likely to be mediated through blood cholesterol levels. In contrast, blood omega-6 poly-unsaturated fatty acid concentrations were associated with lower CHD risk. Blood monounsaturated fatty acids, omega-3 poly-unsaturated fatty acids, and trans-fatty acids were not consistently associated with CHD risk. The authors also noted that within families of fatty acids, individual fatty acids related differently to CHD risk.
What Do These Findings Mean?
These findings suggest that plasma concentrations of saturated fatty acids are associated with increased risk of CHD and that concentrations of omega-6 poly-unsaturated fatty acids are associated with decreased risk of CHD. These findings are consistent with other studies and with current dietary advice for preventing CHD, which encourages substituting foods high in saturated fat with n-6 polyunsaturated fats. The results also suggest that different fatty acids may relate differently to CHD risk and that the overall balance between different fatty acids is important. However, there are limitations to this study, such as that factors other than diet (genetic differences in metabolism, for example) may cause changes to blood fatty acid levels so a major question is to identify what factors influence blood fatty acid concentrations. Nevertheless, these findings suggest that individual fatty acids play a role in increasing or decreasing risks of CHD.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001255.
Information about the EPIC-Norfolk study is available
The American Heart Foundation provides patient-friendly information about different dietary fats as does Medline
The British Heart Foundation also provides patient-friendly information on heart conditions
doi:10.1371/journal.pmed.1001255
PMCID: PMC3389034  PMID: 22802735
6.  Effect of Supplementation of Fish and Canola Oil in the Diet on Milk Fatty Acid Composition in Early Lactating Holstein Cows 
This study examined the effects of supplementation of fish oil and canola oil in the diet on milk yield, milk components and fatty acid composition of Holstein dairy cows in early lactation. Eight multiparous early lactation Holstein cows (42±12 DIM, 40±6 kg daily milk yield) were fed a total mixed ration supplemented with either 0% oil (Control), 2% fish oil (FO), 1% canola oil +1% fish oil (FOCO), or 2% canola oil (CO) according to a double 4×4 Latin square design. Each period lasted 3 wk; experimental analyses were restricted to the last week of each period. Supplemental oils were added to a basal diet which was formulated according to NRC (2001) and consisted of 20% alfalfa, 20% corn silage and 60% concentrate. Milk yield was similar between diets (p>0.05), but dry matter intake (DMI) was lower (p<0.05) in cows fed FO diet compared to other diets. Milk fat percentage and daily yield decreased (p<0.01) with the supplementation of fish and canola oil. The daily yield and percentage of milk protein, lactose and solids-not-fat (SNF) were not affected by diets (p>0.05). The proportion (g/100 g fatty acids) of short chain fatty acids (SCFA) decreased and polyunsaturated fatty acids (PUFA) increased (p<0.05) in milk of all cows fed diets supplemented with oil. The proportions of 6:0, 8:0, 10:0 12:0 and 14:0 fatty acids in milk fat decreased (p<0.01) for all diets supplemented with oil, but the proportions of 14:1, 16:0 and 16:1 fatty acids were not affected by diets (p>0.05). The proportion of trans(t)-18:1 increased (p<0.01) in milk fat of cows fed FO and FOCO diets, but CO diet had the highest proportion of cis(c)-11 18:1 (p<0.01). The concentration of t-10, c-12 18:2, c-9 t-11 18:2, 18:3, eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) increased (p<0.05) in FO and FOCO diets in comparison with the other two diets. These data indicate that including fish oil in combination with canola oil significantly modifies the fatty acid composition of milk.
doi:10.5713/ajas.2010.10014
PMCID: PMC4092963  PMID: 25049568
Fish Oil; Canola Oil; Milk Fatty Acid Composition; Holstein Dairy Cows
7.  Insulin-tumour interrelationships in EL4-lymphoma or thymoma-bearing mice. II. Effects of dietary omega-3 and omega-6 polyunsaturated fatty acids. 
British Journal of Cancer  1990;62(6):897-902.
Male C57BL/65 mice received a basal diet supplemented with 4% soya-bean oil, linseed oil or fish oil, in which the major polyunsaturated fatty acids were linoleic acid, alpha-linolenic acid and long chain omega-3 fatty acids, respectively. Groups of animals were injected into the right flank with EL4-lymphoma cells, others with thymoma cells. Tumour implantation caused a gradual decrease in food consumption with both types of tumour, while body weight increased, especially in the EL4-bearing animals receiving the soya-bean diet. The weight gain was due to body water accumulation and was accompanied by decreases in body fat and minor changes in carcass protein and ash contents. The dietary treatments did not produce significant differences in tumour incidence and mortality, but tumour size was decreased by diets supplying omega-3 fatty acids: in the EL4 mice tumour weight was markedly depressed by linseed oil, compared to soya-bean oil, whereas thymoma tumour weight was lowest in mice receiving fish oil and highest in the soya-bean oil group. Both types of tumour caused pronounced hypoglycaemia and hyperinsulinaemia in the hosts, and the effect was modulated by the diets in the EL4 but not in the thymoma animals: the plasma glucose level was especially low in the linseed oil group and relatively highest in the soya-bean oil treatment. The degree of hyperinsulinaemia depended on the diet only in the thymoma-bearing mice, with linseed and fish oils producing higher insulin levels than soya-bean oil. A slight hyperinsulinaemia was also observed in linseed and fish oil-fed control mice. Serum triglycerides were elevated in tumour-bearing animals, without consistent differences between dietary treatments. Although no clear pattern emerged concerning total cholesterol and LDL levels, HDL values were strongly affected by the type of oil: in the control animals linseed oil caused an increase in HDL-cholesterol compared to the other two oils. The thymoma-bearing mice responded to the linseed and fish oil diets with greatly elevated HDL-cholesterol levels. The results point to important differences in the responses of the two implanted tumours and hosts not only to the omega-6 and omega-3 fatty acids, but also to the type of dietary omega-3 fatty acids, namely alpha-linolenic acid and long chain fish oil polyunsaturated fatty acids.
PMCID: PMC1971575  PMID: 2124137
8.  rhBSSL Improves Growth and LCPUFA Absorption in Preterm Infants Fed Formula or Pasteurized Breast Milk 
ABSTRACT
Objectives:
Preterm infants often experience suboptimal growth, which can affect organ development. The aim of this study was to improve growth by treatment with bile salt–stimulated lipase (BSSL), naturally present in breast milk, but lost after pasteurization, and absent in formula.
Methods:
Two clinical trials were performed with a predefined analysis of combined data to investigate the effects of recombinant human BSSL (rhBSSL) treatment on growth velocity and fat absorption in preterm infants. The studies were randomized and double-blinded comparing 7-day treatment with rhBSSL and placebo, administered in pasteurized breast milk or formula, using a crossover design.
Results:
Sixty-three infants were evaluated for safety. At randomization, the mean (standard deviation) weight was 1467 (193) g and mean postmenstrual age was 32.6 (0.5) weeks. Sixty and 46 infants were evaluated for growth velocity and fat absorption, respectively. rhBSSL treatment significantly improved mean growth velocity by 2.93 g · kg−1 · day−1 (P < 0.001) compared with placebo (mean 16.86 vs 13.93 g · kg−1 · day−1) and significantly decreased the risk of suboptimal growth (<15 g · kg−1 · day−1) (30% vs 52%, P = 0.004). rhBSSL significantly increased absorption of the long-chain polyunsaturated fatty acids, docosahexaenoic acid, and arachidonic acid by 5.76% (P = 0.013) and 8.55% (P = 0.001), respectively, but had no significant effect on total fat absorption. The adverse-event profile was similar to placebo.
Conclusions:
In preterm infants fed pasteurized breast milk or formula, 1 week of treatment with rhBSSL was well tolerated and significantly improved growth and long-chain polyunsaturated fatty acid absorption compared to placebo. This publication presents the first data regarding the use of rhBSSL in preterms and the results have led to further clinical studies.
doi:10.1097/MPG.0000000000000365
PMCID: PMC4086776  PMID: 25222806
clinical study; fat absorption; growth velocity; preterm infant; recombinant human bile-salt-stimulated lipase
9.  Preservation of hepatocyte nuclear factor 4α contributes to the beneficial effect of dietary medium chain triglyceride on alcohol-induced hepatic lipid dyshomeostasis in rats 
Background
Alcohol consumption is a major cause of fatty liver, and dietary saturated fats have been shown to protect against alcoholic fatty liver. This study investigated the mechanisms of how dietary saturated fat may modulate alcohol-induced hepatic lipid dyshomeostasis.
Methods
Rats were pair-fed with 3 isocaloric liquid diets, control, alcohol, and medium chain triglyceride (MCT)/alcohol, respectively, for 8 weeks. The control and alcohol diets were based on the Lieber-DeCarli liquid diet formula with 30% total calories derived from corn oil (rich in unsaturated long chain fatty acids). The corn oil was replaced by MCT, which consists of exclusive saturated fatty acids, in the MCT/alcohol diet. HepG2 cell culture was conducted to test the effects of unsaturated fatty acids on HNF4α and the role of HNF4α in regulating hepatocyte lipid homeostasis.
Results
Alcohol feeding caused significant lipid accumulation, which was attenuated by dietary MCT. The major effect of alcohol on hepatic gene expression is the up-regulation of CYP4A1, CD36 and GPAT3, and down-regulation of apolipoprotein B (ApoB). Dietary MCT further up-regulated CYP4A1 gene, normalized ApoB gene and up-regulated MTTP and SCD1 genes. The protein level of hepatocyte nuclear factor-4α (HNF4α), a master transcription factor of the liver, was reduced by alcohol feeding, which was normalized by dietary MCT. Fatty acid profiling demonstrated that alcohol feeding dramatically increased hepatic unsaturated long chain fatty acyl species, particularly linoleic acid and oleic acid, which was attenuated by dietary MCT. Dietary MCT attenuated alcohol-reduced serum triglyceride level and modulated the fatty acid composition of the serum triglycerides. Cell culture study demonstrated polyunsaturated linoleic acid rather than monounsaturated oleic acid inactivated HNF4α in HepG2 cells. Knockdown HNF4α caused lipid accumulation in HepG2 cells due to dysregulation of very low density lipoprotein secretion.
Conclusions
Results suggest that dietary MCT prevents alcohol-induced hepatic lipid accumulation, at least partially, through reducing hepatic polyunsaturated long chain fatty acids and preserving HNF4α.
doi:10.1111/acer.12013
PMCID: PMC3618617  PMID: 23126616
Alcoholic fatty liver; Corn oil; Medium chain triglyceride; Lipid metabolism; HNF4α
10.  Short term effects of dietary medium-chain fatty acids and n-3 long-chain polyunsaturated fatty acids on the fat metabolism of healthy volunteers 
Background
The amount and quality of dietary fatty acids can modulate the fat metabolism.
Objective
This dietary intervention is based on the different metabolic pathways of long-chain saturated fatty acids (LCFA), which are mostly stored in adipocytic triacylglycerols, medium-chain fatty acids (MCFA) which are preferentially available for hepatic mitochondrial β-oxidation and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) suggested to modulate fat oxidation and storage by stimulating the peroxisomal β-oxidation. Combined dietary MCFA and n-3 LCPUFA without LCFA may synergistically stimulate fatty acid oxidation resulting in blood lipid clearance and LCFA release from adipocytes.
Design
In a short term, parallel, randomized, double-blind trial effects on the fatty acid metabolism of 10 healthy volunteers (Body Mass Index 25–30) of a formula containing 72% MCFA and 22% n-3 LCPUFA without LCFA (intake: 1.500 kcal/day; fat: 55.5% of energy) were measured in comparison to an isoenergetic formula with equal fat amount and LCFA dominated lipid profile.
Results
The plasma triacylglycerol (p < 0.1) and cholesterol (p < 0.05) content decreased in the test group. The n-3/n-6 LCPUFA (≥ C 20) ratio increased (p < 0.0001) after 4 days treatment. The LCFA content was similar in both groups despite missing LCFA in the test formula indicating LCFA release from adipocytes into the plasma. Both groups significantly reduced body weight considerably 4 kg (p < 0.01) and fat mass up to 50% of weight loss (p < 0.05).
Conclusion
Combined dietary 72% MCFA and 22% n-3 LCPUFA without LCFA stimulate the fatty acid oxidation and release from adipocytes without affecting any safety parameters measured.
doi:10.1186/1476-511X-2-10
PMCID: PMC317357  PMID: 14622442
metabolic syndrome; medium-chain fatty acids; long-chain polyunsaturated fatty acids
11.  Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants. 
The influence of dietary long chain polyunsaturated fatty acid (LCP) supply, and especially of docosahexaenoic acid (DHA), on evoked potential maturation, was studied in 58 healthy preterm infants using flash visual evoked potentials (VEPs), flash electroretinography (ERG), and brainstem acoustic evoked potentials (BAEPs) at 52 weeks of postconceptional age. At the same time, the fatty acid composition of red blood cell membranes was examined. The infants were fed on breast milk (n = 12), a preterm formula supplemented with LCP (PF-LCP) (n = 21), or a traditional preterm formula (PF) (n = 25). In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar; in the PF group the morphology was quite different and the wave latencies were significantly longer. This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower. Moreover, a higher level of erythrocyte LCP, especially DHA, was found in breast milk and PF-LCP groups compared with the PF group. ERG and BAEP recordings were the same in all three groups. These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available.
PMCID: PMC1061173  PMID: 8949693
12.  The Tsim Tsoum Approaches for Prevention of Cardiovascular Disease 
The Tsim Tsoum Concept means that humans evolved on a diet in which nature recommends to ingest fatty acids in a balanced ratio (polyunsaturated(P) : saturated(S) =w-6 : w-3 = 1 : 1)as part of dietary lipid pattern where monounsaturated fatty acids(MUFA) is the major fatty acid(P : M : S = 1 : 6 : 1) in the background of other dietary factors; antioxidants, vitamins, minerals and fiber as well as physical activity and low mental stress. Several hundred years ago, our diet included natural foods; fruits, vegetables, green vegetables, seeds, eggs and honey. Fish, and wild meat were also available to pre-agricultural humans which shaped modern human genetic nutritional requirement. Cereal grains (refined), and vegetable oils that are rich in w-6 fatty acids are relatively recent addition to the human diet that represent dramatic departure from those foods to which we are adapted. Excess of linoleic acid, trans fatty acids (TFA), saturated and total fat as well as refined starches and sugar are proinflammatory. Low dietary MUFA and n-3 fatty acids and other long chain polyunsarurated fatty acids (LCPUFA) are important in the pathogenesis of metabolic syndrome. Increased sympathetic activity with greater secretion of neurotransmitters in conjunction of underlying long chain PUFA deficiency, and excess of proinflammatory nutrients, may damage the neurons via proinflammatory cytokines, in the ventromedial hypothalamus and insulin receptors in the brain.Since, 30–50% of the fatty acids in the brain are LCPUFA, especially omega-3 fatty acids, which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may be protective.Blood lipid composition does reflect one's health status: (a) circulating serum lipoproteins and their ratio provide information on their atherogenicity to blood vessels and (b) circulating plasma fatty acids, such as w-6/w-3 fatty acid ratio, give indication on proinflammatory status of blood vessels, cardiomyocytes, liver cells and neurones; (a) and (b) are phenotype-related and depend on genetic, environmental and developmental factors. As such, they appear as universal markers for holistic health and these may be important in the pathogenesis of cardiovascular diseases and cancer, which is the main consideration of Tsim Tsoum concept.
doi:10.4061/2010/824938
PMCID: PMC2910415  PMID: 20671994
13.  A Protective Lipidomic Biosignature Associated with a Balanced Omega-6/Omega-3 Ratio in fat-1 Transgenic Mice 
PLoS ONE  2014;9(4):e96221.
A balanced omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratio has been linked to health benefits and the prevention of many chronic diseases. Current dietary intervention studies with different sources of omega-3 fatty acids (omega-3) lack appropriate control diets and carry many other confounding factors derived from genetic and environmental variability. In our study, we used the fat-1 transgenic mouse model as a proxy for long-term omega-3 supplementation to determine, in a well-controlled manner, the molecular phenotype associated with a balanced omega-6/omega-3 ratio. The fat-1 mouse can convert omega-6 to omega-3 PUFAs, which protect against a wide variety of diseases including chronic inflammatory diseases and cancer. Both wild-type (WT) and fat-1 mice were subjected to an identical diet containing 10% corn oil, which has a high omega-6 content similar to that of the Western diet, for a six-month duration. We used a multi-platform lipidomic approach to compare the plasma lipidome between fat-1 and WT mice. In fat-1 mice, an unbiased profiling showed a significant increase in the levels of unesterified eicosapentaenoic acid (EPA), EPA-containing cholesteryl ester, and omega-3 lysophosphospholipids. The increase in omega-3 lipids is accompanied by a significant reduction in omega-6 unesterified docosapentaenoic acid (omega-6 DPA) and DPA-containing cholesteryl ester as well as omega-6 phospholipids and triacylglycerides. Targeted lipidomics profiling highlighted a remarkable increase in EPA-derived diols and epoxides formed via the cytochrome P450 (CYP450) pathway in the plasma of fat-1 mice compared with WT mice. Integration of the results of untargeted and targeted analyses has identified a lipidomic biosignature that may underlie the healthful phenotype associated with a balanced omega-6/omega-3 ratio, and can potentially be used as a circulating biomarker for monitoring the health status and the efficacy of omega-3 intervention in humans.
doi:10.1371/journal.pone.0096221
PMCID: PMC3997567  PMID: 24760204
14.  Cheek cell fatty acids reflect n-3 PUFA in blood fractions during linseed oil supplementation: a controlled human intervention study 
Background
Adequate biomarkers for the dietary supply of fatty acids (FA) are FA of adipose tissue and blood fractions. In human studies, invasive sample collection is unpleasant for subjects. In contrast, cheek cell sampling can be considered as a non-invasive alternative to investigate FA status.
The aim of this study was to analyze whether cheek cell FA composition reflect the supplementation of alpha-linolenic acid (ALA) using a linseed oil mixture compared to olive oil supplementation. Additionally, it was investigated if cheek cell FA composition correlates with the FA composition of plasma, red blood cells (RBC) and peripheral blood mononuclear cells (PBMC) before and during both interventions.
Methods
During a 10-week randomized, controlled, double-blind human intervention study, 38 subjects provided cheek cell and blood samples. After a two-week run-in period, the test group (n = 23) received 17 g/d of an ALA-rich linseed oil mixture, while the control group (n = 15) received 17 g/d of an omega-3 (n-3) polyunsaturated FA (PUFA)-free olive oil. Cheek cells and blood were collected on days 0, 7 and 56 of the 8-week intervention period.
Results
Compared to olive oil, the linseed oil intervention increased ALA and also the endogenously converted long-chain n-3 metabolites eicosatetraenoic-, eicosapentaenoic- and docosapentaenoic acid in cheek cells (P ≤ 0.05). Docosahexaenoic acid remained unchanged. Reflecting the treatment, the n-6/n-3 ratio decreased in the test group. In general, cheek cell FA reflected the changes of FA in blood fractions. Independent of treatment, significant correlations (P ≤ 0.05) of n-6 PUFA and n-3 PUFA between cheek cells and plasma, RBC and PBMC were found, except for linoleic acid and ALA.
Conclusions
The changes in FA composition of cheek cells confirmed that ALA from linseed oil increased endogenously derived n-3 PUFA in cheek cell lipids. These changes in cheek cells and their correlation to the respective FA in blood fractions indicate the cheek cell FA profile as an adequate non-invasive biomarker for short-term n-3 PUFA intake and metabolism. Therefore, cheek cell FA can be used in human intervention studies or large-scale epidemiological studies, especially for assessment of the n-3 PUFA status.
Trial registration
ClinicalTrials.gov, IDNCT01317290
doi:10.1186/1476-511X-12-173
PMCID: PMC3842671  PMID: 24229084
Oral mucosa; Alpha-linolenic acid; Long-chain n-3 PUFA; Buccal cells; Fatty acid supplementation; Plasma; Red blood cells; Peripheral blood mononuclear cells; Olive oil
15.  Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats 
AIM: To evaluate the effects of different types of dietary fats on the hepatic lipid content and oxidative stress parameters in rat liver with experimental non-alcoholic fatty liver disease (NAFLD).
METHODS: A total of 32 Sprague-Dawley rats were randomly divided into five groups. The rats in the control group (n = 8) were on chow diet (Group 1), rats (n = 6) on methionine choline-deficient diet (MCDD) (Group 2), rats (n = 6) on MCDD enriched with olive oil (Group 3), rats (n = 6) on MCDD with fish oil (Group 4) and rats (n = 6) on MCDD with butter fat (Group 5). After 2 mo, blood and liver sections were examined for lipids composition and oxidative stress parameters.
RESULTS: The liver weight/rat weight ratio increased in all treatment groups as compared with the control group. Severe fatty liver was seen in MCDD + fish oil and in MCDD + butter fat groups, but not in MCDD and MCDD + olive oil groups. The increase in hepatic triglycerides (TG) levels was blunted by 30% in MCDD + olive oil group (0.59 ± 0.09) compared with MCDD group (0.85 ± 0.04, p < 0.004), by 37% compared with MCDD + fish oil group (0.95 ± 0.07, p < 0.001), and by 33% compared with MCDD + butter group (0.09 ± 0.1, p < 0.01). The increase in serum TG was lowered by 10% in MCDD + olive oil group (0.9 ± 0.07) compared with MCDD group (1.05 ± 0.06). Hepatic cholesterol increased by 15-fold in MCDD group [(0.08 ± 0.02, this increment was blunted by 21% in MCDD + fish oil group (0.09 ± 0.02)]. In comparison with the control group, ratio of long-chain polyunsaturated fatty acids omega-6/omega-3 increased in MCDD + olive oil, MCDD + fish oil and MCDD + butter fat groups by 345-, 30- and 397-fold, respectively. In comparison to MCDD group (1.58 ± 0.08), hepatic MDA contents in MCDD + olive oil (3.3 ± 0.6), MCDD + fish oil (3.0 ± 0.4), and MCDD + butter group (2.9 ± 0.36) were increased by 108%, 91% and 87%, respectively (p < 0.004). Hepatic paraoxonase activity decreased significantly in all treatment groups, mostly with MCDD + olive oil group (-68%).
CONCLUSION: Olive oil decreases the accumulation of triglyceride in the liver of rats with NAFLD, but does not provide the greatest antioxidant activity.
doi:10.3748/wjg.v13.i3.361
PMCID: PMC4065889  PMID: 17230603
Fatty liver; Non-alcoholic steatohepatitis; Dietary fat; Fatty acids; Methionine choline-deficient diet; Insulin resistance; Olive oil; Oxidative stress; Paraoxonase
16.  Effect of Echium oil compared with marine oils on lipid profile and inhibition of hepatic steatosis in LDLr knockout mice 
Background
In an effort to identify new alternatives for long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) supplementation, the effect of three sources of omega 3 fatty acids (algae, fish and Echium oils) on lipid profile and inflammation biomarkers was evaluated in LDL receptor knockout mice.
Methods
The animals received a high fat diet and were supplemented by gavage with an emulsion containing water (CON), docosahexaenoic acid (DHA, 42.89%) from algae oil (ALG), eicosapentaenoic acid (EPA, 19.97%) plus DHA (11.51%) from fish oil (FIS), and alpha-linolenic acid (ALA, 26.75%) plus stearidonic acid (SDA, 11.13%) from Echium oil (ECH) for 4 weeks.
Results
Animals supplemented with Echium oil presented lower cholesterol total and triacylglycerol concentrations than control group (CON) and lower VLDL than all of the other groups, constituting the best lipoprotein profile observed in our study. Moreover, the Echium oil attenuated the hepatic steatosis caused by the high fat diet. However, in contrast to the marine oils, Echium oil did not affect the levels of transcription factors involved in lipid metabolism, such as Peroxisome Proliferator Activated Receptor α (PPAR α) and Liver X Receptor α (LXR α), suggesting that it exerts its beneficial effects by a mechanism other than those observed to EPA and DHA. Echium oil also reduced N-6/N-3 FA ratio in hepatic tissue, which can have been responsible for the attenuation of steatosis hepatic observed in ECH group. None of the supplemented oils reduced the inflammation biomarkers.
Conclusion
Our results suggest that Echium oil represents an alternative as natural ingredient to be applied in functional foods to reduce cardiovascular disease risk factors.
doi:10.1186/1476-511X-12-38
PMCID: PMC3627902  PMID: 23510369
Atherosclerosis; Inflammation; Echium; Stearidonic; Omega 3; Steatosis
17.  Breast milk docosahexaenoic acid (DHA) correlates with DHA status of malnourished infants 
Archives of Disease in Childhood  2000;82(6):493-494.
AIM—To investigate whether low docosahexaenoic acid (22:6ω3; DHA) status of malnourished, mostly breast fed infants is a result of low ω3 fatty acid intake via breast milk.
METHODS—Fatty acid composition of breast milk of eight Pakistani mothers, and of the erythrocytes of their malnourished children was analysed.
RESULTS—The milk of the Pakistani mothers contained low percentages of all ω3 and most ω6 fatty acids, compared with milk of Dutch mothers. Breast milk DHA was positively correlated with infant erythrocyte DHA and arachidonic acid (20:4ω6).
CONCLUSION—DHA status of these malnourished children is strongly dependent on the ω3 fatty acid intake from breast milk. Augmentation of the infants' ω3 long chain polyunsaturated fatty acid status, or the ω3 and ω6 fatty acid status in general, by supplementation is indicated in deprived circumstances where access to fresh fish is difficult. However, in terms of prevention, maternal supplementation of these long chain polyunsaturated fatty acids, preferably from early pregnancy onwards, may be a better option.


doi:10.1136/adc.82.6.493
PMCID: PMC1718344  PMID: 10833187
18.  Association of an ACSL1 gene variant with polyunsaturated fatty acids in bovine skeletal muscle 
BMC Genetics  2011;12:96.
Background
The intramuscular fat deposition and the fatty acid profiles of beef affect meat quality. High proportions of unsaturated fatty acids are related to beef flavor and are beneficial for the nutritional value of meat. Moreover, a variety of clinical and epidemiologic studies showed that particularly long-chain omega-3 fatty acids from animal sources have a positive impact on human health and disease.
Results
To screen for genetic factors affecting fatty acid profiles in beef, we initially performed a microsatellite-based genome scan in a F2 Charolais × German Holstein resource population and identified a quantitative trait locus (QTL) for fatty acid composition in a region on bovine chromosome 27 where previously QTL affecting marbling score had been detected in beef cattle populations. The long-chain acyl-CoA synthetase 1 (ACSL1) gene was identified as the most plausible functional and positional candidate gene in the QTL interval due to its direct impact on fatty acid metabolism and its position in the QTL interval. ACSL1 is necessary for synthesis of long-chain acyl-CoA esters, fatty acid degradation and phospholipid remodeling. We validated the genomic annotation of the bovine ACSL1 gene by in silico comparative sequence analysis and experimental verification. Re-sequencing of the complete coding, exon-flanking intronic sequences, 3' untranslated region (3'UTR) and partial promoter region of the ACSL1 gene revealed three synonymous mutations in exons 6, 7, and 20, six noncoding intronic gene variants, six polymorphisms in the promoter region, and four variants in the 3' UTR region. The association analysis identified the gene variant in intron 5 of the ACSL1 gene (c.481-233A>G) to be significantly associated with the relative content of distinct fractions and ratios of fatty acids (e.g., n-3 fatty acids, polyunsaturated, n-3 long-chain polyunsaturated fatty acids, trans vaccenic acid) in skeletal muscle. A tentative association of the ACSL1 gene variant with intramuscular fat content indicated that an indirect effect on fatty acid composition via modulation of total fat content of skeletal muscle cannot be excluded.
Conclusions
The initial QTL analysis suggested the ACSL1 gene as a positional and functional candidate gene for fatty acid composition in bovine skeletal muscle. The findings of subsequent association analyses indicate that ACSL1 or a separate gene in close proximity might play a functional role in mediating the lipid composition of beef.
doi:10.1186/1471-2156-12-96
PMCID: PMC3260110  PMID: 22078495
19.  Effect of dietary selenium and omega-3 fatty acids on muscle composition and quality in broilers 
Background
Human health may be improved if dietary intakes of selenium and omega-3 fatty acids are increased. Consumption of broiler meat is increasing, and the meat content of selenium and omega-3 fatty acids are affected by the composition of broiler feed. A two-way analyses of variance was used to study the effect of feed containing omega-3 rich plant oils and selenium enriched yeast on broiler meat composition, antioxidation- and sensory parameters. Four different wheat-based dietary treatments supplemented with 5% rapeseed oil or 4% rapeseed oil plus 1% linseed oil, and either 0.50 mg selenium or 0.84 mg selenium (organic form) per kg diet was fed to newly hatched broilers for 22 days.
Results
The different dietary treatments gave distinct different concentrations of selenium and fatty acids in thigh muscle; one percent linseed oil in the diet increased the concentration of the omega-3 fatty acids 18:3, 20:5 and 22:5, and 0.84 mg selenium per kg diet gave muscle selenium concentration at the same level as is in fish muscle (0.39 mg/kg muscle). The high selenium intake also resulted in increased concentration of the long-chain omega-3 fatty acids EPA (20:5), DPA (22:5) and DHA (22:6), thus it may be speculated if high dietary selenium might have a role in increasing the concentration of EPA, DPA and DHA in tissues after intake of plant oils contning omega-3 fatty acids.
Conclusion
Moderate modifications of broiler feed may give a healthier broiler meat, having increased content of selenium and omega-3 fatty acids. High intakes of selenium (organic form) may increase the concentration of very long-chain omega-3 fatty acids in muscle.
doi:10.1186/1476-511X-6-29
PMCID: PMC2186313  PMID: 17967172
20.  Fish Oil Supplementation Alters the Plasma Lipidomic Profile and Increases Long-Chain PUFAs of Phospholipids and Triglycerides in Healthy Subjects 
PLoS ONE  2012;7(8):e42550.
Background
While beneficial health effects of fish and fish oil consumption are well documented, the incorporation of n-3 polyunsaturated fatty acids in plasma lipid classes is not completely understood. The aim of this study was to investigate the effect of fish oil supplementation on the plasma lipidomic profile in healthy subjects.
Methodology/Principal Findings
In a double-blinded randomized controlled parallel-group study, healthy subjects received capsules containing either 8 g/d of fish oil (FO) (1.6 g/d EPA+DHA) (n = 16) or 8 g/d of high oleic sunflower oil (HOSO) (n = 17) for seven weeks. During the first three weeks of intervention, the subjects completed a fully controlled diet period. BMI and total serum triglycerides, total-, LDL- and HDL-cholesterol were unchanged during the intervention period. Lipidomic analyses were performed using Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (QTOFMS), where 568 lipids were detected and 260 identified. Both t-tests and Multi-Block Partial Least Square Regression (MBPLSR) analysis were performed for analysing differences between the intervention groups. The intervention groups were well separated by the lipidomic data after three weeks of intervention. Several lipid classes such as phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, sphingomyelin, phosphatidylserine, phosphatidylglycerol, and triglycerides contributed strongly to this separation. Twenty-three lipids were significantly decreased (FDR<0.05) in the FO group after three weeks compared with the HOSO group, whereas fifty-one were increased including selected phospholipids and triglycerides of long-chain polyunsaturated fatty acids. After seven weeks of intervention the two intervention groups showed similar grouping.
Conclusions/Significance
In healthy subjects, fish oil supplementation alters lipid metabolism and increases the proportion of phospholipids and triglycerides containing long-chain polyunsaturated fatty acids. Whether the beneficial effects of fish oil supplementation may be explained by a remodeling of the plasma lipids into phospholipids and triglycerides of long-chain polyunsaturated fatty acids needs to be further investigated.
Trial Registration
ClinicalTrials.gov NCT01034423
doi:10.1371/journal.pone.0042550
PMCID: PMC3429454  PMID: 22952598
21.  "Added lactose" and "added sucrose" cow's milk formulae in nutrition of low birthweight babies. 
Archives of Disease in Childhood  1975;50(6):409-418.
During the manufacture of dried milks for infant feeding the composition of cow's milk may be modified by the addition of extra carbohydrate powder to lower the relative proportions of protein and minerals, and in practice various carbohydrates are used in a largely empirical manner. In other circumstances it is known that the quality of dietary carbohydrate affects intestinal tolerance, deposition of body fat (in rats), and concentrations of plasma lipids (in man). Therefore, in this study the effects of feeding newborn infants on added lactose formula and added sucrose formula have been investigated. 29 low birthweight babies were observed throughout the first 3 months of life. The added carbohydrate achieved a satisfactory composition in terms of mineral and protein concentration of the reconstituted milk, but the "added lactose" group experienced more diarrhoea and a greater degree of metabolic acidosis during the first week of life. The added lactose group was slightly fatter and the plasma triglyceride concentration slightly higher than in the "added sucrose" group. Despite teleological evidence in favour of lactose, we found no objective contraindication to the addition of sucrose to cow's milk in the manufacture of infant feeding formulae. Both milks contained only small quantities of linoleic acid and the polyunsaturated fatty acid content of the plasma and adipose tissue lipids fell to low levels, but no clinical evidence of "essential fatty acid deficiency" was found.
PMCID: PMC1544542  PMID: 1096831
22.  Effect of stearidonic acid-enriched soybean oil on fatty acid profile and metabolic parameters in lean and obese Zucker rats 
Background
Consumption of marine-based oils high in omega-3 polyunsaturated fatty acids (n3PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to protect against obesity-related pathologies. It is less clear whether traditional vegetable oils with high omega-6 polyunsaturated fatty acid (n6PUFA) content exhibit similar therapeutic benefits. As such, this study examined the metabolic effects of a plant-based n3PUFA, stearidonic acid (SDA), in polygenic obese rodents.
Methods
Lean (LZR) and obese Zucker (OZR) rats were provided either a standard westernized control diet (CON) with a high n6PUFA to n3PUFA ratio (i.e., 16.2/1.0) or experimental diet modified with flaxseed (FLAX), menhaden (FISH), or SDA oil that resulted in n6PUFA to n3PUFA ratios of 1.7/1.0, 1.3/1.0, and 1.0/0.8, respectively.
Results
After 12 weeks, total adiposity, dyslipidemia, glucose intolerance, and hepatic steatosis were all greater, whereas n3PUFA content in liver, adipose, and muscle was lower in OZR vs. LZR rats. Obese rodents fed modified FISH or SDA diets had lower serum lipids and hepatic fat content vs. CON. The omega-3 index (i.e., ΣEPA + DHA in erythrocyte membrane) was 4.0, 2.4, and 2.0-fold greater in rodents provided FISH, SDA, and FLAX vs. CON diet, irrespective of genotype. Total hepatic n3PUFA and DHA was highest in rats fed FISH, whereas both hepatic and extra-hepatic EPA was higher with FISH and SDA groups.
Conclusions
These data indicate that SDA oil represents a viable plant-derived source of n3PUFA, which has therapeutic implications for several obesity-related pathologies.
doi:10.1186/1476-511X-12-147
PMCID: PMC4015945  PMID: 24139088
Stearidonic acid; Soybean oil; Obesity; Zucker; Fish oil; Flaxseed oil; Lipids; Hepatic steatosis
23.  Meta-analysis of Long-Chain Polyunsaturated Fatty Acid Supplementation of Formula and Infant Cognition 
Pediatrics  2012;129(6):1141-1149.
BACKGROUND AND OBJECTIVE:
Infant formula is supplemented with long-chain polyunsaturated fatty acids (LCPUFAs) because they are hypothesized to improve cognition. Several randomized controlled clinical trials have examined the effect of LCPUFA supplementation of infant formula on cognitive development. We conducted this meta-analysis to examine the efficacy of LCPUFA supplementation of infant formula on early cognitive development.
METHODS:
Two authors searched PubMed, PsychInfo, and Scopus for randomized controlled clinical trials assessing the efficacy of LCPUFA supplementation of infant formulas on cognition. Our analysis was restricted to randomized controlled clinical trials that examined the effect of LCPUFA supplementation on infant cognition using Bayley Scales of Infant Development. Our primary outcome was the weighted mean difference in Bayley Scales of Infant Development score between infants fed formula supplemented with LCPUFA compared with unsupplemented formula. We conducted secondary subgroup analyses and meta-regression to examine the effects of study sample, LCPUFA dose, and trial methodologic quality on measured efficacy of supplementation.
RESULTS:
Twelve trials involving 1802 infants met our inclusion criteria. Our meta-analysis demonstrated no significant effect of LCPUFA supplementation of formula on infant cognition. There was no significant heterogeneity or publication bias between trials. Secondary analysis failed to show any significant effect of LCPUFA dosing or prematurity status on supplementation efficacy.
CONCLUSIONS:
LCPUFA supplementation of infant formulas failed to show any significant effect on improving early infant cognition. Further research is needed to determine if LCPUFA supplementation of infant formula has benefits for later cognitive development or other measures of neurodevelopment.
doi:10.1542/peds.2011-2127
PMCID: PMC3362904  PMID: 22641753
infant formula; unsaturated fatty acids; infant cognition; long-chain polyunsaturated fatty acids; meta-analysis; Bayley Scales of Infant Development
24.  Nutritional Factors Influencing Intestinal Health of the Neonate12 
Advances in Nutrition  2012;3(5):687-696.
Dietary nutrients are essential for gastrointestinal (GI) growth and function, and nutritional support of GI growth and development is a significant component of infant care. For healthy full-term neonates, nutritional provisions of the mother’s milk and/or formula will support normal maturation of structure and function of the GI tract in most infants. The composition of breast milk affects GI barrier function and development of a competent mucosal immune system. The functional nutrients and other bioactive components of milk support a microenvironment for gut protection and maturation. However, premature infants struggle with feeding tolerance impairing normal GI function, leading to intestinal dysfunction and even death. The high prevalence worldwide of enteric diseases and dysfunction in neonates has led to much interest in understanding the role of nutrients and food components in the establishment and maintenance of a functioning GI tract. Neonates who do not receive enteral feeding as either mother’s milk or formula are supported by total parental nutrition (TPN). The lack of enteral nutrition can compound intestinal dysfunction, leading to high morbidity and mortality in intestinally compromised infants. Reciprocally, enteral stimulation of an immature GI tract can also compound intestinal dysfunction. Therefore, further understanding of nutrient interactions with the mucosa is necessary to define nutritional requirements of the developing GI tract to minimize intestinal complications and infant morbidity. Piglet models of intestinal development and function are similar to humans, and this review summarizes recent findings regarding nutrient requirements for growth and maintenance of intestinal health. In particular, this article reviews the role of specific amino acids (arginine, glutamine, glutamate, and threonine), fatty acids (long chain polyunsaturated, medium chain, and short chain), various prebiotic carbohydrates (short-chain fructo-oligosaccharide, fructo--oligosaccharide, lacto-N-neotetraose, human milk oligosaccharide, polydextrose, and galacto-oligosaccharide), and probiotics that have been examined in the suckling piglet model of intestinal health.
doi:10.3945/an.112.002683
PMCID: PMC3648750  PMID: 22983847
25.  Comparison of long chain polyunsaturated fatty acid content in human milk in preterm and term deliveries and its correlation with mothers’ diet 
Background:
Human milk (HM) is the main food for infants, and phospholipids, especially long chain polyunsaturated fatty acids (LCPUFAs), play an essential role in the growth and brain development. This study was designed to evaluate the fatty acid composition in HM of mothers with preterm and full-term newborns and to determine the relationships of dietary intake of docosahexaenoic acid (DHA) and arachidonic acid (AA) of mothers and the content of these fatty acids in their milks.
Materials and Methods:
The AA and DHA of HM were determined by gas chromatography at the 3rd day after birth from mothers of 59 term and 58 preterm infants. Mothers were selected from those who delivered in Shahid Beheshti Hospital, a referral teaching hospital affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. Dietary fat composition of mothers was examined by a food-frequency questionnaire. Total fat content, and DHA and AA levels of HM were compared in both groups. The correlation of dietary DHA and AA with DHA and AA of HM was determined in both groups.
Results:
We found that maternal age, body mass index (BMI), and self-reported food-frequency questionnaire did not differ in the two groups. The mean AA (0.19 ± 0.10 mg/ml and 0.16 ± 0.09 mg/ml, respectively), DHA (0.10 ± 0.06 mg/ml and 0.08 ± 0.05 mg/ml, respectively), and total fat content (2.58 ± 2.16 g/dl and 2.06 ± 1.22 g/dl, respectively) of HM of mothers with preterm neonates were non-significantly higher than in mothers with term neonates. The percentage of DHA in the HM fat of preterm and term groups (0.45 ± 0.16% and 0.45 ± 0.18%, respectively) and the percentage of AA (0.85 ± 0.26% and 0.84 ± 0.20%, respectively) were comparable with worldwide standards. No correlations were documented between DHA and AA intake and DHA and AA content of HM in both groups.
Conclusion:
Although DHA and AA content of HM in preterm group was higher than in term group, this difference were not significant. In Isfahan, the percentage of DHA and AA was acceptable in the milk fat of mothers with term and preterm neonates.
PMCID: PMC3719218  PMID: 23901333
Human milk; polyunsaturated fatty acids; premature neonate

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