Brain Health and Function
Published Clinical Studies
Plasma free fatty acid and lipoproteins as sources of polyunsaturated fatty acid for the brain.
Spector AA.
Department of Biochemistry, College of Medicine, University of Iowa, Iowa City 52242, USA. arthur-spector@uiowa.edu
J Mol Neurosci. 2001 Apr-Jun;16(2-3):159-65; discussion 215-21.
AbstractPolyunsaturated fatty acids (PUFA), which comprise 25-30% of the fatty acids in the human brain, are necessary for normal brain development and function. PUFA cannot be synthesized de novo and must be supplied to the brain by the plasma. It is necessary to know the PUFA content and composition of the various plasma lipids and lipoproteins in order to understand how these fatty acids are taken up and metabolized by the brain. Human plasma free fatty acid (FFA) ordinarily contains about 15% linoleic acid (18:2n-6) and 1% arachidonic acid (AA) (20:4n-6). Plasma triglycerides, phospholipids, and cholesterol esters also are rich in linoleic acid, and the phospholipids and cholesterol esters contain about 10% AA. These findings suggest that the brain probably can obtain an adequate supply of n-6 PUFA from either the plasma FFA or lipoproteins. By contrast, the plasma ordinarily contains only one-tenth as much n-3 PUFA, and the amounts range from 1% alpha-linolenic acid (18:3n-3) in the plasma FFA to 2% docosahexaenoic acid (22:6n-3, DHA) in the plasma phospholipids. The main n-3 PUFA in the brain is DHA. Therefore, if the plasma FFA is the primary source of fatty acid for the brain, much of the DHA must be synthesized in the brain from n-3 PUFA precursors. Alternatively, if the brain requires large amounts of preformed DHA, the phospholipids contained in plasma lipoproteins are the most likely source.
PMID: 11478370 [PubMed - indexed for MEDLINE]
The role of dietary n-6 and n-3 fatty acids in the developing brain.
Innis SM.
Department of Paediatrics, University of British Columbia, Vancouver, B.C., Canada. sinnis@interchange.ubc.ca
Dev Neurosci. 2000 Sep-Dec;22(5-6):474-80.
AbstractThe dietary requirements for essential fatty acids and the possibility of a specific role for the polyunsaturated fatty acid docosahexaenoic acid (DHA) is one of the most controversial areas in infant nutrition. DHA is found in unusually high concentrations in the brain and is selectively accumulated during fetal and infant brain growth. DHA can be synthesised through a complex series of chain elongation-desaturation reactions from alpha-linolenic acid, but the efficiency of this process in young infants is not clear. Clinical studies on the potential benefits to neural development of dietary DHA have yielded conflicting results. Recent studies have provided evidence that plasma DHA is available to developing brain and that DHA is involved in dopamine and serotonin metabolism. These findings should guide clinical studies to more sensitive measures of the functional roles of dietary n-3 fatty acids and to clinical conditions where n-3 fatty acids may have benefit.
PMID: 11111165 [PubMed - indexed for MEDLINE]
Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing.
Bourre JM.
INSERM Research Director. Unit U26 Neuro-pharmaco-nutrition. Hopital Fernand Widal, 200 rue du Faubourg Saint Denis. 75745 Paris cedex 10. jean-marie.bourre@fwidal.inserm.fr
J Nutr Health Aging. 2004;8(3):163-74.
AbstractAmong various organs, in the brain, the fatty acids most extensively studied are omega-3 fatty acids. Alpha-linolenic acid (18:3omega3) deficiency alters the structure and function of membranes and induces minor cerebral dysfunctions, as demonstrated in animal models and subsequently in human infants. Even though the brain is materially an organ like any other, that is to say elaborated from substances present in the diet (sometimes exclusively), for long it was not accepted that food can have an influence on brain structure, and thus on its function. Lipids, and especially omega-3 fatty acids, provided the first coherent experimental demonstration of the effect of diet (nutrients) on the structure and function of the brain. In fact the brain, after adipose tissue, is the organ richest in lipids, whose only role is to participate in membrane structure. First it was shown that the differentiation and functioning of cultured brain cells requires not only alpha-linolenic acid (the major component of the omega-3, omega3 family), but also the very long omega-3 and omega-6 carbon chains (1). It was then demonstrated that alpha-linolenic acid deficiency alters the course of brain development, perturbs the composition and physicochemical properties of brain cell membranes, neurones, oligodendrocytes, and astrocytes (2). This leads to physicochemical modifications, induces biochemical and physiological perturbations, and results in neurosensory and behavioural upset (3). Consequently, the nature of polyunsaturated fatty acids (in particular omega-3) present in formula milks for infants (premature and term) conditions the visual and cerebral abilities, including intellectual. Moreover, dietary omega-3 fatty acids are certainly involved in the prevention of some aspects of cardiovascular disease (including at the level of cerebral vascularization), and in some neuropsychiatric disorders, particularly depression, as well as in dementia, notably Alzheimer's disease. Recent results have shown that dietary alpha-linolenic acid deficiency induces more marked abnormalities in certain cerebral structures than in others, as the frontal cortex and pituitary gland are more severely affected. These selective lesions are accompanied by behavioural disorders more particularly affecting certain tests (habituation, adaptation to new situations). Biochemical and behavioural abnormalities are partially reversed by a dietary phospholipid supplement, especially omega-3-rich egg yolk extracts or pig brain. A dose-effect study showed that animal phospholipids are more effective than plant phospholipids to reverse the consequences of alpha-linolenic acid deficiency, partly because they provide very long preformed chains. Alpha-linolenic acid deficiency decreases the perception of pleasure, by slightly altering the efficacy of sensory organs and by affecting certain cerebral structures. Age-related impairment of hearing, vision and smell is due to both decreased efficacy of the parts of the brain concerned and disorders of sensory receptors, particularly of the inner ear or retina. For example, a given level of perception of a sweet taste requires a larger quantity of sugar in subjects with alpha-linolenic acid deficiency. In view of occidental eating habits, as omega-6 fatty acid deficiency has never been observed, its impact on the brain has not been studied. In contrast, omega-9 fatty acid deficiency, specifically oleic acid deficiency, induces a reduction of this fatty acid in many tissues, except the brain (but the sciatic nerve is affected). This fatty acid is therefore not synthesized in sufficient quantities, at least during pregnancy-lactation, implying a need for dietary intake. It must be remembered that organization of the neurons is almost complete several weeks before birth, and that these neurons remain for the subject's life time. Consequently, any disturbance of these neurons, an alteration of their connections, and impaired turnover of their constituents at any stage of life, will tend to accelerate ageing. The enzymatic activities of sytivities of synthesis of long-chain polyunsaturated fatty acids from linoleic and alpha-linolenic acids are very limited in the brain: this organ therefore depends on an exogenous supply. Consequently, fatty acids that are essential for the brain are arachidonic acid and cervonic acid, derived from the diet, unless they are synthesized by the liver from linoleic acid and alpha-linolenic acid. The age-related reduction of hepatic desaturase activities (which participate in the synthesis of long chains, together with elongases) can impair turnover of cerebral membranes. In many structures, especially in the frontal cortex, a reduction of cervonic and arachidonic acids is observed during ageing, predominantly associated with a reduction of phosphatidylethanolamines (mainly in the form of plasmalogens). Peroxisomal oxidation of polyunsaturated fatty acids decreases in the brain during ageing, participating in decreased turnover of membrane fatty acids, which are also less effectively protected against peroxidation by free radicals.
PMID: 15129302 [PubMed - indexed for MEDLINE]
Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk.
Devore EE, Grodstein F, van Rooij FJ, Hofman A, Rosner B, Stampfer MJ, Witteman JC, Breteler MM.
Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
Am J Clin Nutr. 2009 Jul;90(1):170-6. Epub 2009 May 27.
AbstractBACKGROUND: Greater fish and omega-3 (n-3) polyunsaturated fatty acid (PUFA) intake may reduce dementia risk; however, previous studies have reported conflicting results, which were largely based on short-term follow-up.
OBJECTIVE: The objective was to study the dietary consumption of fish and omega-3 PUFAs in relation to long-term dementia risk.
DESIGN: We studied 5395 participants aged > or =55 y in the Rotterdam Study who were free of dementia and reported dietary information at baseline. We used age- and sex-adjusted Cox proportional hazard and multivariate-adjusted models to evaluate the relative risk of dementia and Alzheimer disease (AD) across categories of typical fish intake (none, low, and high) and fish type consumed (none, lean, and fatty). We also evaluated dementia and AD risk across tertiles of omega-3 PUFA intake, specifically, total long-chain omega-3 fatty acids: eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), alpha-linolenic acid, and EPA and DHA individually.
RESULTS: During an average follow-up of 9.6 y, dementia developed in 465 participants (365 with a diagnosis of AD). In multivariate-adjusted models, total fish intake was unrelated to dementia risk (P for trend = 0.7). Compared with participants who typically ate no fish, those with a high fish intake had a similar dementia risk (hazard ratio: 0.95; 95% CI: 0.76, 1.19), as did those who typically ate fatty fish (hazard ratio: 0.98; 95% CI: 0.77, 1.24). Dietary intakes of omega-3 PUFAs were also not associated with dementia risk, and the results were similar when we considered AD specifically.
CONCLUSION: In this Dutch cohort, who had a moderate consumption of fish and omega-3 PUFAs, these dietary factors do not appear to be associated with long-term dementia risk.
PMID: 19474131 [PubMed - indexed for MEDLINE]
Brain lipid concentrations in bipolar disorder.
Igarashi M, Ma K, Gao F, Kim HW, Greenstein D, Rapoport SI, Rao JS.
Brain Physiology and Metabolism Section, National Institute on Aging, Bethesda, MD 20892, USA. miki.i@uci.edu
J Psychiatr Res. 2010 Feb;44(3):177-82. Epub 2009 Sep 19.
AbstractReduced concentrations of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) have been reported in the postmortem bipolar disorder (BD) brain. Additionally, an increased prevalence of BD has been related to low dietary intake of fish, and dietary supplements containing fish products or DHA have been reported to ameliorate BD symptoms. These observations suggest that brain lipid metabolism, particularly involving DHA, is disturbed in BD. To test this suggestion, concentrations of different lipids were measured using internal standards in postmortem frontal cortex from eight BD patients and six matched controls. Compared with control cortex, the BD cortex showed no statistically significant difference in mean concentrations (per gram wet weight) of "stable" lipids (total lipid, total phospholipid, individual phospholipids, or cholesterol), of unesterified fatty acids, or of esterified DHA or AA within stable lipids. Fractional esterified AA and DHA concentrations also did not differ significantly between groups. Some fatty acid concentration differences were found in low-abundant cholesteryl ester. These results do not support the hypothesis of disturbed brain lipid concentrations, including concentrations of AA and DHA, in BD. Positron emission tomography might be used, however, to see if brain AA or DHA kinetics are disturbed in the disease.
PMID: 19767014 [PubMed - indexed for MEDLINE]
Fatty acid composition of frontal, temporal and parietal neocortex in the normal human brain and in Alzheimer's disease.
Fraser T, Tayler H, Love S.
Dementia Research Group, Institute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Bristol, BS16 1LE, UK.
Neurochem Res. 2010 Mar;35(3):503-13. Epub 2009 Nov 11.
AbstractDietary omega3-polyunsaturated fatty acids are thought to influence the risk of Alzheimer's disease (AD), and supplemental docosahexaenoic acid (DHA; 22:6n-3) has been reported to reduce neurodegeneration in mouse models of AD. We have analysed the fatty acid composition of frontal, temporal and parietal neocortex in 58 normal and 114 AD brains. Significant reductions were found for stearic acid (18:0) in frontal and temporal cortex and arachidonic acid (20:4n-6) in temporal cortex in AD, and increases in oleic acid in frontal and temporal cortex (18:1n-9) and palmitic acid (16:0) in parietal cortex. DHA level varied more in AD than controls but the mean values were not significantly different. Fatty acid composition was not related to APOE genotype, age, gender or post-mortem delay. Further research is needed to distinguish between alterations that are secondary to AD and those that contribute to the disease process.
PMID: 19904605 [PubMed - indexed for MEDLINE]
Omega-3 fatty acid treatment and T(2) whole brain relaxation times in bipolar disorder.
Hirashima F, Parow AM, Stoll AL, Demopulos CM, Damico KE, Rohan ML, Eskesen JG, Zuo CS, Cohen BM, Renshaw PF.
Brain Imaging Center, McLean Hospital, Belmont, MA, USA. fuyuki@alum.dartmouth.org.
Am J Psychiatry. 2004 Oct;161(10):1922-4.
AbstractOBJECTIVE: The authors hypothesized that changes in brain membrane composition resulting from omega-3 fatty acid administration in patients with bipolar disorder would result in greater membrane fluidity, as detected by reductions in T(2) values.
METHOD: Women with bipolar disorder (N=12) received omega-3 fatty acids for 4 weeks. A cohort of bipolar subjects (N=9) and a group without bipolar disorder (N=12) did not receive omega-3 fatty acids. T(2) values were acquired at baseline and after 4 weeks.
RESULTS: Bipolar subjects who received omega-3 fatty acids had significant decreases in T(2). There was a dose-dependent effect when the bipolar omega-3 fatty acid group was subdivided into high- and low-dose cohorts.
CONCLUSIONS: Omega-3 fatty acids lowered T(2) values, consistent with the hypothesis that the fluidity of cell membranes was altered. Further studies are needed to clarify the significance of alterations in brain physiology induced by omega-3 fatty acids, as reflected in T(2) values.
PMID: 15465995 [PubMed - indexed for MEDLINE]
Significantly reduced docosahexaenoic and docosapentaenoic acid concentrations in erythrocyte membranes from schizophrenic patients compared with a carefully matched control group.
Assies J, Lieverse R, Vreken P, Wanders RJ, Dingemans PM, Linszen DH.
Department of Adolescent Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Biol Psychiatry. 2001 Mar 15;49(6):510-22.
AbstractBACKGROUND: Fatty acid research in schizophrenia has demonstrated an altered cell membrane phospholipid metabolism. Erythrocyte membrane phospholipid composition closest reflects that of neuronal membranes.
METHODS: (Poly)(un)saturated fatty acid concentrations were measured in the erythrocyte membranes of 19, consecutively admitted, medicated young schizophrenic patients and then compared with matched control subjects. Psychiatric symptomatology was rated with the Positive and Negative Symptom Scale and Montgomery-Asberg Depression Rating Scale. Because diet, hormones, and cannabis influence fatty acid metabolism, we included these factors in our study.
RESULTS: The most distinctive findings concerned the omega-3 series: C22:5 omega-3, C22:6 omega-3 (docosahexaenoic acid), and the sum of omega-3 fatty acids were significantly decreased. Interestingly, C20:4 omega-6 (arachidonic acid) was not lowered. In the omega-9 series, higher levels of C22:1 omega-9 and lower levels its elongation product, C24:1 omega-9 (nervonic acid), were found. Interestingly, the other arm of the desaturation-elongation sequence of C18:1 omega-9, C20:3 omega-9, was lower in patients. The total omega-9 fatty acid levels were also lower in patients.
CONCLUSIONS: Significant differences in erythrocyte fatty acid composition were found. The differences were not due to diet or hormonal status and could not be explained by the medication or cannabis use. No consistent pattern emerged from the different fatty acid abnormalities and the clinical symptom scores.
PMID: 11257236 [PubMed - indexed for MEDLINE]
Nutritional therapies for mental disorders.
Lakhan SE, Vieira KF.
Global Neuroscience Initiative Foundation, Los Angeles, CA, USA. slakhan@gnif.org
Nutr J. 2008 Jan 21;7:2.
AbstractAccording to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD). Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. One way for psychiatrists to overcome this noncompliance is to educate themselves about alternative or complementary nutritional treatments. Although in the cases of certain nutrients, further research needs to be done to determine the best recommended doses of most nutritional supplements, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained.
PMID: 18208598 [PubMed - indexed for MEDLINE]
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Pregnancy and Ante/Post-Natal Health
Published Clinical Studies
Docosahexaenoic acid supplementation in pregnancy and lactation.
Carlson SE.
Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS 66160, USA. scarlson@kumc.edu
Am J Clin Nutr. 2009 Feb;89(2):678S-84S. Epub 2008 Dec 30.
AbstractThe goal of the Experimental Biology symposium on maternal supplementation was to review all available lines of evidence, delineate unanswered questions, and develop, if it seemed reasonable, a research agenda to determine whether maternal supplementation with specific nutrients might be beneficial. In the case of maternal docosahexaenoic acid (DHA) status, the topic addressed in this article, few clinical studies show benefits of maternal DHA supplementation during pregnancy or lactation for the infant or child. However, quite a large number of observational studies link higher intrauterine DHA exposure to a number of positive developmental outcomes. This article reviews the factors known to contribute to DHA status of women and their offspring during the reproductive cycle, relates maternal DHA status to that of the developing fetus and newborn, and reviews the evidence for functional differences in behavior related to DHA status, including the available evidence related to DHA supplementation of women pregnant and lactating and their offspring. Other outcomes for infants and children and for women themselves appear plausible and are also addressed as part of a research agenda for future work.
PMID: 19116324 [PubMed - indexed for MEDLINE]
Is there a dietary requirement for DHA in pregnancy?
Makrides M.
Women's and Children's Health Research Institute, Level 7, Clarence Rieger Building, Women's and Children's Hospital, 72 King William Road, North Adelaide, SA 5006, Australia. maria.makrides@health.sa.gov.au
Prostaglandins Leukot Essent Fatty Acids. 2009 Aug-Sep;81(2-3):171-4. Epub 2009 Jun 4.
AbstractThe metabolic demand for docosahexaenoic acid (22:6 n-3, DHA) is increased during pregnancy because of the extra needs of the fetus, expanded maternal cell mass and placenta. In Western countries maternal dietary DHA intake in pregnancy is low and it is not clear whether adaptive metabolic mechanisms, such as increased DHA synthesis from precursor fatty acids, are capable of meeting the increased DHA need in pregnancy. Consequently randomized controlled trials are important to determine whether additional dietary DHA in pregnancy modifies maternal or infant health outcomes. The available randomized comparisons of DHA supplements vs placebo have assessed outcomes as diverse as maternal depression, infant visual acuity and development, and infant growth and allergy. The outcomes of these trials have not been conclusive because they have often been limited by small sample size. On the other hand, large-scale trials assessing marine oil supplementation with large doses indicate that DHA supplementation in pregnancy is safe.
PMID: 19500960 [PubMed - indexed for MEDLINE]
The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations.
Koletzko B, Lien E, Agostoni C, Böhles H, Campoy C, Cetin I, Decsi T, Dudenhausen JW, Dupont C, Forsyth S, Hoesli I, Holzgreve W, Lapillonne A, Putet G, Secher NJ, Symonds M, Szajewska H, Willatts P, Uauy R; World Association of Perinatal Medicine Dietary Guidelines Working Group.
Department of Pediatrics, University of Munich, München, Germany. Berthold.Koletzko@med.uni-muenchen.de
J Perinat Med. 2008;36(1):5-14.
Comment in:
1 J Perinat Med. 2008;36(6):548-9.
AbstractThis 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.
PMID: 18184094 [PubMed - indexed for MEDLINE]
Effects of supplementing LCPUFA to the diet of pregnant women: data from RCT.
Decsi T.
Department of Paediatrics, University of Pécs, Pécs, Hungary. tamas.decsi@aok.pte.hu
Adv Exp Med Biol. 2009;646:65-9.
AbstractRandomised controlled trials (RCTs) investigating the effect of n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation on pregnancy outcomes were recently systematically reviewed for both low-risk (uncomplicated) and high-risk pregnancies. The duration of pregnancy was found to be significantly enhanced by n-3 LCPUFA supplementation in low-risk (two systematic reviews, weighted mean difference: 2.55 and 1.57 days, 95% CI: 1.13-4.07 and 0.35-2.78 days), but not in high-risk pregnancies. The relative risk of giving birth before the 34th week of gestation was found to be reduced by n-3 LCPUFA supplementation both in low-risk (0.69, 95% CI: 0.49-0.99) and in high-risk (0.39, 95% CI: 0.19-0.84) pregnancies. Recent evidence indicates that enhancement of maternal intake of n-3 LCPUFA prolongs the duration of gestation in low-risk pregnancies and may contribute to the prevention of early preterm birth in both low-risk and high-risk pregnancies.
PMID: 19536664 [PubMed - indexed for MEDLINE]
Omega-3 fatty acid supplementation in perinatal settings.
Blanchard DS.
The Birthplace Williamsport Hospital and Medical Center, Susquehanna Health System, Williamsport, PA, USA. hrblanchard@suscom.net
MCN Am J Matern Child Nurs. 2006 Jul-Aug;31(4):250-6.
AbstractThe purpose of this article is (a) to explain the role of omega-3 fatty acids in human health, specifically in fetal/neonatal development, (b) to summarize the recent research behind the innovations in infant formula manufacturing and advertisement of omega-3 fatty acid supplementation for pregnant and lactating mothers, and (c) to relate the research findings to clinical practice. Omega-3 fatty acid supplementation in perinatal settings is discussed here from three vantage points: (a) supplementation of the third-trimester pregnant woman to enhance fetal development, (b) supplementation of the lactating mother to enhance development of the breastfeeding infant, and (c) supplementation of infant formulas to enhance development of the bottle-feeding infant. Supplementation can occur by increasing one's intake of foods high in omega-3 fatty acids or by ingesting fatty acid nutritional supplements. The challenge of supplementation for vegan and vegetarian women is also addressed.
PMID: 16940822 [PubMed - indexed for MEDLINE]
Long-chain omega-3 fatty acid supply in pregnancy and lactation.
Cetin I, Koletzko B.
Institute of Obstetrics and Gynecology, IRCCS Fondazione Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy. Irene.Cetin@unimi.it
Curr Opin Clin Nutr Metab Care. 2008 May;11(3):297-302.
AbstractPURPOSE OF REVIEW: Long-chain omega-3 fatty acids are essential for the developing fetus. Docosahexaenoic acid, the most important omega-3 fatty acid, is an important component of neural and retinal membranes, and rapidly accumulates in the brain during gestation and the postnatal period. Positive associations have been shown between maternal intake of fish, seafood and omega-3 fatty acids during pregnancy and/or lactation and visual and cognitive development.
RECENT FINDINGS: The review focuses on new findings by both observational and interventional studies on the influence of omega-3 fatty acids during pregnancy or lactation on gestation length and birth weight, preterm delivery, preeclampsia, maternal depression and infant visual function and neural development.
SUMMARY: Omega-3 fatty acids have been associated with reduced risk of cardiovascular and other diseases. Observational and interventional studies indicate a significant association with prolonging gestation and reducing the risk of preterm delivery both in low-risk and in high-risk pregnancies. Further benefits have been suggested for intrauterine growth restriction, preeclampsia and postpartum depression, but the evidence is inconclusive. Higher maternal docosahexaenoic acid intake both in pregnancy and lactation is associated with positive infant neurodevelopmental outcomes. Women of reproductive age should achieve an average dietary docosahexaenoic acid intake of at least 200 mg/day.
PMID: 18403927 [PubMed - indexed for MEDLINE]
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Skin Health
Published Clinical Studies
Inhibition of leukocyte-endothelial interactions by oxidized omega-3 fatty acids: a novel mechanism for the anti-inflammatory effects of omega-3 fatty acids in fish oil.
Sethi S.
Department of Pathology, 5243 RCP, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA. sanjeev-sethi@uiowa.edu
Redox Rep. 2002;7(6):369-78.
AbstractOmega-3 fatty acids which are abundant in fish oil improve the prognosis of several chronic inflammatory diseases that are characterized by leukocyte-mediated tissue injury. The omega-3 fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. Our data suggest that the beneficial effects of fish oil may be due to the oxidative modification of omega-3 fatty acids. The oxidized products inhibit leukocyte adhesion receptor expression and leukocyte-endothelial interactions. Oxidized EPA is a potent inhibitor of leukocyte interactions with the endothelium compared to native EPA, both in vitro and in an in vivo context of inflammation. The effects of oxidized EPA are mediated through activation of PPARalpha and subsequent inhibition of NF-kappaB, leading to the down-regulation of leukocyte adhesion receptor expression required for leukocyte-endothelial interactions. We propose that oxidation of EPA and its activation of PPARalpha and subsequent inhibition of NF-kappaB is the underlying mechanism for the beneficial effects of fish oil.
PMID: 12625944 [PubMed - indexed for MEDLINE]
n-3 fatty acids in psoriasis.
Mayser P, Grimm H, Grimminger F.
Department of Dermatology and Andrology, Justus Liebig University, Giessen, Germany. Peter.Mayser@derma.med.uni-giessen.de Increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Replacement of arachidonic acid by alternative precursor polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), which can be metabolized via the same enzymatic pathways as AA, might be a therapeutic option in psoriasis. However the results of studies evaluating the therapeutic benefit of dietary fish oil have been conflicting and not clearly dose-dependent. To overcome the slow kinetics and limited availability of oral supplementation, we have performed three studies to assess the effectiveness and safety of an intravenously administered fish oil derived lipid emulsion on different forms of psoriasis. Patients received daily infusions of either an n-3 fatty acid-based lipid emulsion (Omegaven) or a conventional n-6 lipid emulsion (Lipoven) in different time and dose regimens. In addition to an overall assessment of the clinical course of psoriasis, EPA- and AA-derived neutrophil 5-lipoxygenase (LO)--products, thromboxane (TX) B2/B3, PAF and plasma free fatty acids were investigated. Treatment with n-3 fatty acids resulted in a considerably higher response rate than infusion of n-6 lipids. A more than 10-fold increase in neutrophil EPA-derived 5-LO product formation was noted in the n-3 group, accompanied by a rapid increase in plasma-free EPA within the first days. In conclusion, intravenous n-3-fatty acid administration causes reduction of psoriasis, which may be related to changes in inflammatory eicosanoid generation. The rapidity of the response to intravenous n-3 lipids exceeds by orders of magnitude the hitherto reported kinetics of improvement of psoriatic lesions upon use of oral supplementation.
PMID: 11895157 [PubMed - indexed for MEDLINE]
Effects of micronutrient supplements on u.v.-induced skin damage.
Jackson MJ, Jackson MJ, McArdle F, Storey A, Jones SA, McArdle A, Rhodes LE.
Department of Medicine, University of Liverpool, Liverpool L69 3GA, UK. mjj@liv.ac.uk
Development of an orally-administered systemic agent that could reduce the effects of u.v. exposure on skin could potentially have a major effect on the incidence of skin cancers and photo-ageing. A number of micronutrients have been suggested to have metabolic properties that could induce this protection, and our data indicate that n-3 polyunsaturated fatty acids are particularly effective in this role. The mechanisms of action of n-3 polyunsaturated fatty acids appear to depend on their anti-inflammatory properties, acting to reduce the u.v.-induced release of cytokines and other mediators from a variety of skin cell types.
PMID: 12133200 [PubMed - indexed for MEDLINE]
The significance of polyunsaturated fatty acids in cutaneous biology.
Ziboh VA.
Department of Dermatology, University of California, Davis, USA.
The skin epidermis displays a highly active metabolism of polyunsaturated fatty acids (PUFA). Dietary deficiency of linoleic acid (LA) and 18-carbon (n-6) PUFA results in characteristic scaly skin disorder and excessive epidermal water loss. Arachidonic acid, a 20-carbon (n-6) PUFA is metabolized via the cyclooxygenase pathway into predominantly prostaglandin E2 (PGE2) PGF2 alpha, and PGD2 and via the lipoxygenase pathway into predominantly 15-hydroxyeicosatetraenoic acid (15-HETE). The prostaglandins modulate normal skin physiological processes at low concentrations and inflammatory reactions at high concentrations. Similarly, the very active epidermal 15-lipoxygenase transforms dihomogammalinolenic acid (DGLA) into 15-hydroxy eicosatrienoic acid (15-HETrE), eicosapentaenoic acid (EPA) into 15-hydroxyeicosapentaenoic acid (15-HEPE) and docosahexaenoic acid (DHA) into 17-hydroxydocosahexaenoic acid (17-HDoHE), respectively. These monohydroxy acids exhibit anti-inflammatory properties. In contrast, the 18-carbon (n-6) PUFA is transformed into 13-hydroxy-9,11-octadecadienoic acid (13-HODE), which exerts antiproliferative properties in the tissue. Thus, the supplementation of diets with appropriate purified vegetable oils and/or fish oil may generate local cutaneous anti-inflammatory metabolites which could serve as a less toxic in vivo monotherapy or as adjuncts to standard therapeutic regimens for the management of skin inflammatory disorders.
PMID: 8729128 [PubMed - indexed for MEDLINE]
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