quinta-feira, 20 de outubro de 2011

DHA e EPA (inglês)

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Health Benefits of Docosahexaenoic Acid (DHA)
Horrocks LA, Yeo YK
Docosa Foods Ltd, 1275 Kinnear Road,
Columbus, OH, 43212-1155, USA,
Pharmacol Res 1999 Sep; 40(3):211-225


Docosahexaenoic acid (DHA) is essential for the growth and functional development of the brain in infants. DHA is also required for maintenance of normal brain function in adults. The inclusion of plentiful DHA in the diet improves learning ability, whereas deficiencies of DHA are associated with deficits in learning. DHA is taken up by the brain in preference to other fatty acids. The turnover of DHA in the brain is very fast, more so than is generally realized. The visual acuity of healthy, full-term, formula-fed infants is increased when their formula includes DHA. During the last 50 years, many infants have been fed formula diets lacking DHA and other omega-3 fatty acids. DHA deficiencies are associated with foetal alcohol syndrome, attention deficit hyperactivity disorder, cystic fibrosis, phenylketonuria, unipolar depression, aggressive hostility, and adrenoleukodystrophy. Decreases in DHA in the brain are associated with cognitive decline during aging and with onset of sporadic Alzheimer disease. The leading cause of death in western nations is cardiovascular disease. Epidemiological studies have shown a strong correlation between fish consumption and reduction in sudden death from myocardial infarction. The reduction is approximately 50% with 200 mg day(-1)of DHA from fish. DHA is the active component in fish. Not only does fish oil reduce triglycerides in the blood and decrease thrombosis, but it also prevents cardiac arrhythmias. The association of DHA deficiency with depression is the reason for the robust positive correlation between depression and myocardial infarction. Patients with cardiovascular disease or Type II diabetes are often advised to adopt a low-fat diet with a high proportion of carbohydrate. A study with women shows that this type of diet increases plasma triglycerides and the severity of Type II diabetes and coronary heart disease. DHA is present in fatty fish (salmon, tuna, mackerel) and mother's milk. DHA is present at low levels in meat and eggs, but is not usually present in infant formulas. EPA, another long-chain n-3 fatty acid, is also present in fatty fish. The shorter chain n-3 fatty acid, alpha-linolenic acid, is not converted very well to DHA in man. These longchain n-3 fatty acids (also known as omega-3 fatty acids) are now becoming available in some foods, especially infant formula and eggs in Europe and Japan. Fish oil decreases the proliferation of tumour cells, whereas arachidonic acid, a longchain n-6 fatty acid, increases their proliferation. These opposite effects are also seen with inflammation, particularly with rheumatoid arthritis, and with asthma. DHA has a positive effect on diseases such as hypertension, arthritis, atherosclerosis, depression, adult-onset diabetes mellitus, myocardial infarction, thrombosis, and some cancers.

A new category of psychotropic drugs: neuroactive lipids as exemplified by ethyl eicosapentaenoate (E-E)
Horrobin DF.
Laxdale Ltd., Kings Park House,
Laurelhill Business Park, Stirling, FK7 9JQ Scotland.
Prog Drug Res 2002;59:171-99


New treatments for psychiatric disorders are urgently required. Recent reviews show that there have been no improvements in efficacy of drugs for either affective disorders or schizophrenia since the first compounds were introduced over 40 years ago. Neuroactive lipids represent an entirely novel class of psychotropic compounds. Ethyl eicosapentaenoate is the first example of this group. Placebo-controlled studies have found it to be effective in depression, in treatment-unresponsive schizophrenia and in tardive dyskinesia. It is extremely well tolerated with none of the usual side-effects of either antidepressants or neuroleptics. It probably works by modulating postreceptor signal transduction processes.

omega-3 Fatty acid treatment of women with borderline personality disorder: a double-blind, placebo-controlled pilot study
Zanarini MC, Frankenburg FR.
Laboratory for the Study of Adult Development,
McLean Hospital, Belmont, MA 02478, USA.
Am J Psychiatry 2003 Jan;160(1):167-9


OBJECTIVE: The purpose of this study was to compare the efficacy of ethyl-eicosapentaenoic acid (E-EPA) and placebo in the treatment of female subjects with borderline personality disorder. METHOD: The authors conducted an 8-week, placebo-controlled, double-blind study of E-EPA in 30 female subjects meeting Revised Diagnostic Interview for Borderlines and DSM-IV criteria for borderline personality disorder. RESULTS: Twenty subjects were randomly assigned to 1 g of E-EPA; 10 subjects were given placebo. Ninety percent of those in both groups completed all 8 weeks of the trial. Analyses that used random-effects regression modeling and controlled for baseline severity showed E-EPA to be superior to placebo in diminishing aggression as well as the severity of depressive symptoms. CONCLUSIONS: The results of this study suggest that E-EPA may be a safe and effective form of monotherapy for women with moderately severe borderline personality disorder.

Two double-blind placebo-controlled pilot studies of
eicosapentaenoic acid in the treatment of schizophrenia
Peet M, Brind J, Ramchand CN, Shah S, Vankar GK.
Academic Department of Psychiatry,
Northern General Hospital,
The Longley Centre,
Norwood Grange Drive, S5 7JT,
Sheffield, UK
Schizophr Res 2001 Apr 30;49(3):243-51


Evidence that the metabolism of phospholipids and polyunsaturated fatty acids (PUFA) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation. An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies. The first study was designed to distinguish between the possible effects of two different n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA, DHA or placebo for 3months. Improvement on EPA measured by the Positive and Negative Syndrome Scale (PANSS) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS. EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures. In the second placebo-controlled study, EPA was used as a sole treatment, though the use of antipsychotic drugs was still permitted if this was clinically imperative. By the end of the study, all 12 patients on placebo, but only eight out of 14 patients on EPA, were taking antipsychotic drugs. Despite this, patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study. It is concluded that EPA may represent a new treatment approach to schizophrenia, and this requires investigation by large-scale placebo-controlled trials.

Docosahexanoic acid and omega-3 fatty acids in depression
Mischoulon D, Fava M
Depression Clinical and Research Program,
Department of Psychiatry,
Massachusetts General Hospital and Harvard Medical School,
Boston, Massachusetts, USA.
Psychiatr Clin North Am 2000 Dec; 23(4):785-94


Geographic areas where consumption of DHA is high are associated with decreased rates of depression. DHA deficiency states, such as alcoholism and the postpartum period, also are linked with depression. Individuals with major depression have marked depletions in omega-3 FAs (especially DHA) in erythrocyte phospholipids compared with controls. These data suggest that DHA may be associated with depression, and the limited data available on supplementation with DHA or other omega-3 FAs seem to support the hypothesis that DHA may have psychotropic effects. Overall, the use of EFAs is promising, particularly in view of the many illnesses potentially treatable with these substances; however, larger, carefully designed studies are needed to establish whether DHA is an effective and safe antidepressant, mood stabilizer, or antipsychotic. A few preliminary trials of DHA are in progress, but no studies comparing DHA against placebo or against an established antidepressant have been carried out. Studies to address this issue are being developed at the Massachusetts General Hospital. Studies likely will require escalating doses of DHA, eventually reaching high levels so as to ensure that patients will avoid a potentially ineffective subclinical dose. Careful monitoring of dietary intake among subjects also will necessary because a high intake of omega-3-rich foods may confound results. Finally, large-scale, placebo-controlled, double-blind trials comparing the efficacy and safety of DHA against standard antidepressants are required before psychiatrists can recommend DHA therapy as effective and safe for the treatment of depression and other mood disorders. Given the popularity of self-medication by patients who already are taking marketed antidepressants, studies examining the use of DHA as an augmentor to standard antidepressants may answer whether DHA can occupy a niche as an augmenting agent for patients who have made a partial response or have not responded to conventional antidepressants. Considering that natural medications generally seem best for treating mild to moderate illness, the role of DHA as a therapy for minor and subsyndromal depression also should be considered. It is hoped that studies of these types will help to clarify some of the knowledge gaps outlined in this article.

The role of polyunsaturated fatty acids in term
and preterm infants and breastfeeding mothers
Heird WC.
Department of Pediatrics, Section of Nutrition,
USDA/ARS Children's Nutrition Research Center,
Baylor College of Medicine, Houston, Texas, USA.
Pediatr Clin North Am 2001 Feb;48(1):173-88


DHA and AA, which are components of breast milk but not infant formulas marketed in the United States and some other countries, are important components of the brain, and DHA is a major component of the retina. Also, many studies have demonstrated advantages of breastfeeding versus formula-feeding on subsequent cognitive and visual function; however, available data are insufficient to justify the conclusion that the presence of DHA and AA in breast milk is partially or soley responsible for the apparent advantages of breastfeeding. On the other hand, many studies of DHA (and AA)-supplemented versus unsupplemented formulas have shown clear advantages of the supplemented formulas on visual acuity at 2 and 4 months of age or neurodevelopmental status at 12 to 18 months of age. Although one logically may assume that these early effects may have long-term effects, this assumption is not warranted by the available data. One of the major problems is the difficulty of assessing visual and cognitive function of infants. Scores on standard neurodevelopmental tests at 1 year of age, for example, are only weakly correlated with performance at school age (when more definitive assessments are possible), and little is known about the predictability of later visual function from behavioral or electrophysiologic assessments of visual function early in life. Even prematurely born infants can synthesize DHA and AA and other omega-3 and omega-6 LC-PUFAs from the dietary EFAs, LA and ALA. Nonetheless, plasma, erythrocyte and brain lipid levels of DHA are lower in infants whose diets do not contain DHA. Whether more optimal intakes of ALA result in higher plasma and tissue levels of this FA is unclear. The breast-milk content of LC-PUFAs is not regulated by the mammary gland but, rather, reflects the concentrations of LC-PUFAs in maternal plasma lipids that, in turn, are dependent on maternal diet and, probably, maternal activities of the desaturases and elongases involved in converting dietary LA and ALA to LC-PUFAs. This occurrence suggests that some infants receive sufficient LC-PUFA to support normal rates of deposition, whereas others may not. Also, some infants probably can synthesize additional LC-PUFAs from the LA and ALA contents of human milk. Thus, depending on maternal diet and maternal and infant desaturase and elongase activities, some breastfed infants may receive less than adequate LC-PUFAs to support normal rates of deposition. Clearly, the role of LC-PUFAs in infant development is not a simple issue. Also, no foolproof method exists to ensure an adequate but not excessive intake. Thus, because some evidence shows that dietary LC-PUFA (DHA, AA, or both) as components of breast milk or formula confers at least transient developmental benefits, supplementation of infant formulas with LC-PUFAs is supportable provided that the supplements used are safe. The safety of all available supplements is unknown; however, some trials reveal few reasons for major concerns about the safety of single-cell oils, low-EPA fish oil, or egg-yolk phospholipid or triglyceride fractions.

Omega-3 Fatty Acids in Inflammation
and Autoimmune Diseases
Simopoulos AP.
The Center for Genetics,
Nutrition and Health, Washington, D.C.K.
J Am Coll Nutr 2002 Dec;21(6):495-505


Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-are more biologically potent than alpha-linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene _expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.

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.
J Nutr Health Aging. 2004;8(3):163-74


Among 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.   

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