Fiskeolje mot depresjon?

[Gjest nrjs]

Alltid like pålitelige Mozon skriver at fiskeoljer hjelper mot depresjoner. http://www.mozon.no/alternativt/andre_saker/fiskeoljer_mot_depresjoner__1

Senere i artikkelen viser det seg at undersøkelsen er gjort på bipolare. Men da virket fiskeolje like bra som litium. Noen som kjenner til denne undersøkelsen? Er den seriøs?

[Gjest caputt]

Jeg har brukt Omega 3,6 og 9 over en to mnd.periode. Brukte Udo`s choice først. Den smaker fryktelig vondt, så gikk jeg over til Eye Q. Den er ok på smak.

Vet at mange foreldre av barn med ADHD-problematikk og/eller andre adferdsproblem, har brukt Eye Q med god erfaring.

[Nils Håvard Dahl, psykiater]

Problemet med artikkelen på mozon er at den ikke har henvisning til de orginale vitenskapelige artikler. Dermed kan en ikke vite hva som egentlig er skrevet og hva som er referentens eget tankegods.

Dette problemet har en også hatt blant enkelte referenter her på DOL og ikke minst i programmet PULS.

Under Winterworkshop om schizofreni i Davos i uke 6, la den norke forskeren Håvard Bentsen frem den klart største og beste studien hittil om fiskeolje og antioksydanter til personer med schizofreni. Ingen av pasientene ble bedre. En undergruppe ble klart dårligere.

Forskningen gir hitil ikke entydige svar.

Slik jeg ser det, er fiskeolje lovende ved bipolar lidelse. Jeg mener det overhode ikke finnes dekning for å si at det kan erstatte vanlige medisiner. Men det kan være nyttig tilleggsbehandling.

[Svimern]

Problemet med artikkelen på mozon er at den ikke har henvisning til de orginale vitenskapelige artikler. Dermed kan en ikke vite hva som egentlig er skrevet og hva som er referentens eget tankegods.

Dette problemet har en også hatt blant enkelte referenter her på DOL og ikke minst i programmet PULS.

Under Winterworkshop om schizofreni i Davos i uke 6, la den norke forskeren Håvard Bentsen frem den klart største og beste studien hittil om fiskeolje og antioksydanter til personer med schizofreni. Ingen av pasientene ble bedre. En undergruppe ble klart dårligere.

Forskningen gir hitil ikke entydige svar.

Slik jeg ser det, er fiskeolje lovende ved bipolar lidelse. Jeg mener det overhode ikke finnes dekning for å si at det kan erstatte vanlige medisiner. Men det kan være nyttig tilleggsbehandling.

Jeg for min del synes det var interessant å merke seg at de her formulerte seg slik: "uvesentlige bivirkninger som diare....." i forbindelse med inntak av fiskeolje.

Denne bivirkningen i sammenheng med AD blir stort sett alltid fremstilt som negativ.

[Gjest Aina E]

Problemet med artikkelen på mozon er at den ikke har henvisning til de orginale vitenskapelige artikler. Dermed kan en ikke vite hva som egentlig er skrevet og hva som er referentens eget tankegods.

Dette problemet har en også hatt blant enkelte referenter her på DOL og ikke minst i programmet PULS.

Under Winterworkshop om schizofreni i Davos i uke 6, la den norke forskeren Håvard Bentsen frem den klart største og beste studien hittil om fiskeolje og antioksydanter til personer med schizofreni. Ingen av pasientene ble bedre. En undergruppe ble klart dårligere.

Forskningen gir hitil ikke entydige svar.

Slik jeg ser det, er fiskeolje lovende ved bipolar lidelse. Jeg mener det overhode ikke finnes dekning for å si at det kan erstatte vanlige medisiner. Men det kan være nyttig tilleggsbehandling.

Tja, litt forskning på området, så kan du mene hva du vil:

Peer-Reviewed Professional Journals

· Adams, P., et al. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids. 31(Supplement):S157-S161, 1996.

In this study of 20 moderately to severely depressed patients, diagnosed using current research diagnostic criteria and excluding known bipolar affective disorder and reactive depression, the authors investigated relationships between severity of depression and levels and ratios of n-3 and n-6 long-chain polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids (PL). Severity of depression was measured using the 21-item Hamilton depression rating scale (HRS) and a second linear rating scale (LRS) of severity of depressive symptoms that omitted anxiety symptoms. There was a significant correlation between the ratio of erythrocyte PL arachidonic acid (AA) to eicosapentaenoic acid (EPA) and severity of depression as rated by the HRS (P

· Colin, A., et al. [Lipids, depression and suicide]. Encephale. 29(Part 1):49-58, 2003.

Universite de Liege, CUP La Clairiere, Bertrix.

Polyunsatured fatty acids are made out of a hydrocarbonated chain of variable length with several double bonds. The position of the first double bond (omega) differentiates polyunsatured omega 3 fatty acids (for example: alpha-linolenic acid or alpha-LNA) and polyunsatured omega 6 fatty acids (for example: linoleic acid or LA). These two classes of fatty acids are said to be essential because they cannot be synthetised by the organism and have to be taken from alimentation. The omega 3 are present in linseed oil, nuts, soya beans, wheat and cold water fish whereas omega 6 are present in maize, sunflower and sesame oil. Fatty acids are part of phospholipids and, consequently, of all biological membranes. The membrane fluidity, of crucial importance for its functioning, depends on its lipidic components. Phospholipids composed of chains of polyunsatured fatty acids increase the membrane fluidity because, by bending some chains, double bonds prevent them from compacting themselves perfectly. Membrane fluidity is also determined by the phospholipids/free cholesterol ratio, as cholesterol increases membrane viscosity. A diet based on a high proportion of essential polyunsatured fatty acids (fluid) would allow a higher incorporation of cholesterol (rigid) in the membranes to balance their fluidity, which would contribute to lower blood cholesterol levels. Brain membranes have a very high content in essential polyunsatured fatty acids for which they depend on alimentation. Any dietary lack of essential polyunsatured fatty acids has consequences on cerebral development, modifying the activity of enzymes of the cerebral membranes and decreasing efficiency in learning tasks. The prevalence of depression seems to increase continuously since the beginning of the century. Though different factors most probably contribute to this evolution, it has been suggested that it could be related to an evolution of alimentary patterns in the Western world, in which polyunsatured omega 3 fatty acids contained in fish, game and vegetables have been largely replaced by polyunsatured omega 6 fatty acids of cereal oils. Some epidemiological data support the hypothesis of a relation between lower depression and/or suicide rates and a higher consumption of fish. These data do not however prove a relation of causality. Several cohort studies (on nondepressed subjects) have assessed the relationship between plasma cholesterol and depressive symptoms with contradictory results. Though some results found a significant relationship between a decrease of total cholesterol and high scores of depression, some other did not. Studies among patients suffering from major depression signalled more constantly an association between low cholesterol and major depression. Besides, some trials showed that clinical recovery may be associated with a significant increase of total cholesterol. The hypothesis that a low cholesterol level may represent a suicidal risk factor was discovered accidentally following a series of epidemiological studies which revealed an increase of the suicidal risk among subjects with a low cholesterol level. Though some contradictory studies do exist, this relationship has been confirmed by several subsequent cohort studies. These findings have challenged the vast public health programs aimed at promoting the decrease of cholesterol, and even suggested to suspend the administration of lipid lowering drugs. Recent clinical studies on populations treated with lipid lowering drugs showed nevertheless a lack of significant increase of mortality, either by suicide or accident. In addition, several controlled studies among psychiatric patients revealed a decrease of the concentrations of plasma cholesterol among patients who had attempted suicide in comparison with other patients. In major depression, all studies revealed a significant decrease of the polyunsaturated omega 3 fatty acids and/or an increase of the omega 6/omega 3 ratio in plasma and/or in the membranes of the red cells. In addition, two studies found a higher severity of depression when the level of polyunsaturated omega 3 fatty acids or the ratio omega 3/omega 6 was low. Parallel to these modifications, other biochemical perturbations have been reported in major depression, particularly an activation of the inflammatory response system, resulting in an increase of the pro-inflammatory cytokines (interleukins: IL-1b, IL-6 and interferon g) and eicosanoids (among others, prostaglandin E2) in the blood and the CSF of depressed patients. These substances cause a peroxidation and, consequently a catabolism of membrane phospholipids, among others those containing polyunsaturated fatty acids. The cytokines and eicosanoids derive from polyunsaturated fatty acids and have opposite physiological functions according to their omega 3 or omega 6 precursor. Arachidonic acid (omega 6) is, among others, precursor of pro-inflammatory prostaglandin E2 (PGE2), whereas polyunsaturated omega 3 fatty acids inhibit the formation of PGE2. It has been shown that a dietary increase of polyunsaturated omega 3 fatty acids reduced strongly the production of IL-1 beta, IL-2, IL-6 and TNF-alpha (tumor necrosis factor-alpha). In contrast, diets with a higher supply of linoleic acid (omega 6) increased significantly the production of pro-

inflammatory cytokines, like TNF-alpha. Therefore, polyunsaturated omega 3 fatty acids could be associated at different levels in the pathophysiology of major depression, on the one hand through their role in the membrane fluidity which influences diverse steps of neurotransmission and, on the other hand, through their function as precursor of pro-inflammatory cytokines and eicosanoids disturbing neurotransmission. In addition, antidepressants could exhibit an immunoregulating effect by reducing the release of pro-inflammatory cytokines, by increasing the release of endogenous antagonists of pro-inflammatory cytokines like IL-10 and, finally, by acting like inhibitors of cyclo-oxygenase. Data available concerning the administration of supplements of DHA (docosahexanoic acid) or other polyunsaturated fatty acids omega 3 are limited. In a double blind placebo-controlled study on 30 patients with bipolar disorder, the addition of polyunsaturated omega 3 fatty acids was associated with a longer period of remission. Moreover, nearly all the other prognosis measures were better in the omega 3 group. Very recently, a controlled trial showed the benefits of adding an omega 3 fatty acid, eicosopentanoic acid, among depressed patients. After 4 weeks, six of the 10 patients receiving the fatty acid were considered as responders in comparison with only one of the ten patients receiving placebo. Some epidemiological, experimental and clinical data favour the hypothesis that polyunsaturated fatty acids could play a role in the pathogenesis and/or the treatment of depression. More studies however are needed in order to better precise the actual implication of those biochemical factors among the various aspects of depressive illness.

· Carlezon, W. A., Jr., et al. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 57(4):343-350, 2005.

Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA.

Brain phospholipid metabolism and membrane fluidity may be involved in the pathophysiology of mood disorders. The authors demonstrated previously that cytidine, which increases phospholipid synthesis, has antidepressant-like effects in the forced swim test (FST) in rats, a model used in depression research. Because cytidine and uridine both stimulate synthesis of cytidine 5'-diphosphocholine (CDP-choline, a critical substrate for phospholipid synthesis), the authors examined whether uridine would also produce antidepressant-like effects in rats. They also examined the effects of omega-3 fatty acids (OMG), which increase membrane fluidity and reportedly have antidepressant effects in humans, alone and in combination with uridine. The authors first examined the effects of uridine injections alone and dietary supplementation with OMG alone in the FST. They then combined sub-effective treatment regimens of uridine and OMG to determine whether these agents would be more effective if administered together. Uridine dose-dependently reduced immobility in the FST, an antidepressant-like effect. Dietary supplementation with omega-3 fatty acids reduced immobility when given for 30 days, but not for 3 or 10 days. A sub-effective dose of uridine reduced immobility in rats given sub-effective dietary supplementation with Uridine and OMG each have antidepressant-like effects in rats. Less of each agent is required for effectiveness when the treatments are administered together.

· Edwards, R., et al. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord. 48(2-3):149-155, 1998.

There is a hypothesis that lack of superunsaturated fatty acids is of aetiological importance in depression. Docosahexaenoic acid, a member of the superunsaturated fatty acids family, is a crucial component of synaptic cell membranes. The aim of this study was to measure red blood cell membrane fatty acids in a group of depressed patients relative to a well matched healthy control group. Red blood cell membrane levels, and dietary superunsaturated fatty acids intake were measured in 10 depressed patients and 14 matched healthy control subjects. There was a significant depletion of red blood cell membrane superunsaturated fatty acids in the depressed subjects which was not due to reduced calorie intake. Severity of depression correlated negatively with red blood cell membrane levels and with dietary intake of superunsaturated fatty acids |The authors concluded that lower red blood cell membrane superunsaturated fatty acids are associated with the severity of depression. The findings raise the possibility that depressive symptoms may be alleviated by supplementation with superunsaturated fatty acids.

· Edwards, R., et al. Depletion of docosahexaenoic acid in red blood cell membranes of depressive patients. Biochem Soc Trans. 26:S142, 1998.

This study found that EPA, DHA and total superunsaturated fatty acid levels were significantly lower in the red blood cell membranes of depressed subjects compared to a control group.

· Hibbeln, J., et al. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. American Journal of Clinical Nutrition. 62:1-9, 1995.

Recent studies have both offered and contested the proposition that lowering plasma cholesterol by diet and medications increases suicide, homicide, and depression. Significant confounding factors include the quantity and distribution of dietary n-6 and n-3 polyunsaturated essential fatty acids that influence serum lipids and alter the biophysical and biochemical properties of cell membranes. Epidemiological studies in various countries and in the United States in the last century suggest that decreased n-3 fatty acid consumption correlates with increasing rates of depression. This is consistent with a well-established positive correlation between depression and coronary artery disease. Long-chain n-3 polyunsaturate deficiency may also contribute to depressive symptoms in alcoholism, multiple sclerosis, and post-partum depression. We postulate that adequate long-chain polyunsaturated fatty acids, particularly docosahexaenoic acid, may reduce the development of depression just as n-3 polyunsaturated fatty acids may reduce coronary artery disease.

· Maes, M., et al. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord. 38(1):35-46, 1996.

Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

· Mamalakis, G., et al. Depression and adipose essential polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids. 67(5):311-318, 2002.

Department of Social and Preventive Medicine, University of Crete, Iraklion, Crete, Greece

The objective of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake, and depression. The sample consisted of 247 healthy adults (146 males, 101 females) from the island of Crete. The number of subjects with complete data on all variables studied was 139. Subjects were examined at the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the Zung Self-rating Depression Scale. Mildly depressed subjects had significantly reduced (-34.6%) adipose tissue docosahexaenoic acid (DHA) levels than non-depressed subjects. Multiple linear regression analysis indicated that depression related negatively to adipose tissue DHA levels. In line with the findings of other studies, the observed negative relation between adipose tissue DHA and depression, in the present study, appears to indicate increasing long-term dietary DHA intakes with decreasing depression. This is the first literature report of a relation between adipose tissue DHA and depression. Depression has been reported to be associated with increased cytokine production, such as IL-1, IL-2, IL-6, INF-gamma and INF-alpha. On the other hand, fish oil and omega-3 fatty acids have been reported to inhibit cytokine synthesis. The observed negative relation between adipose DHA and depression, therefore, may stem from the inhibiting effect of DHA on cytokine synthesis.

· Peet, M., et al. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry. 43(5):315-319, 1998.

It has been hypothesized that depletion of cell membrane n3 polyunsaturated fatty acids (PUFA), particularly docosahexanoic acid (DHA), may be of etiological importance in depression. The authors measured the fatty acid composition of phospholipid in cell membranes from red blood cells (RBC) of 15 depressive patients and 15 healthy control subjects. Depressive patients showed significant depletions of total n3 PUFA and particularly DHA. Incubation of RBC from control subjects with hydrogen peroxide abolished all significant differences between patients and controls. These findings suggest that RBC membranes in depressive patients show evidence of oxidative damage.

· Monograph: fish oil. Alternative Medicine Review. 5(6), 2000.

Several studies have shown that low levels of superunsaturated fatty acids are predictive of a greater severity of depression.

· Omega-3 fatty acids in the treatment of depression. Harv Ment Health Lett. 18(4):4-5, 2001.

Laypersons’ Publications

· Schmidt, M. A. Smart Fats: How Dietary Fats and Oils Affect Mental, Physical and Emotional Intelligence. Frog Ltd. Berkeley, California, USA. 1997:5.

Peer-Reviewed Professional Medical Journals

· Adams, P. B., et al. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids. 31(Supplement):S157-S161, 1996.

In this study of 20 moderately to severely depressed patients, diagnosed using current research diagnostic criteria and excluding known bipolar affective disorder and reactive depression, the authors investigated relationships between severity of depression and levels and ratios of n-3 and n-6 long-chain polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids (PL). Severity of depression was measured using the 21-item Hamilton depression rating scale (HRS) and a second linear rating scale (LRS) of severity of depressive symptoms that omitted anxiety symptoms. There was a significant correlation between the ratio of erythrocyte PL arachidonic acid (AA) to eicosapentaenoic acid (EPA) and severity of depression as rated by the HRS (P

· Colin, A., et al. [Lipids, depression and suicide]. Encephale. 29(Part 1):49-58, 2003.

Universite de Liege, CUP La Clairiere, Bertrix.

Polyunsatured fatty acids are made out of a hydrocarbonated chain of variable length with several double bonds. The position of the first double bond (omega) differentiates polyunsatured omega 3 fatty acids (for example: alpha-linolenic acid or alpha-LNA) and polyunsatured omega 6 fatty acids (for example: linoleic acid or LA). These two classes of fatty acids are said to be essential because they cannot be synthetised by the organism and have to be taken from alimentation. The omega 3 are present in linseed oil, nuts, soya beans, wheat and cold water fish whereas omega 6 are present in maize, sunflower and sesame oil. Fatty acids are part of phospholipids and, consequently, of all biological membranes. The membrane fluidity, of crucial importance for its functioning, depends on its lipidic components. Phospholipids composed of chains of polyunsatured fatty acids increase the membrane fluidity because, by bending some chains, double bonds prevent them from compacting themselves perfectly. Membrane fluidity is also determined by the phospholipids/free cholesterol ratio, as cholesterol increases membrane viscosity. A diet based on a high proportion of essential polyunsatured fatty acids (fluid) would allow a higher incorporation of cholesterol (rigid) in the membranes to balance their fluidity, which would contribute to lower blood cholesterol levels. Brain membranes have a very high content in essential polyunsatured fatty acids for which they depend on alimentation. Any dietary lack of essential polyunsatured fatty acids has consequences on cerebral development, modifying the activity of enzymes of the cerebral membranes and decreasing efficiency in learning tasks. The prevalence of depression seems to increase continuously since the beginning of the century. Though different factors most probably contribute to this evolution, it has been suggested that it could be related to an evolution of alimentary patterns in the Western world, in which polyunsatured omega 3 fatty acids contained in fish, game and vegetables have been largely replaced by polyunsatured omega 6 fatty acids of cereal oils. Some epidemiological data support the hypothesis of a relation between lower depression and/or suicide rates and a higher consumption of fish. These data do not however prove a relation of causality. Several cohort studies (on nondepressed subjects) have assessed the relationship between plasma cholesterol and depressive symptoms with contradictory results. Though some results found a significant relationship between a decrease of total cholesterol and high scores of depression, some other did not. Studies among patients suffering from major depression signalled more constantly an association between low cholesterol and major depression. Besides, some trials showed that clinical recovery may be associated with a significant increase of total cholesterol. The hypothesis that a low cholesterol level may represent a suicidal risk factor was discovered accidentally following a series of epidemiological studies which revealed an increase of the suicidal risk among subjects with a low cholesterol level. Though some contradictory studies do exist, this relationship has been confirmed by several subsequent cohort studies. These findings have challenged the vast public health programs aimed at promoting the decrease of cholesterol, and even suggested to suspend the administration of lipid lowering drugs. Recent clinical studies on populations treated with lipid lowering drugs showed nevertheless a lack of significant increase of mortality, either by suicide or accident. In addition, several controlled studies among psychiatric patients revealed a decrease of the concentrations of plasma cholesterol among patients who had attempted suicide in comparison with other patients. In major depression, all studies revealed a significant decrease of the polyunsaturated omega 3 fatty acids and/or an increase of the omega 6/omega 3 ratio in plasma and/or in the membranes of the red cells. In addition, two studies found a higher severity of depression when the level of polyunsaturated omega 3 fatty acids or the ratio omega 3/omega 6 was low. Parallel to these modifications, other biochemical perturbations have been reported in major depression, particularly an activation of the inflammatory response system, resulting in an increase of the pro-inflammatory cytokines (interleukins: IL-1b, IL-6 and interferon g) and eicosanoids (among others, prostaglandin E2) in the blood and the CSF of depressed patients. These substances cause a peroxidation and, consequently a catabolism of membrane phospholipids, among others those containing polyunsaturated fatty acids. The cytokines and eicosanoids derive from polyunsaturated fatty acids and have opposite physiological functions according to their omega 3 or omega 6 precursor. Arachidonic acid (omega 6) is, among others, precursor of pro-inflammatory prostaglandin E2 (PGE2), whereas polyunsaturated omega 3 fatty acids inhibit the formation of PGE2. It has been shown that a dietary increase of polyunsaturated omega 3 fatty acids reduced strongly the production of IL-1 beta, IL-2, IL-6 and TNF-alpha (tumor necrosis factor-alpha). In contrast, diets with a higher supply of linoleic acid (omega 6) increased significantly the production of pro-

inflammatory cytokines, like TNF-alpha. Therefore, polyunsaturated omega 3 fatty acids could be associated at different levels in the pathophysiology of major depression, on the one hand through their role in the membrane fluidity which influences diverse steps of neurotransmission and, on the other hand, through their function as precursor of pro-inflammatory cytokines and eicosanoids disturbing neurotransmission. In addition, antidepressants could exhibit an immunoregulating effect by reducing the release of pro-inflammatory cytokines, by increasing the release of endogenous antagonists of pro-inflammatory cytokines like IL-10 and, finally, by acting like inhibitors of cyclo-oxygenase. Data available concerning the administration of supplements of DHA (docosahexanoic acid) or other polyunsaturated fatty acids omega 3 are limited. In a double blind placebo-controlled study on 30 patients with bipolar disorder, the addition of polyunsaturated omega 3 fatty acids was associated with a longer period of remission. Moreover, nearly all the other prognosis measures were better in the omega 3 group. Very recently, a controlled trial showed the benefits of adding an omega 3 fatty acid, eicosopentanoic acid, among depressed patients. After 4 weeks, six of the 10 patients receiving the fatty acid were considered as responders in comparison with only one of the ten patients receiving placebo. Some epidemiological, experimental and clinical data favour the hypothesis that polyunsaturated fatty acids could play a role in the pathogenesis and/or the treatment of depression. More studies however are needed in order to better precise the actual implication of those biochemical factors among the various aspects of depressive illness.

· Frasure-Smith, N., et al. Major depression is associated with lower omega-3 fatty acid levels in patients with recent acute coronary syndromes. Biol Psychiatry. 55(9):891-896, 2004.

Polyunsaturated fatty acids (PUFAs) are intrinsic cell membrane components and closely involved in neurotransmission and receptor function. Lower omega-3 levels are associated with increased risk of coronary artery disease (CAD), increases in cardiac events in CAD patients, and depression. The authors sought to examine relationships between depression and serum levels of omega-3 and omega-6 PUFAs in patients recovering from acute coronary syndromes (ACS). The authors carried out a case-control study of serum PUFA levels and current major depression in 54 age- and sex-matched pairs approximately 2 months following ACS. Depressed patients had significantly lower concentrations of total omega-3 and docosahexaenoic acid (DHA), and higher ratios of arachidonic acid (AA) to DHA, AA to eicosapentaenoic acid (EPA), and n-3 to n-6 than controls. There were no baseline differences in any potential risk or protective factors for depression. Results are consistent with previous reports in depressed patients without CAD, and with literature concerning omega-3 levels and risk of CAD events. Dietary, genetic, and hormonal factors may all play a role in both depression and CAD. Both prospective studies and randomized trials are needed to help clarify the interrelationships.

· Huan, M., et al. Suicide attempt and n-3 fatty acid levels in red blood cells: A case control study in China. Biol Psychiatry. 56(7):490-796, 2004.

Division of Clinical Application (MH, KH, MI, SW, TH), Department of Clinical Sciences, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama-City, Japan.

Epidemiologic studies show that low fish intake is a risk factor of suicidality; however, there are no case-control studies investigating suicide attempt risk and tissue n-3 fatty acid levels. The authors recruited 100 suicide-

attempt cases and another 100 control patients injured by accidents who were admitted to three hospitals affiliated with Dalian Medical University in Dalian, China. Case and control subjects were matched for age, gender, and smoking status. Those who were inebriated at the time of hospitalization were excluded. Blood was sampled immediately after admission to a hospital. Washed red blood cells (RBCs) were obtained, and the fatty acid composition of the total RBC phospholipid fraction was analyzed by gas chromatography. Eicosapentaenoic acid (EPA) levels in RBC in the case subjects were significantly lower than those of the control subjects (.74 +/-.52% vs. 1.06 +/-.62%, p <.0001 when the highest and lowest quartiles of epa in rbc were compared odds ratios suicide attempt was.12 quartile confidence interval:.04-.36 p for trend=".0001)" after adjustment possible confounding factors these findings suggest that low n-3 fatty acid levels tissues a risk factor attempt. further studies including intervention with fish oil are warranted.>

· Maes, M., et al. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord. 38(1):35-46, 1996.

Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

· Su, K. P., et al. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 13(4):267-271, 2003.

Department of Psychiatry, China Medical College Hospital, Taichung, Taiwan.

Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs), including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents (red blood cell membrane, plasma, etc.) and dietary intake. However, more evidence is needed to support its relation. The authors conducted an 8-week, double-blind, placebo-controlled trial, comparing omega-3 PUFAs (9.6 g/day) with placebo, on the top of the usual treatment, in 28 patients with major depressive disorder. Patients in the omega-3 PUFA group had a significantly decreased score on the 21-

item Hamilton Rating Scale for Depression than those in the placebo group (P

[Nils Håvard Dahl, psykiater]

Tja, litt forskning på området, så kan du mene hva du vil:

Peer-Reviewed Professional Journals

· Adams, P., et al. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids. 31(Supplement):S157-S161, 1996.

In this study of 20 moderately to severely depressed patients, diagnosed using current research diagnostic criteria and excluding known bipolar affective disorder and reactive depression, the authors investigated relationships between severity of depression and levels and ratios of n-3 and n-6 long-chain polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids (PL). Severity of depression was measured using the 21-item Hamilton depression rating scale (HRS) and a second linear rating scale (LRS) of severity of depressive symptoms that omitted anxiety symptoms. There was a significant correlation between the ratio of erythrocyte PL arachidonic acid (AA) to eicosapentaenoic acid (EPA) and severity of depression as rated by the HRS (P

· Colin, A., et al. [Lipids, depression and suicide]. Encephale. 29(Part 1):49-58, 2003.

Universite de Liege, CUP La Clairiere, Bertrix.

Polyunsatured fatty acids are made out of a hydrocarbonated chain of variable length with several double bonds. The position of the first double bond (omega) differentiates polyunsatured omega 3 fatty acids (for example: alpha-linolenic acid or alpha-LNA) and polyunsatured omega 6 fatty acids (for example: linoleic acid or LA). These two classes of fatty acids are said to be essential because they cannot be synthetised by the organism and have to be taken from alimentation. The omega 3 are present in linseed oil, nuts, soya beans, wheat and cold water fish whereas omega 6 are present in maize, sunflower and sesame oil. Fatty acids are part of phospholipids and, consequently, of all biological membranes. The membrane fluidity, of crucial importance for its functioning, depends on its lipidic components. Phospholipids composed of chains of polyunsatured fatty acids increase the membrane fluidity because, by bending some chains, double bonds prevent them from compacting themselves perfectly. Membrane fluidity is also determined by the phospholipids/free cholesterol ratio, as cholesterol increases membrane viscosity. A diet based on a high proportion of essential polyunsatured fatty acids (fluid) would allow a higher incorporation of cholesterol (rigid) in the membranes to balance their fluidity, which would contribute to lower blood cholesterol levels. Brain membranes have a very high content in essential polyunsatured fatty acids for which they depend on alimentation. Any dietary lack of essential polyunsatured fatty acids has consequences on cerebral development, modifying the activity of enzymes of the cerebral membranes and decreasing efficiency in learning tasks. The prevalence of depression seems to increase continuously since the beginning of the century. Though different factors most probably contribute to this evolution, it has been suggested that it could be related to an evolution of alimentary patterns in the Western world, in which polyunsatured omega 3 fatty acids contained in fish, game and vegetables have been largely replaced by polyunsatured omega 6 fatty acids of cereal oils. Some epidemiological data support the hypothesis of a relation between lower depression and/or suicide rates and a higher consumption of fish. These data do not however prove a relation of causality. Several cohort studies (on nondepressed subjects) have assessed the relationship between plasma cholesterol and depressive symptoms with contradictory results. Though some results found a significant relationship between a decrease of total cholesterol and high scores of depression, some other did not. Studies among patients suffering from major depression signalled more constantly an association between low cholesterol and major depression. Besides, some trials showed that clinical recovery may be associated with a significant increase of total cholesterol. The hypothesis that a low cholesterol level may represent a suicidal risk factor was discovered accidentally following a series of epidemiological studies which revealed an increase of the suicidal risk among subjects with a low cholesterol level. Though some contradictory studies do exist, this relationship has been confirmed by several subsequent cohort studies. These findings have challenged the vast public health programs aimed at promoting the decrease of cholesterol, and even suggested to suspend the administration of lipid lowering drugs. Recent clinical studies on populations treated with lipid lowering drugs showed nevertheless a lack of significant increase of mortality, either by suicide or accident. In addition, several controlled studies among psychiatric patients revealed a decrease of the concentrations of plasma cholesterol among patients who had attempted suicide in comparison with other patients. In major depression, all studies revealed a significant decrease of the polyunsaturated omega 3 fatty acids and/or an increase of the omega 6/omega 3 ratio in plasma and/or in the membranes of the red cells. In addition, two studies found a higher severity of depression when the level of polyunsaturated omega 3 fatty acids or the ratio omega 3/omega 6 was low. Parallel to these modifications, other biochemical perturbations have been reported in major depression, particularly an activation of the inflammatory response system, resulting in an increase of the pro-inflammatory cytokines (interleukins: IL-1b, IL-6 and interferon g) and eicosanoids (among others, prostaglandin E2) in the blood and the CSF of depressed patients. These substances cause a peroxidation and, consequently a catabolism of membrane phospholipids, among others those containing polyunsaturated fatty acids. The cytokines and eicosanoids derive from polyunsaturated fatty acids and have opposite physiological functions according to their omega 3 or omega 6 precursor. Arachidonic acid (omega 6) is, among others, precursor of pro-inflammatory prostaglandin E2 (PGE2), whereas polyunsaturated omega 3 fatty acids inhibit the formation of PGE2. It has been shown that a dietary increase of polyunsaturated omega 3 fatty acids reduced strongly the production of IL-1 beta, IL-2, IL-6 and TNF-alpha (tumor necrosis factor-alpha). In contrast, diets with a higher supply of linoleic acid (omega 6) increased significantly the production of pro-

inflammatory cytokines, like TNF-alpha. Therefore, polyunsaturated omega 3 fatty acids could be associated at different levels in the pathophysiology of major depression, on the one hand through their role in the membrane fluidity which influences diverse steps of neurotransmission and, on the other hand, through their function as precursor of pro-inflammatory cytokines and eicosanoids disturbing neurotransmission. In addition, antidepressants could exhibit an immunoregulating effect by reducing the release of pro-inflammatory cytokines, by increasing the release of endogenous antagonists of pro-inflammatory cytokines like IL-10 and, finally, by acting like inhibitors of cyclo-oxygenase. Data available concerning the administration of supplements of DHA (docosahexanoic acid) or other polyunsaturated fatty acids omega 3 are limited. In a double blind placebo-controlled study on 30 patients with bipolar disorder, the addition of polyunsaturated omega 3 fatty acids was associated with a longer period of remission. Moreover, nearly all the other prognosis measures were better in the omega 3 group. Very recently, a controlled trial showed the benefits of adding an omega 3 fatty acid, eicosopentanoic acid, among depressed patients. After 4 weeks, six of the 10 patients receiving the fatty acid were considered as responders in comparison with only one of the ten patients receiving placebo. Some epidemiological, experimental and clinical data favour the hypothesis that polyunsaturated fatty acids could play a role in the pathogenesis and/or the treatment of depression. More studies however are needed in order to better precise the actual implication of those biochemical factors among the various aspects of depressive illness.

· Carlezon, W. A., Jr., et al. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 57(4):343-350, 2005.

Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA.

Brain phospholipid metabolism and membrane fluidity may be involved in the pathophysiology of mood disorders. The authors demonstrated previously that cytidine, which increases phospholipid synthesis, has antidepressant-like effects in the forced swim test (FST) in rats, a model used in depression research. Because cytidine and uridine both stimulate synthesis of cytidine 5'-diphosphocholine (CDP-choline, a critical substrate for phospholipid synthesis), the authors examined whether uridine would also produce antidepressant-like effects in rats. They also examined the effects of omega-3 fatty acids (OMG), which increase membrane fluidity and reportedly have antidepressant effects in humans, alone and in combination with uridine. The authors first examined the effects of uridine injections alone and dietary supplementation with OMG alone in the FST. They then combined sub-effective treatment regimens of uridine and OMG to determine whether these agents would be more effective if administered together. Uridine dose-dependently reduced immobility in the FST, an antidepressant-like effect. Dietary supplementation with omega-3 fatty acids reduced immobility when given for 30 days, but not for 3 or 10 days. A sub-effective dose of uridine reduced immobility in rats given sub-effective dietary supplementation with Uridine and OMG each have antidepressant-like effects in rats. Less of each agent is required for effectiveness when the treatments are administered together.

· Edwards, R., et al. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord. 48(2-3):149-155, 1998.

There is a hypothesis that lack of superunsaturated fatty acids is of aetiological importance in depression. Docosahexaenoic acid, a member of the superunsaturated fatty acids family, is a crucial component of synaptic cell membranes. The aim of this study was to measure red blood cell membrane fatty acids in a group of depressed patients relative to a well matched healthy control group. Red blood cell membrane levels, and dietary superunsaturated fatty acids intake were measured in 10 depressed patients and 14 matched healthy control subjects. There was a significant depletion of red blood cell membrane superunsaturated fatty acids in the depressed subjects which was not due to reduced calorie intake. Severity of depression correlated negatively with red blood cell membrane levels and with dietary intake of superunsaturated fatty acids |The authors concluded that lower red blood cell membrane superunsaturated fatty acids are associated with the severity of depression. The findings raise the possibility that depressive symptoms may be alleviated by supplementation with superunsaturated fatty acids.

· Edwards, R., et al. Depletion of docosahexaenoic acid in red blood cell membranes of depressive patients. Biochem Soc Trans. 26:S142, 1998.

This study found that EPA, DHA and total superunsaturated fatty acid levels were significantly lower in the red blood cell membranes of depressed subjects compared to a control group.

· Hibbeln, J., et al. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. American Journal of Clinical Nutrition. 62:1-9, 1995.

Recent studies have both offered and contested the proposition that lowering plasma cholesterol by diet and medications increases suicide, homicide, and depression. Significant confounding factors include the quantity and distribution of dietary n-6 and n-3 polyunsaturated essential fatty acids that influence serum lipids and alter the biophysical and biochemical properties of cell membranes. Epidemiological studies in various countries and in the United States in the last century suggest that decreased n-3 fatty acid consumption correlates with increasing rates of depression. This is consistent with a well-established positive correlation between depression and coronary artery disease. Long-chain n-3 polyunsaturate deficiency may also contribute to depressive symptoms in alcoholism, multiple sclerosis, and post-partum depression. We postulate that adequate long-chain polyunsaturated fatty acids, particularly docosahexaenoic acid, may reduce the development of depression just as n-3 polyunsaturated fatty acids may reduce coronary artery disease.

· Maes, M., et al. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord. 38(1):35-46, 1996.

Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

· Mamalakis, G., et al. Depression and adipose essential polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids. 67(5):311-318, 2002.

Department of Social and Preventive Medicine, University of Crete, Iraklion, Crete, Greece

The objective of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake, and depression. The sample consisted of 247 healthy adults (146 males, 101 females) from the island of Crete. The number of subjects with complete data on all variables studied was 139. Subjects were examined at the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the Zung Self-rating Depression Scale. Mildly depressed subjects had significantly reduced (-34.6%) adipose tissue docosahexaenoic acid (DHA) levels than non-depressed subjects. Multiple linear regression analysis indicated that depression related negatively to adipose tissue DHA levels. In line with the findings of other studies, the observed negative relation between adipose tissue DHA and depression, in the present study, appears to indicate increasing long-term dietary DHA intakes with decreasing depression. This is the first literature report of a relation between adipose tissue DHA and depression. Depression has been reported to be associated with increased cytokine production, such as IL-1, IL-2, IL-6, INF-gamma and INF-alpha. On the other hand, fish oil and omega-3 fatty acids have been reported to inhibit cytokine synthesis. The observed negative relation between adipose DHA and depression, therefore, may stem from the inhibiting effect of DHA on cytokine synthesis.

· Peet, M., et al. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry. 43(5):315-319, 1998.

It has been hypothesized that depletion of cell membrane n3 polyunsaturated fatty acids (PUFA), particularly docosahexanoic acid (DHA), may be of etiological importance in depression. The authors measured the fatty acid composition of phospholipid in cell membranes from red blood cells (RBC) of 15 depressive patients and 15 healthy control subjects. Depressive patients showed significant depletions of total n3 PUFA and particularly DHA. Incubation of RBC from control subjects with hydrogen peroxide abolished all significant differences between patients and controls. These findings suggest that RBC membranes in depressive patients show evidence of oxidative damage.

· Monograph: fish oil. Alternative Medicine Review. 5(6), 2000.

Several studies have shown that low levels of superunsaturated fatty acids are predictive of a greater severity of depression.

· Omega-3 fatty acids in the treatment of depression. Harv Ment Health Lett. 18(4):4-5, 2001.

Laypersons’ Publications

· Schmidt, M. A. Smart Fats: How Dietary Fats and Oils Affect Mental, Physical and Emotional Intelligence. Frog Ltd. Berkeley, California, USA. 1997:5.

Peer-Reviewed Professional Medical Journals

· Adams, P. B., et al. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids. 31(Supplement):S157-S161, 1996.

In this study of 20 moderately to severely depressed patients, diagnosed using current research diagnostic criteria and excluding known bipolar affective disorder and reactive depression, the authors investigated relationships between severity of depression and levels and ratios of n-3 and n-6 long-chain polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids (PL). Severity of depression was measured using the 21-item Hamilton depression rating scale (HRS) and a second linear rating scale (LRS) of severity of depressive symptoms that omitted anxiety symptoms. There was a significant correlation between the ratio of erythrocyte PL arachidonic acid (AA) to eicosapentaenoic acid (EPA) and severity of depression as rated by the HRS (P

· Colin, A., et al. [Lipids, depression and suicide]. Encephale. 29(Part 1):49-58, 2003.

Universite de Liege, CUP La Clairiere, Bertrix.

Polyunsatured fatty acids are made out of a hydrocarbonated chain of variable length with several double bonds. The position of the first double bond (omega) differentiates polyunsatured omega 3 fatty acids (for example: alpha-linolenic acid or alpha-LNA) and polyunsatured omega 6 fatty acids (for example: linoleic acid or LA). These two classes of fatty acids are said to be essential because they cannot be synthetised by the organism and have to be taken from alimentation. The omega 3 are present in linseed oil, nuts, soya beans, wheat and cold water fish whereas omega 6 are present in maize, sunflower and sesame oil. Fatty acids are part of phospholipids and, consequently, of all biological membranes. The membrane fluidity, of crucial importance for its functioning, depends on its lipidic components. Phospholipids composed of chains of polyunsatured fatty acids increase the membrane fluidity because, by bending some chains, double bonds prevent them from compacting themselves perfectly. Membrane fluidity is also determined by the phospholipids/free cholesterol ratio, as cholesterol increases membrane viscosity. A diet based on a high proportion of essential polyunsatured fatty acids (fluid) would allow a higher incorporation of cholesterol (rigid) in the membranes to balance their fluidity, which would contribute to lower blood cholesterol levels. Brain membranes have a very high content in essential polyunsatured fatty acids for which they depend on alimentation. Any dietary lack of essential polyunsatured fatty acids has consequences on cerebral development, modifying the activity of enzymes of the cerebral membranes and decreasing efficiency in learning tasks. The prevalence of depression seems to increase continuously since the beginning of the century. Though different factors most probably contribute to this evolution, it has been suggested that it could be related to an evolution of alimentary patterns in the Western world, in which polyunsatured omega 3 fatty acids contained in fish, game and vegetables have been largely replaced by polyunsatured omega 6 fatty acids of cereal oils. Some epidemiological data support the hypothesis of a relation between lower depression and/or suicide rates and a higher consumption of fish. These data do not however prove a relation of causality. Several cohort studies (on nondepressed subjects) have assessed the relationship between plasma cholesterol and depressive symptoms with contradictory results. Though some results found a significant relationship between a decrease of total cholesterol and high scores of depression, some other did not. Studies among patients suffering from major depression signalled more constantly an association between low cholesterol and major depression. Besides, some trials showed that clinical recovery may be associated with a significant increase of total cholesterol. The hypothesis that a low cholesterol level may represent a suicidal risk factor was discovered accidentally following a series of epidemiological studies which revealed an increase of the suicidal risk among subjects with a low cholesterol level. Though some contradictory studies do exist, this relationship has been confirmed by several subsequent cohort studies. These findings have challenged the vast public health programs aimed at promoting the decrease of cholesterol, and even suggested to suspend the administration of lipid lowering drugs. Recent clinical studies on populations treated with lipid lowering drugs showed nevertheless a lack of significant increase of mortality, either by suicide or accident. In addition, several controlled studies among psychiatric patients revealed a decrease of the concentrations of plasma cholesterol among patients who had attempted suicide in comparison with other patients. In major depression, all studies revealed a significant decrease of the polyunsaturated omega 3 fatty acids and/or an increase of the omega 6/omega 3 ratio in plasma and/or in the membranes of the red cells. In addition, two studies found a higher severity of depression when the level of polyunsaturated omega 3 fatty acids or the ratio omega 3/omega 6 was low. Parallel to these modifications, other biochemical perturbations have been reported in major depression, particularly an activation of the inflammatory response system, resulting in an increase of the pro-inflammatory cytokines (interleukins: IL-1b, IL-6 and interferon g) and eicosanoids (among others, prostaglandin E2) in the blood and the CSF of depressed patients. These substances cause a peroxidation and, consequently a catabolism of membrane phospholipids, among others those containing polyunsaturated fatty acids. The cytokines and eicosanoids derive from polyunsaturated fatty acids and have opposite physiological functions according to their omega 3 or omega 6 precursor. Arachidonic acid (omega 6) is, among others, precursor of pro-inflammatory prostaglandin E2 (PGE2), whereas polyunsaturated omega 3 fatty acids inhibit the formation of PGE2. It has been shown that a dietary increase of polyunsaturated omega 3 fatty acids reduced strongly the production of IL-1 beta, IL-2, IL-6 and TNF-alpha (tumor necrosis factor-alpha). In contrast, diets with a higher supply of linoleic acid (omega 6) increased significantly the production of pro-

inflammatory cytokines, like TNF-alpha. Therefore, polyunsaturated omega 3 fatty acids could be associated at different levels in the pathophysiology of major depression, on the one hand through their role in the membrane fluidity which influences diverse steps of neurotransmission and, on the other hand, through their function as precursor of pro-inflammatory cytokines and eicosanoids disturbing neurotransmission. In addition, antidepressants could exhibit an immunoregulating effect by reducing the release of pro-inflammatory cytokines, by increasing the release of endogenous antagonists of pro-inflammatory cytokines like IL-10 and, finally, by acting like inhibitors of cyclo-oxygenase. Data available concerning the administration of supplements of DHA (docosahexanoic acid) or other polyunsaturated fatty acids omega 3 are limited. In a double blind placebo-controlled study on 30 patients with bipolar disorder, the addition of polyunsaturated omega 3 fatty acids was associated with a longer period of remission. Moreover, nearly all the other prognosis measures were better in the omega 3 group. Very recently, a controlled trial showed the benefits of adding an omega 3 fatty acid, eicosopentanoic acid, among depressed patients. After 4 weeks, six of the 10 patients receiving the fatty acid were considered as responders in comparison with only one of the ten patients receiving placebo. Some epidemiological, experimental and clinical data favour the hypothesis that polyunsaturated fatty acids could play a role in the pathogenesis and/or the treatment of depression. More studies however are needed in order to better precise the actual implication of those biochemical factors among the various aspects of depressive illness.

· Frasure-Smith, N., et al. Major depression is associated with lower omega-3 fatty acid levels in patients with recent acute coronary syndromes. Biol Psychiatry. 55(9):891-896, 2004.

Polyunsaturated fatty acids (PUFAs) are intrinsic cell membrane components and closely involved in neurotransmission and receptor function. Lower omega-3 levels are associated with increased risk of coronary artery disease (CAD), increases in cardiac events in CAD patients, and depression. The authors sought to examine relationships between depression and serum levels of omega-3 and omega-6 PUFAs in patients recovering from acute coronary syndromes (ACS). The authors carried out a case-control study of serum PUFA levels and current major depression in 54 age- and sex-matched pairs approximately 2 months following ACS. Depressed patients had significantly lower concentrations of total omega-3 and docosahexaenoic acid (DHA), and higher ratios of arachidonic acid (AA) to DHA, AA to eicosapentaenoic acid (EPA), and n-3 to n-6 than controls. There were no baseline differences in any potential risk or protective factors for depression. Results are consistent with previous reports in depressed patients without CAD, and with literature concerning omega-3 levels and risk of CAD events. Dietary, genetic, and hormonal factors may all play a role in both depression and CAD. Both prospective studies and randomized trials are needed to help clarify the interrelationships.

· Huan, M., et al. Suicide attempt and n-3 fatty acid levels in red blood cells: A case control study in China. Biol Psychiatry. 56(7):490-796, 2004.

Division of Clinical Application (MH, KH, MI, SW, TH), Department of Clinical Sciences, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama-City, Japan.

Epidemiologic studies show that low fish intake is a risk factor of suicidality; however, there are no case-control studies investigating suicide attempt risk and tissue n-3 fatty acid levels. The authors recruited 100 suicide-

attempt cases and another 100 control patients injured by accidents who were admitted to three hospitals affiliated with Dalian Medical University in Dalian, China. Case and control subjects were matched for age, gender, and smoking status. Those who were inebriated at the time of hospitalization were excluded. Blood was sampled immediately after admission to a hospital. Washed red blood cells (RBCs) were obtained, and the fatty acid composition of the total RBC phospholipid fraction was analyzed by gas chromatography. Eicosapentaenoic acid (EPA) levels in RBC in the case subjects were significantly lower than those of the control subjects (.74 +/-.52% vs. 1.06 +/-.62%, p <.0001 when the highest and lowest quartiles of epa in rbc were compared odds ratios suicide attempt was.12 quartile confidence interval:.04-.36 p for trend=".0001)" after adjustment possible confounding factors these findings suggest that low n-3 fatty acid levels tissues a risk factor attempt. further studies including intervention with fish oil are warranted.>

· Maes, M., et al. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord. 38(1):35-46, 1996.

Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

· Su, K. P., et al. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 13(4):267-271, 2003.

Department of Psychiatry, China Medical College Hospital, Taichung, Taiwan.

Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs), including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents (red blood cell membrane, plasma, etc.) and dietary intake. However, more evidence is needed to support its relation. The authors conducted an 8-week, double-blind, placebo-controlled trial, comparing omega-3 PUFAs (9.6 g/day) with placebo, on the top of the usual treatment, in 28 patients with major depressive disorder. Patients in the omega-3 PUFA group had a significantly decreased score on the 21-

item Hamilton Rating Scale for Depression than those in the placebo group (P

1. Så vidt jeg kan se beskriver alle dissse studiene korrelasjoner av konsentrajonen mellom varianter av flerumettede fettsyrer i ulike deler av mennesket og bla depresjoner.

Dette er veldokumentert. Dette har har vært hypoteseskapende til at _behandling_ med disse stoffene skulle kunne være virksom mot depresjon.

Entydige funn i slike behandlingsstudier finnes fortsatt ikke. Muligens vil de komme.

Et annet "bevis" for at slik behandling fortsatt ikke er dokumentert, er følgende faktum. Straks noen kunne dokumentere slik effekt, ville det åpne seg et enormt marked med ekstreme fortjenestemuligheter. Industrien ville kaste seg over helsevesenet for å selge sine varer på linje med dagens legemidler. Hittil har de glimret med sitt fravær.

2. Jeg har gjort den desidert største studien i verden på sammenhengen mellom kolesterol og depresjon. Der er det ingen sammenheng :-(

[Gjest Aina E]

1. Så vidt jeg kan se beskriver alle dissse studiene korrelasjoner av konsentrajonen mellom varianter av flerumettede fettsyrer i ulike deler av mennesket og bla depresjoner.

Dette er veldokumentert. Dette har har vært hypoteseskapende til at _behandling_ med disse stoffene skulle kunne være virksom mot depresjon.

Entydige funn i slike behandlingsstudier finnes fortsatt ikke. Muligens vil de komme.

Et annet "bevis" for at slik behandling fortsatt ikke er dokumentert, er følgende faktum. Straks noen kunne dokumentere slik effekt, ville det åpne seg et enormt marked med ekstreme fortjenestemuligheter. Industrien ville kaste seg over helsevesenet for å selge sine varer på linje med dagens legemidler. Hittil har de glimret med sitt fravær.

2. Jeg har gjort den desidert største studien i verden på sammenhengen mellom kolesterol og depresjon. Der er det ingen sammenheng :-(

Tja, man burde nesten være redde for at fettsyrer skal ha en slik effekt, for da får man vel bare kjøpt dette også på resept, i likhet med en drøss andre naturlige ting vi trenger.

Det burde være en menneskerett å få lov å få i seg det kroppen mangler, siden det er industrien som har ført til at mangler oppstår i kostholdet. PS. Det finnes faktisk saker som er trukket frem for menneskerettighetsdomstolen, da man mener at ufarlige, reseptpliktige f.eks. aminosyrer ikke fås kjøpt fritt som et nødvendig tilskudd for ikke å bli syk.

Ellers pleier det å holde for folk flest å vite at det er veldokumentert at enkelte sammensetninger av fettsyrer kan gi positiv effekt på psykiske lidelser...

De fleste lurer ikke på forholdene av konsentrasjonen mellom de forskjellige variantene...!

Et enkelt holdepunkt er f.eks å se etter forholdet EPA og DHA som bør være minst 3:1, dvs 3 deler EPA mot 1 del DHA.

Som lege utdannet i skolemedisin, ville vel uansett dere ikke falle for fristelsen å kalle det "behandling" så lenge kuren består av naturlige stoffer...? Så da foreslår jeg at dere "behandler" med antispsykotika og antidepressiva, så forebygger vi naturterapeuter med naturmidler og det som finnes naturlig i kroppen.

Det er jo helt logisk at det funker på mange, jeg mener... Hos enkelte er det jo mangel på fettsyrer som er den direkte årsak til sykdom. Hvorfor skulle det ikke da fungere å tilføre kroppen det som mangler? Hvorfor MÅ man behandle med kjemiske og syntetiske midler, eller dokumentere det?

Det du nevner om entydige funn, finnes ikke på et eneste legemiddel så vidt jeg vet.

En annen ting er at de flotte studiene som gjøres på enkelte medikamenter er jammen ikke dokumentert godt nok til å kunne forhindre dødsfall en gang. Ta cox-2 f.eks. Eller det som ble kalt "lykkepiller". Hvor den alvorligste bivirkningen var økt selvmordsfare...! Hallo?

Eller AD hvor en sjelden bivirkning var manier, men DET var det ingen som greide å få med i felleskatalogen da de kom på markedet i Norge. Ikke før et par år senere, gitt.

Så for meg og en del andre, vil nok alternativene omega3, vitamin E og C være gode nok alternativer.

Kan jeg forresten spørre om du under studien fant noe ut om forholdet frie radikaler/stress/depresjoner og om antioksydanter kan ha noen effekt på oksidativt stress? (Som igjen ofte fører til høye kolestrolverdier).

Mvh.

[Nils Håvard Dahl, psykiater]

Tja, man burde nesten være redde for at fettsyrer skal ha en slik effekt, for da får man vel bare kjøpt dette også på resept, i likhet med en drøss andre naturlige ting vi trenger.

Det burde være en menneskerett å få lov å få i seg det kroppen mangler, siden det er industrien som har ført til at mangler oppstår i kostholdet. PS. Det finnes faktisk saker som er trukket frem for menneskerettighetsdomstolen, da man mener at ufarlige, reseptpliktige f.eks. aminosyrer ikke fås kjøpt fritt som et nødvendig tilskudd for ikke å bli syk.

Ellers pleier det å holde for folk flest å vite at det er veldokumentert at enkelte sammensetninger av fettsyrer kan gi positiv effekt på psykiske lidelser...

De fleste lurer ikke på forholdene av konsentrasjonen mellom de forskjellige variantene...!

Et enkelt holdepunkt er f.eks å se etter forholdet EPA og DHA som bør være minst 3:1, dvs 3 deler EPA mot 1 del DHA.

Som lege utdannet i skolemedisin, ville vel uansett dere ikke falle for fristelsen å kalle det "behandling" så lenge kuren består av naturlige stoffer...? Så da foreslår jeg at dere "behandler" med antispsykotika og antidepressiva, så forebygger vi naturterapeuter med naturmidler og det som finnes naturlig i kroppen.

Det er jo helt logisk at det funker på mange, jeg mener... Hos enkelte er det jo mangel på fettsyrer som er den direkte årsak til sykdom. Hvorfor skulle det ikke da fungere å tilføre kroppen det som mangler? Hvorfor MÅ man behandle med kjemiske og syntetiske midler, eller dokumentere det?

Det du nevner om entydige funn, finnes ikke på et eneste legemiddel så vidt jeg vet.

En annen ting er at de flotte studiene som gjøres på enkelte medikamenter er jammen ikke dokumentert godt nok til å kunne forhindre dødsfall en gang. Ta cox-2 f.eks. Eller det som ble kalt "lykkepiller". Hvor den alvorligste bivirkningen var økt selvmordsfare...! Hallo?

Eller AD hvor en sjelden bivirkning var manier, men DET var det ingen som greide å få med i felleskatalogen da de kom på markedet i Norge. Ikke før et par år senere, gitt.

Så for meg og en del andre, vil nok alternativene omega3, vitamin E og C være gode nok alternativer.

Kan jeg forresten spørre om du under studien fant noe ut om forholdet frie radikaler/stress/depresjoner og om antioksydanter kan ha noen effekt på oksidativt stress? (Som igjen ofte fører til høye kolestrolverdier).

Mvh.

1. Medisiner kommer kun på resept om de kan ha negative effekter.

2. I studien hadde vi kun disse opplysningene: angst, depresjon (begge målt med HADS), totalkolesterol, HDL.LDL og triglycerider.

[Gjest Aina E]

1. Medisiner kommer kun på resept om de kan ha negative effekter.

2. I studien hadde vi kun disse opplysningene: angst, depresjon (begge målt med HADS), totalkolesterol, HDL.LDL og triglycerider.

Hm, da håper jeg du kan gi meg noen negative bivirkninger av f.eks. glukosamin, l-glutamin, tryptofan o.l.?

Og hva med kondroitin, eller genistein? Bor, molybden og vanadium?

Dette er jo aminosyrer, hormoner, mineraler og isoflavoner, m.m. som industrien har så og si fjernet fra kosten vår, men som er helt nødvendig for en god helse.

Hvis man ikke har lov å kjøpe det reseptfritt, heller ikke får det igjennom kosten, og legen ikke kan måle mangler, hvordan skal vi da kunne opprettholde en bra helse?

Man får jo kun glukosamin av legen, dersom man er så uheldig å kunne påvise sykdom pga mangelen... Det er ikke alle som blir syke en gang, hva om man slapp å mangle i det hele tatt?