Posted by Larry Hoover on February 2, 2003, at 8:23:39
In reply to Let's back up: what we KNOW about fish oil » Larry Hoover, posted by andys on February 1, 2003, at 21:11:41
> Thanks, Larry, very informative, and you've convinced me to quit chasing this E-EPA.
Good. <grin> Best is high fish consumption. Second best is fish oil. Trailing the pack by quite a distance is E-EPA.
> But let's back up to what we KNOW for sure about fish oil. To my knowledge, the only true clinical trial that proved the efficacy of fish oil was Dr. Andrew Stoll's (I've got his book).
> THE PROBLEM is that the 9.6 grams of fish oil used in his trial is impractical.You really have to understand Stoll's study design in its context; limited funding forced him to design a rather drastic intervention. Because his was a preliminary study, he desperately needed to show a significant correlation between fish oil consumption and mood stabilization if he was going to get funding for a larger study which assessed various dosing levels in a variety of populations. So, he decided to give the subjects the most massive dose of fish oil (he only had eight weeks of funding) that they could tolerate. There is no clear evidence that you need to take that much to have a benefit. The larger study was funded, and I believe it is now in the data interpretation stage. You can expect publication sometime later this year?
> 1- I'm sure that, even with a full meal, the "fish burps" would be unbelievable (given what I got on 10 Omegabrites).
Just to emphasize a major point, it is very important that you take the fish oil with a large and *fatty* meal. The fattier the better. If you take it with an e.g. carb-heavy meal, the total amount of fat from the fish oil may be insufficient to up-regulate the fat-absorption processes, and the oil "stagnates" in the stomach where it can be degraded by hydrochloric acid yielding fish burps.
> 2- The cost would be substantial
Only if you insist on expensive brands like Omegabrite.
> 3- I would be worried about the level of mercury I'm getting (keeping in mind the trial was not done using "processed" or "altered" fish oil).
There are no heavy metals in fish oil. Heavy metals bind to protein, so the very process that separates the fish oils from the fish meal also partitions the heavy metals into the protein-based products. Just for the record, the protein is not discarded. It is sold to meat producers, particularly fish farming and poultry operations.
> To my knowledge, the supposition that higher EPA is more beneficial (also theorized by Stoll himself) is theoretical, and never proven in a trial.
Quite correct. In fact, the literature shows that DHA may be more important. See below.
>And I believe it was in Stoll's book that high DHA could actually increase depression.
I've never seen data suggesting that.
> SO, TAKING OUR OWN POLL, HAS ANYONE OUT THERE GOTTEN BENEFIT FROM OMEGA-3? AND IN WHAT FORM?
Fish oil has helped my brain work, well, smoother. I'm more resilient. Stress is less of an impact. Mood swings are dampened. I'm dysthymic by nature, so I have not become euthymic, but my dysthymia is much easier to bear.
I've collected together a few abstracts, and I'll make a few introductory comments for each (marked with **).
**Adipose tissue is the familiar storage around the tummy, hips, and thighs. Fats stored there tend to be saturated or mono-unsaturated, but polyunsaturates present tend to reflect a "running average" of the concentration in the blood over an extended period. The idea that DHA inhibits cytokine formation provides just another way that fish oil can modulate health and mood.
Prostaglandins Leukot Essent Fatty Acids 2002 Nov;67(5):311-8
Depression and adipose essential polyunsaturated fatty acids.Mamalakis G, Tornaritis M, Kafatos A.
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.
**Here is a case report showing remission of suicidality and structural brain changes (increase in brain tissue volume) with EPA supplementation.Int J Clin Pract 2001 Oct;55(8):560-3
Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover.
Puri BK, Counsell SJ, Hamilton G, Richardson AJ, Horrobin DF.
MRI Unit, Imperial College School of Medicine, Hammersmith Hospital, London, W12 0HS, UK.
The n-3 essential fatty acid eicosapentaenoic acid (EPA) was added to the conventional antidepressant treatment of a treatment-resistant severely depressed and suicidal male patient with a seven-year history of unremitting depressive symptoms. The niacin skin flush test and cerebral magnetic resonance scanning were carried out at baseline and nine months later. The addition of ethyl-EPA led to a dramatic and sustained clinical improvement in all the symptoms of depression, including a cessation of previously unremitting severe suicidal ideation, within one month. Symptoms of social phobia also improved dramatically. During the nine-month period the volumetric niacin response increased by 30%, the relative concentration of cerebral phosphomonesters increased by 53%, and the ratio of cerebral phosphomonesters to phosphodiesters increased by 79%, indicating reduced neuronal phospholipid turnover. Registered difference images showed that the EPA treatment was accompanied by structural brain changes including, in particular, a reduction in the lateral ventricular volume.
**This next article should have seen heavy exposure in the popular press, IMHO. The correlation between DHA concentration and post-partum depressive symptoms is incredibly robust. Despite the high correlation with DHA, *no relationship* was noted between EPA and PPD.J Affect Disord 2002 May;69(1-3):15-29
Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis.Hibbeln JR.
Laboratory of Membrane Biophysics and Biochemistry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Park 5, Room 150, 12420 Parklawn Drive, 20892, Rockville, MD, USA
BACKGROUND: Mothers selectively transfer docosahexaenoic acid (DHA) to their fetuses to support optimal neurological development during pregnancy. Without sufficient dietary intake, mothers become depleted of DHA and may increase their risk of suffering major depressive symptoms in the postpartum period. We postulated that the DHA content of mothers' milk and seafood consumption would both predict prevalence rates of postpartum depression across countries. METHODS: Published prevalence data for postpartum depression were included that used the Edinburgh Postpartum Depression Scale (n=14532 subjects in 41 studies). These data were compared to the DHA, eicosapentaenoic acid (EPA) and arachidonic acid (AA) content in mothers' milk and to seafood consumption rates in published reports from 23 countries. RESULTS: Higher concentrations of DHA in mothers' milk (r=-0.84, p<0.0001, n=16 countries) and greater seafood consumption (r=-0.81, p<0.0001, n=22 countries) both predicted lower prevalence rates of postpartum depression in simple and logarithmic models, respectively. The AA and EPA content of mothers' milk were unrelated to postpartum depression prevalence. LIMITATIONS: These findings do not prove that higher omega-3 status cause lower prevalence rates of postpartum depression. Data on potentially confounding factors were not uniformly available for all countries. CONCLUSIONS: Both lower DHA content in mothers' milk and lower seafood consumption were associated with higher rates of postpartum depression. These results do not appear to be an artifact of cross-national differences in well-established risk factors for postpartum depression. Interventional studies are needed to determine if omega-3 fatty acids can reduce major postpartum depressive symptoms.
**Another ecological study (simple observation of existing populations) showing that fish consumption is negatively correlated with depression.Psychiatr Serv 2001 Apr;52(4):529-31
Fish consumption and depressive symptoms in the general population in Finland.Tanskanen A, Hibbeln JR, Tuomilehto J, Uutela A, Haukkala A, Viinamaki H, Lehtonen J, Vartiainen E.
Department of Psychiatry, University of Kuopio, Finland. antti.tanskanen@kuh.fi
Fish contains high concentrations of omega-3 polyunsaturated fatty acids. Several studies have reported depletions of omega-3 fats among depressed patients, and a cross-national comparison has revealed a significant inverse correlation between annual prevalence of major depression and fish consumption. In a sample of 3,204 Finnish adults, depressive symptoms were estimated with the Beck Depression Inventory. A frequency question was used to measure fish consumption. Multiple logistic regression analysis was conducted to assess the association between depression and fish consumption. After the analysis adjusted for potential confounders, the likelihood of having depressive symptoms was significantly higher among infrequent fish consumers than among frequent consumers.
**Evidence that fish oils are positively correlated with total levels of serotinergic and dopaminergic brain function. 5-HIAA is the break-down product of serotonin, whereas homovanillic is the product of dopamine.
Biol Psychiatry 1998 Aug 15;44(4):235-42
Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics.Hibbeln JR, Linnoila M, Umhau JC, Rawlings R, George DT, Salem N Jr.
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
BACKGROUND: Impulsive violence, suicide, and depression are strongly associated with low concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA). Increased suicide and trauma reported in some cholesterol-lowering trials may be related to altered concentrations of polyunsaturated fatty acids rather than cholesterol, a possible surrogate marker. METHODS: CSF 5-HIAA and homovanillic acid (HVA), total cholesterol, and plasma fatty acid concentrations were examined in 176 subjects, including 49 healthy volunteers, and 88 early- and 39 late-onset alcoholics. RESULTS: Among each group, polyunsaturated fatty acids predicted both CSF 5-HIAA and CSF HVA concentrations, but total cholesterol was unrelated to either neurotransmitter metabolite. The relationships between plasma 22: 6n3 and CSF 5-HIAA were significantly different when healthy volunteers (r = .35) were compared to early-onset alcoholics (r = -.38) (p < .0002). CONCLUSIONS: Dietary studies are indicated to determine if essential fatty acid supplementation can influence central nervous system serotonin and dopamine metabolism and modify impulsive behaviors related to these neurotransmitters.
**The link between depression and heart disease is robust. Two major shared risk factors are omega-3 deficiency and disordered SAMe metabolism (as measured by homocysteine buildup). Fish oil is good for your health even if it doesn't improve your mood! (Homocysteine can be lowered by taking B6 and B12, and by taking supplemental betaine.)Harv Rev Psychiatry 2001 Nov-Dec;9(6):280-93
Omega-3 fatty acids, homocysteine, and the increased risk of cardiovascular mortality in major depressive disorder.
Severus WE, Littman AB, Stoll AL.
Psychopharmacology Research Laboratory, McLean Hospital, Belmont, MA, USA. severus@zedat.fu-berlin.de
Depression is associated with elevated rates of cardiovascular morbidity and mortality. This elevation seems to be due to a significantly increased risk of coronary artery disease and myocardial infarction and, once the ischemic heart disease is established, sudden cardiac death. Recent data suggest that the increased rates of cardiovascular disease in patients with depression may be the result of one or more still-unrecognized underlying physiological factors that predispose a patient to both depression and cardiovascular disease. Two possibly related factors that may have a causal relation with both depressive disorders and cardiovascular disease are an omega-3 fatty acid deficiency and elevated homocysteine levels. We present the available data connecting cardiovascular disease, depression, omega-3 fatty acids, and homocysteine. In addition, we suggest research strategies and some preliminary treatment recommendations that may reduce the increased risk of cardiovascular mortality in patients with major depressive disorder.
**Just in case you weren't convinced, here is a review article showing some of the benefits of DHA supplementation. Take fish oils for your general health; mood effects are bonus.Pharmacol Res 1999 Sep;40(3):211-25
Comment in:
Pharmacol Res. 1999 Sep;40(3):203.
Pharmacol Res. 1999 Sep;40(3):205-6.
Health benefits of docosahexaenoic acid (DHA)Horrocks LA, Yeo YK.
Docosa Foods Ltd, 1275 Kinnear Road, Columbus, OH 43212-1155, USA,
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. Copyright 1999 Academic Press.
Comments, questions welcome.Lar
poster:Larry Hoover
thread:138737
URL: http://www.dr-bob.org/babble/20030130/msgs/138872.html