Depression and Omega-3 Fatty Acid Assessment

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Depression and Omega-3 Fatty Acid Assessment

http://www.vitasearch.com/CP/experts/JSontropAT11-28-06.htm

Sontrop, PhD (candidate)

Department of Epidemiology and Biostatistics

Kresge Bldg, K201

The University of Western Ontario

London, Ontario, Canada N6A 5C1

/ (FAX)

jsontrop@...

“Omega-3 Polyunsaturated Fatty Acids and Depression: A Review of the

Evidence and a Methodological Critique,”

Prev Med, 2006 Jan;42(1):4-13. Epub 2005 Dec 7. 44637 (12/2006)

Kirk Hamilton: Can you please share with us your educational

background and current position?

Sontrop: Currently, I am working on a PhD with the

Department of Epidemiology & Biostatistics at the University of Western

Ontario in London, Canada. I entered the program as a Master's student

in 2001 and transferred to the PhD program in 2003. Prior to that, I

obtained a Bachelor of Science degree in Chemistry with Environmental

Science from the University of Western Ontario.

KH: What got you interested in the role of omega-3 fatty acids and

depression?

JS: I became interested in the relationship between omega-3 fatty

acids and depression after reading the literature in this area, which I

found quite compelling. My PhD thesis involved looking at the

relationship between intake of omega-3 PUFAs and depressive symptoms

during pregnancy and the postpartum period.

KH: When you talk about omega-3 fatty acids and depression are you

talking specifically of eicosapentaenoic acid (EPA), docosahexaenoic

acid (DHA) and/or alpha-linolenic acid (ALA)?

JS: The majority of research in this area suggests that an inverse

relationship exists between depression and EPA and DHA, however a few

studies have reported it for ALA as well. ALA is a relatively poor

source of EPA and DHA: stable-isotope tracer studies indicate that only

9% of plasma ALA is metabolized to DHA in women of childbearing age and

less than 1% is metabolized in men. This process may be further

restricted by an increased dietary ratio of LA to ALA (LA, linoleic

acid, is an omega-6 fatty acid); LA and ALA compete for the same

desaturase and elongase enzyme systems, and a high intake of LA relative

to ALA can inhibit the synthesis of EPA and DHA by competitive

inhibition . Thus, fish consumption constitutes the major source of EPA

and DHA for most people.

KH: Why would supplementation with EPA or DHA from a

neurophysiological point of view improve or reduce depression?

JS: PUFAs are a principal component of cell membrane phospholipids

and are abundant in the central nervous system. The proper function of

all membranes, including neuronal membranes, is dependent upon membrane

PUFA composition. Omega-3 PUFAs, in particular, are essential for the

function of the nervous system, and all brain cells and organelles

contain high concentrations of these fatty acids; even small alterations

may adversely affect membrane functions such as neurotransmission,

signal transduction, and prostaglandin synthesis. The amount of DHA in

the human brain increases 30-fold during a brain growth spurt between 25

weeks gestation and 18 weeks post-delivery. DHA constitutes

approximately 30-40% of the phospholipids of the grey matter of the

cerebral cortex and photoreceptor cells in the retina, and is required

for the proper development of the fetal and infant brain and retina. One

mechanism linking depression with EPA+DHA involves the regulation of the

serotonergic neurotransmitter system. ph Hibbeln has shown that

higher concentrations of plasma DHA predict higher concentrations of

cerebrospinal fluid 5-hydroxyindolacetic acid (5-HIAA), a metabolite of

serotonin. Abnormalities in serotonergic function and low levels of

5-HIAA in particular, are widely reported to be associated with violent,

impulsive behavior; depression and suicide. In animal models, a diet

deficient in n-3 PUFAs induced modifications of the dopaminergic and

sertonergic neurotransmission system.

KH: Does depression have an inflammatory component and that is why

EPA/DHA have an positive effect? Or does EPA/DHA help make healthy

membranes for better neurochemical signaling and communication?

JS: The macrophage theory of depression is supported by evidence

that 1) major depression is accompanied by an over activity of the

inflammatory response of the immune system, namely, increased secretions

of inflammatory cytokines and eicosanoids, and 2) immunotherapy with

inflammatory cytokines is known to induce clinical depression. PUFAs

have important effects on inflammatory pathways, and omega-6 and omega-3

PUFAs have opposing effects with respect to inflammation. The omega-6

PUFA arachidonic acid, the primary metabolite of LA, is the principal

precursor for the pro-inflammatory series of eicosanoids whereas EPA and

DHA decrease production of these eicosanoids. It is of interest to note

that a high ratio of omega-6 to omega-3 PUFAs is associated with

depression as well as other autoimmune and inflammatory disorders, and

may be exacerbated by low intakes or impaired metabolism of omega-3

PUFAs. The serotonergic and macrophage mechanisms are not mutually

exclusive, however. For instance, depression induced by cytokine therapy

remits following treatment cessation, but also with administration of

paroxetine, a selective serotonin-reuptake inhibitor. In other studies,

proinflammatory cytokines were observed to reduce serotonin synthesis by

lowering the availability of tryptophan.

KH: Can you tell us about your study and the basic results?

JS: The study you are asking about was a review and evaluation of

the literature linking omega-3 PUFAs and depression. Our review found

fairly consistent evidence in non-experimental studies (case-control,

cohort, cross-sectional, and ecological) that people with clinical

depression have lower levels of omega-3 fatty acids measured from blood

samples than people who were not depressed. As well, an inverse

relationship between fish consumption and depression was observed in

population-level studies (across countries) and individual-level studies

(within a single population). While these findings do not appear to be

the result of confounding, failure to detect confounding may be due to

lack of power in some studies and incomplete control in others.

Of seven double-blind randomized controlled trials that we evaluated,

four showed a significant improvement in depression upon treatment with

at least 1 g/day of EPA. The three trials that did not observe a

beneficial effect used a much lower dose of EPA or only administered

supplements with DHA. As well, in each of the four positive trials, all

participants (those receiving the placebo and those receiving the

supplement) were taking antidepressant medication concurrently, thus, it

not possible to discern whether treatment with EPA and/or DHA exhibited

effects independent of antidepressant treatment or acted as an adjuvant.

It is also possible that there is some type of synergistic interaction

between omega-3 PUFAs and antidepressants. While clinical significance

was consistently demonstrated in these studies, preservation of blinding

may be a limitation in this area of research due to a noticeable fishy

aftertaste, and it remains unclear whether omega-3 supplementation is

efficacious for depressed patients in general or only those with

abnormally low levels or impaired metabolism of these PUFAs.

KH: What was the average therapeutic dose of omega-3 fatty acids in

the amount of EPA and/or DHA per day?

JS: Evidence from the randomized controlled trials we reviewed

suggests that EPA treatment with at least 1 g/day of EPA, alone or in

combination with DHA, was successful in treating depression.

KH: Were there any side effects from the EPA/DHA?

JS: No serious side effects have been reported. Minor side effects

include a fishy aftertaste, gaseousness and loose stools.

KH: How and in whom do you recommend the use of EPA/DHA in the

treatment of depression?

JS: To date, no trials have demonstrated efficacy of EPA/DHA

treatment in the absence of antidepressant therapy, so it would be

irresponsible to recommend that patients forgo treatment with a proven

therapy for an unproven one (research consistently demonstrates that the

most effective treatment for depression is a combination of cognitive

behavioral therapy and antidepressants). However, given that there is

only benefit to be had from taking EPA+DHA supplements, supplementation

with 1 g/day of EPA may be useful as an adjunct therapy or in people

with treatment resistant depression. The FDA considers up to 3 g/day of

EPA+DHA as " generally regarded as safe " . That said, among pregnant women

there is increasing evidence that antidepressant treatment may cause a

withdrawal syndrome among newborns and other studies show a small, but

increased risk of congenital anomalies. As a result, many women

discontinue or avoid treatment with antidepressants during pregnancy.

Ideally, a depressed pregnant woman should receive professional

psychiatric counseling; however, there may be no harm in recommending

supplementation with EPA, and other studies have shown a reduced risk of

preterm birth with EPA and DHA supplementation. Most pregnant women do

not consume sufficient amounts of EPA and DHA (average consumption in

Canada and the United States is approximately 150 g/day); The

International Society for the Study of Fatty Acids and Lipids recommends

the consumption of 450 g/day. Compared to some fish species which

contain relatively high concentrations of mercury, supplements

containing EPA and DHA or fish oil are relatively devoid of mercury and

organochlorine pollutants.

KH: Do you recommend doing fatty acid analysis in patients to screen

for deficiency or imbalanced states?

JS: I think this is a good idea, but before this would be useful,

we first need to define what constitutes a deficient or imbalanced state.

KH: Is it the DHA component of fish oil that has a more positive

effect on depression or does EPA in-and-of itself have a positive effect

on depression aside from being the precursor to DHA? In other words why

not just give a DHA fatty acid supplement? Can you comment on the

difference in importance and function between the two forms of omega-3

fatty acids?

JS: Theoretically, DHA should have as beneficial an effect on

depression as EPA; however, evidence from experimental studies suggests

that 1 g/day of EPA (alone or in combination with DHA) is effective in

treating depression. Randomized controlled trials that administered DHA

alone or EPA at a dose lower than 1 g/day did not achieve clinical or

statistical significance. Thus, it is not possible to make conclusions

about the efficacy of DHA in regards to treating depression until

further dose-ranging trials are conducted.

--

ne Holden, MS, RD < fivestar@... >

" Ask the Parkinson Dietitian " http://www.parkinson.org/

" Eat well, stay well with Parkinson's disease "

" Parkinson's disease: Guidelines for Medical Nutrition Therapy "

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