Introduction

The purpose of this study was to conduct a

systematic review of the scientific-medical

literature to identify, appraise, and synthesize the

human evidence for the effects of omega-3 fatty

acids on mental health. The review was requested

and funded by the Office of Dietary

Supplements, National Institutes of Health. It was

undertaken as part of a consortium involving

three Evidence-based Practice Centers (EPCs),

which investigated the value of omega-3 fatty acid

supplementation across 11 health/disease areas.

The three EPCs are Southern California-RAND,

Tufts-New England Medical Center, and the

University of Ottawa. To ensure consistency of

approach, the three EPCs collaborated on selected

methodologic elements, including literature

search strategies, rating of evidence, and data table

design.

While the intention was to evaluate the

spectrum of psychiatric disorders or conditions

(i.e., behavior or symptoms which, while their

consequences could be serious, do not warrant

receipt of a formal psychiatric diagnosis), certain

foci were beyond the scope of the review (see

Methods). At the same time, a mental health

disorder or condition did not require extant

animal or basic science data or models to justify

the investigation of their evidence. Nevertheless,

justification for the study of two disorders exists

in the literature: depression and schizophrenia. 

The mechanism by which diet may affect

health, including depression or cardiovascular

disease, has been thought to involve low levels of

omega-3 fatty acid content in biomarkers (e.g.,

red blood cells [RBCs]).1,2 An omega-3 fatty acid

deficiency hypothesis of depression has been put

forward, which has helped justify treatment with

omega-3 fatty acid supplementation.3 The

membrane phospholipid hypothesis of

schizophrenia has been proposed in an attempt to

develop a model explaining its etiology.4 It

describes the presumed biochemical dynamics

underpinning a neurodevelopmental theory.

Some of the evidence used to support this

perspective suggests the existence of phospholipid

and polyunsaturated fatty acid (PUFA) metabolic

abnormalities in schizophrenia.4-6 It has been

posited that modifications to diet could mitigate

or even aggravate an underlying abnormality of

phospholipid metabolism.4

However, the present review was not

conducted to test these hypotheses. Rather, the

rationale for this 2-year project investigating the

possible health benefits of omega-3 fatty acids was

to systematically review the evidence to aid in the

development of a research agenda. Nevertheless,

these emerging models regarding depression and

schizophrenia do suggest plausible bases for the

use of omega-3 fatty acids to treat or prevent

these psychiatric disorders. 

Evidence Report/Technology Assessment

Number 116

Effects of Omega-3 Fatty Acids on Mental Health

Summary

Authors: Schachter HM, Kourad K, Merali Z, Lumb A, Tran K, Miguelez M, et al. 

Agency for Healthcare Research and Quality

Advancing Excellence in Health Care • www.ahrq.gov

Agency for Healthcare Research and Quality Evidence-Based

Practice
2

Key Questions

Four basic questions were investigated with respect to each

psychiatric disorder or condition for which evidence meeting

eligibility criteria could be identified. To illustrate, the questions

pertaining to depression were:

• Are omega-3 fatty acids efficacious as (primary or

supplemental) treatment for depression? 

• Is omega-3 fatty acid intake, including diet and/or

supplementation, associated with the onset, continuation,

or recurrence of depression (i.e., primary or secondary

prevention)? 

• Is the onset, continuation, or recurrence of depression

associated with omega-3 or omega-6/omega-3 fatty acid

content of biomarkers (i.e., primary or secondary

prevention)?

• What is the evidence in review-relevant studies concerning

mental health that adverse events (e.g., side effects) or

contraindications are associated with the intake of omega3 fatty acids?

Where data permitted, the impact of effect modifiers (e.g.,

covariates) was investigated with respect to the following study

characteristics:

• Population (e.g., primary diagnosis, disorder severity,

smoker status, alcohol consumption).

• Intervention/exposure (e.g., source, type, dose or serving

size, and method to deliver the omega-3 fatty acids;

intervention length; dietary omega-6/omega-3 fatty acid

content).

• Comparator/control (e.g., type of placebo material, a

“gold standard” medication).

• Cointerventions (e.g., concurrent psychotropic

medication, other supplement use).

Methods

A Technical Expert Panel (TEP) consisting of nine members

was convened to provide advisory support to the project,

including refining the questions and highlighting key variables

requiring consideration in the evidence synthesis. 

Study Identification

Several electronic databases were searched: MEDLINE®,

EMBASE®, the Cochrane Library including the Cochrane

Central Register of Controlled Trials, PsycINFO, and CAB

Health®. Searches were not restricted by language of

publication, publication type, or study design, except with

respect to the MeSH® term “dietary fats,” which was limited

by study design to increase its specificity. Search elements

included: scientific terms, with acronyms, as well as generic and

trade names relating to the exposure and its sources (e.g.,

eicosapentaenoic acid (EPA), omega-3 fatty acids, MaxEPA®);

and relevant population terms (e.g., depression). Additional

published or unpublished literature was sought through manual

searches of reference lists of included studies and key review

articles, and from the files of content experts. A final set of

1,212 unique references was identified and posted to an

Internet-based software system for review.

Studies were considered relevant if they described live human

populations of any age with any or no comorbidity, exhibiting

a psychiatric status consistent with one of the above-noted

research questions concerning treatment or prevention (i.e.,

with or without [a known elevated risk to develop] a psychiatric

diagnosis or condition). Studies also had to investigate at least

one pertinent clinical outcome (e.g., symptom improvement,

incidence of a disorder). 

As markers of omega-3 fatty acid metabolism, the following

fatty acid compositions or concentrations, from any source

(e.g., plasma phospholipids), were considered relevant as

possible predictors of the onset, continuation, or recurrence of

psychiatric disorders or conditions: EPA, docosahexaenoic acid

(DHA), arachidonic acid (AA)/EPA, AA/DHA, and

AA/EPA+DHA. Studies exclusively evaluating the role of other

biomarkers (e.g., cytokine production, eicosanoid levels) were

not included. Populations with degenerative (e.g., Alzheimer’s)

and peroxisomal (e.g., Zellweger’s) disorders were excluded

since each was addressed in Southern California-RAND’s year2 review of the evidence concerning omega-3 fatty acids in

neurology. 

Treatment studies, as well as those investigating the possible

association between omega-3 fatty acid intake and the onset,

continuation, or recurrence of psychiatric disorders or

conditions, had to investigate foods or supplements known to

contain omega-3 fatty acids of any type (e.g., EPA), from any

source (e.g., walnuts), any serving size or dose, delivered in any
fashion (e.g., capsules, PUFA-rich diet), and for any length of

time. In all studies, some method had to have been employed

to suggest the presence of omega-3 fatty acid content in the

exposure, if not its actual amount (e.g., g/d). Studies

investigating “PUFAs” or “ long-chain PUFAs,” or even types

of diet one might presume would contain marine or land

sources of omega-3 fatty acids (e.g., “Mediterranean diet”) at

minimum had to highlight at least one source of the omega-3

fatty acid content (e.g., oily fish servings). No restrictions were

placed on the types or doses of pre- or on-study cointerventions

(e.g., psychotropic medication, omega-6 fatty acid intake). 

Controlled studies employing any control were required to

address questions of intervention efficacy (or effectiveness),

with randomized controlled trials (RCTs) being the gold

standard method to investigate these questions.7 Any type of

research design other than noncomparative case series or case

studies was deemed appropriate for questions concerning the

possible association between the intake of omega-3 fatty acids

and the onset, continuation, or recurrence of psychiatric

disorders or conditions. A special interpretative emphasis was

placed on results from prevention RCTs and other controlled

prospective designs. Controlled studies involving any control

were required to address the questions of the possible

association between the fatty acid content of biomarkers and

the onset, continuation, or recurrence of psychiatric disorders

or conditions. These decisions were made with the assistance of

our TEP. 

Two initial levels of screening for relevance, and two

reviewers per level, were directed at bibliographic records and

then full articles. A third dual-assessor relevance screening

identified and thereby excluded uncontrolled studies with

respect to questions of intervention efficacy or the possible

protective role of lipid biomarker content. Calibration exercises

preceded each step of the screening process. Excluded studies

were noted as to the reason for their ineligibility using a

modified QUOROM format.8 Disagreements were resolved by

forced consensus and, if necessary, third party intervention. 

Data Abstraction 

Following a calibration exercise, seven reviewers

independently abstracted the contents of each included study

using an electronic data abstraction form. A second reviewer

verified these data. Data included the characteristics of the

report (e.g., publication status), study (e.g., research design),

population (e.g., diagnosis), intervention/exposure (e.g., omega3 fatty acid type), comparator group(s), cointerventions (e.g.,

medications), withdrawals or dropouts, and outcomes (i.e.,

symptom improvement, biomarker status, adverse events). 

After calibration exercises, each study’s quality (internal

validity) and applicability (external validity) were formally

assessed. Dual-review appraised RCTs’ quality while only

single-assessor evaluations could be conducted for other

research designs. For the RCTs, disagreements were resolved by

forced consensus and, if necessary, third party intervention.

RCTs’ reporting of randomization, double blinding,

withdrawals and dropouts, and the concealment of allocation,

were evaluated using Jadad’s9 and Schulz’s validated

instruments.10 The validated Newcastle-Ottawa Scale (NOS)

assessed case-control and cohort study designs, while all other

designs were evaluated using modifications of the NOS,11

Jadad’s instrument,9 or items from Downs and Black’s validated

27-item tool.12 Applicability was defined as the extent to which

a given study’s sample population was representative of a

“typical” North American population. The method of diagnosis

and the omega-6/omega-3 fatty acid ratio in the background

diet were the key variables defining the reference population of

North Americans identified with a psychiatric disorder. The

omega-6/omega-3 fatty acid ratio in the background diet

defined the reference population of North Americans who did

not exhibit a psychiatric disorder.

Data Synthesis

A summary table provided a question-specific overview of

included studies’ relevant data presented in greater detail in

evidence tables. A question-specific summary matrix situated

each study in terms of its quality and applicability ratings.

Question-specific qualitative syntheses of the evidence were

derived. A dearth of studies best suited to address a particular

kind of question (i.e., RCTs, prospective and controlled

observational studies), as well as limitations on, or the strong

clinical heterogeneity of, available studies (e.g., divergent

intervention-comparator contrasts, use of complex

interventions where it was impossible to tease out the possible

specific benefit of omega-3 fatty acids, failure to control for key

confounders), made it impossible to perform meta-analysis for

any question other than the supplemental treatment for

schizophrenia.

3
4

Results

Literature Search

Of 1,212 records entered into the initial screening for

relevance, 955 were excluded. All but seven of the remaining

257 reports were then retrieved and subjected to a more

detailed relevance assessment.13-21 A second relevance screening

then excluded 137 reports. A third screening excluded 27

reports of uncontrolled studies. In total, 86 reports, describing

79 unique studies, were deemed relevant for the systematic

review, with six studies each described by more than one report.

To simplify matters, only one report per study is referred to in

this summary. Yet, data from all of a study’s documents were

included in qualitative and quantitative syntheses. Some studies

addressed more than one question.

Of the included studies, only one failed to be described by at

least one published report.22 It was reported in abstract format.

Sixteen relevant studies were identified by manual search. One

report required translation from Chinese.23 All the other

included reports were written in English. 

Overall, depression (n=22 studies) and schizophrenia (n=28)

were the most frequently studied disorders. Only the 10 studies

investigating attention-deficit/hyperactivity disorder (AD/HD)

enrolled pediatric populations. Many of the studies exhibited

poor quality or weak applicability to North American

populations. Synopses of evidence are presented according to

seven cross-cutting topics:

Adverse Events 

A number of study reports explicitly stated that no exposurerelated adverse events had been observed.24-32 Ten RCTs

described at least one mild adverse event associated with an

omega-3 fatty acid intervention/exposure.2,33-41 Results from

these studies suggest that the exposures were well tolerated. In

spite of a small number of discontinuations presumed to have

been instigated by an adverse event, it is unlikely that moderate

or severe side effects were ever observed in relation to an

omega-3 fatty acid exposure. Reported difficulties tended to be

mild and transient, often involving gastrointestinal upset or

nausea. Occasionally, adverse events were linked to the intake

of oily substances, rather than to the omega-3 fatty acid

contents in the oils. Aside from the mild adverse effects

associated with Stoll et al.’s very high dose of 9.6 g/d

EPA+DHA (i.e., three patients had to decrease the number of

capsules swallowed per day, yet none were required to

discontinue),38 no other patterns were discerned regarding the

impact of dose, type (e.g., DHA, EPA) or source (e.g., marine,

plant) of omega-3 fatty acids on safety. In one study, a child

with AD/HD in the active treatment group had to leave the

study due to problems swallowing the capsules.41 Few of the

events described in two trials by Hamazaki et al., which

enrolled healthy volunteers, suggested that the adverse effects

had been directly related to the exposure.39,40

Primary Treatment

One RCT examined omega-3 fatty acids as primary

treatment for depression.34 It found no benefit for 2 g/d DHA

as primary treatment despite an increase in the absolute RBC

levels of DHA in the active treatment group.34 Reasons for this

null result could include the use of too small a dose, too short

an intervention period, the “wrong” omega-3 fatty acid, broken

blinding, low power, or failure to modify the on-study

background intake of omega-6 fatty acids. 

Notwithstanding the noncomparability of interventions,

comparators, and populations (i.e., with32,42,43 or without a

formal diagnosis of AD/HD,41 with32 or without significant

comorbidity41,43), the complex definitions of the intervention

where it was impossible to tease out the possible specific benefit

of omega-3 fatty acids,41 evidence for selection bias,43 or the

failure to specify study enrollees’ specific diagnostic subtype of

AD/HD (e.g., inattentive),44 the results of the three RCTs32,41,42

and the comparative before-after study43 addressing the

question about the primary treatment of AD/HD were

inconsistent. Thus, no definitive conclusions can be drawn

about the value of omega-3 fatty acids as primary treatment for

AD/HD. 

One RCT examined ethyl (E)-EPA as primary treatment for

borderline personality disorder and observed significant clinical

effects, as the E-EPA group had, at study end, significantly

lower mean scores on both clinical outcomes compared with

the placebo group.31 Despite its strong applicability to the

North American population, this is a small study requiring

replication.

While the results of Peet et al.’s trial37 indicate placebocontrolled benefits accruing to omega-3 fatty acids as primary

treatment for schizophrenia, this was a small, albeit

methodologically adequate, pilot trial with little applicability to

a North American population. More work is required before we

can determine omega-3 fatty acids’ promise in this context. 
Supplemental Treatment

Peet et al.’s dose-ranging RCT of E-EPA as supplemental

treatment for depression found that only 1 g/d for 12 weeks

had a significant impact on various clinical outcomes.2 Two

RCTs of shorter duration also showed significant benefits

associated with 2 g/d E-EPA and 6.6 g/d of EPA+DHA,

respectively;27,33 the significant clinical effect reported by Su et

al. was associated with a significant increase in RBC EPA

exclusively in the active treatment group.33 However, we

decided to forego meta-analysis due to study differences on the

basis of the intervention (i.e., type, dose, followup length) and

comparator (i.e., placebo source). Also, unlike the other two

trials, Peet et al.’s did not formally identify patients with a

depressive disorder.2 This may account for their finding that 1

g/d E-EPA had a beneficial effect on depressive

symptomatology.2 A low dose might not have helped the

treatment-resistant depressive disorders investigated in the other

RCTs. Yet, this likely cannot explain why Peet et al.’s higher

doses (2 g/d, 4 g/d) did not likewise ameliorate depressive

symptoms, or why more responders (i.e., 50 percent

improvement) were found in the placebo group than in the 2

g/d E-EPA group. Su et al.’s trial may have been confounded by

uncontrolled combinations of medication.33 The question of

omega-3 fatty acids as supplemental treatment for depression

requires additional investigation.

Two studies, one a RCT38 and one defined merely as

“controlled,”45 evaluated the supplemental treatment of bipolar

disorder. Only the RCT report gave us an opportunity to assess

its study parameters and results.38 While it had to be stopped

prematurely, their very high dose of 9.6 g/d EPA+DHA

produced a significantly longer period of remission in the active

treatment group compared with controls. This study’s

limitations (i.e., loss of power due to its stoppage, broken

blind) require its replication. Therefore, the evidence base is too

limited to allow us to conclude anything about the value of

omega-3 fatty acids as supplemental therapy for bipolar

disorder. Likewise, one underpowered and flawed crossover

RCT, which failed to show that E-EPA is effective as

supplemental treatment for obsessive-compulsive disorder, is

insufficient to permit drawing a definitive conclusion.25

Inconsistencies in the results produced by three RCTs, the

occasional use of a complex intervention making it impossible

to tease out the possible specific benefit of omega-3 fatty

acids,46 the confirmation by parents—but not by

professionals—of an AD/HD diagnosis,46 interventions that did

not last long enough,30,42,46 and failures to weight-adjust doses of

omega-3 fatty acids prevent us from identifying clear

conclusions about their value as supplemental treatment for

AD/HD.30,42,46

Three of four good quality placebo-controlled RCTs

investigating the supplemental treatment of schizophrenia26,35-37

reported significant clinical effects in favor of EPA using total

Positive and Negative Syndrome Scale (PANSS) scores,26,36,37

although Peet et al.’s study observed this effect only for those

receiving clozapine as primary treatment.36 Yet, the Emsley et al.

study found a nonsignificant trend towards greater reduction in

total PANSS scores in participants taking typical antipsychotic

medication, compared with those receiving clozapine.26 Results

of our meta-analysis of two studies’ PANSS total data revealed

that dose influenced outcome. A or significant placebocontrolled effect was identified for 2 g/d EPA yet not for doses

of at least 3g/d EPA.36,37 However, these results might have been

different had we been able to analyze data by type of

psychotropic medication, had both studies used either the

purified or unpurified form of EPA as well as the same placebo

oils, had their intervention periods lasted longer, or had both

trials employed capsules to deliver the omega-3 fatty acids.

While the findings are suggestive, they remain inconclusive

given that the data subjected to meta-analysis were derived

from two small trials exhibiting certain limitations. 

Primary Prevention (i.e., Onset) Via Omega-3

Fatty Acid Intake

Inconsistent results, in addition to too few studies exhibiting

sound methodologies or research designs that are ideally suited

to investigate this question (e.g., prospective, controlled, with

subject-level data), suggest that it is too early to conclude

whether or not the intake of omega-3 fatty acids protects

against the onset of depressive disorders or

symptomatology.1,24,28,47-55 The same issues prevent us from

concluding whether or not the intake of omega-3 fatty acids

protects against the onset of suicidal ideation or behavior.51,55

Given the inability of any cross-national ecological analysis to

provide meaningful subject-level data, and the failure to control

for key confounders (i.e., socioeconomic status, urban/rural

ratio, educational level, marital status, alcohol consumption,

smoker status, or family history), we cannot conclude anything

about the value of seafood consumption as protection against

the onset of bipolar disorder.

56

5
Two RCTs failed to clarify the protective value of omega-3

fatty acid intake with respect to the onset of symptoms, not

disorders, of anxiety.28,47 However, these small studies do not

constitute optimal tests of this potential. Based on one crosssectional study, which controlled for age, income, smoking,

alcohol consumption, and eating patterns, mental health

difficulties were more prevalent in those consuming no fish.57

However, this design precludes inferring a causal link between

fish consumption and the onset of mental health difficulties.

Four RCTs,28,39,40,58 three of which enrolled healthy volunteers,

one single population cross-sectional survey59 and one crossnational ecological analysis60 studied the possible association

between omega-3 fatty acid intake and the onset of tendencies

or behavior with the potential to harm others. Overall, their

findings are too inconsistent and involve too few research

designs permitting the drawing of causal inferences or too

many different definitions of the exposure, population, or

outcome to permit us to draw a consistent, individual/patientlevel conclusion regarding the value of omega-3 fatty acid

intake to protect against tendencies or behavior with the

potential to harm others. 

We could not identify the research designs which, due to

their prospective and controlled nature, are most appropriate

for addressing the question of the possible relationship between

intake of omega-3 fatty acids (e.g., via breastfeeding) and the

onset of schizophrenia. Five case-control designs,22,61-64 one

single prospective cohort,65 and three cross-national ecological

analyses50,56,66 were found. The only prospective study was not

controlled, and its followup was very short.65 Moreover, failure

to control for confounders was common (e.g., maternal feeding

patterns, sex of children, maternal age, socioeconomic status,

early mother-infant contact). Thus, nothing definitive can be

asserted about a reliable association between omega-3 fatty acid

intake and the onset of schizophrenia. 

Secondary Prevention (i.e., Continuation,

Recurrence) Via Omega-3 Fatty Acid Intake

One small, multiple-group cross-sectional study revealing

that, relative to healthy controls, AD/HD children consumed

significantly lesser amounts of linoleic acid and alpha linolenic

acid (ALA) is insufficient to permit us to conclude anything

definitive regarding the potential of these PUFAs to alter the

course, or continuation, of AD/HD.23 Likewise, a single RCT

demonstrating that a complex intervention including omega-3

fatty acids—whose independent effect could not be

ascertained—provided young adult prisoners with some

protection against committing new offences29 is insufficient to

determine its capacity to prevent the recurrence of tendencies

or behavior with the potential to harm others (i.e., antisocial

behavior).29

Primary Prevention (i.e., Onset) Via Lipid

Biomarker Content

Inconsistent results as well as too few studies exhibiting

sound methodologies (e.g., protection against selection bias;

control for smoking, alcohol use, and psychotropic medication)

or research designs (e.g., prospective, controlled) that are ideally

suited to investigate this question suggest that it is too early to

conclude whether or not omega-3 fatty or omega-6/omega-3

acid content in biomarkers protects against the onset of

depressive disorders or symptomatology. One RCT24 and seven

multiple-group cross-sectional studies1,67-72 were included. 

The inconsistency in findings across two multiple-group

cross-sectional studies,73,74 which is potentially attributable to

the fact that the studies obtained their PUFA samples from

different biomarker sources, in addition to the recognition that

this type of research design is less than an ideal test of the

research question, and the observation that the studies failed to

control for different key confounders together indicate that

nothing definitive can be concluded about the ability of specific

lipid biomarker content to protect against the onset of bipolar

disorder. Irrespective of the limited agreement in observing that

both ALA and total omega-6 fatty acid levels in plasma

phospholipids were significantly lower in anorexic patients

compared with controls, the use of cross-sectional designs in

two small studies prevent the drawing of causal inferences

regarding the role of lipid biomarker content in the onset of

anorexia nervosa.75,76 Inconsistent findings from three multiplegroup cross-sectional studies whose designs are of limited use in

investigating the research question,77-79 the failures to control for

dietary intake,77 to formally rule out the presence of

psychopathology in the control subjects, or to employ formal

diagnostic criteria (i.e., DSM-III) to identify their hyperactive

subjects,78 made it impossible to draw causal inferences about

the role of omega-3 or omega-6/omega-3 fatty acid content in

biomarkers to prevent the onset of AD/HD. 

Three multiple-group cross-sectional studies examined the

possible association of the onset of tendencies or behavior with

the potential to harm others with the omega-3 or omega6/omega-3 fatty acid content of biomarkers.80-82 Inconsistent

results, small sample sizes, and the exclusive use of crosssectional designs preclude deriving clear inferences regarding

6
etiology. Two multiple-group cross-sectional studies investigated

the possible association of the onset of alcoholism with the

omega-3 or omega-6/omega-3 fatty acid content of

biomarkers.83,84 However, conflicting results and the use of

cross-sectional designs do not allow us to draw conclusions

regarding this possible etiology of alcoholism.

Medication status may have had somewhat of an influence

on between-group differences in RBC or plasma phospholipid

fatty acid content when the comparison group was healthy

controls. However, because these data were obtained exclusively

from twelve multiple-group cross-sectional studies74,85-95 or two

single prospective cohort studies with methodologic flaws,96,97

no meaningful possibility exists to permit drawing causal

inferences regarding patterns of lipid biomarker content and

the onset of schizophrenia. The same criticism relating to crosssectional designs applies to the single study examining

biomarkers data with respect to the onset of autism.98

Secondary Prevention (i.e., Continuation,

Recurrence) Via Lipid Biomarker Content

This question could not be evaluated since studies meeting

eligibility criteria were not identified. 

Discussion

A notable safety profile (i.e., beyond occasional and mild

discomfort) for any type or dose of omega-3 fatty acid

supplementation was not observed. Overall, other than for the

topics of schizophrenia and depression, few efficacy or safety

studies were identified. 

Only with respect to the supplemental treatment of

schizophrenia is the evidence even somewhat suggestive of

omega-3 fatty acids’ potential as short-term intervention.

However, these meta-analytic results exclusively pertaining to 2

g/d EPA require replication using design and method

refinements. Additional research might reveal the short-term or

long-term therapeutic value of omega-3 fatty acids. 

One study demonstrating a significant placebo-controlled

clinical effect related to 1 g/d E-EPA given over 12 weeks to 17

patients with depressive symptoms—rather than depressive

disorders—cannot be taken to support the view of the utility of

this exposure as a supplemental treatment for depressive

symptomatology or disorders. Nothing can yet be concluded

concerning the clinical utility of omega-3 fatty acids as

supplemental treatment for any other psychiatric disorder or

condition, or as a primary treatment for all psychiatric disorders

or conditions examined in our review. Primary treatment

studies were rare. 

Much more research, implementing design and methods

improvements, is needed before we can begin to ascertain the

possible utility of (foods or supplements containing) omega-3

fatty acids as primary prevention for psychiatric disorders or

conditions. Studies of omega-3 fatty acids’ primary protective

potential in mental health could be “piggybacked” onto

longitudinal studies of their impact on general health and

development. 

Overall, almost nothing is known about the therapeutic or

preventive potential of each source, type, dose, or combination

of omega-3 fatty acids. Likewise, limitations within the

evidence base prevented us from identifying the influence of

key covariables (e.g., smoking, alcohol use, psychotropic

medication) on the relationship between omega-3 fatty acid

content and clinical outcomes.

Because of limited study designs, little is known about the

relationship between PUFA biomarker profiles and the onset of

any psychiatric disorder or condition. Studies examining the

possible association between the intake of omega-3 fatty acids,

or the PUFA content of biomarkers, and the continuation or

recurrence of psychiatric disorders or conditions were virtually

nonexistent. 

If future research is going to produce data that are

unequivocally applicable to North Americans, it will need to

enroll either North American populations or populations

exhibiting a high omega-6/omega-3 fatty acid intake ratio

similar to what has been observed in the diet of North

Americans. Furthermore, if a reasonable view is that omega-3

fatty acids may play a role in mental health, then given the

observed or proposed inter-relationships among omega-3 and

omega-6 fatty acid contents both in the human diet and

metabolism, researchers should likely consider taking into

account the possible therapeutic or preventive influence of the

dietary omega-6/omega-3 fatty acid intake ratio. 

Availability of the Full Report

The full evidence report from which this summary was taken

was prepared for the Agency for Healthcare Research and

Quality (AHRQ) by the University of Ottawa Evidence-based

Practice Center under Contract No. 290-02-0021. It is

expected to be available in July 2005. At that time, printed

7
copies may be obtained free of charge from the AHRQ

Publications Clearinghouse by calling 800-358-9295.

Requesters should ask for Evidence Report/Technology

Assessment No. 116, Effects of Omega-3 Fatty Acids on Mental

Health. In addition, Internet users will be able to access the

report and this summary online through AHRQ’s Web site at

www.ahrq.gov.

Suggested Citation

Schachter HM, Kourad K, Merali Z, Lumb A, Tran K,

Miguelez M, et al. Effects of Omega-3 Fatty Acids on Mental

Health. Summary, Evidence Report/Technology Assessment

No. 116. (Prepared by the University of Ottawa Evidence-based

Practice Center under Contract No. 290-02-0021.) AHRQ

Publication No. 05-E022-1. Rockville, MD: Agency for

Healthcare Research and Quality. July 2005.

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3. Horrobin DF, Bennett CN. Depression and bipolar disorder:

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