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Effects of Omega-3 Fatty Acids on Mental Health
Evidence Reports/Technology Assessments, No. 116
Investigators: Howard M Schachter, PhD, Kader Kourad, MD, PhD, Zul Merali, PhD, Andrew Lumb, BA, Khai Tran, PhD, Maia Miguelez, PhD, Gabriela Lewin, MD, Margaret Sampson, MLIS, Nick Barrowman, PhD, Hope Senechal, BSc, Candice McGahern, HRA, Li Zhang, BSc, Andra Morrison, BSc, Jakov Shlik, MD, PhD, Yi Pan, MSc, Elizabeth C Lowcock, BScH, Isabelle Gaboury, MSc, Jacques Bradwejn, MD, and Anne Duffy, MD.
Structured Abstract
Context:
One popular view holds that psychiatric problems reflect disorders of brain functioning. Fifty percent to 60% of the adult brain is composed of lipids (dry weight), of which 35% are phospholipids comprised of unsaturated fatty acids. Of these, the polyunsaturated fatty acids docosahexaenoic acid (an omega-3 fatty acid) and arachidonic acid (an omega-6 fatty acid) are found in the highest concentrations. Thus, it has been proposed that omega-3 fatty acids could play an important role in mental health.
Objectives:
The purpose of this study was to conduct a systematic review of the scientific-medical literature to identify, appraise and synthesize the evidence for the effects of omega-3 fatty acids in mental health. Evidence was sought to permit the investigation of three basic questions: the efficacy and safety of omega-3 fatty acids as (primary or supplemental) treatment of psychiatric disorders or conditions (e.g., symptoms alone); the association between intake of omega-3 fatty acids and the onset, continuation or recurrence of psychiatric disorders or conditions; and, the association between the fatty acid content of biomarkers and the onset, continuation or recurrence of psychiatric disorders or conditions. The latter two questions examined the protective value of omega-3 fatty acid content in the diet and/or blood lipid biomarkers. The impact of effect modifiers was examined as well. The results will be used largely to inform a research agenda.
Data Sources:
A comprehensive search for citations was conducted using five databases (Medline, Embase, 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]; fish oil); and, relevant population terms (e.g., mental disorders). Additional published or unpublished literature was sought through manual searches of references lists of included studies and key review articles, and from the files of content experts.
Study Selection:
Studies were considered relevant if they described live human populations of any age, investigated the use of any foods or supplements known to contain omega-3 fatty acids, and utilized mental health outcomes. Studies examining the questions concerning treatment efficacy or the fatty acid content of biomarkers had to employ a controlled research design, whereas any type of design other than a case series or case study was permitted to address the possible association of the intake of omega-3 fatty acids and clinical outcomes. Three levels of screening for relevance, and two reviewers per level, were employed. Disagreements were resolved by forced consensus and, if necessary, third party intervention.
Data Extraction:
All data were abstracted by one reviewer, then verified by another. Data included characteristics of the report, study, population, intervention/exposure, comparator(s), cointerventions, discontinuations (and reasons), and outcomes (i.e., clinical, biomarkers, safety). Study quality (internal validity) and applicability (external validity) were appraised.
Data Synthesis:
Question-specific qualitative syntheses of the evidence were derived. Meta-analysis was conducted with data concerning the supplemental treatment of schizophrenia. Limited numbers of studies addressing the other research questions precluded further meta-analysis. Eighty-six reports, describing 79 studies, were deemed relevant for the systematic review, with each of 6 studies described by more than one report.
Conclusions:
A notable safety profile 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 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 methods refinements. Additional research might reveal the short-term or longterm 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. Overall, almost nothing is known about the therapeutic or preventive potential of each source, type, dose or combination of omega-3 fatty acids. Studies of their primary protective potential in mental health could be “piggybacked” onto longitudinal studies of their impact on general health and development. 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 likely 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 between omega-3 and omega-6 fatty acid contents both in the regular diet and in the human biosystem, it may behoove researchers to investigate the possible therapeutic or preventive value of the dietary omega-6/omega-3 fatty acid intake ratio.
Contents
- Preface
- Acknowledgments
- 1. Introduction
- Metabolism and Biological Effects of Essential Fatty Acids
- Metabolic Pathways of Omega-3 and Omega-6 Fatty Acids
- U.S. Population Intake of Omega-3 Fatty Acids
- Dietary Sources of Omega-3 Fatty Acids
- Disorders of Mental Health: an Overview
- Affective Disorders
- Anxiety Disorders
- Anorexia Nervosa
- Attention Deficit/Hyperactivity Disorder
- Tendencies or Behaviors With the Potential to Harm Others: the Spectrum of Anger/Hostility, Aggression and Violence
- Alcoholism
- Borderline Personality Disorder
- Schizophrenia
- Autism
- Omega-3 Fatty Acids and Mental Health
- 2. Methods
- 3. Results
- Results of Literature Search
- Report and Study Design Characteristics of Included Studies
- Are Omega-3 Fatty Acids Efficacious as Primary Treatment for Depression?
- Are Omega-3 Fatty Acids Efficacious as Supplemental Treatment for Depression?
- Is Omega-3 Fatty Acid Intake, Including Diet and/or Supplementation, Associated With the Onset, Continuation or Recurrence of Depression?
- Is the Onset, Continuation or Recurrence of Depression Associated With Omega-3 or Omega-6/Omega-3 Fatty Acid Content of Biomarkers?
- Is Omega-3 Fatty Acid Intake, Including Diet and/or Supplementation, Associated With the Onset, Continuation or Recurrence of Suicidal Ideation or Behavior?
- Are Omega-3 Fatty Acids Efficacious as Supplemental Treatment for Bipolar Disorder?
- Is Omega-3 Fatty Acid Intake, Including Diet and/or Supplementation, Associated With the Onset, Continuation or Recurrence of Bipolar Disorder?
- Is the Onset, Continuation or Recurrence of Bipolar Disorder Associated With Omega-3 or Omega-6/Omega-3 Fatty Acid Content of Biomarkers?
- Is Omega-3 Fatty Acid Intake, Including Diet and/or Supplementation, Associated With the Onset, Continuation or Recurrence of Anxiety?
- Are Omega-3 Fatty Acids Efficacious as Supplemental Treatment for Obsessive-Compulsive Disorder?
- Is the Onset, Continuation or Recurrence of Anorexia Nervosa Associated With Omega-3 or Omega-6/Omega-3 Fatty Acid Content of Biomarkers?
- Are Omega-3 Fatty Acids Efficacious as Primary Treatment for Attention Deficit/Hyperactivity Disorder?
- Are Omega-3 Fatty Acids Efficacious as Supplemental Treatment for Attention Deficit/Hyperactivity Disorder?
- Is Omega-3 Fatty Acid Intake, Including Diet and/or Supplementation, Associated With the Onset, Continuation or Recurrence of Attention Deficit/Hyperactivity Disorder?
- Is the Onset, Continuation or Recurrence of Attention Deficit/Hyperactivity Disorder Associated With Omega-3 or Omega-6/Omega-3 Fatty Acid Content of Biomarkers?
- Is Omega-3 Fatty Acid Intake, Including Diet and/or Supplementation, Associated With the Onset, Continuation or Recurrence of Mental Health Status Difficulties?
- Is Omega-3 Fatty Acid Intake, Including Diet and/or Supplementation, Associated With the Onset, Continuation or Recurrence of Tendencies or Behaviors With the Potential to Harm Others?
- Is the Onset, Continuation or Recurrence of Tendencies or Behaviors With the Potential to Harm Others Associated With Omega-3 or Omega-6/Omega-3 Fatty Acid Content of Biomarkers?
- Is the Onset, Continuation or Recurrence of Alcoholism Associated With Omega-3 or Omega-6/Omega-3 Fatty Acid Content of Biomarkers?
- Are Omega-3 Fatty Acids Efficacious as Primary Treatment for Borderline Personality Disorder?
- Are Omega-3 Fatty Acids Efficacious as Primary Treatment for Schizophrenia?
- Are Omega-3 Fatty Acids Efficacious as Supplemental Treatment for Schizophrenia?
- Is Omega-3 Fatty Acid Intake, Including Diet and/or Supplementation, Associated With the Onset, Continuation or Recurrence of Schizophrenia?
- Is the Onset, Continuation or Recurrence of Schizophrenia Associated With Omega-3 or Omega-6/Omega-3 Fatty Acid Content of Biomarkers?
- Is the Onset, Continuation or Recurrence of Autism Associated With Omega-3 or Omega-6/Omega-3 Fatty Acid Content of Biomarkers?
- What is the Evidence That, in Review-Relevant Studies Concerning Mental Health, Adverse Events (e.g., Side Effects) or Contraindications are Associated With the Intake of Omega-3 Fatty Acids?
- 4. Discussion
- Summary Tables
- Table of Studies Investigating Each Question: organized by the order of presentation in the text
- Abbreviations
- Appendixes
- References and Included Studies
- Listing of Excluded Studies at Level 2 Screening
- Listing of Excluded Studies at Level 3 Screening
- Listing of Reports of Included Studies
Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.1 Contract No. 290-02-0021. Prepared by: University of Ottawa Evidence-based Practice Center at The University of Ottawa, Ottawa, Canada.
Suggested citation:
Schachter H, Kourad K, Merali Z, Lumb A, Tran K, Miguelez M, et al. Effects of Omega-3 Fatty Acids on Mental Health. 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-E022-2. Rockville, MD: Agency for Healthcare Research and Quality. July 2005.
This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
AHRQ is the lead Federal agency charged with supporting research designed to improve the quality of health care, reduce its cost, address patient safety and medical errors, and broaden access to essential services. AHRQ sponsors and conducts research that provides evidence-based information on health care outcomes; quality; and cost, use, and access. The information helps health care decisionmakers—patients and clinicians, health system leaders, and policymakers—make more informed decisions and improve the quality of health care services.
The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.
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540 Gaither Road, Rockville, MD 20850. www
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- Effects of Omega-3 Fatty Acids on Mental HealthEffects of Omega-3 Fatty Acids on Mental Health
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