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Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials

  • Katherine H. O. Deane (a1), Oluseyi F. Jimoh (a2), Priti Biswas (a3), Alex O'Brien (a4), Sarah Hanson (a5), Asmaa S. Abdelhamid (a6), Chris Fox (a7) and Lee Hooper (a8)...

Abstract

Background

There is strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety.

Aims

To assess effects of increasing omega-3, omega-6 or total polyunsaturated fat on prevention and treatment of depression and anxiety symptoms.

Method

We searched widely (Central, Medline and EMBASE to April 2017, trial registers to September 2016, ongoing trials updated to August 2019), including trials of adults with or without depression or anxiety, randomised to increased omega-3, omega-6 or total polyunsaturated fat for ≥24 weeks, excluding multifactorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, and authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment.

Results

We included 31 trials assessing effects of long-chain omega-3 (n = 41 470), one of alpha-linolenic acid (n = 4837), one of total polyunsaturated fat (n = 4997) and none of omega-6. Meta-analysis suggested that increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (risk ratio 1.01, 95% CI 0.92–1.10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety symptoms (standardised mean difference 0.15, 95% CI 0.05–0.26, I2 = 0%, median dose 1.1 g/d, duration 6 months; both moderate-quality evidence). Evidence of effects on depression severity and remission in existing depression were unclear (very-low-quality evidence). Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Increasing alpha-linolenic acid by 2 g/d may increase risk of depression symptoms very slightly over 40 months (number needed to harm, 1000).

Conclusions

Long-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms.

Declaration of interest

L.H. and A.A. were funded to attend the World Health Organization Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health meetings and present review results. The authors report no other conflicts of interest.

Copyright

Corresponding author

Correspondence: Lee Hooper, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK. Email: l.hooper@uea.ac.uk

References

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Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials

  • Katherine H. O. Deane (a1), Oluseyi F. Jimoh (a2), Priti Biswas (a3), Alex O'Brien (a4), Sarah Hanson (a5), Asmaa S. Abdelhamid (a6), Chris Fox (a7) and Lee Hooper (a8)...

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Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials

  • Katherine H. O. Deane (a1), Oluseyi F. Jimoh (a2), Priti Biswas (a3), Alex O'Brien (a4), Sarah Hanson (a5), Asmaa S. Abdelhamid (a6), Chris Fox (a7) and Lee Hooper (a8)...
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eLetters

Response to “Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials” by Deane et al. (2019)

Kuan-Pin Su, Professor and Director of general psychiatry, China Medical University (Taiwan)
Ta-Wei Guu, Attending psychiatrist and chief of the educational division, China Medical University Beigang Hospital(Taiwan)
Felice Jacka, President, International Society of Nutritional Psychiatry Research
Wolfgang Marx, Head of the Nutraceutical Research stream, Food & Mood Centre
ISNPR Guideline Panel, International Society of Nutritional Psychiatry Research
02 December 2019

Correspondence

Response to “Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials” by Deane et al. (2019)

Kuan-Pin Sua, b*, Ta-wei Guua, c, David Mischoulond, Jerome Sarrise, f, Joseph Hibbelng,

Robert K. McNamarah, Kei Hamazakii, Marlene P. Freemanj; Michael Maesk,

Yutaka J. Matsuokal, R.H. Belmakerm; Felice Jackan, Carmine Parianteo,

Michael Berkp, Wolfgang Marxn

On behalf of the panel of “International Society of Nutritional Psychiatry Research (ISNPR) Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder”

aDepartments of Psychiatry and Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, TAIWAN

bDepression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

cDivision of Psychiatry, Departments of Internal Medicine, China Medical University Beigang Hospital, Yunlin, TAIWAN

dDepression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

eNICM, Health Research Institute, Western Sydney University, Westmead, NSW, AUSTRALIA

fThe Melbourne Clinic, Professorial Unit, Department of Psychiatry, Melbourne University, VIC, AUSTRALIA

gSection on Nutritional Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA

hDepartment of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, USA

iDepartment of Public Health, Faculty of Medicine, University of Toyama, Toyama, Japan

jClinical Trials Network and Institute, Massachusetts General Hospital, Boston, MA, USA

kDepartment of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

lDivision of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, Tokyo Japan

mBen Gurion University of the Negev, Beersheba, Israel

nDeakin University, Faculty of Health, School of Medicine, IMPACT, the Institute for Mental and Physical Health and Clinical Translation, Food & Mood Centre, Australia

oStress, Psychiatry and Immunology Laboratory, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK

pDepartment of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia

*Address correspondence to:

Prof. Kuan-Pin Su

Department of Psychiatry,

China Medical University Hospital

No. 2, Yuh-Der Road, Taichung 404, TAIWAN

Telephone number: 886-4-22062121 ext. 1076

Fax number: 886-4-22361230

E-mail: cobolsu@gmail.com

Short title: Antidepressant effects of omega-3 could disappear in problematic meta-analyses

Keywords: Omega-3, Meta-analysis, Heterogeneity, Major depressive disorder (MDD), Treatment

Article: 468 words

Deane et al. published a meta-analysis and concluded “Long-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms,” and “Physicians should not recommend omega-3 supplements for reducing depression or anxiety risk.”1 However, we wish to raise the following limitations in the methods of this review and the existing clinical trial literature.

In this BJP paper, the authors excluded a large literature of clinical trials which substantially biases their analyses. The authors excluded trials of less than 24 weeks, claiming that fatty acids come to steady state in most body tissues including brain only after 24 weeks; however the paper they cite actually reported incorporation into some tissues within days and critically did not measure nor report on brain compositions.2

Besides, the main reasons of inconsistent results from this and many other meta-analyses in non-drug trials are due to complex yet common methodological issues.3-5 These can include pooling heterogeneous clinical trials, applying non-standardized diagnostic procedures and unreliable outcome measurements, and implementing improper intervention methods. The prevention effects of one single intervention for complex disorders like depression and anxiety with multiple etiological drivers are generally small, and consequently, require randomized controlled trials (RCTs) with very large samples sizes; smaller RCTs with inconsistent methods invariably lead to inconsistent results.5, 6

In this paper, the authors included many problematic clinical trials that investigated the potential of omega-3 for the prevention of depression and anxiety. In the methodology, the authors state: "Participants could have a current or previous diagnosis of clinical depression or anxiety, but this was not necessary (Line 11-12, Page 2)." In fact, most of the included studies consisted of trials lacking any formal assessment for clinical depression/anxiety. Most of the included participants were patients with other medical conditions, such as cardiovascular events after myocardial infarction (Ref 301), The Age-Related Eye Disease Study 2 (AREDS2) (Ref 311), Alzheimer’s disease and mild cognitive impairment (Ref 321), angina (Ref 331), impaired glucose tolerance (Ref 341), sporadic colorectal tumors (Ref 351), hyperlipidemia (Ref 361), nonalcoholic steatohepatitis (Ref 371), Huntington’s disease (Ref 391), oldest elderly in Japanese nursing homes (Ref 401), healthy older adults (Ref 411), taking statins (Ref 421), Alzheimer’s disease (Ref 431), and so on. None of these studies were designed a priori to assess prevention of depression and are all secondary analyses; it was not possible to determine if the studies were adequately powered to assess this question.

Heterogeneity, that many studies did not require clinically depressed individuals as well as a lack of formal diagnoses undermine the possibility of detecting the small signals in clinical trials for omega-3’ antidepressant and anxiolytic effects. When included data are heterogeneous, the results will be inconsistent and unreliable. As such, we suggest that this meta-analysis cannot confirm or disconfirm a lack of effect of omega-3 supplementation for depression and anxiety.

Declaration of Interest: The authors have no conflicts of interests to report.

References:

1. Deane KHO, Jimoh OF, Biswas P, O'Brien A, Hanson S, Abdelhamid AS, et al. Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials. Br J Psychiatry. 2019: 1-8.

2. Browning LM, Walker CG, Mander AP, West AL, Madden J, Gambell JM, et al. Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish. Am J Clin Nutr. 2012; 96(4): 748-58.

3. Lin PY, Mischoulon D, Freeman MP, Matsuoka Y, Hibbeln J, Belmaker RH, et al. Are omega-3 fatty acids antidepressants or just mood-improving agents? The effect depends upon diagnosis, supplement preparation, and severity of depression. Mol Psychiatry. 2012; 17(12): 1161-3; author reply 3-7.

4. Senthil Kumaran S, Shih Y-H, Su K-P. Detecting the modest signals of omega-3 fatty acids' antidepressant effects by homogenizing depressed patient groups. 2016; 28(5-6): 86-7.

5. Su KP. Are we all the same? The critical role of translational brain, behavior, and immunity research in East Asia. Brain Behav Immun. 2019; 82: 1-2.

6. Guu TW, Mischoulon D, Sarris J, Hibbeln J, McNamara RK, Hamazaki K, et al. International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder. Psychother Psychosom. 2019: 1-11.

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Conflict of interest: None declared

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