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. 2021 Mar;66(3):262-273.
doi: 10.1177/0706743720961734. Epub 2020 Sep 23.

A Systematic Review of Nutraceuticals for the Treatment of Bipolar Disorder

Melanie M Ashton  1   2   3 , Bianca E Kavanagh  1 , Wolfgang Marx  1 , Michael Berk  1   2   4   5   6 , Jerome Sarris  3   7 , Chee H Ng  3 , Malcolm Hopwood  2   8 , Lana J Williams  1 , Olivia M Dean  1   2   4
Affiliations

A Systematic Review of Nutraceuticals for the Treatment of Bipolar Disorder

Melanie M Ashton et al. Can J Psychiatry. 2021 Mar.

Abstract
in English, French

Background: Certain nutrient supplements (nutraceuticals) may target neurobiological pathways perturbed in bipolar disorder (BD) such as inflammation, oxidative stress, and mitochondrial dysfunction. Nutraceuticals thus may have a potential role as adjunctive treatments for BD.

Methods: A search of Embase via embase.com, PubMed via PubMed, Cumulated index to nursing and allied health literature (CINAHL) Complete via EBSCO, and Cochrane Central Register of Controlled Clinical Trials via cochranelibrary.com was conducted to identify published randomized controlled trials assessing the efficacy of nutraceuticals on mood symptomatology in adults with BD. Search terms for BD, nutraceuticals, and clinical trials (total search terms = 75) were used to search from inception to February 20, 2020. The Cochrane Collaboration's tool for assessing the risk of bias in randomized trials was used to assess the risk of bias.

Results: A total of 1,712 studies were identified through the search. After rigorous screening, 22 studies were included in the review. There was large variability across the studies with 15 different nutraceutical agents assessed and as such insufficient homogeneity for a meta-analysis to be conducted (I2 > 50%). Studies revealed promising, albeit conflicting, evidence for omega-3 fatty acids and N-acetylcysteine. Isolated positive results were reported for coenzyme Q10.

Conclusion: Given nutraceuticals are tolerable and accessible, they may be useful as potential adjunctive treatments for BD. Nutraceuticals targeting neuroinflammation or mitochondrial activity may have the most potential for the depressive phase. However, further studies are required to determine efficacy.

Contexte:: Certains suppléments diététiques (les nutraceutiques) peuvent cibler des circuits neurobiologiques perturbés dans le trouble bipolaire comme l’inflammation, le stress oxydant et la dysfonction mitochondriale. Les nutraceutiques peuvent donc avoir un rôle potentiel comme traitements d’appoint du trouble bipolaire.

Méthodes:: Une recherche d’Embase a été menée dans embase.com, PubMed dans PubMed, CINAHL complète par EBSCO, et le registre Cochrane central des essais contrôlés par cochranelibrary.com, afin d’identifier les essais cliniques randomisés contrôlés publiés évaluant l’efficacité des nutraceutiques pour la symptomatologie de l’humeur chez les adultes souffrant du trouble bipolaire. Les termes de recherche du trouble bipolaire, nutraceutiques et essais cliniques (total des termes de recherche = 75) servaient à chercher du début jusqu’au 20 février 2020. L’outil de collaboration Cochrane qui évalue le risque de biais dans les essais randomisés a servi à évaluer le risque de biais.

Résultats:: La recherche a produit un total de 1 712 études. Après un dépistage rigoureux, 22 études ont été incluses dans la revue. Il y avait une importante variabilité entre les études et 15 différents agents nutraceutiques ont été évalués et à ce titre, l’homogénéité était insuffisante pour mener une méta-analyse (I2 > 50%). Les études ont révélé des données probantes prometteuses, quoique conflictuelles, pour les acides gras omega-3 et la N-acétylcystéine. Des résultats positifs isolés ont été rapportés pour le coenzyme Q10.

Conclusion:: Étant donné que les nutraceutiques sont tolérables et accessibles, ils peuvent être utiles à titre de traitement d’appoint potentiel du trouble bipolaire. Les nutraceutiques qui ciblent la neuro-inflammation ou l’activité mitochondriale peuvent avoir le plus de potentiel pour la phase dépressive. Toutefois, il faut d’autres études pour en déterminer l’efficacité.

Keywords: bipolar disorder; depression; dietary supplement; mania; mental health; neuroscience; nutraceuticals; psychiatry.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MMA has received grant/research support from Deakin University, Australasian Society for Bipolar Depressive Disorders, Lundbeck, Australian Rotary Health, Ian Parker Bipolar Research Fund, and Cooperative Research Centre for Mental Health. MB has received grant support from NIH, Simons Autism Foundation, Cancer Council of Victoria, CRC for Mental Health, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Organon, Novartis, Mayne Pharma, and Servier. MB also has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant, and the Harry Windsor Foundation; has been a speaker for Astra Zeneca, Lundbeck, Merck, and Pfizer; and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer, and Servier—all unrelated to this work. MH has received grant support from ISSCR, Ramsay Health Foundation, Lyndra, Praxis, Servier, US DOD, and Bionomics; has been a speaker for Janssen-Cilag, Lundbeck, and Servier; and has been a consultant for AstraZeneca, Eli Lilly, Grunbiotics, Janssen-Cilag, Lundbeck, and, Servier. BEK has received grant/research support from the Australian Government Research Training Program Scholarship, Australian Rotary Health Ian Scott PhD Scholarship, and the International Society for the Study of Personality Disorders. JS has received either presentation honoraria, travel support, clinical trial grants, book royalties, or independent consultancy payments from Australian Natural Therapeutics Group Integria Healthcare & MediHerb, Pfizer, Scius Health, Key Pharmaceuticals, Taki Mai, Bioceuticals & Blackmores, Soho-Flordis, Healthworld, HealthEd, HealthMasters, Elsevier, Chaminade University, International Society for Affective Disorders, Complementary Medicines Australia, Terry White Chemists, ANS, Society for Medicinal Plant and Natural Product Research, UBiome, Omega-3 Centre, the National Health and Medical Research Council, and CR Roper Fellowship. OMD is a R. D. Wright Biomedical NHMRC Career Development Fellow (APP 1145634) and has received grant support from the Brain and Behavior Foundation, Simons Autism Foundation, Stanley Medical Research Institute, Deakin University, Lilly, NHMRC, and ASBDD/Servier. She has also received in-kind support from BioMedica Nutraceuticals, NutritionCare, and Bioceuticals.

Figures

Figure 1.
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart for eligibility of studies in systematic review.
Figure 2.
Figure 2.
Risk of bias summary: Review authors’ judgments about each risk of bias item for each included study.
See this image and copyright information in PMC

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