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N-3 PUFA supplementation alleviates anxiety symptoms by manipulating erythrocyte fatty acid levels in depression

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Abstract

Purpose

Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels.

Methods

A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression.

Results

Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ2 = 96.36, p = 0.000). The n-3 index (χ2 = 10.59, p = 0.001), EPA (χ2 = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ2 = 10.71, p = 0.001) were increased, while C22:4n6 (χ2 = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05).

Conclusion

These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

None.

Funding

This work was supported by National Natural Science Foundation of China [grant number 81803233, 82301686], the Natural Science Foundation of Hunan Province [grant number 2023JJ30938], the Natural Science Foundation of Changsha City [grant number kq2208387], and Hospital Pharmacy Innovation Project for the youth established by Chinese Pharmaceutical Association and Servier (Tianjin) Pharmaceutical Co. Ltd. [grant number CPA-B04-ZC-2024-001].

Author information

Author notes

  1. Lu Wang and Ting Liu are co-first authors.

Authors and Affiliations

  1. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

    Ting Liu, Tingyu Zhao & Mimi Tang

  2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China

    Ting Liu, Tingyu Zhao & Mimi Tang

  3. The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders and Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, China

    Lu Wang, Feifei Wang & Fang Dong

  4. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China

    Lu Wang, Feifei Wang & Fang Dong

  5. Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, and China National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China

    Lu Wang, Hui Tang, Feifei Wang, Fang Dong & Jindong Chen

  6. College of Materials Sciences and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China

    Jimin Guo

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Contributions

Conceptualization, M.T. and L.W.; methodology, L.T., M.T. and L.W.; validation, M.T., J.C. and T.Z.; formal analysis, L.W. and L.T.; writing—original draft preparation, L.W. and L.T.; writing—review and editing, M.T. and J.G.; supervision, M.T. and J.C.; project administration, L.W. H.T., F.W. and F.D.; funding acquisition, M.T. and L.W. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Mimi Tang.

Ethics declarations

Human rights statement and informed consent

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of the Second Xiangya Hospital of Central South University (MDD201610, 2017/06/23). Informed consent was obtained from all subjects involved in the study.

Conflict of interest

The authors declare no conflict of interest.

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Wang, L., Liu, T., Guo, J. et al. N-3 PUFA supplementation alleviates anxiety symptoms by manipulating erythrocyte fatty acid levels in depression. Eur J Nutr (2024). https://doi.org/10.1007/s00394-024-03421-y

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