Clinical outcomes of mitochondrial-enhancing nutraceutical supplementation in psychiatric disorders: A systematic review.

BACKGROUND

Nutraceutical supplementation targeting mitochondrial function has been proposed as a beneficial therapeutic strategy to improve physical and mental health in psychiatric patients.

AIMS: To summarise the results of studies evaluating nutraceutical supplementation targeting mitochondrial function in patients with psychiatric disorders.

METHODS

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed, Embase and Scopus databases from 1 January 2007 to 30 April 2024. Reports were included if they evaluated outcomes of nutraceutical supplementation in patients with psychiatric disorders or related conditions. Additionally, we performed a risk-of-bias analysis of the studies compatible with the RoB2 tool.

RESULTS

Of the 2061 records identified, 122 studies met the inclusion criteria, evaluating vitamin D3, N-acetylcysteine, acetyl-L-carnitine, coenzyme Q10, alpha-lipoic acid, magnesium, vitamin B6, vitamin B7, folic acid, vitamin B12, vitamin E, vitamin A, vitamin C and vitamin B3. The most studied nutraceuticals were vitamin D3 (27.05%) and N-acetylcysteine (15.6%). Among randomised controlled clinical trials (RCTs), vitamin D3 was the most extensively investigated and accounted for the highest number of trials reporting improvements in clinical outcomes, although findings were heterogeneous. Notably, 14.8% of the studies evaluated combinations of three or more nutraceuticals. Dietary supplements were extensively evaluated for autism spectrum disorder (28 studies), schizophrenia spectrum disorder (27 studies), major depressive disorder or related depressive symptoms (22 studies), attention-deficit hyperactivity disorder (9 studies) and bipolar spectrum disorder (6 studies). A substantial proportion of studies were not RCTs but open-label single-arm trials or case reports. Significant heterogeneity was observed in the nutraceutical components used, treatment duration and the outcomes assessed. Overall, the risk of bias was high, and the methodological quality was generally low.

CONCLUSIONS

Promising findings in nutraceutical studies for psychiatric disorders face challenges, including small sample sizes, short follow-up periods and a lack of treatment standardisation. Future research requires robust RCTs with standardised protocols and validated biomarkers of efficacy.