A summary of the study on “Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trial”
This research study by Strodl et al (2024), published in Scientific Reports on 6 September 2024, investigated the efficacy of a combination of probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus), magnesium orotate, and coenzyme Q10 (CoQ10) for treating major depressive disorder (MDD). The study aimed to build on previous pilot studies that showed promising results for this combination.
Background
Given that MDD is a leading cause of disability worldwide and existing treatments like antidepressant medication and psychotherapy have limitations with significant non-response and adverse events, the researchers sought to explore alternative treatment options. While some meta-analyses suggest probiotics can reduce depressive symptoms, the evidence for their use in MDD has been mixed. The rationale for combining probiotics with magnesium orotate was based on the hypothesis that magnesium orotate might enhance the effectiveness of probiotics through direct influence on gut function and modulation of the gut microbiota. CoQ10 was included due to suggestions of its potential role in the pathophysiology of depression.
Methodology
The study employed a 16-week double-blinded, randomised placebo-controlled clinical trial. A total of 120 adults diagnosed with MDD were randomised to receive either the active intervention (NRGBiotic™, containing the specified probiotics, 1600 mg of magnesium orotate, and 150 mg of CoQ10) or a placebo daily for 8 weeks, followed by an 8-week follow-up period where the intervention ceased. The placebo consisted of identical capsules containing lake carmoisine, exalake quinolone, and rice flour. Participants were assessed at baseline, week 4, week 8, and week 16.
The primary outcome measures were the frequency of MDD diagnosis (assessed using the SCID-5-RV) and the severity of self-rated depressive symptoms (measured by the BDI-II). Secondary outcomes included self-rated symptoms of anxiety (GAD-7) and stress (PSS). Adherence was tracked using dosage logs, and adverse events were recorded. Statistical analyses included intent-to-treat (ITT) and per-protocol (PP) analyses.
Results
The ITT analysis revealed a significantly lower frequency of MDD diagnosis in the intervention group at the end of the 8-week treatment phase compared to placebo. However, this difference was not sustained at the 16-week follow-up. Both categorical and continuous measures of depressive symptoms showed a significant difference between the two groups at 4 weeks, but not at 8 and 16 weeks.
Regarding secondary outcomes, the ITT and PP analyses showed an overall significant reduction in self-rated symptoms of anxiety and stress in the active treatment group compared with placebo across time. Specifically, the intervention group reported lower stress at week 16 in both analyses, and lower anxiety at week 16 in the PP analysis.
No serious adverse events were reported, and the number of mild to moderate adverse events was similar in both groups. Adherence to the study protocol was also comparable between the groups.
Conclusion
The authors concluded that the combination of probiotics, magnesium orotate, and coenzyme Q10 may be an effective treatment for MDD over an 8-week period, particularly evident at week 4. While the effect on MDD diagnosis and depressive symptoms was not maintained at the 16-week follow-up, the reductions in anxiety and stress symptoms appeared to be more sustained. The lack of long-term maintenance for depressive symptoms could be due to an insufficient treatment duration, the need for prebiotics to support colonisation, or a requirement for longer magnesium orotate dosage. The study acknowledges limitations such as the significant placebo effect observed in both groups and the strict exclusion criteria limiting generalisability. Despite these limitations, this study, being the largest double-blind RCT to examine this intervention for MDD to date, provides further evidence that such a combination may be a beneficial and safe short-term treatment option for MDD.
References
Strodl, E., Bambling, M., Parnam, S., Ritchie, G., Cramb, S., & Vitetta, L. (2024). Probiotics and magnesium orotate for the treatment of major depressive disorder: A randomised double blind controlled trial. Scientific Reports, 14(1), 20841. https://doi.org/10.1038/s41598-024-71093-z
This post is based on Open Access research and is for informational purposes only.
