Abstract Objective: to perform a systematic literature review to examine the effects of high-dose, B-complex multivitamin/mineral supplementation on physical, mental, and energy outcomes in healthy and ‘at-risk' (suboptimal nutritional status/subclinical symptoms at baseline) adult populations. Methods: PubMed was searched for relevant randomized controlled trials until January 2020. Results: overall, 136 publications were identified. In the seven randomised, double-blind, placebo-controlled studies considered eligible for inclusion, supplementation in healthy populations predominantly showed improvements in perceived stress, physical stamina, concentration, and general mental health, and significant reductions in anxiety and improvements in self-reported vigour. However, not all of these outcomes were significant, and statistical correction for multiple outcomes was not commonly employed. Studies investigating brain mapping following supplementation indicated increased functional activity in brain regions related to processing of attention, executive control, and working memory during cognitive tasks. Conclusions: while there is certainly a need for further studies on the neurocognitive and physical benefits of micronutrient supplementation, this review provides generally supportive evidence for the benefits of a high-dose, B-complex multivitamin/mineral supplement in healthy and at-risk populations in terms of physical, mental, and energy outcomes.

Resumen Objetivo: realizar una revisión sistemática de la literatura para valorar los efectos de la administración de suplementos multivitamínicos/minerales del complejo B en dosis altas sobre los resultados físicos, mentales y energéticos en poblaciones adultas sanas y en situaciones especiales de riesgo (estado nutricional subóptimo/síntomas subclínicos al inicio del estudio). Métodos: se realizaron búsquedas en PubMed de ensayos controlados aleatorios relevantes hasta enero de 2020. Resultados: en total se identificaron 136 publicaciones. En los siete estudios aleatorizados, doble ciego y controlados con placebo considerados elegibles para la inclusión, la suplementación en poblaciones sanas mostró predominantemente mejoras en la percepción del estrés, la resistencia física, la concentración y la salud mental general, así como una reducción significativa de la ansiedad y mejoras en la vitalidad según la autoevaluación de los participantes. Sin embargo, no todos estos resultados fueron significativos y la corrección estadística para múltiples resultados no se empleó habitualmente. Los estudios sobre el mapeo cerebral después de la suplementación, indicaron un aumento de la actividad funcional en las regiones del cerebro relacionadas con el procesamiento de la atención, el control ejecutivo y la memoria de trabajo durante tareas cognitivas. Conclusiones: si bien ciertamente existe la necesidad de realizar más estudios sobre los beneficios neurocognitivos y físicos de la suplementación con micronutrientes, esta revisión proporciona evidencia en general sobre los beneficios de un suplemento multivitamínico/mineral del complejo B en dosis altas, en poblaciones sanas y en situaciones de riesgo, en términos de resultados físicos, mentales y energéticos.

Objective: Bipolar depression is characterized by neurobiological features including perturbed oxidative biology, reduction in antioxidant levels, and a concomitant rise in oxidative stress markers. Bipolar depression manifests systemic inflammation, mitochondrial dysfunction, and changes in brain growth factors. The depressive phase of the disorder is the most common and responds the least to conventional treatments. Garcinia mangostana Linn, commonly known as mangosteen, is a tropical fruit. The pericarp’s properties may reduce oxidative stress and inflammation and improve neurogenesis, making mangosteen pericarp a promising add-on therapy for bipolar depression. Methods: Participants will receive 24 weeks of either 1,000 mg mangosteen pericarp or placebo per day, in addition to their usual treatment. The primary outcome is change in severity of mood symptoms, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), over the treatment phase. Secondary outcomes include global psychopathology, quality of life, functioning, substance use, cognition, safety, biological data, and cost-effectiveness. A follow-up interview will be conducted 4 weeks post-treatment. Conclusion: The findings of this study may have implications for improving treatment outcomes for those with bipolar disorder and may contribute to our understanding of the pathophysiology of bipolar depression. Clinical trial registration: Australian and New Zealand Clinical Trial Registry, ACTRN12616000028404.

Objective: Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder. Methods: This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase. Results: The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment. Conclusion: This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression. Trial registration: Australian and New Zealand Clinical Trial Registry ACTRN12612000830897.