Protocol for a randomised, double-blind, placebo-controlled clinical trial on the effects of high-dose vitamin B multivitamin supplementation with and without <i>Passiflora incarnata</i> on neural connectivity and oxidative metabolism in healthy adults.

Abstract

B-vitamins and herbal supplements such as <i>Passiflora incarnata</i> have demonstrated potential benefits for cognitive and neurological functions. This study aims to evaluate the neural and biochemical effects of high-dose vitamin B multivitamin supplementation, with and without <i>P. incarnata</i>, in healthy adults using multimodal neuroimaging and biomarker assessments. This is a phase I/II, randomised, double-blind, placebo-controlled clinical trial involving 108 healthy adults aged 30-55 years, allocated to three groups: (A) high-dose vitamin B multivitamin supplementation with <i>P. incarnata</i>; (B) high-dose vitamin B multivitamin supplementation alone; and (C) placebo. Participants will take two tablets daily for 24 weeks. The primary outcomes are changes in default mode network connectivity assessed using resting-state functional magnetic resonance imaging and diffusion magnetic resonance imaging, together with safety outcomes including vital signs, clinical laboratory parameters and adverse event monitoring. Secondary outcomes include regional brain metabolite concentrations measured by proton magnetic resonance spectroscopy and plasma biomarkers of one-carbon metabolism, including vitamin B₆, vitamin B₁₂, folate and homocysteine. Ethics approval was granted by the Medical Research Ethics Committee, Ministry of Health Malaysia (NMRR-19-379-46101 (ISR); Protocol Number: Exec B). Results will be disseminated through peer-reviewed publications and scientific conferences. ACTRN12622001150730.