High-dose B vitamins with Passiflora may alter brain connectivity in healthy adults
A phase I/II trial in 108 healthy adults will test whether high-dose B-vitamin supplementation, with or without the herbal extract Passiflora incarnata, changes default mode network connectivity on brain imaging and markers of one-carbon metabolism over 24 weeks.
Researchers are launching a randomised, double-blind, placebo-controlled trial to examine whether high-dose B-vitamin supplements—taken alone or combined with Passiflora incarnata, a traditional herbal remedy—affect brain function and biochemistry in healthy adults. The study will enroll 108 participants aged 30–55 and divide them into three groups: one receiving B vitamins plus Passiflora, one receiving B vitamins alone, and one receiving placebo, all taken as two tablets daily for 24 weeks.
The primary measure is change in default mode network connectivity using resting-state functional magnetic resonance imaging and diffusion imaging, plus safety monitoring via vital signs and lab work. Secondary outcomes include brain metabolite concentrations measured by magnetic resonance spectroscopy and blood markers tied to one-carbon metabolism—specifically vitamin B6, B12, folate, and homocysteine levels. B-vitamins are cofactors in methyl transfer reactions essential for neurotransmitter synthesis and myelin maintenance, while Passiflora has been traditionally used for anxiety and sleep, though its neurochemical mechanism remains unclear. This is a protocol paper announcing the trial design; actual efficacy results are not yet available, so the magnitude and clinical relevance of any connectivity changes remain unknown.
The protocol reveals several methodological strengths: the study uses multimodal neuroimaging (structural, functional, and metabolite measures) rather than a single brain outcome, improving sensitivity to subtle effects; the 24-week duration is long enough to detect biochemical shifts in one-carbon metabolism. However, important limitations are already evident. First, only healthy adults aged 30–55 are included, so findings may not generalise to older populations or those with cognitive complaints. Second, the trial does not pre-specify which connectivity changes would constitute clinical benefit—researchers will measure default mode network function, but without a priori thresholds, post-hoc selective reporting is a risk. Third, while homocysteine elevation is linked to cognitive decline in some observational studies, it is unclear whether B-vitamin supplementation in people with normal baseline levels actually prevents decline or improves cognition. The inclusion of Passiflora alongside B vitamins makes it harder to isolate which ingredient, if either, drives any effect.
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