Combining flavonoid with vitamin B6 may help preserve cognitive function

Vitamin B6 deficiency is linked to cognitive impairment, and new research offers an innovative approach to maintaining adequate B6 levels.

A study in mice found that the natural flavonoid 7,8-dihydroxyflavone can bind to and inhibit the enzyme that breaks down B6, thus helping to maintain B6 levels in the brain.

The enzyme in question is called pyridoxal phosphatase (PDXP).

This study follows previous work by the same team, led by Antje Gohl, PhD, of the Institute of Pharmacology and Toxicology at the University of Würzburg in Germany. They previously demonstrated improved spatial learning and memory in mice when pyridoxal phosphatase was deactivated.

The Link Between Vitamin B6 and Cognitive Health

Jackilyn Becker, PhD, a neuropsychologist and public health researcher at the Icahn School of Medicine at Mount Sinai, was not involved in the study. She explains that vitamin B6 is necessary for optimal neurotransmitter synthesis and homocysteine metabolism, which directly impacts cognitive function.

Vitamin B6 deficiency has long been linked to cognitive impairment, particularly in areas related to hippocampal function. In the brain, vitamin B6 promotes the synthesis of neurotransmitters (e.g., serotonin, dopamine, gamma-aminobutyric acid) and helps reduce homocysteine levels in the blood.

Problems with B6 Supplements

Until now, the benefits of increasing B6 levels through supplements have been unclear. Clinical trials have produced conflicting results, particularly in areas related to hippocampal function.

A new study may explain this: Gohl’s team found that PDXP is significantly upregulated in the hippocampus of middle-aged mice compared to young mice. This is consistent with age-related memory loss. This suggests that therapeutic vitamin B6 supplements may not be enough to boost brain B6 levels, as the added vitamin B6 is immediately destroyed by hyperactive PDXP.

Differences between mice and humans

Previous work by the team showed that spatial learning and memory in mice improved when PDXP was genetically knocked out. In the new study, mice were sacrificed and the researchers used small molecule screening, protein crystallography, and biolayer interferometry to observe the effects of 7,8-dihydroxyflavone on pyridoxal phosphatase.

Despite differences between mice and humans, key functions of vitamin B6 in cognitive processes, such as neurotransmitter synthesis and homocysteine metabolism, are considered mechanistically interchangeable between mice and humans.

The Future of 7,8-Dihydroxyflavone

The team expects that 7,8-dihydroxyflavone will inhibit PDXP in the brain and, together with B6 supplements, increase B6 levels in cells. Whether this will improve cognitive performance remains to be seen and will be addressed in future studies.

More research is needed to determine the role of B6 supplementation in neurodegenerative diseases, its bioavailability in synthetic (versus dietary) forms, and appropriate doses. Most likely, the therapeutic potential of B6 administration will need to be assessed on an individual basis, in combination with appropriate diet, nutrition, and lifestyle optimized to support cognitive and mental health.