Scientists find a natural compound to inhibit vitamin B6 degradation

28 Jun 2024 --- Inhibiting the intracellular degradation of vitamin B6 can effectively increase its levels in cells, according to a new study. Consuming supplements with the vitamin crucial for brain metabolism is insufficient to prevent or treat brain function disorders.

The researchers posited that inhibiting pyridoxal phosphatase, an enzyme controlling the levels of the active form of vitamin B6 (pyridoxal 5’-phosphate or PLP), would offer an alternative way to manage low vitamin B6 levels, although inhibitors to test the concept were lacking.

“We were already able to show in earlier studies that genetically switching off the vitamin B6-degrading enzyme pyridoxal phosphatase in mice improves the animals’ spatial learning and memory capacity,” explains Antje Gohla, professor of biochemical pharmacology at the Julius-Maximilians-Universitӓt Würzburg, Germany, and lead researcher. 

“In our experiments, we identified a natural substance that can inhibit pyridoxal phosphatase and thus slow down the degradation of vitamin B6.” 

Through this natural substance — 7,8-dihydroxyflavone — the researchers were able to increase vitamin B6 levels in nerve cells involved in learning and memory processes. 

Mental molecule 
Earlier research articles describe 7,8-dihydroxyflavone as a molecule that may improve learning and memory processes in disease models for mental disorders. 

Although the molecule has been studied extensively in brain disorder models, the authors note that its mechanism of action is “actively debated.” The study explains the compound’s effectiveness and may represent a new drug approach to treat brain disorders. 

Vitamin B6 deficiency has been linked with impaired learning abilities and depression, and with declining memory in seniors.For the study, published in eLife, researchers combined small-molecule screening, protein crystallography and biolayer interferometry to discover, visualize and analyze the compound as a direct and potent inhibitor of the vitamin B6-degrading enzyme. 

Vitamin B6 deficiency
Low vitamin B6 levels are associated with impaired memory and learning abilities, a depressive mood and depression. Moreover, in older people, vitamin B6 deficiency is associated with declining memory and dementia. 

The researchers note that the precise role of the vitamin in these disorders and the benefits of supplementation are unclear. They explain that the vitamin covers several interchangeable molecules, with only one “bioactive” form that has a biological role in cells. 

They underscore that the identification of 7,8-dihydroxyflavone is a first step in the discovery of more efficient inhibitors of pyridoxal phosphatase that could be used in combination with supplements. 

Moreover, pyridoxal phosphatase inhibitors would be valuable tools to study whether increasing the levels of bioactive vitamin B6 helps people with mental health conditions associated with impaired memory, learning and mood. 

Health benefits 
Innova Market Insight data indicates that B vitamins, especially B6, are key ingredients for brain health. The use of vitamin B6 in supplements launched with brain support claims grew from 24% in 2019 to 26% in 2023. Industry experts expect that B vitamins will continue to dominate the nutrition sector, along with vitamin C and D3. 

Data from the market researcher also indicates a substantial growth in brain support supplements, tracking an average annual growth of 14% in product launches. 

Meanwhile, researchers also uncovered a promising role of vitamin B6 in targeting pancreatic cancer. The vitamin supports immune cells, but in pancreatic cancer patients, cancer cells use all the vitamin, blocking their function. 

By Jolanda van Hal