- A new study in mice shows that natural flavonoids can slow the breakdown of vitamin B6 in the brain.
- Vitamin B6 deficiency has long been linked to cognitive decline.
- When vitamin B6 was supplemented alone to improve cognitive function, trials have shown mixed results.
- The study authors hope that combining flavonoids with B6 supplements may result in greater cognitive benefits.
Deficiency of vitamin B6 has been linked to cognitive impairment, and new research offers a new approach to maintaining adequate B6 levels.
Studies in mice have shown that the natural flavonoid
This enzyme is pyridoxal phosphatase (PDXP).
This study follows an earlier study by the same team led by Dr. Antje Gora of the Institute of Pharmacology and Toxicology at the University of Würzburg in Germany, which demonstrated improved spatial learning and memory abilities in mice in which pyridoxal phosphatase was inactivated.
This study E-Life.
Dr. Jacqueline Becker, a neuropsychologist and health services researcher in the department of general medicine at the Icahn School of Medicine at Mount Sinai, was not involved in the study.
“Several studies have investigated the impact of vitamin B6 on cognitive function,” Becker says. “Specifically, maintaining adequate levels of B vitamins, and particularly vitamin B6, is essential for optimal neurotransmitter synthesis and homocysteine metabolism, which may directly impact cognitive function.”
“Vitamin B6 deficiency has long been associated with cognitive impairment, particularly in areas that correlate with hippocampal function,” Becker said.
The hippocampus is thought to play an important role in age-related memory consolidation and learning, and therefore cognition.
In the brain, vitamin B6 “helps to synthesize neurotransmitters like serotonin, dopamine, and gamma-aminobutyric acid, and helps lower levels of homocysteine in the blood,” says Becker.
She also noted that vitamin B6 is linked to mood, which is a known factor in cognitive health.
“Cognitive impairment, particularly deficits in attention and psychomotor speed, is a cardinal symptom of depression,” she noted.
So far, the benefit of boosting vitamin B6 levels with supplements as a treatment is unclear: clinical trials have shown mixed results, “particularly in areas that correlate with hippocampal function,” Becker said.
The new study may help explain that: Gola said her team found that “PDXP is significantly upregulated.” [or strengthened] “The difference was more pronounced in the hippocampus of middle-aged mice compared with young mice.”
This is consistent with the age-related memory loss that occurs with age.
“This suggests that therapeutic vitamin B6 supplements alone may not be sufficient to increase B6 concentrations in the brain, because supplemental B6 is quickly degraded by overactive PDXP,” Gora said.
“In contrast, combining a B6 supplement with a PDXP inhibitor, which blocks the breakdown of B6, may be much more effective at boosting intracellular B6 levels,” the study found.
In a previous study, the team found that genetically turning off PDXP improved spatial learning and memory in mice, whose performance was compared with that of mice with normal PDXP.
The researchers investigated the cognitive function of mice
In the maze, mice were placed on an uncomfortably brightly lit platform with a number of holes through which the mice could potentially escape, only some of which were actually usable.
” [PDXP-less] “The mice learn to find the correct escape route with the help of visual cues, such as colored shapes and patterns placed around the platform,” Gora said.
In the new study, subject mice were sacrificed and the researchers used small molecule screening, protein crystallography and biolayer interferometry to observe how 7,8-dihydroxyflavone directly affected the activity of pyridoxal phosphatase.
Given the differences between mice and humans, some may be concerned that the findings may not generalize to humans.
But Becker said, “two functions of vitamin B6 in cognition – neurotransmitter synthesis and homocysteine metabolism – are thought to be mechanistically compatible between mice and humans.”
“that’s why, [the research] “This would hold true if we excluded obvious environmental confounding factors (such as alcohol consumption or unhealthy diet),” Becker said.
“We expect that 7,8-dihydroxyflavone will inhibit PDXP in the brain and, together with supplemental vitamin B6, increase intracellular vitamin B6 concentrations. Whether and how this enhances cognition remains an open question that we will address in future studies,” Gora said.
She pointed out the complexity, saying, “There are many enzymes in the brain that depend on vitamin B6, including some that regulate neurotransmitter levels and nerve signaling.”
Among the things that are unknown is whether a single enzyme or transmitter is the key factor or whether multiple such factors are involved.
“Further research is needed to determine the actual role of vitamin B6 supplementation in neurodegenerative diseases, its bioavailability in synthetic forms (vs. food forms), and appropriate dosages,” Becker said.
Becker hypothesized that the therapeutic effect of B6 administration would need to be evaluated on an individual basis.
She suggested that the greatest benefits are likely to be achieved when combined with “an appropriate diet/nutrition and lifestyle optimized to support cognitive function and mental health, for example, when considering other B vitamins (e.g., B12) and other micronutrients important to brain health (e.g., folate).”
