- A new study in mice shows that a natural flavonoid can slow down the degradation of vitamin B6 in the brain.
- Vitamin B6 deficiency has long been associated with poorer cognitive function.
- Vitamin B6 supplementation alone to improve cognition has produced mixed results in trials.
- The study authors hope that greater cognitive benefits can be achieved by combining the flavonoid with B6 supplementation.
Insufficient vitamin B6 is linked to cognitive impairment, and a new study presents a new approach to maintaining adequate B6 levels.
Study in mice reveals that a natural flavonoid,
The enzyme is pyridoxal phosphatase (PDXP).
The study follows earlier work by the same team led by Antje Gohla, PhD, at the Institute of Pharmacology and Toxicology of the University of Würzburg in Germany. That work demonstrated improved spatial learning ability and memory in mice when their pyridoxal phosphatase was disabled.
The study was published in eLife.
Jacqueline Becker, PhD, a neuropsychologist and health services researcher at the Icahn School of Medicine in the Division of General Internal Medicine at Mount Sinai, was not involved in the study.
“Several studies have examined the impact of B6 on cognition,” Becker said. “In particular, maintaining adequate levels of B vitamins, and vitamin B6 in particular, is essential for optimal neurotransmitter synthesis and homocysteine metabolism, and thus may have a direct impact on cognitive function.”
“Vitamin B6 deficiency has long been associated with cognitive impairment, particularly in areas related to hippocampal functioning,” Becker said.
The hippocampus is believed to be important for the consolidation of memory and age-dependent learning and, therefore, cognition.
In the brain, Becker said, B6 “helps synthesize neurotransmitters—eg, serotonin, dopamine, gamma-aminobutyric acid—and helps lower homocysteine levels in the blood.”
She also noted that B6 is linked to mood, a known factor in cognitive health.
“Cognitive dysfunction is a major symptom of depression, especially lack of attention and psychomotor speed,” she emphasized.
So far, the benefits of increasing B6 levels through supplementation as a therapeutic method are unclear. Clinical trials have yielded mixed results, “particularly in areas related to hippocampal functioning,” according to Becker.
The new study may help explain this. Gohla said her team found that “PDXP is significantly regulated – [or strengthened] — in the hippocampus of middle-aged compared to young rats.”
This is consistent with the age-related memory loss that occurs with aging.
Said Gohla, “This suggests that therapeutic vitamin B6 supplementation alone may not be sufficient to raise B6 levels in the brain—simply because the supplemented B6 would be immediately degraded by hyperactive PDXP.”
“In contrast,” the study finds, “combining B6 supplements with PDXP inhibitors that block B6 degradation may be much more effective at increasing cellular B6 levels.”
In the team’s previous work, they found that the spatial learning and memory capacity of mice improved when PDXP was genetically switched off. Their performance was compared to mice with intact PDXP.
The researchers assessed the cognitive functioning of the mice using a
In the “maze”, rats are placed on a platform with unpleasantly bright lighting. While there were a number of potential “escape” holes for rats on the platform, only a few were available for use.
“The [PDXP-less] rats learn to find the correct escape hole with the help of visual cues, such as shapes or colored patterns, that are placed around the platform,” Gohla said.
In the new study, subject mice were sacrificed and the researchers used small molecule screening, protein crystallography and biolayer interferometry to observe 7,8-dihydroxyflavone directly affecting the action of pyridoxal phosphatase.
Given the differences between mice and humans, there may be concerns that the study’s findings will not be applicable to humans.
Becker said, however, that “the two known functions of B6 in cognition—eg, neurotransmitter synthesis and homocysteine metabolism—are thought to be mechanistically interchangeable between mice and humans.”
“So it is conceivable that [the research] would be translated by excluding obvious environmental confounders (eg, alcohol consumption, poor diet, etc.),” Becker said.
“We expect,” Gohla said, “that 7,8-dihydroxyflavone will inhibit PDXP in the brain and, together with supplemented B6, will increase cellular B6 levels. Whether and how this might enhance recognition is an open question that we will address in future work.”
She noted the complexity involved, saying, “there are many B6-dependent enzymes in the brain, including those that regulate neurotransmitter levels and neuronal signaling.”
Among the things that are not known are whether a single enzyme or transmitter is vital, or whether many such factors are involved.
“More studies,” Becker said, “are needed to determine the actual role of B6 supplementation in neurodegenerative diseases, as well as its availability in synthetic forms (as opposed to diets) and appropriate dosages.”
Becker hypothesized that the therapeutic potential of B6 administration would have to be evaluated on an individual basis.
She suggested that the greatest benefit is likely to occur when “combined with appropriate diet/nutrition and lifestyle that is optimized to support cognition and mental health – for example, taking into account other B vitamins (e.g. , B12) and other micronutrients that are critical for brain health (eg folic acid, etc.)”
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