February 17, 2025 • 9 mins
In this episode of Daily Value, we look at the latest research on B vitamins and their in neuropsychiatric disorders. A newly published meta-analysis suggests a causal relationship between B vitamin deficiencies and neuropsychiatric disorders. We will break down the scientific findings on B6, B12, and folate, shedding light on their roles in conditions like Parkinson’s disease.
Discussion Points:
- How recent genetic studies support a causal link between B vitamin deficiencies and mental health conditions.
- The role of B vitamins in reducing neurotoxicity and slowing brain atrophy.
- How vitamin B12 may protect against dopamine neuron loss and disease progression.
- Evidence linking low B6 levels to neurotransmitter imbalances and schizophrenia risk.
- The impact of folate on one-carbon metabolism and its protective role in neurodegeneration.
https://pubmed.ncbi.nlm.nih.gov/26757190/
https://pubmed.ncbi.nlm.nih.gov/32257364/
https://pubmed.ncbi.nlm.nih.gov/30858560/
https://pubmed.ncbi.nlm.nih.gov/32424116/
https://pubmed.ncbi.nlm.nih.gov/33941768/
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 0 (00:00):
For the first time, a meta-analysis was just
published suggesting a causalrelationship between B vitamins,
specifically not getting enoughof certain B vitamins, and the
development of neuropsychiatricdisorders.
Hello everyone and welcome backto Daily Value.
I'm William Walsh and todaywe're taking a look at how B
vitamins influence our mentalhealth and brain function.
(00:20):
In today's episode we'll breakdown the latest evidence on this
topic, examining how B vitaminsrelate to neuropsychiatric
disorders overall, how theyinteract with homocysteine and
mild cognitive impairment, andtheir roles in Parkinson's
disease and schizophrenia.
We'll start with themeta-analysis I mentioned and
then look at individual Bvitamins to see how they may be
(00:41):
exerting their effects.
This meta-analysis that isslated for publication in the
March issue of Nerve Science andBehavioral Reviews titled
Causal Relationship Between BVitamins and Neuropsychiatric
Disorders a Systematic Reviewand Meta-Analysis.
This review focused on studiesthat use Mendelian randomization
(01:03):
.
This was unique because thesetypes of studies use genetic
variants as proxies for anexposure, like levels of B
vitamins, to test whether thatexposure is causally related to
an outcome such as aneuropsychiatric disorder.
Because genetic variants arerandomly assorted to people at
conception, this methodminimizes the confounding
factors and reverse causationthat often affect observational
(01:26):
studies.
This meta-analysis found thatindividual B vitamins have
distinct impacts on mentalhealth.
For instance, vitamin B12 isprotective against the
development of Parkinson'sdisease, vitamin B6 was found to
be protective againstschizophrenia, and vitamin B9,
that's folate is protectiveagainst intellectual
disabilities and Alzheimer'sdisease.
(01:47):
When broken down into subgroups, all three B vitamins were
found to be strongly protectivefactors against the development
of Alzheimer's and Parkinson'sdisease.
What do all three of these Bvitamins have in common?
Well, they're all cornerstonenutrients of what's called
one-carbon metabolism.
I covered this topic in episode27, but I will briefly explain
it again here.
One-carbon metabolism is anetwork of biochemical pathways
(02:11):
that transfers single-carbonunits between molecules to
support essential cellularfunctions like supporting DNA
synthesis, repair andmethylation.
These three B vitamins areresponsible for converting
homocysteine, a neurotoxic aminoacid, into methionine, a
precursor toS-adenosylmethionine, or SAMe as
(02:33):
most of us know it.
Same is a universal methyldonor involved in DNA
methylation.
It's well known that abnormallyhigh levels of homocysteine
often accompany neuropsychiatricdisorders, with potential
mechanisms behind this,including oxidative stress,
vascular damage andneurotransmitter dysfunctions.
Genetic variants in one-carbonmetabolism pathways have been
(02:54):
linked to altered B vitaminmetabolism and increased
susceptibility toneuropsychiatric disorders.
Homocysteine has also beenshown to interfere with
metabolism of amyloid betaplaques, these plaques being one
of the pathological hallmarksof Alzheimer's disease.
One particular study, known asthe VITACOG trial, looked at
whether B vitaminsupplementation, specifically
(03:16):
800 micrograms of folate, 20milligrams of vitamin B6, and
500 micrograms of vitamin B12,could slow cognitive decline.
In this study, b vitaminsupplementation slowed brain
atrophy by up to 30% inparticipants with elevated
homocysteine levels, that'shomocysteine over 11 micromoles
(03:36):
per liter.
Those results were found inpeople who had the best omega-3
status, showing the importanceof how multiple nutrients work
together as it pertains toParkinson's disease.
Vitamin B12 has the strongestrelationship of the B vitamin
families.
Research has consistently shownthat patients with Parkinson's
often present with lower vitaminB12 levels at the time of
(03:57):
diagnosis, compared to patientswith other neurodegenerative
conditions, such as progressivesupranuclear palsy,
frontotemporal dementia ordementia with Lewy bodies.
One study reported that whilevitamin B12 levels in
Parkinson's patients were, onaverage, lower, the rate of
decline in vitamin B12 was farmore striking.
(04:18):
Parkinson's patients exhibit adecline in blood vitamin B12
levels between 17 and 47picograms per milliliter per
year.
In a healthy person over 65years old, b12 levels should
only drop around 5 picograms permilliliter per year.
Now there are two active formsof vitamin B12.
There is methylcobalamin, whichis the form involved in
(04:40):
one-carbon metabolism and thebreakdown of homocysteine.
And then there is the lesserappreciated adenosylcobalamin,
which is the form involved inone-carbon metabolism and the
breakdown of homocysteine.
And then there is thelesser-appreciated
adenosylcobalamin, which servesa different function.
It is situated insidemitochondria and is used by the
enzyme methylmalonyl-CoA mutaseto convert methylmalonyl-CoA
into succinyl-CoA.
If adenosylcobalamin is lacking, methylmalonyl-coa will convert
(05:06):
into methylmalonic acid, whichis a marker of vitamin B12
deficiency.
Now a very interesting andgroundbreaking molecular-based
study published in 2019 showedthat adenosylcobalamin acts as
what is known as a mixed-typeallosteric inhibitor of LRK2
kinase, a protein whosehyperactivity is closely linked
to neurotoxicity in Parkinson's.
Mutations to LRK2 are the mostcommon causal genetic variants
(05:30):
for Parkinson's disease.
When this enzyme activity isincreased, alpha-synuclein
proteins form and build up.
These are toxic to dopamineneurons In vitro, so this was
again a mechanistic cell-basedstudy.
Adenosylcobalamin inhibitedLRK2 activity.
This study also had ananimal-based portion, where
adenosylcobalamin not onlyreduced LRK2 hyperactivity, but
(05:53):
also improved dopamine releaseand sustained the life of
dopamine neurons, which areeventually overcome by toxic
protein buildup caused by someLRK2 mutations in Parkinson's
disease.
Collectively, the body of worksuggests that adequate B12
levels might not only preventdeficiency-related complications
, but they could also modulateB12.
Disease processes at themolecular level in Parkinson's
(06:16):
disease.
Now on to vitamin B6 and itsinteresting connection to
schizophrenia.
Several meta-analyses haveshown that individuals with
schizophrenia have significantlylower levels of vitamin B6,
specifically reduced pyridoxallevels, compared to healthy
controls.
Three clinical trials between2010 and 2014 showed that
(06:38):
peripheral blood levels ofpyridoxal in patients with
schizophrenia was significantlyless than that of healthy
controls.
This was replicated by anotherstudy in 2014 and yet another in
2018.
Interestingly, a review paperpublished in 2020 by Carvalho et
al screened 162 peripheralbiomarkers for major mental
(06:58):
disorders and determined thatvitamin B6 may be the most
compelling evidence as aperipheral biomarker for
schizophrenia, meaning thatblood levels may be useful when
attempting to diagnose someonewith schizophrenia or evaluating
risk for schizophrenia.
There was a notable rodent studypublished in 2021 by Toriumi et
al, where the researchersgenerated a mouse model of
(07:21):
vitamin B6 deficiency.
In these vitamin B6 deficientmice, vitamin B6 levels dropped
to just 2.9%.
Behaviorally, these miceexhibited striking social
deficits and significantimpairments in recognition
memory.
Social deficits and significantimpairments in recognition
memory.
Beyond behavior, biochemicalanalysis revealed that, while
baseline levels of noradrenalinein the brain remained unchanged
(07:43):
, the release of noradrenalinewas significantly enhanced in
both the prefrontal cortex andthe striatum.
This hyperactivation of thenoradrenergic system is thought
to contribute to the social andcognitive impairments that are
seen in schizophrenia.
Importantly, when researchersadministered vitamin B6 directly
into the brain of the rodents,the behavioral deficits were
(08:06):
restored nearly to normal.
Collectively available evidenceto date points to reduced
vitamin B6 contributing toschizophrenia's pathophysiology
by disrupting neurotransmitterbalance.
And finally, let's turn tofolate.
The meta-analysis referenced atthe beginning of this episode
suggests that folate was linkedto a significantly reduced risk
(08:28):
of developing Alzheimer's, withan odds ratio of around 0.35.
This suggests that individualswith higher folate levels may
have approximately a 65% lowerrisk of Alzheimer's compared to
those with lower levels offolate.
Again, this finding isinteresting because Mendelian
randomization helps confirm thatthe association isn't merely
(08:49):
correlational but is more likelyto reflect a causal
relationship.
To sum up, the emergingevidence from genetic studies,
clinical trials and animalmodels converges on one key
message B vitamins are potentmodulators of brain health, each
with a unique profile ofbenefits and risks.
Vitamin B6, while protectiveagainst Alzheimer's and
(09:10):
schizophrenia, its deficiencymight exacerbate symptoms of
schizophrenia throughhyperactivation of the
neuroadrenergic system.
On the other hand, it'simportant to note that, while
moderate vitamin B6 supportsneurotransmitter balance,
excessive intake has been linkedto sensory neuropathy.
Vitamin B12 deficiency isprevalent in Parkinson's disease
(09:30):
and may directly impact diseaseprogression by modulating gene
activity that is thought to becausal to Parkinson's disease.
While folate not only supportscognitive function through all
life stages, it also appears tobe protective against
Alzheimer's disease, likelythrough its role in one-carbon
metabolism.
Thank you for joining me todayon Daily Value.
(09:51):
If you found this episodeinsightful, please share with
your network.
As always, stay curious andstay healthy.
For the first time, a meta-analysis was just
published suggesting a causalrelationship between B vitamins,
specifically not getting enoughof certain B vitamins, and the
development of neuropsychiatricdisorders.
Hello everyone and welcome backto Daily Value.
I'm William Walsh and todaywe're taking a look at how B
vitamins influence our mentalhealth and brain function.
(00:20):
In today's episode we'll breakdown the latest evidence on this
topic, examining how B vitaminsrelate to neuropsychiatric
disorders overall, how theyinteract with homocysteine and
mild cognitive impairment, andtheir roles in Parkinson's
disease and schizophrenia.
We'll start with themeta-analysis I mentioned and
then look at individual Bvitamins to see how they may be
(00:41):
exerting their effects.
This meta-analysis that isslated for publication in the
March issue of Nerve Science andBehavioral Reviews titled
Causal Relationship Between BVitamins and Neuropsychiatric
Disorders a Systematic Reviewand Meta-Analysis.
This review focused on studiesthat use Mendelian randomization
(01:03):
.
This was unique because thesetypes of studies use genetic
variants as proxies for anexposure, like levels of B
vitamins, to test whether thatexposure is causally related to
an outcome such as aneuropsychiatric disorder.
Because genetic variants arerandomly assorted to people at
conception, this methodminimizes the confounding
factors and reverse causationthat often affect observational
(01:26):
studies.
This meta-analysis found thatindividual B vitamins have
distinct impacts on mentalhealth.
For instance, vitamin B12 isprotective against the
development of Parkinson'sdisease, vitamin B6 was found to
be protective againstschizophrenia, and vitamin B9,
that's folate is protectiveagainst intellectual
disabilities and Alzheimer'sdisease.
(01:47):
When broken down into subgroups, all three B vitamins were
found to be strongly protectivefactors against the development
of Alzheimer's and Parkinson'sdisease.
What do all three of these Bvitamins have in common?
Well, they're all cornerstonenutrients of what's called
one-carbon metabolism.
I covered this topic in episode27, but I will briefly explain
it again here.
One-carbon metabolism is anetwork of biochemical pathways
(02:11):
that transfers single-carbonunits between molecules to
support essential cellularfunctions like supporting DNA
synthesis, repair andmethylation.
These three B vitamins areresponsible for converting
homocysteine, a neurotoxic aminoacid, into methionine, a
precursor toS-adenosylmethionine, or SAMe as
(02:33):
most of us know it.
Same is a universal methyldonor involved in DNA
methylation.
It's well known that abnormallyhigh levels of homocysteine
often accompany neuropsychiatricdisorders, with potential
mechanisms behind this,including oxidative stress,
vascular damage andneurotransmitter dysfunctions.
Genetic variants in one-carbonmetabolism pathways have been
(02:54):
linked to altered B vitaminmetabolism and increased
susceptibility toneuropsychiatric disorders.
Homocysteine has also beenshown to interfere with
metabolism of amyloid betaplaques, these plaques being one
of the pathological hallmarksof Alzheimer's disease.
One particular study, known asthe VITACOG trial, looked at
whether B vitaminsupplementation, specifically
(03:16):
800 micrograms of folate, 20milligrams of vitamin B6, and
500 micrograms of vitamin B12,could slow cognitive decline.
In this study, b vitaminsupplementation slowed brain
atrophy by up to 30% inparticipants with elevated
homocysteine levels, that'shomocysteine over 11 micromoles
(03:36):
per liter.
Those results were found inpeople who had the best omega-3
status, showing the importanceof how multiple nutrients work
together as it pertains toParkinson's disease.
Vitamin B12 has the strongestrelationship of the B vitamin
families.
Research has consistently shownthat patients with Parkinson's
often present with lower vitaminB12 levels at the time of
(03:57):
diagnosis, compared to patientswith other neurodegenerative
conditions, such as progressivesupranuclear palsy,
frontotemporal dementia ordementia with Lewy bodies.
One study reported that whilevitamin B12 levels in
Parkinson's patients were, onaverage, lower, the rate of
decline in vitamin B12 was farmore striking.
(04:18):
Parkinson's patients exhibit adecline in blood vitamin B12
levels between 17 and 47picograms per milliliter per
year.
In a healthy person over 65years old, b12 levels should
only drop around 5 picograms permilliliter per year.
Now there are two active formsof vitamin B12.
There is methylcobalamin, whichis the form involved in
(04:40):
one-carbon metabolism and thebreakdown of homocysteine.
And then there is the lesserappreciated adenosylcobalamin,
which is the form involved inone-carbon metabolism and the
breakdown of homocysteine.
And then there is thelesser-appreciated
adenosylcobalamin, which servesa different function.
It is situated insidemitochondria and is used by the
enzyme methylmalonyl-CoA mutaseto convert methylmalonyl-CoA
into succinyl-CoA.
If adenosylcobalamin is lacking, methylmalonyl-coa will convert
(05:06):
into methylmalonic acid, whichis a marker of vitamin B12
deficiency.
Now a very interesting andgroundbreaking molecular-based
study published in 2019 showedthat adenosylcobalamin acts as
what is known as a mixed-typeallosteric inhibitor of LRK2
kinase, a protein whosehyperactivity is closely linked
to neurotoxicity in Parkinson's.
Mutations to LRK2 are the mostcommon causal genetic variants
(05:30):
for Parkinson's disease.
When this enzyme activity isincreased, alpha-synuclein
proteins form and build up.
These are toxic to dopamineneurons In vitro, so this was
again a mechanistic cell-basedstudy.
Adenosylcobalamin inhibitedLRK2 activity.
This study also had ananimal-based portion, where
adenosylcobalamin not onlyreduced LRK2 hyperactivity, but
(05:53):
also improved dopamine releaseand sustained the life of
dopamine neurons, which areeventually overcome by toxic
protein buildup caused by someLRK2 mutations in Parkinson's
disease.
Collectively, the body of worksuggests that adequate B12
levels might not only preventdeficiency-related complications
, but they could also modulateB12.
Disease processes at themolecular level in Parkinson's
(06:16):
disease.
Now on to vitamin B6 and itsinteresting connection to
schizophrenia.
Several meta-analyses haveshown that individuals with
schizophrenia have significantlylower levels of vitamin B6,
specifically reduced pyridoxallevels, compared to healthy
controls.
Three clinical trials between2010 and 2014 showed that
(06:38):
peripheral blood levels ofpyridoxal in patients with
schizophrenia was significantlyless than that of healthy
controls.
This was replicated by anotherstudy in 2014 and yet another in
2018.
Interestingly, a review paperpublished in 2020 by Carvalho et
al screened 162 peripheralbiomarkers for major mental
(06:58):
disorders and determined thatvitamin B6 may be the most
compelling evidence as aperipheral biomarker for
schizophrenia, meaning thatblood levels may be useful when
attempting to diagnose someonewith schizophrenia or evaluating
risk for schizophrenia.
There was a notable rodent studypublished in 2021 by Toriumi et
al, where the researchersgenerated a mouse model of
(07:21):
vitamin B6 deficiency.
In these vitamin B6 deficientmice, vitamin B6 levels dropped
to just 2.9%.
Behaviorally, these miceexhibited striking social
deficits and significantimpairments in recognition
memory.
Social deficits and significantimpairments in recognition
memory.
Beyond behavior, biochemicalanalysis revealed that, while
baseline levels of noradrenalinein the brain remained unchanged
(07:43):
, the release of noradrenalinewas significantly enhanced in
both the prefrontal cortex andthe striatum.
This hyperactivation of thenoradrenergic system is thought
to contribute to the social andcognitive impairments that are
seen in schizophrenia.
Importantly, when researchersadministered vitamin B6 directly
into the brain of the rodents,the behavioral deficits were
(08:06):
restored nearly to normal.
Collectively available evidenceto date points to reduced
vitamin B6 contributing toschizophrenia's pathophysiology
by disrupting neurotransmitterbalance.
And finally, let's turn tofolate.
The meta-analysis referenced atthe beginning of this episode
suggests that folate was linkedto a significantly reduced risk
(08:28):
of developing Alzheimer's, withan odds ratio of around 0.35.
This suggests that individualswith higher folate levels may
have approximately a 65% lowerrisk of Alzheimer's compared to
those with lower levels offolate.
Again, this finding isinteresting because Mendelian
randomization helps confirm thatthe association isn't merely
(08:49):
correlational but is more likelyto reflect a causal
relationship.
To sum up, the emergingevidence from genetic studies,
clinical trials and animalmodels converges on one key
message B vitamins are potentmodulators of brain health, each
with a unique profile ofbenefits and risks.
Vitamin B6, while protectiveagainst Alzheimer's and
(09:10):
schizophrenia, its deficiencymight exacerbate symptoms of
schizophrenia throughhyperactivation of the
neuroadrenergic system.
On the other hand, it'simportant to note that, while
moderate vitamin B6 supportsneurotransmitter balance,
excessive intake has been linkedto sensory neuropathy.
Vitamin B12 deficiency isprevalent in Parkinson's disease
(09:30):
and may directly impact diseaseprogression by modulating gene
activity that is thought to becausal to Parkinson's disease.
While folate not only supportscognitive function through all
life stages, it also appears tobe protective against
Alzheimer's disease, likelythrough its role in one-carbon
metabolism.
Thank you for joining me todayon Daily Value.
(09:51):
If you found this episodeinsightful, please share with
your network.
As always, stay curious andstay healthy.
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