Where might this be? Read on to find out
Key takeaway points
· Some people with autism will experience gains when taking a vitamin A supplement. While the short-term improvement might be modest, it is a simple step to take. There may also be longer term benefits as indicated in today's post.
· The best option is a healthy diet, plus a daily multivitamin with 100% RDA for vitamin A (for males 14 and over this is 3,000 IU or 900 mcg RAE)
· China is at the centre of this research, where children with autism are found to be deficient in vitamin A. Their autism improved when this was corrected.
· Good job Maja in Belgrade and Beata in Zagreb
8 years ago our reader Maja, in
Belgrade, shared with us that a small dose of fish oil, containing vitamin A,
had the same beneficial effect as oxytocin on her daughter and she figured out
why this was the case. When reading some recent Chinese research from a group
very interested in vitamin D and autism, I recalled Maja’s discovery.
Beata, another doctor, not far away in Zagreb, has made her own discovery. She is a virologist with stage 3 breast cancer and when her cancer returned she created her own novel viral therapy to treat it. She wanted to share her discovery with the world but a dozen publications refused to publish her case report. "The major concern was always ethical issues."
Taking the initiative and treating yourself is frowned upon in the medical world today, but many medical discoveries were actually made this way.
Croatian virologist treats her own breast cancer with experimental virus therapy
Beata
Halassy is the head of a research unit at the University of Zagreb but stresses
that she isn't a specialist in oncolytic virotherapy (OVT). Her
proficiency in cultivating and purifying viruses in the laboratory gave her the
confidence to pursue this unproven treatment. She used two types of viruses: a
strain of the measles virus commonly used in childhood vaccines, and a
vesicular stomatitis virus (VSV) known to cause, at worst, mild influenza-like
symptoms. Both viruses have good safety records and are known to infect the
type of cells from which her tumor originated.
Her
idea was that the virus would attack the tumor and direct her immune system to
the location of the viral intruder in her body. "An immune response was,
for sure, elicited," Halassy stated. She self-administered the treatment
by injecting the lab-grown viruses directly into her tumor for two months.
During this period, her condition was continuously monitored by oncologists at
the University Hospital of Zagreb, who were prepared to intervene with
chemotherapy if necessary.
The
size of Halassy's tumor initially swelled but then decreased during the
treatment. After two months, it had shrunk, become softer, and the surrounding
tissue had loosened, making it easier for doctors to remove surgically. As a
result, the tumor could be successfully surgically removed. Analysis of the
tissue showed that her immune system had indeed attacked the tumor, as it was
thoroughly infiltrated with immune cells called lymphocytes. She experienced
some mild side effects but no serious adverse reactions occurred during her
treatment.
As
of today, she has remained cancer-free for four years.
The case report was finally published and here it is:
An Unconventional Case Study of Neoadjuvant Oncolytic Virotherapy for Recurrent Breast Cancer
A great success for Beata and her colleagues, but it
highlights the obstacles in the way of new ideas in the field of medicine.
As for Maja, I still recall her
comment and that I wrote a post about it in 2016
Vitamin A (and ATRA) Upregulate Oxytocin via CD38
Enter Chongqing, China.
Chongqing - a sprawling city of 32 million people you may not have heard of. Nearly as populous as Shanghai.
Researchers at Chongqing Medical University started to show an interest in vitamin D and autism around 2018.
Autism
spectrum disorders (ASD) are complicated neurodevelopmental disorders. Many
studies have demonstrated that children with autism have multiple nutritional
deficiencies and increased serum 5-hydroxytryptamine (5-HT) levels. In our previous study, 77.9% of
autistic children were found to have vitamin A deficiency, and the
concentration of vitamin A was negatively associated with the CARS score. In
the present study, we sought to test whether vitamin A supplementation could
improve autistic symptoms and decrease serum 5-HT levels. The DSM-V criteria
and CARS score were used for symptom description and symptom assessment of the
patients, respectively, before and after vitamin A supplementation (VAS). Serum
retinol and 5-HT levels, mRNA levels of RAR α, β, and γ and TpH 1 expression
were detected in autistic children before and after VAS and in normal children.
Serum retinol levels in children with ASD were significantly lower than in
control children. Serum 5-HT levels in children with ASD were higher than in
control children, which were correlated with symptom severity of children with
autism. After VA
supplementation, the children with ASD exhibited significant improvement in
autism symptoms. Serum retinol concentrations of children with ASD were
significantly increased, and serum 5-HT levels were decreased. Moreover,
statistically significant changes were observed in mRNA expression levels of
RAR α, RAR γ and TpH 1 after VAS compared to baseline. This study suggested
that VA supplementation may improve symptoms and reduce 5-HT levels in children
with ASD, indicating that VA supplementation is a reasonable therapy at least
for a subset of children with autism.
Children
with autism were requested to complete an interview with a developmental
pediatrician and submit to a baseline blood collection. Then a single vitamin A
supplementation (VAS) at a dose of 200,000 IU was performed in the thirty-three
ASD patients. All evaluations and blood collection were conducted again
6 months after VAS, based on the principle that a single, large dose of vitamin
A is well absorbed and stored in the liver, and then mobilized, as needed, over
an extended period of time
200,000 IU Dose vs. the vitamin A RDA
o
1,300
IU of vitamin A per day is the RDA for a 5 year old
o
This
single one-off dose is equivalent to 150 times the RDA for a single day.
o
This
high dose is designed to supply vitamin A needs over 4–6 months, based on the
liver's capacity to store and gradually release it.
This shows vitamin A (retinol) in
blood in non-ASD kids, the ASD kids and then the ASD kids after the megadose
supplement.
Also of interest to some will be this finding:
A significant amount of serotonin (5
hydroxytryptamine) is produced in the gut. The gut-brain axis plays a role in
ASD, and altered gut microbiota and/or gut serotonin production can influence
brain function, exacerbating ASD symptoms.
This was studied in the later research
studies.
In 2021 they published a summary of
their work
Research
Progress in Vitamin A and Autism Spectrum Disorder
https://pmc.ncbi.nlm.nih.gov/articles/PMC8670912/
Autism
spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder.
Over the past few decades, many studies have investigated the effects of VA
supplementation in ASD patients and the relationship between vitamin A (VA)
levels and ASD. VA is an essential micronutrient that plays an important role
in various systems and biological processes in the form of retinoic acid (RA).
Recent studies have shown that serum VA concentration is negatively correlated with the severity of
ASD. The lack of VA during pregnancy or early fetal development can
affect brain development and lead to long-term or even permanent impairment in
the learning process, memory formation, and cognitive function. In addition, VA deficiency has been reported
to have a major impact on the gastrointestinal function of children with ASD,
while VA supplementation has been shown to improve the symptoms of ASD to a
certain extent. This paper provides a comprehensive review of the
relationship between VA and ASD.
The multiple effects of VA in ASD. In the nervous system, VAD can lead to amnesia, cognitive impairment, and social impairment. In the GI system, VAD affects GI bacteria, causing associated symptoms. In the immune system, VAD can lead to a decrease in serum 5-HT and OXT through the CD38-OXT pathway. In addition, the nervous system and the GI system can interact with each other by modulating the microbiota-gut-brain axis.
In 2025 they came up with some new insights.
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by a complex pathogenesis and a rising incidence rate annually. The activation and polarization of microglia are critical factors in the development of autism. The myeloid cell triggering receptor 2 (TREM2) is an immune-related protein predominantly expressed in microglia within the brain. A deficiency in TREM2 cause aberrant activation and polarization of microglia. The proteolytic cleavage of TREM2 leads to the formation of soluble TREM2, which can be detected in the bloodstream and serves as a peripheral biomarker of TREM2 expression in the brain. Retinoic acid (RA) is a biologically active metabolite of vitamin A, and the RA / retinoic acid receptor alpha (RARα) -mediated signaling is implicated in the activation and polarization of microglia, as well as in the regulation of TREM2 expression. This pathway may consequently influence ASD-related behavioral phenotypes in rats. We hypothesized that TREM2 deficiency disrupts retinoic acid signaling, leading to microglial dysfunction and ASD-like behaviors. To further elucidate the role of TREM2 in ASD, we conducted a study involving the knockdown of TREM2 expression in the brains of wild-type littermates. Here, we demonstrate that TREM2 knockdown in rat prefrontal cortex induced ASD-like social deficits, accompanied with abnormal activation of microglia, unusual synaptic pruning, a decrease in serum soluble TREM2 levels, a reduction in RA expression, and an increase in RARα expression. Strikingly, daily RA administration (6mg/kg,i.g.,PND 22-42) rescued these phenotypes. These data establish the significant role of TREM2 in the pathogenesis of ASD. To our knowledge, this is the first demonstration that RA supplementation rescues synaptic pruning defects in a TREM2-deficient ASD model, revealing a novel crosstalk between vitamin A metabolism and microglial regulation. Our findings position serum sTREM2 as a potential diagnostic biomarker and suggest RA-based combination therapies for ASD patients with TREM2 variants, thereby offering novel insights for the diagnosis and treatment of autism
Emerging
therapeutic approaches are focusing on modulating the TREM2 pathway as a
potential therapeutic target for neurological disorders. Novel interventions
that regulate TREM2 expression and its downstream signaling pathways could
potentially mitigate pathological conditions linked to synaptic dysfunction. RA
levels are diminished in children with ASD and inversely correlate with symptom
severity. RA plays a pivotal role in neurodevelopment by binding to RARα, which
is predominantly expressed in the cerebral cortex and hippocampus. RARα has
been identified as a critical regulator of microglial activity.
The
present study demonstrates that TREM2 knockdown in normal rats induces abnormal
microglial activation, polarization, and synaptic pruning, culminating in
autistic-like behaviors. RA supplementation restored microglial function and
synaptic pruning, improving these autistic-like behaviors. These findings
position TREM2 as a critical regulator of microglial activity and synaptic
pruning. By activating
RARα via RA supplementation, TREM2 expression may be upregulated, offering a
novel therapeutic avenue for ASD treatment
Conclusion
In the 2018 study in Chongqing, China,
they administered 200,000 IU of vitamin A to 5-year-old children and this aligns
with WHO guidelines for high-dose Vitamin A Supplementation (VAS) in children
aged 12–59 months living in regions where vitamin A deficiency (VAD) is a
public health concern. However, there are some nuances to consider when
applying this dose to children with autism.
If the child has sufficient or high
baseline vitamin A levels, administering such a high dose may risk of
hypervitaminosis A.
Our reader Maja achieved her positive
results with a modest dose of fish oil (using 40% of one capsule containing
3000 IU of vitamin A).
There are multiple mechanisms whereby this therapy can potentially improve the symptoms of autism. Some will be immediate, like the increase in oxytocin, whereas improved synaptic pruning may take years to become evident and impossible to really prove in humans. Synaptic pruning continues to about 25 years of age.
I suppose the restricted diet of many
people with autism is a major contributor to vitamin A deficiency, but there
may be other factors at play.
My own choice is a healthy varied diet,
plus a daily multivitamin with 100% RDA for vitamin A (for males 14 and over this
is 3,000 IU or 900 mcg RAE).
You can have too much vitamin A and then things like weak bones will follow. The tolerable upper limit is about 3 times the RDA. You cannot "overdose" on vitamin A from vegetables, because it will not be converted by the body from provitamin A to the active form.
Note that today's post was all about RARα.
There is a very similarly sounding receptor called RORα. RORα (Retinoic
Acid-Related Orphan Receptor Alpha) is considered a key regulator in pathways
associated with autism.
https://www.epiphanyasd.com/search/label/ROR%CE%B1
The schematic illustrates a mechanism through which the observed reduction in RORA in autistic brain may lead to increased testosterone levels through downregulation of aromatase. Through AR, testosterone negatively modulates RORA, whereas estrogen upregulates RORA through ER.
androgen receptor = AR
estrogen receptor = ER
A link between RORα
and RARα? Probably …
While RORα and RARα are distinct
receptors with different main activating molecules, they are interconnected
through retinoid signaling and shared regulatory pathways. Their interactions
are particularly relevant in neurodevelopment, immune function, and oxidative
stress regulation. These links make both receptors potential targets for
therapeutic strategies in conditions like autism and other neurological or
developmental disorders.
Wait ten years and read about it in the research from China !!!
