You might have already been flooded by many advertisements and information
about vitamin D in the media.
Do you take vitamin D supplement? 7 signs and symptoms you may have a vitamin
D deficiency and the list goes on…
While many scientific studies described the role of vitamin D in cancer
prevention, its role in autism development is only now emerging.
In this blog, we will describe the most recent studies showing a link between
a lack of vitamin D and autism development in children and we will put
in perspective how a vitamin D deficiency in the mother during pregnancy
could affect fetal brain development thus leading to autism in the offspring.
- Vitamin D in children affected by Autism
a- Vitamin D levels in children with Autism: few facts
Vitamin D deficiency has recently been proposed as a possible environmental
risk factor for ASD.
Many studies showed that
children with ASD have significantly lower serum levels of 25-hydroxy vitamin
D (25[OH] D), the active form of vitamin D, than healthy children (1-3) with some autistic children having severe vitamin D deficiency (2).
In addition, anti-brain autoantibodies, namely anti-myelin-associated
glycoprotein (anti-MAG) autoantibodies that could be responsible for brain
damage, were found to be higher in autistic children compared to healthy
serum level of vitamin D was found to be inversely correlated with MAG
auto-antibodies level showing that vitamin D has protective effects on the brain.
Although a vast majority of autistic children used dietary supplements,
almost one third of them remain deficient for vitamin D (4).
A growing body of evidences suggests that vitamin D [25(OH)D] supplementation
may minimize symptoms in autistic children (5).
In a recent case control study, a 3-year-old autistic boy showed dramatic
improvements based on three different standard ASD rating scales after
being given 150,000 IU/month of vitamin D3 for two months (6). Another
study found that 5000 IU/day of vitamin D3 given to 86 ASD children (aged
3–9 years) for 3 months showed 80% of them had significant improvement
on the CARS, an ASD rating scale (7).
A recent and very interesting prospective study investigated the effect
of vitamin D on siblings of autistic children when administrated during
pregnancy to their mother (5000 IU/day) and given to the newborn siblings
for the first three years (1000 IU/day). Results showed that only 5% of
children developed autism (8) while the literature shows a 20% autism
occurrence in siblings of autistic children (9).
b- Vitamin D deficiency, autism and genetic
The CHARGE study, including 474 children with ASD, 281 healthy control
children and their parents, examined the associations between ASD and
functional polymorphisms in vitamin D pathways. Results showed that lower
levels of vitamin D, found in ASD children, were associated with specific
CYP27B1 genotypes (an enzyme involved in vitamin D synthesis) (10).
c- What is the role of Vitamin D in brain development?
The active form of vitamin D (calcitriol), regulates over 200 genes in
human and play a crucial role in brain development by modulating 36 proteins
involved in neurotransmission, synapse plasticity and provides neuroprotection.
A deficiency in vitamin D has been shown to induce
inflammation that impact neural development and leads to
brain damage (11).
Vitamin D acts at multiple levels:
- It protects DNA from mutation by stabilizing the genome and protecting
it from oxidative stress injuries (12).
- By inducing Treg cells, it plays a key role in the establishment of immunological
self-tolerance thus preventing autoimmunity (13).
- It increases brain glutathione production, a very powerful anti-oxidant
that gets rid of heavy-metal, which are neurotoxic to brain (14).
- Vitamin D represses the production of inflammatory cytokines production
in the brain and induces anti-inflammatory IL-10 production (15).
- It induces the secretion of neurotropin, a key factor in neuroprotection (16).
- It may protect the mitochondrial function (17).
- Role of maternal Vitamin D deficiency in Autism development in the offspring
Vitamin D inhibits cell proliferation (18). Because autism is characterized
by brain overgrowth (19), a lack of maternal vitamin D could be responsible
for excessive neurons number (20-21).
Study in animals showed that a severe vitamin D deficiency during pregnancy
leads to anatomical abnormalities in pups similar to those found in autism
including changes in its volume, shape (20, 22).
a- Vitamin D levels in mothers giving birth to a child with autism: few facts
Vitamin D deficiencies are very common in pregnant women (23-24).
Because the fetus is entirely dependent on maternal vitamin D supply,
a deficiency in pregnant women directly impact vitamin D levels in the
fetus/new born (25).
Prenatal vitamin D deficiency has now been proposed as a risk factor for
Many studies led in dark-skinned immigrant population illustrated the crucial
role of a lack of maternal vitamin D in autism development in the offspring.
Darker skinned individuals have higher levels of cutaneous melanin which
is a potent sunscreen therefore children born from dark-skinned mother
should be more prone to develop autism because of more severe vitamin
D deficiency in their mother.
This fact is perfectly illustrated by a Swedish study showing that black
children from mother who emigrates from Uganda develop autism up to 200
times more than the fair-skinned general population (27). Other studies
showed that children born from Somalian mothers in Sweden (low sun exposure)
have a very high prevalence of severe ASD with intellectual disability
(28-29). Indeed, an American study showed than 45% of black women but
only 2% of white women have a severe vitamin D deficiency during pregnancy
explaining, in part, the prevalence of autism in Black-American children (30).
Regardless of maternal ethnicity, a retrospective Swedish study that analyzes
vitamin D concentration in blood samples of children
at birth showed that children who will develop ASD later on, had lower 25(OH)D
vitamin levels at birth compared to non-ASD children (31) which clearly
pinpoints the key role of vitamin D during fetal development.
b- How maternal vitamin D deficiency could lead to autism in the offspring?
As stated in the first paragraph, vitamin D has pleiotropic effects and
a deficit in maternal supply could severely impact the developing brain through:
- An increase of de novo DNA mutations that could affect the developing fetus.
- Lack of tolerance towards the embryo with an increase of autoimmunity.
- Increase of oxidation and production of neurotoxic factors to the brain.
in utero maternal inflammation thus leading to brain injuries.
- Lack of neurotropin secretion, a key factor in neuroprotection.
A growing body of evidences continues to accumulate indicating that adequate
levels of vitamin D are required for normal brain development and function.
During the very highly susceptible period of pregnancy,
adequate levels of vitamin D should be provided to the future mother to support the ongoing pregnancy and help preventing autism development
in her future child.