Vitamin D: a key trigger in Autism development

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.

  1. 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 children. Moreover, 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).
  1. 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 autism (26).

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.
  • Increase of 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.

References

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