Vitamin D deficiency linked to neurodevelopmental issues

A major Danish study, published in The Lancet Psychiatry, links low neonatal vitamin D levels to an increased risk of schizophrenia, ADHD, and autism. Using dried blood spot samples from over 88,000 individuals born between 1981 and 2005, researchers found:

• Higher vitamin D levels at birth reduced risks:

  • 18% lower risk of schizophrenia

  • 11% lower risk of ADHD

  • 7% lower risk of autism

• No link was found with depression or bipolar disorder, likely due to their later onset.

• The research team measured 25-hydroxyvitamin D [25(OH)D], the standard biomarker of vitamin D status, and vitamin D-binding protein, which transports vitamin D in the bloodstream and extends its biological activity.

Genetic Evidence:

Researchers used:

• Polygenic Risk Scores (PRS) to indicate inherited vitamin D levels

• Mendelian Randomisation to establish possible causality
  These tools suggested a biological link, especially for ADHD, though confounding factors and pleiotropy (genes affecting multiple traits) remain concerns.

Limitations:

• Vitamin D was measured only at birth, not throughout pregnancy.

• A 2024 Danish trial found no effect of supplementation from week 24 on later autism/ADHD — suggesting timing and deficiency status matter.

• Study participants were mostly European, so findings may not fully apply to diverse populations.

India-Specific Findings:

Despite abundant sunlight, vitamin D deficiency is widespread in India:

• 74% of infants and 85.5% of mothers at AIIMS Rishikesh were deficient.

• A Bengaluru study found 92.1% newborns deficient.

• Vitamin D levels don’t rise during pregnancy without dietary/supplemental support.

A 2024 Indian study showed a strong correlation between maternal and infant vitamin D levels, underscoring the intergenerational transmission of deficiency.

"Vitamin D constitutes a form of biological inheritance transmitted across generations, significantly influencing skeletal health by ensuring proper bone development and preventing disorders such as rickets in children."

Vitamin D3 (Cholecalciferol):

• Main source: Synthesized in skin via UVB sunlight; minor dietary sources include fatty fish, eggs, dairy, and fortified foods.

• Skin production: Skin cells (keratinocytes) must synthesize their own vitamin D3.

• Functions:

  • Enters blood and is delivered to all body tissues.

  • Helps DNA repair, reduces UV-induced skin damage, and fights infections, autoimmune diseases, and inflammation.

  • Can cross placenta and is transferred via breast milk if maternal levels are adequate.

• Potency:

  • 1000× more potent than 25(OH)D, and 10× more than 1,25(OH)2D.

• Half-life: ~24 hours.

25-hydroxyvitamin D [25(OH)D / Calcifediol]:

• Primary circulating form, formed by hydroxylation of vitamin D3 in the liver.

• Measured in blood to assess vitamin D status.

• Functions:

  • Taken up by immune, brain, heart, and other cells.

  • Precursor to the hormonal form (1,25D).

  • Modulates T-cell activation and acts as a local signaling molecule.

• Half-life: ~2–3 weeks.

• Clinical relevance: Can be supplemented directly in immune emergencies (e.g., COVID-19).

1,25-dihydroxyvitamin D [1,25(OH)2D / Calcitriol]:

• Hormonal and most active form, formed mainly in kidneys from 25(OH)D via parathyroid hormone (PTH) regulation.

• Functions:

  • Regulates intestinal calcium absorption and bone turnover.

  • Also synthesized locally in cells during immune responses (paracrine function).

• Half-life: ~4 hours.