Vitamin D Deficiency


This topic covers the commonly acquired vitamin D deficiency and not type II vitamin D–resistant rickets/type I pseudovitamin D–resistant rickets (both rare autosomal recessive disorders).


  • Vitamin D is a hormone and a vitamin.
  • Cholecalciferol (D3) is synthesized in the skin by exposure to ultraviolet B (UV-B) radiation. Ergocalciferol (D2) and D3 are present in foods.
  • D2 and D3 are hydroxylated in the liver to 25 vitamin D (calcidiol), the major circulating form.
  • Calcidiol is further hydroxylated in the kidney to the active metabolite 1,25 vitamin D (calcitriol).
  • Hypocalcemia stimulates parathyroid hormone (PTH) secretion, which prompts increased conversion of 25 vitamin D to 1,25 vitamin D.
    • 1,25 vitamin D decreases renal calcium and phosphorus excretion, increases intestinal calcium and phosphorus absorption, and increases osteoclast activity. The net result is an increase in serum calcium.


The overall prevalence rate of vitamin D deficiency has been reported to be around 40%. Rates are highest rate in blacks (82%), followed by Hispanics (69%). Vitamin D deficiency was more common among individuals who were obese, had no college education, were in poor overall health, had hypertension, had low high-density lipoprotein (HDL), and did not consume milk regularly.

Pediatric Considerations
NHANES data suggest 70% of children do not have sufficient 25-OH vitamin D serum levels (9% deficient and 61% insufficient); deficiency has been associated with an increase in BP and decrease in HDL cholesterol.

Etiology and Pathophysiology

  • Insufficient dietary intake of vitamin D and/or lack of UV-B exposure (in sunlight) results in low levels of vitamin D.
    • This limits calcium absorption, causing excess PTH release.
  • PTH stimulates osteoclast activity, which helps to normalize calcium and phosphorous but results in osteomalacia.
  • Dietary deficiency
    • Inadequate vitamin D intake
  • Inadequate sunlight exposure
    • Institutionalized/hospitalized patients
  • Chronic illness: liver/kidney disease
  • Malabsorptive states (including inflammatory bowel diseases)

Vitamin D–dependent rickets type 1 occurs due to inactivating mutation of the 1α-hydroxylase gene; as a result, calcidiol is not hydroxylated to calcitriol.

Risk Factors

  • Inadequate sun exposure; dark skin
  • Female; elderly; obesity
  • Low socioeconomic status; immigrant populations; rates higher in blacks and Hispanics
  • Latitudes higher than 38 degrees
  • Institutionalized; depression
  • Medications (phenobarbital, phenytoin); gastric bypass surgery/malabsorption syndromes

General Prevention

  • Adequate exposure to sunlight and dietary sources of vitamin D (plants, fish); many foods are fortified with vitamins D2 and D3.
  • Recommended minimum daily requirement is 600 IU/day from age 1 to 70 years and 800 IU/day for those aged >70 years. Up to 4,000 IU/day is safe in healthy adults without risk of toxicity.
  • For ages 51 to 70 years, minimally recommended supplementation is 800 IU/day to prevent nonvertebral fractures.

Pediatric Considerations

    • The American Academy of Pediatrics (AAP) recommends all breastfed babies receive 400 IU/day of vitamin D beginning “within the first few days of life.”
    • 2016 Global Consensus Recommendations suggest all infants, regardless of feeding method, begin vitamin D 400 IU within a few days of birth.
  • Midgestational vitamin D deficiency doubled the risk of autism spectrum disorder in European cohort.
  • The AAP states percentage of US infants who meet the AAP’s guidelines for vitamin D intake has not increased; only 27% of infants overall and <40% of infants in nearly all demographic subgroups met intake recommendations.

Pregnancy Considerations
Insufficient data to recommend routine screening of all pregnancies; only “at risk” should be screened; it is safe to take 1,000 to 2,000 IU/day during pregnancy (1)[B].

Commonly Associated Conditions

  • Osteomalacia, osteoporosis
  • Premenstrual syndrome
  • Rickets
  • Celiac disease; gastric bypass
  • Chronic renal disease
  • Bacterial vaginosis in pregnant women
  • Hypertension
  • Cohort study found that vitamin D deficiency is correlated with increased risk of all-cause mortality.
Vitamin D deficiency is associated with risk of myocardial infarction (MI) and all-cause mortality (2)[A].

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