Description

• Vitamin D is a hormone and a fat-soluble vitamin.
• Vitamin D undergoes a series of metabolic processes to become calcitriol, which is the biologically active form.
• The skin synthesizes vitamin D₃ (cholecalciferol) by exposure to sunlight (ultraviolet B), and vitamin D₂ (Ergocalciferol) can be obtained from certain foods or supplements.
• 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.

Epidemiology

The overall prevalence rate of vitamin D deficiency has been reported to be around 40%.

• Geographical variation: more common in regions with limited sunlight; higher prevalence in northern latitudes
• Seasonal variability: lower vitamin D levels in winter; higher levels in summer with more sun exposure
• Age and life stage: Infants, children, and adolescents are at risk. Older adults can have reduced skin synthesis.
• Skin pigmentation: Darker skin may lead to reduced vitamin D production. Rates are the highest in blacks (82%), followed by Hispanics (69%).
• Cultural practices and clothing: Covered skin for religious or cultural reasons can increase risk.
• Obesity and health conditions: Obesity may reduce vitamin D bioavailability. Some health conditions and medications can affect vitamin D metabolism.
• Dietary intake: Limited access to vitamin D-rich foods increases risk. Fortified foods can help address deficiencies.
• Public health interventions: Some countries implement supplementation and fortification policies. Targeted interventions for at-risk populations are in place.

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 high-density lipoprotein (HDL) cholesterol.

Etiology and Pathophysiology

• Inadequate sun exposure: Lack of sufficient sunlight exposure is one of the primary causes of vitamin D deficiency. The skin produces vitamin D when exposed to ultraviolet B rays from the sun.
• Dietary insufficiency: A strict vegetarian diet or a diet low in vitamin D-rich foods that include fatty fish (e.g., salmon, mackerel), egg yolks, and cod liver oil can contribute to deficiency.
• Malabsorption disorders: Certain medical conditions that affect the gastrointestinal (GI) tract, such as celiac disease, Crohn disease, and inflammatory bowel disease (IBD), can impair the absorption of vitamin D from the diet. Conditions like liver disease can also affect the conversion of vitamin D into its active form.
• Obesity: Vitamin D is a fat-soluble vitamin, and excess body fat can sequester vitamin D, making it less bioavailable to the body.
• Medications: Certain medications, such as anticonvulsants, glucocorticoids, and weight-loss drugs, can interfere with vitamin D metabolism and absorption, leading to deficiency.
• Chronic kidney disease: The kidneys play a crucial role in converting vitamin D into its active form. Individuals with chronic kidney disease may have impaired vitamin D activation, leading to deficiency.
• Pregnancy and lactation: Pregnancy and breastfeeding increase the body’s demand for vitamin D, and women who do not receive adequate sun exposure or dietary sources may become deficient.
• Inflammatory conditions: Chronic inflammatory conditions, such as rheumatoid arthritis, can lead to increased breakdown of vitamin D and reduced effectiveness.
• Excessive alcohol consumption: Chronic excessive alcohol intake can impair the liver’s ability to convert vitamin D into its active form.

Genetics
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.

General Prevention

• Adequate exposure to sunlight and dietary sources of vitamin D (plants, fish); many foods are fortified with vitamins D₂ and D₃.
• The recommended intake of vitamin D can vary depending on factors like age, gender, and life stage. In general, the recommended dietary allowance (RDA) for vitamin D in the United States is as follows:
  • Infants (ages 0 to 12 months): 400 to 1,000 IU (10 to 25 μg) per day
  • Children and adolescents (ages 1 to 18 years): 600 to 1,000 IU (15 to 25 μg) per day
  • Adults (ages 19 to 70 years): 600 to 800 IU (15 to 20 μg) per day
  • Older adults (ages ≥71 years): 800 to 1,000 IU (20 to 25 μg) per day
  • Pregnant and lactating women: 600 to 800 IU (15 to 20 μg) per day

Pediatric Considerations

• Midgestational vitamin D deficiency doubled the risk of autism spectrum disorder in European cohort.
• The AAP states percentage of U.S. 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.

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.