Vitamin D

• Vitamin D, often called the “sunshine vitamin,” is produced in the skin during exposure to sunlight.
• It is crucial for maintaining normal serum calcium levels, which are essential for musculoskeletal health.

Deficiency and Recommended Levels:

• Vitamin D deficiency is defined as having 25-hydroxyvitamin D (25 OH D) levels below 30 ng/mL.
• The Endocrine Society recommends a preferred range of 40 to 60 ng/mL for optimal health.
• Recommended daily intake varies by age group:
  • Infants (<1 year): 400 to 1000 IU
  • Children and adolescents (1-18 years): 600 to 1000 IU
  • Adults: 1500 to 2000 IU
• Risk Factors: Infants
  • Anticonvulsants
  • Chronic disease with fat malabsorption
  • Exclusively Breast-fed infant without Vitamin D supplementation
  • Low maternal Vitamin D levels
  • Lack of Sun Exposure
    1. Direct sunlight avoidance is recommended by AAP for those under 6 months
    2. Darker skin pigmentation (requires 3-6 fold more Sun Exposure)
• Risk Factors: Adults
  • Age over 65 years
    1. Related to housebound status and decreased Vitamin D absorption
  • Comorbid illness
  • Malnourished
  • Total Parenteral Nutrition
  • Lack of Sun Exposure (or thorough sun screen use)
    1. Those with darker skin require 3-6 fold more exposure
  • Renal disease (Renal Failure, Nephrotic Syndrome)
    1. Renal losses of Vitamin D
  • Hepatic disease (Cirrhosis)
  • Gastrointestinal malabsorption
    1. Gastric surgery (resection or Gastric Bypass)
    2. Crohn’s Disease
    3. Cystic Fibrosis
    4. Celiac Disease
  • Small Bowel Resection
  • Medications
    1. Anticonvulsant use (e.g. Phenobarbital, Phenytoin)
       1. Requires 2-5 fold more Vitamin D intake daily
    2. Corticosteroids (long-term use) or other Immunosuppressants
    3. Rifampin
    4. Antiviral medications

Who should be tested for vitamin D deficiency?

Australian Therapeutic Guidelines on disorders of bone and calcium homeostasis only recommend vitamin D testing for people at heightened risk of vitamin D deficiency.

A 2014 Department of Health MBS review reported that the number of MBS claims for vitamin D testing increased each year over the 10 years between 2003–4 and 2012–13 (https://www.nps.org.au/radar/articles/mbs-item-number-changes-for-vitamin-b12-folate-and-vitamin-d-tests)

Although, testing volumes initially decreased following the introduction of new items with specific appropriate use criteria in 2014, a report for the MBS Review Taskforce by the Diagnostic Medicine Clinical Committee in 2018 found that the overall use of vitamin D testing was still higher than expected

Apply a 12-month frequency restriction on the testing of 25-hydroxyvitamin D.

• limited skin exposure to UVB radiation from sunlight
  • due to lifestyle factors, chronic illness or hospitalisation
• dark skin
• fat malabsorption conditions
  • coeliac disease
  • inflammatory bowel disease
• medical conditions
  • obesity
  • end-stage liver disease
  • kidney disease
• medicines
  • rifampicin or antiepileptics

Effects of Deficiency:

• In Children: Vitamin D deficiency can result in rickets, a condition characterized by poor bone development, impaired growth, and failure to reach genetically determined height.
• In Adults: Vitamin D deficiency leads to osteomalacia, where the collagen matrix in bones becomes abnormally mineralized, causing weak bones that are more susceptible to fractures. Individuals may experience aching bones, muscle weakness, and pain. Approximately 40% to 60% of patients with generalized myalgias and bone pain have vitamin D deficiency.

Dietary and Supplement Sources

1. Fish (Vitamin D3, most in fatty fish)
   1. Salmon (450 IU per 3 oz)
   2. Sardines
   3. Fish oils
   4. Tuna (150 IU per 3 oz)
2. Egg yolk (40 IU or 1 mcg)
3. Butter
4. Liver and other organ meats
5. Vitamin D Fortified Milk contains 100 IU (2.5 mcg) per cup
6. Fortified Orange Juice contains 80 to 120 IU (2 to 3 mcg) per cup
7. Multi-Vitamin Contains 400 IU (10 mcg) Vitamin D per tablet

Mechanism of Action:

• UVB Radiation:
  • Ultraviolet B (UVB) radiation from sunlight converts 7-dehydrocholesterol in the skin into previtamin D
  • represents 90% of Vitamin D synthesis in humans
  • On average, about 10-30 minutes of sunlight exposure to the arms, legs, and face a few times a week is sufficient for many people to meet their vitamin D needs.
  • Sun Exposure resulting in light pink skin (1 minimal erythema dose) = 20,000 IU (500 mcg) Oral Vitamin D
  • factors effecting skin synthesis include:
    • skin pigmentation
    • sunscreen use – Sunscreen with a high sun protection factor (SPF) can block UVB rays and inhibit vitamin D synthesis. Therefore, spending limited time without sunscreen is necessary
    • angle of sunlight during different seasons
• Diet:
  • Dietary Vitamin D2 or D3
  • Typically represents only 10% of Vitamin D source (unless specifically supplemented)
  • Both vitamin D2 and vitamin D3 are absorbed in the small intestine in response to dietary fat
  • Vitamin D3 (Cholecalciferol):
    • The half-life of vitamin D3 in the bloodstream is relatively long, estimated to be around 15 to 30 days. This means that it remains active in the body for a significant period after ingestion.
  • Vitamin D2 (Ergocalciferol):
    • Vitamin D2 has a shorter half-life compared to vitamin D3, estimated to be around 4 to 7 days.
• Liver Metabolism:
  • Previtamin D is further converted to vitamin D then to 25-hydroxyvitamin D (25 OH D) in the liver.
  • Measuring 25-hydroxyvitamin D (25 OH D) levels is commonly used to assess vitamin D status.
• Kidney Conversion:
  • In the kidneys, 25-hydroxyvitamin D (25 OH D) is converted to the biologically active form:
  • 1,25-dihydroxy vitamin D (1,25 (OH)) – aka – Calcitriol
  • this process regulated by parathyroid, calcium, and phosphorus levels.
  • Calcitriol (1,25 Hydroxycholecalciferol)
    • Promotes renal and gastrointestinal Calcium absorption, and calcification of bone
    • In excess, Vitamin D triggers Calcium absorption from bone

Monitoring:

• To assess vitamin D status
  • 25-hydroxyvitamin D (25 OH D) is preferred because it has a longer half-life (2 weeks)
  • The biologically active form, 1,25-dihydroxy vitamin D (1,25 (OH)), has a shorter half-life (< 4 hours) and should not be used to assess VItamin D levels
• mild = 30 to 49 nmol/L
• moderate = 12.5 to 29 nmol/L
• severe = lower than 12.5 nmol/L.
• It is advisable to monitor circulating vitamin D levels (25-hydroxyvitamin D) at least twice a year:
  • once in the spring (reflecting low levels after winter)
  • once in the fall (reflecting higher levels after summer)
• Dosage adjustments can be made based on monitoring results.

Vitamin D Supplementation

• Treatment varies based on the degree of deficiency and underlying risk factors.
• Recommendations include vitamin D3 supplementation for both prevention and management.
• Dosing is adjusted according to serum 25(OH)D levels.
• Mild Deficiency:
  • Calcium 1200 to 1500 mg orally daily.
  • Multiple vitamin D supplementation options.
• Severe Deficiency:
  • Vitamin D 50,000 IU orally daily for 1-3 weeks.
  • Follow-up with mild deficiency doses.
• Monitoring and Goals:
  • Check Vitamin D level at 6-8 weeks after starting therapy.
  • Goal: 25-Hydroxyvitamin D >30-40 ng/ml.

Toxicity:

• Vitamin D intoxication is extremely rare.
• Vitamin D intoxication from sun exposure does not occur as the skin destroys excess vitamin D.
• The only way a person may get vitamin D toxicity is by ingestion of extremely high doses of vitamin D for a prolonged period.
• Concentrations over 150 ng/mL (325 nmoL/L) may result in vitamin D intoxication and are associated with hypercalcemia.
• Symptoms may include:
  • Headache
  • Metallic Taste
  • Vascular calcinosis or nephrocalcinosis
  • Pancreatitis
  • Nausea or Vomiting
  • constipation
  • polydipsia (excessive thirst)
  • polyuria (excessive urination)
  • confusion