Vitamin D

Aka: Vitamin D, Vitamin D Replacement, Cholecalciferol, Ergocalciferol, Dihydrotachysterol

1. See also
   1. Vitamin D Deficiency
   2. Bone
2. Physiology: General
   1. See Serum Calcium for Calcium Metabolism
   2. Images
      1. 
   3. Vitamin D2 (Ergocalciferol) and D3 (Cholecalciferol) are fat soluble
   4. Although termed a Vitamin, it is actually a steroid Hormone
   5. Sources
      1. Vitamin D is synthesized in skin after exposed to sun (ultraviolet light)
      2. Also may be ingested and absorbed from Small Intestine
   6. Vitamin D circulates in blood as Calcifediol (Calcidiol, 25-hydroxyvitamin D3)
   7. Active form is Calcitriol (1,25 Hydroxycholecalciferol)
      1. Promotes renal and gastrointestinal Calcium absorption, and calcification of bone
      2. In excess, Vitamin D triggers Calcium absorption from bone
3. Physiology: Synthesis
   1. Step 1a: Start with 7-Dehydrocholesterol (Cholesterol precursor)
      1. Skin exposure to sunlight or other ultraviolet light (290-315 nm of UV-B radiation)
      2. This pathway represents 90% of Vitamin D synthesis in humans
      3. Sun Exposure resulting in light pink skin (1 minimal erythema dose) = 20,000 IU (500 mcg) Oral Vitamin D
   2. Step 1b: Start with Dietary Vitamin D2 or D3
      1. Proceed to step 2 (bypasses sunlight-mediated synthesis pathway)
      2. Typically represents only 10% of Vitamin D source (unless specifically supplemented)
   3. Step 2: Cholecalciferol (Vitamin D3)
      1. Metabolized in liver by Vitamin D3-25 hydroxylase to 25-HYdroxycholecalciferol
   4. Step 3: Calcidiol (25-hydroxycholecalciferol, or 25-hydroxyvitamin D3)
      1. Metabolized in Kidney by 25-OH-D3-1a hydroxylase to 1, 25 Hydroxycholecalciferol (Calcitriol)
      2. Triggered by Parathyroid Hormone
   5. Step 4: Calcitriol (1, 25 Hydroxycholecalciferol)
      1. Calcitriol is the active form of Vitamin D)
4. Pathophysiology
   1. Vitamin D Excess
      1. Hypercalcemia
      2. Ureteral Stones
   2. Vitamin D Deficiency
      1. Risk Factors
         1. Homebound elderly
         2. Inhabitants of Northern States
      2. Vitamin D Deficiency related conditions
         1. Children: Rickets
         2. Adults: Osteomalacia, Osteoporosis
5. Indications: Vitamin D Supplementation or Replacement
   1. Osteoporosis Prevention
   2. Vitamin D Deficiency
6. Contraindications: Vitamin D Supplementation
   1. Granulomatous disease (e.g. Tuberculosis, Sarcoidosis)
   2. Metastatic bone disease
   3. Williams Syndrome
7. Preparations: 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 (USA) 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
8. Signs: Vitamin D Deficiency
   1. See Vitamin D Deficiency
   2. Osteomalacia
   3. Muscular hypotonia
9. Signs: Vitamin D Toxicity (related to Hypercalcemia)
   1. Headache
   2. Metallic Taste
   3. Vascular calcinosis or nephrocalcinosis
   4. Pancreatitis
   5. Nausea or Vomiting
10. Dosing (higher than current RDA)
    1. Children and Adolescents: 400 IU (10 mcg) per day
    2. Adults Age 18-50 years: 400-800 IU (10-20 mcg) per day
    3. Adults Age >50 years or Osteoporosis (higher levels are controversial)
       1. Southern regions: 800 IU (20 mcg) per day
       2. Northern climates: 1000-2000 IU (25-50 mcg) per day may be required
    4. Expect a 0.4 ng/ml increase for every 40 IU (1 mcg) daily of Vitamin D
       1. Expect 4 ng/ml increase from 400 IU (10 mcg) daily
       2. Expect 40 ng/ml increase from 4000 IU (100 mcg) daily
    5. Vitamin D is fat soluble and is best absorbed with fat in the meal
11. Dosing: Supplementation in Infants and Children under age 2 years
    1. Indications
       1. See Vitamin D Deficiency for risk factors
       2. Breastfed Infants
       3. Children and adolescents consuming <1 Liter (34 oz) Vitamin D Fortified milk daily
    2. Supplements with daily dose of 1 drop (equivalent to 400 IU or 10 mcg) for age under 2 years
       1. Carlson Baby D Drops
    3. Supplements with daily dose of 1 ml (equivalent to 400 IU or 10 mcg) for age under 2 years
       1. Enfamil Poly-Vi-Sol Multivitamin Supplement drops
       2. Enfamil Poly-Vi-Sol Vitamins A, C and D with Iron
       3. Sunlight Vitamins Just D Infant Vitamin Drops
       4. Twinlab Infant Care Multivitamin Drops with DHA
    4. References
       1. Casey (2010) Am Fam Physician 81(6): 745-50 [PubMed]
12. Dosing: Children with Vitamin D Deficiency (Rickets)
    1. Ergocalciferol (D2, Calciferol)
       1. Dose: 25-125 mcg (1-5000 IU) PO/IM for 6-12 weeks
    2. Cholecalciferol (D3, 40,000 IU/mg)
       1. Option 1: 125-250 mcg (5-10,000 IU) PO for 3 months
       2. Option 2: 15,000 mcg (600,000 IU) divided qid x1 day
    3. Dihydrotachysterol (DHT, 120,000 IU/mg)
       1. Option 1: 500 mcg (0.5 mg) for single dose or
       2. Option 2: 13-50 mcg PO per day until resolved
    4. References
       1. Khatib (2005) Consultant Pediatrician 4:33-9 [PubMed]
13. Dosing: Adults with Vitamin D Deficiency
    1. Mild (Serum 25-hydroxyvitamin D 8-15 ng/ml)
       1. Calcium 1200 to 1500 mg orally daily
       2. Vitamin D
          1. Option 1: Vitamin D 50,000 IU PO weekly for 8 weeks (repeat another course if Vitamin D <30 ng/ml)
          2. Option 2: Vitamin D 1000 IU daily per every 10 ng/ml shortfall in addition to maintenance for 6 weeks
             1. Example: Vitamin D 10 ng/ml
                1. Take 2000 IU (50 mcg) replacement in addition to 1000 IU (25 mcg) maintenance daily
          3. Option 3: Vitamin D 20-25 IU/kg IV daily (parenteral for hospitalized patients)
          4. Maintenance after acute replacement: Vitamin D 800-1000 IU (20-25 mcg) PO daily
    2. Severe (Serum 25-hydroxyvitamin D <8 ng/ml)
       1. Vitamin D 50,000 IU (1250 mcg) orally daily for 1-3 weeks
       2. Then maintain as mild deficiency doses above
    3. Monitoring Vitamin D level at 6-8 weeks after starting therapy
       1. Goal 25-Hydroxyvitamin D >30-40 ng/ml
       2. Storage of Vitamin D does not start until 40 ng/ml
14. Efficacy: Vitamin D in Osteoporosis Prevention
    1. Dutch Study of 348 women over age 70 years
       1. Given Vitamin D 400 IU (10 mcg) or Placebo
       2. Vitamin D Group had greater BMD at 2 years
          1. Greater femoral neck Bone Mineral Density
          2. Placebo group had decreased Bone Mineral Density
       3. No change in femoral trachanter or distal radius BMD
    2. References
       1. Ooms (1995) J Clin Endocrinol Metab 80:1052-8 [PubMed]
15. Efficacy: Conditions for which Vitamin D has no proven benefit
    1. Cardiovascular disease primary prevention (no proven benefit)
       1. Manson (2019) N Engl J Med 380(1): 33-44 [PubMed]
    2. Cancer primary prevention (no proven benefit)
       1. Manson (2019) N Engl J Med 380(1): 33-44 [PubMed]
16. References
    1. Holick (2007) N Engl J Med. 357(3):266-81 [PubMed]
    2. LeFevre (2018) Am Fam Physician 97(4): 254-60 [PubMed]
    3. Norman (2007) J Steroid Biochem Mol Biol 103(3):204-5 [PubMed]
    4. Schneider (2006) Curr Opin Endocrinol Diabetes 13(6): 483-90 [PubMed]