Vitamin D

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Sunset

Vitamin D is really more of a hormone than a vitamin and it can be synthesized in the body. It is synthesized in the skin due to sunlight exposure. It is actually a group of sterols with hormone-like activities. 1,25-dihydroxycholecalciferol (Vitamin D3) is the active form.

Good sources: There are two forms of vitamin D that you can obtain in the diet. The first is ergocalciferol (vitamin D2) which is found in plants. The other form is cholecalciferol (vitamin D3) which is found in animal sources (egg yolks, organ meats, fortified milk, and cod liver oil). 7-dehydrocholesterol is an intermediate in cholesterol synthesis. The skin can convert this molecule to cholecalciferol if exposed to UV light (most important source for us). Both of the dietary sources are inactive forms and must be converted to 1,25-dihydroxycholecalciferol to be active. There is no vitamin D in the colostrum of breast milk.

Skin-derived 7-dehydrocholesterol is converted to cholecalciferol (vitamin D by ultraviolet light (most abundant source of vitamin D) – both skin/diet-derived (ergocalciferol in plants, cholecalciferol in animal products) vitamin D are hydroxylated in liver to 25-(OH)-D3 (cholecalciferol or calcidiol)g 25-(OH)-D3 undergoes second hydroxylation (la-hydroxylase) in proximal tubules to form 1,25-(OH)2-D3 (calcitriol) which binds to nuclear receptors and activates gene transcription.

PTH and hypophosphatemia enhance la-hydroxylase synthesis. Hypercalcemia, hyperphosphatemia, and calcitriol inhibit 1-a-hydroxylase: 25-(OH)-D3 is converted into an inactive metabolite called 24,25-(OH)2-D3. Remember that vitamin D that is bought over-the-counter must be reabsorbed and hydroxylated twice before it is active: it is not 1,25-(OH)2-D3

You can see the mechanism that does this in the diagram below.

DRI: 5 mg or 200 IU

Functions: Metabolize calcium and phosphorus (bone and teeth formation). In the intestine, it increases calcium and phosphorus absorption. There is a demineralization of bone if there is not enough vitamin D. In the kidneys it regulates calcium and phosphorus levels.

vitamin D receptors are located in the duodenum, osteoblasts, kidney: (1) vitamin D, like most other steroids, complexes with nuclear receptors and activates gene transcription. (2) vitamin D when causes the releases of alkaline phosphatase (hydrolyzes calcium pyrophosphate and other inhibitors of bone mineralization) from osteoblastsg mineralization (hydroxyapatite crystals- Ca5(OH)(PO4)3) of cartilage and bone
intestinal reabsorption of calcium/phosphorous: (1) helps maintain the normal serum ionized calcium concentrationĀ (2) also establishes a good solubility product for mineralization of bone
increases renal calcium reabsorption but not phosphate reabsorption

Deficiency: Ricketts (bones are soft and pliable) in children, osteomalacia (bone demineralization) in adults, poor growth, and muscle twitching.

hypocalcemia/hypophosphaternia from decreased intestinal reabsorptiong hypocalcernia stimulates PTH, which leads to increased calcium reabsorption from the kidney and decreased reabsorption of phosphate and also mobilizes calcium and phosphate from boneg serum calcium is restored to normal or near normal, while phosphate remains low.
Establishes a low calcium-phosphate solubility product – defective bone and cartilage mineralization (area of growing epiphyseal plate) in children (called rickets) and defective bone remodeling in adults, restricted to the organic matrix at thebone-osteoid interface (called osteomalacia)

Causes of vitamin D deficiency

  • chronic renal failure (CRF) is the most common cause
    • (1) due to a lack of Ļ‰-hydroxylase
    • (2) unlike, non-renal causes of vitamin D deficiency, phosphorous levels are high owing to loss of phosphate excretion: 2o hyperparathyroidism can bring the phosphate levels down into normal or near normal range over time
  • poor diet: alcoholism, elderly
  • malabsorption: e.g., celiac disease
  • liver disease: e.g., cirrhosis: decreased first hydroxylation
  • drugs enhancing cytochrome P-450 system:
    • increases metabolism of 25-(OH)-D3
    • e.g., alcohol, phenytoin, barbiturates
    • e.g., a patient on birth control pills who is taking any of these drugs could become pregnant, since the metabolism of the hormones in the pill is increased
  • hypoparathyroidism/hyperphosphatemia: decreased 1-a hydroxylase synthesis
  • genetic diseases:
    • (1) 1-a-hydroxylase enzyme deficiency: type I vitamin D-dependent rickets
    • (2) deficiency of vitamin D receptors in target tissue: type II vitamin D-dependent rickets

Toxicity: Must be chronic to be toxic. Interestingly, toxicity is more about balance with other vitamins. For example, adequate amounts of Vitamin A & K2 protect against Vitamin D toxicity. It calcifies soft tissue which can cause aortic rupture. It can also cause kidney damage. High doses (100,000 IU for weeks to months) can cause loss of appetite, nausea, thirst, and stupor.