Vitamin D is a hormone the skin creates in response to sunlight. It is also obtained in limited amounts from food, although a standard diet alone does not contain the body’s entire vitamin D requirements.
Vitamin D is a fat-soluble vitamin that dissolves in fats and oils rather than water. The other fat-soluble vitamins are A, E and K.
Vitamin D helps regulate bone mineralisation, hormone secretion and immune function.
Vitamin D Metabolism
Vitamin D originates in three potential places:
- Created in the skin from cholesterol in response to ultraviolet B (UVB) radiation (sunlight)
- Ergocalciferol (vitamin D2) in the diet (primarily from plant sources, fortified foods or supplements)
- Colecalciferol (vitamin D3) in the diet (primarily from animal sources, fortified foods or supplements)
CLINICAL RELEVANCE
The standard treatment for vitamin D deficiency is giving oral colecalciferol (vitamin D3).
In the skin, a photochemical reaction converts 7-dehydrocholesterol (a precursor molecule to cholesterol) into previtamin D3 (pre-colecalciferol). Previtamin D3 is unstable and spontaneously converts into colecalciferol (vitamin D3).
In the liver, an enzyme called 25-hydroxylase converts colecalciferol and ergocalciferol into 25-hydroxyvitamin D (calcidiol).
CLINICAL RELEVANCE
Most vitamin D in the blood is in the form of 25-hydroxyvitamin D. The standard blood test for vitamin D measures 25-hydroxyvitamin D.
In the kidneys, an enzyme called 1-alpha-hydroxylase converts 25-hydroxyvitamin D (calcidiol) into 1,25-dihydroxyvitamin D (calcitriol). Calcitriol is the active form of vitamin D, which carries out activities in the body.
The action of 1-alpha-hydroxylase (converting vitamin D to its active form) is stimulated and accelerated by:
- Parathyroid hormone
- Low phosphate
Calcitriol (the active form of vitamin D) has various actions within the body. In relation to calcium metabolism and bone health, it:
- Increases calcium and phosphate absorption in the small intestine
- Increases calcium reabsorption from the urine to the blood in the distal tubules of the kidneys
- Increases phosphate reabsorption from the urine to the blood in the proximal tubules of the kidneys
- Inhibits parathyroid hormone release (providing negative feedback to the parathyroid glands)
- Regulates the activity of osteoblasts and osteoclasts to support healthy bone mineralisation
Calcitriol also supports and regulates:
- Immune function
- Cell differentiation (into specialised cells), proliferation and apoptosis (programmed cell death)
- Cardiovascular function
Vitamin D Deficiency
Vitamin D deficiency is very common. Factors that increase the risk of vitamin D deficiency include:
- Living somewhere with lower sunlight
- Winter months, when there is less sunlight and less time outside
- Spending more time indoors (e.g., indoor occupations and care home residents)
- Darker skin (those with darker skin require more sun exposure to create the same vitamin D)
- Wearing clothes that reduce sun exposure on the skin
- Older age (vitamin D production is less efficient with age)
- Malabsorption (e.g., inflammatory bowel disease) affecting vitamin D absorption
Patients with vitamin D deficiency and osteomalacia may not have any symptoms. Typical symptoms include:
- Fatigue
- Bone pain
- Muscle weakness
- Muscle aches
- Pathological or abnormal bone fractures
Inadequate vitamin D leads to low serum calcium and phosphate. The main inorganic mineral that forms bone is hydroxyapatite, which contains calcium phosphate. Since calcium and phosphate are required to construct bone, low levels result in defective bone mineralisation. In children, this defective bone mineralisation causes rickets. In adults, it causes osteomalacia.
Low calcium leads to increased parathyroid hormone (PTH) secretion by the parathyroid glands (secondary hyperparathyroidism). Parathyroid hormone promotes calcium reabsorption from the bones, further worsening bone mineralisation.
Prevention of vitamin D deficiency is with a daily vitamin D supplement, specifically colecalciferol. The UK Department of Health and Social Care recommends a daily vitamin D supplement for everyone:
- Under 4 years (infant formula contains the required vitamin D)
- Over 4 years with risk factors (e.g., they have reduced sun exposure)
Treatment of vitamin D deficiency is with higher doses of colecalciferol (vitamin D3). Ergocalciferol (vitamin D2) is an alternative option.
Renal Bone Disease
Severe kidney disease impairs the conversion of 25-hydroxyvitamin D (calcidiol) to the active form of vitamin D, 1,25-dihydroxyvitamin D (calcitriol). A blood test may show a normal level of 25-hydroxyvitamin D, while the active form, calcitriol, is deficient. This leads to the features of vitamin D deficiency, with low calcium, high parathyroid hormone, and impaired bone mineralisation.
The treatment of renal bone disease involves using active forms of vitamin D (e.g., alfacalcidol and calcitriol).
Last updated August 2024
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