Active vitamin D, known as calcitriol, is the active form of vitamin D. It is a hormone, distinct from the inactive vitamin D forms obtained from sun exposure or diet. This compound plays a significant role in regulating mineral balance. Its presence is fundamental for various physiological processes that extend beyond bone health.
The Body’s Activation Process
The body converts inactive vitamin D into calcitriol through a multi-step process. When skin is exposed to sunlight, 7-dehydrocholesterol converts into vitamin D3 (cholecalciferol). Dietary sources and supplements provide both vitamin D2 (ergocalciferol) and vitamin D3. These inactive forms then circulate in the bloodstream, bound to a protein.
The liver converts vitamin D into 25-hydroxyvitamin D (calcidiol). Calcidiol is the primary circulating form of vitamin D and is often measured to assess a person’s vitamin D status. Calcidiol is then transported to the kidneys for the final activation step.
In the kidneys, an enzyme converts calcidiol into 1,25-dihydroxyvitamin D (calcitriol). This conversion is tightly regulated to maintain appropriate calcitriol levels. Parathyroid hormone (PTH) stimulates this renal enzyme, particularly when calcium levels in the blood are low.
Essential Roles in Health
Calcitriol performs many functions within the body, with a primary focus on maintaining mineral balance. It influences calcium and phosphate homeostasis, which is the process of keeping these mineral levels stable in the blood. Calcitriol promotes the absorption of dietary calcium and phosphate from the small intestine.
It also acts on the kidneys, increasing the reabsorption of calcium back into the blood, thereby reducing its excretion in urine. It regulates bone mineralization, ensuring that calcium and phosphate are appropriately deposited to maintain bone strength. In conjunction with parathyroid hormone, calcitriol can stimulate the release of calcium from skeletal stores into the blood when levels are low.
Calcitriol also modulates the immune system. It binds to vitamin D receptors found in various immune cells, including monocytes and activated T and B lymphocytes, affecting their function and response. Calcitriol also regulates cell growth and differentiation in various tissues.
When Levels Are Off: Deficiency and Excess
Both insufficient and excessive active vitamin D levels can lead to health problems. Vitamin D deficiency can impair bone mineralization, leading to bone-softening conditions. In children, severe deficiency causes rickets, characterized by bowed or bent bones, muscle weakness, and bone pain. Adults with low vitamin D may develop osteomalacia, leading to soft bones, muscle weakness, and increased risk of fractures. Prolonged deficiency can also worsen osteoporosis, a condition of reduced bone density, making bones fragile and prone to breaking.
Excessive vitamin D, known as vitamin D toxicity or hypervitaminosis D, usually results from over-supplementation of inactive vitamin D. This leads to hypercalcemia, a buildup of calcium in the blood. Symptoms of hypercalcemia include nausea, vomiting, loss of appetite, increased thirst, frequent urination, and confusion. In severe cases, it can cause kidney stones, kidney injury, and even abnormal heart rhythms.
Sources and Supplementation
Sunlight exposure is the primary natural source, triggering the synthesis of vitamin D3 in the skin. Certain foods also provide vitamin D, including fatty fish like salmon, mackerel, and tuna, as well as some fortified products such as milk, cereals, and orange juice. These dietary and sun-derived forms are inactive and require the body’s multi-step activation process to become calcitriol.
Over-the-counter vitamin D supplements typically contain inactive forms, either vitamin D2 or vitamin D3. These supplements aim to boost the body’s overall vitamin D stores, allowing the liver and kidneys to produce calcitriol as needed. However, in specific medical conditions, such as chronic kidney disease where the kidneys may not be able to activate vitamin D effectively, a prescription form of active vitamin D (calcitriol) may be administered directly. This direct supplementation bypasses the body’s natural activation pathway, providing the biologically active form when the internal conversion process is compromised.