Vitamin D is an essential vitamin that plays a critical role in the body. It influences many processes and systems, including bone health, immune function, and gene expression. One of the main ways vitamin D works in the body is by being converted into a hormone called calcitriol.
Vitamin D Metabolism
There are two main forms of vitamin D – D2 (ergocalciferol) and D3 (cholecalciferol). Vitamin D3 is synthesized in the skin when it is exposed to sunlight, specifically UVB radiation. It can also be obtained through the diet by eating foods like fatty fish, eggs, and fortified dairy products. Vitamin D2 is found in some plants and fungi and is produced through UV irradiation.
Whether ingested or synthesized, vitamin D is biologically inactive. It must first undergo two hydroxylation reactions in the body to become activated. The first occurs in the liver, where vitamin D is converted into calcidiol (25-hydroxyvitamin D). This is the major circulating form used to determine a person’s vitamin D status.
Calcidiol is then transported to the kidneys, where the second hydroxylation takes place. This reaction converts calcidiol into calcitriol (1,25-dihydroxyvitamin D), the active hormonal form of vitamin D.
Calcitriol as a Hormone
Calcitriol meets the definition of a hormone because it is produced in one location (the kidneys) and transports messages to influence cells throughout the body. Hormones are chemical messengers that play an important role in regulating many biological processes.
The conversion of vitamin D into calcitriol is very tightly regulated by the kidneys. Production is stimulated by parathyroid hormone (PTH) and suppressed by high blood calcium levels. This system allows the body to control the amount of activated vitamin D available based on current calcium needs.
Once formed, calcitriol circulates as a hormone and is transported to various target tissues. It plays a role in several physiologic systems, including:
- Bone metabolism – Calcitriol stimulates the absorption of calcium and phosphorus from the intestines and promotes bone mineralization.
- Immune regulation – Calcitriol enhances the innate immune response.
- Cell growth – Calcitriol inhibits proliferation and induces differentiation of many cell types.
The hormone binds to vitamin D receptors (VDRs), which are present in nearly every tissue in the body. The receptors act similarly to nuclear receptors for other steroid hormones like estrogen and testosterone.
Calcitriol and Blood Calcium Levels
One of the main functions of activated vitamin D is to tightly regulate calcium concentrations in the blood. It does this in three primary ways:
- Increases intestinal absorption of calcium – Calcitriol stimulates the expression of proteins involved in intestinal calcium transport, primarily in the duodenum.
- Promotes osteoclast activity – Osteoclasts are bone cells responsible for breaking down bone matrix and mineralization. Calcitriol increases osteoclast formation and activity, releasing calcium stores from bone into circulation.
- Reduces urinary calcium loss – Less than 1% of total body calcium is excreted through urine daily. Calcitriol can minimize urinary calcium excretion when blood levels are low.
These three mechanisms work together to increase blood levels of calcium whenever more is required in the body. This may occur during growth, pregnancy, while breastfeeding, or if dietary calcium intake is inadequate.
Health Effects of Calcitriol
As the active form of vitamin D, calcitriol influences many aspects of health. Some of the main benefits associated with adequate calcitriol levels include:
- Strong bones – By promoting intestinal calcium absorption and bone mineralization, calcitriol helps build and maintain bone density.
- Muscle function – Calcitriol works with calcium and phosphorus to enable muscle contraction.
- Immune regulation – Calcitriol enhances innate immunity by stimulating the expression of antimicrobial proteins.
- Reduce inflammation – Calcitriol may lower inflammation by inhibiting cytokine production and immune cell activity.
- Lower cancer risk – Increased calcitriol levels are associated with decreased risks of colorectal, breast and prostate cancers.
If the body cannot produce enough calcitriol, it can lead to vitamin D deficiency. Symptoms and complications may include:
- Bone loss and increased fracture risk
- Impaired immunity
- Muscle weakness
- Cardiovascular disease
- Autoimmune conditions
- Cognitive impairment
Vitamin D deficiency is estimated to affect around 1 billion people worldwide. Main risk factors include inadequate sunlight exposure, poor dietary intake, kidney/liver disease, older age, and obesity.
Maximizing Calcitriol Levels
To optimize calcitriol levels in the body:
- Spend 5-30 minutes in midday sunlight several times per week. Avoid excess sun exposure.
- Consume foods high in vitamin D like salmon, tuna, egg yolks, and fortified foods.
- Take vitamin D supplements if sun exposure and diet are insufficient.
- Have vitamin D blood levels tested to assess status.
- Address contributing health conditions like kidney disease.
Most experts recommend maintaining 25(OH)D blood levels between 30-60 ng/mL to provide adequate substrate for calcitriol production.
Supplementing with Calcitriol
Calcitriol is available as Rocaltrol, a pharmaceutical supplement used to treat specific medical conditions:
- Hypocalcemia – Low blood calcium
- Hypoparathyroidism – Underactive parathyroid glands
- Osteoporosis – Bone loss
- Rickets – Softening of bones in children
- Psoriasis – Autoimmune skin condition
It is crucial to have these conditions monitored by a healthcare provider before taking calcitriol supplements.
In healthy individuals, high doses of calcitriol can lead to hypercalcemia (elevated blood calcium) and hypercalciuria (excess calcium in urine). Toxicity symptoms may include:
- Nausea, vomiting, constipation
- Increased urination and thirst
- Kidney damage
- Calcification of organs like the heart and blood vessels
- Confusion, disorientation
For this reason, vitamin D supplements use the precursors cholecalciferol or ergocalciferol rather than calcitriol itself. Only under medical supervision can calcitriol be used safely as a supplement.
Key Points
- Vitamin D is converted into the hormone calcitriol through two hydroxylation reactions in the liver and kidneys.
- Calcitriol circulates to regulate calcium absorption, bone mineralization, cell growth, immunity, and other processes.
- Maintaining adequate calcitriol levels provides many health benefits related to bone strength, muscle function, cancer risk, autoimmunity, and inflammation.
- Vitamin D deficiency impairs calcitriol production, requiring treatment with sunlight, diet, or careful supplementation.
- In healthy people, calcitriol supplements must be medically supervised due to toxicity risks.
Conclusion
Vitamin D is converted into the active hormone calcitriol, which plays an essential role in calcium homeostasis and many other biological functions. Adequate sun exposure, dietary intake, and supplementation when required can help maintain healthy calcitriol levels and prevent vitamin D deficiency.
While vitamin D supplements use precursors like cholecalciferol, the bioactive calcitriol is available as a pharmaceutical agent for treating various medical conditions. When used judiciously under professional care, calcitriol supplements can provide therapeutic benefits, but may also pose toxicity risks. Overall, this hormonal form of vitamin D exerts profound effects on health and disease susceptibility.