What is the Difference Between Calcitriol and Cholecalciferol

The key difference between Calcitriol and Cholecalciferol is that calcitriol is the active form of vitamin D produced in the kidneys, while cholecalciferol, also known as vitamin D3, is an inactive precursor of vitamin D produced by the skin when exposed to sunlight.

Calcitriol and cholecalciferol are two forms of vitamin D essential for good health. Vitamin D generally helps maintain calcium and phosphorus levels, metabolic functions, transcription regulation, and bone metabolism. Most people can get enough vitamin D naturally by consuming foods rich in vitamin D, such as eggs, fish, and cheese, and through the natural conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin when exposed to sunlight. However, deficiency can occur due to insufficient exposure to sunlight, lack of vitamin D in the diet, genetic defects, or severe liver/kidney disease. Vitamin D deficiency can lead to rickets or osteomalacia, decreasing calcium levels and increasing parathyroid hormone production, leading to porotic bone conditions. Although both calcitriol and cholecalciferol are essential for human health, calcitriol is much more potent than cholecalciferol.

CONTENTS

1. Overview and Key Difference
2. What is Calcitriol 
3. What is Cholecalciferol
4. Similarities – Calcitriol and Cholecalciferol
5. Calcitriol vs. Cholecalciferol in Tabular Form
6. Summary – Calcitriol vs. Cholecalciferol

What is Calcitriol?

Calcitriol is a biologically active form of calcitrophic hormone associated with anti-osteoporotic, immunomodulatory, anticancer, antioxidant, and mood-stimulatory properties. It is the most potent metabolite of vitamin D with three hydroxyl groups. Calcitriol and parathyroid hormone enhance the absorption of gastrointestinal calcium and phosphate, promote renal absorption of calcium, and stimulate the release of calcium stores to regulate plasma calcium levels. Furthermore, calcitriol also promotes fatty acid synthesis and inhibits lipolysis to increase energy efficiency. Calcitriol is commonly indicated for metabolic bone diseases, hypocalcemia in chronic kidney failure, and osteoporosis.

The main routes of administration of calcitriol include oral, intravenous, and topical forms. Upon oral administration, calcitriol is rapidly absorbed by the intestine and reaches peak plasma concentration within 2 hours. Approximately 99.9% of the calcitriol binds with the plasma proteins distributed into the distal locations. The metabolism of calcitriol is involved in two steps: the production of calcitroic acid and the production of 1a,25R(OH)2-26,23S-lactone D3. The metabolites of the calcitriol are primarily excreted in the feces with an elimination half-life of 5-8 hours. The overdose symptoms of calcitriol include weakness, headache, nausea, anorexia, weight loss, hypertension, and ectopic calcification. Calcitriol is marketed under various trade names, including Rocaltrol, Calcijex, and Decostriol.

What is Cholecalciferol?

Cholecalciferol, also known as vitamin D3, is a preferable form of vitamin D for medical implications due to the structural differences between other forms of vitamin D. It is primarily indicated for refractory rickets, hypoparathyroidism, and familial hypophosphatemia. Furthermore, cholecalciferol can also be helpful in vitamin D deficiency related to osteoporosis and chronic kidney disease. The metabolic conversion of cholecalciferol is associated with two steps. First, the liver hydroxylates cholecalciferol to produce calcifediol (25-hydroxycholecalciferol), while the kidneys perform the second hydroxylation, yielding calcitriol (1,25-dihydroxycholecalciferol). These metabolites then facilitate the active absorption of calcium and phosphorous in the small intestine to increase their serum concentrations.

Cholecalciferol is readily absorbed from the small intestine in the presence of bile. Upon absorption, 50-80% of cholecalciferol is distributed after binding with plasma proteins such as vitamin D-binding proteins (DBP). Both metabolites and un-metabolized forms of cholecalciferol are primarily excreted in the feces. Cholecalciferol overdose can cause hypervitaminosis D, resulting in high calcium levels and related symptoms. Early symptoms of hypercalcemia may cause weakness, fatigue, nausea, vomiting, and dizziness. Manifestations of hypercalcemia may include nephrocalcinosis, renal dysfunction, osteoporosis, impaired growth, anemia, metastatic calcification, pancreatitis, vascular calcification, and seizures. Brand names of cholecalciferol include Adrovance, Animi-3 With Vitamin D, and Citranatal B-calm Kit.

What are the Similarities Between Calcitriol and Cholecalciferol?

• Calcitriol and cholecalciferol are essential nutrients for human health.
• They are both involved in calcium and phosphorus absorption.
• Both these are important for bone health.
• They bind to specific vitamin D receptors.
• Both calcitriol and cholecalciferol are used clinically to treat conditions related to vitamin D deficiency, such as rickets and osteoporosis.

What is the Difference Between Calcitriol and Cholecalciferol?

Calcitriol and cholecalciferol are distinct forms of vitamin D with different characteristics and functions. Calcitriol is the active form of vitamin D produced in the kidneys. In contrast, cholecalciferol, also known as vitamin D3, is an inactive precursor of vitamin D produced by the skin when exposed to sunlight. Thus, this is the key difference between Calcitriol and Cholecalciferol.

Calcitriol plays a central role in regulating calcium and phosphate levels in the body. It promotes calcium absorption from the intestines, facilitates calcium reabsorption in the kidneys, and regulates calcium release from bones. In comparison, cholecalciferol serves as a precursor to calcitriol. It is converted to calcitriol in the liver and kidneys, where it becomes biologically active. Furthermore, calcitriol is 100 times more potent than cholecalciferol. Calcitriol is a powerful hormone, and it should only be used under the supervision of a healthcare provider. It may be prescribed for people with certain medical conditions, such as kidney failure or hypoparathyroidism. For most people, cholecalciferol is the best form of vitamin D to supplement with. It is safe and effective at raising blood levels, which is the most important marker of vitamin D status.

Below is a summary of the difference between Calcitriol and Cholecalciferol in tabular form for side-by-side comparison.

Summary – Calcitriol vs. Cholecalciferol

Calcitriol and cholecalciferol are two vitamin D forms essential for human health. Calcitriol is the active form of vitamin D, while cholecalciferol is an inactive precursor. Calcitriol is produced in the kidneys, while cholecalciferol is made in the skin when exposed to sunlight. Calcitriol is more potent than cholecalciferol and is used to treat specific medical conditions, such as chronic kidney disease, parathyroid disorders, and certain rickets. Cholecalciferol is often used as a dietary supplement to prevent or treat vitamin D deficiency. Among these two, cholecalciferol is the safest and most effective vitamin D supplement for increasing blood levels and improving vitamin D status. Hence, this is the summary of the difference between Calcitriol and Cholecalciferol.

Reference:

1. Vieth, Reinhold. “Vitamin D supplementation: Cholecalciferol, calcifediol, and Calcitriol.” European Journal of Clinical Nutrition, vol. 74, no. 11, 2020, pp. 1493–1497.
2. Peppone, L. J., et al. “The efficacy of calcitriol therapy in the management of bone loss and fractures: A Qualitative Review.” Osteoporosis International, vol. 21, no. 7, 2009, pp. 1133–1149.

Image Courtesy:

1. “Calcitriol” ByAyacop assumed – No machine-readable source provided. Own work assumed (based on copyright claims). (Public Domain) via Commons Wikimedia
2. “Cholecalciferol” By Calvero – Own work (made with ChemDraw) (Public Domain) via Commons Wikimedia