From the Guidelines
The main difference between 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D lies in their biological activity and role in the body, with 25-hydroxyvitamin D serving as the primary storage form and 1,25-dihydroxyvitamin D functioning as a hormone regulating calcium and phosphate absorption, bone mineralization, and immune function.
Key Differences
- 25-hydroxyvitamin D (calcidiol) is the major circulating form of vitamin D in the bloodstream, produced in the liver when vitamin D from diet or skin synthesis is hydroxylated, and has limited biological activity but is what doctors typically measure in blood tests to assess vitamin D status 1.
- 1,25-dihydroxyvitamin D (calcitriol) is the biologically active form of vitamin D, produced primarily in the kidneys when 25-hydroxyvitamin D undergoes a second hydroxylation, and regulates calcium and phosphate absorption in the intestines, promotes bone mineralization, and influences immune function 1.
Clinical Implications
- The conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D is tightly regulated by parathyroid hormone, calcium, and phosphate levels to maintain proper mineral homeostasis 1.
- While 25-hydroxyvitamin D has a relatively long half-life of 2-3 weeks, 1,25-dihydroxyvitamin D has a much shorter half-life of only 4-6 hours, reflecting its potent hormonal activity that requires precise regulation 1.
Recommendations
- The 25(OH)D level should be above 30 ng/mL for optimal health benefit, and an upper safety limit for 25(OH)D of 100 ng/mL is recommended 1.
- A large correcting dose can be proposed initially, followed by a maintenance treatment of 800 IU/day (or equivalent with intermittent dosing), which can be increased if levels remain insufficient during monitoring 1.
From the FDA Drug Label
Man’s natural supply of vitamin D depends mainly on exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol in the skin to vitamin D3 (cholecalciferol). Vitamin D3 must be metabolically activated in the liver and the kidney before it is fully active as a regulator of calcium and phosphorus metabolism at target tissues The initial transformation of vitamin D3 is catalyzed by a vitamin D3-25-hydroxylase enzyme (25-OHase) present in the liver, and the product of this reaction is 25-hydroxyvitamin D3 [25-(OH)D3] Hydroxylation of 25-(OH)D3 occurs in the mitochondria of kidney tissue, activated by the renal 25-hydroxyvitamin D3-1 alpha-hydroxylase (alpha-OHase), to produce 1,25-(OH)2D3 (calcitriol), the active form of vitamin D3
The main difference between 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D is the level of hydroxylation and their roles in the body.
- 25-hydroxyvitamin D is the product of the initial transformation of vitamin D3 in the liver, catalyzed by the vitamin D3-25-hydroxylase enzyme.
- 1,25-dihydroxyvitamin D (calcitriol) is the active form of vitamin D3, produced by the hydroxylation of 25-hydroxyvitamin D3 in the kidney, and it plays a critical role in regulating calcium and phosphorus metabolism at target tissues 2.
From the Research
Vitamin D Forms
- 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D are two forms of vitamin D.
- 25-hydroxyvitamin D is the major circulating metabolite of vitamin D and is widely used as a biomarker of vitamin D status 3.
- 1,25-dihydroxyvitamin D, also known as calcitriol, is the vitamin D hormone and is essential for maintaining mineral homeostasis and skeletal integrity 4.
Difference Between 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D
- 25-hydroxyvitamin D is the storage form of vitamin D, while 1,25-dihydroxyvitamin D is the active form of vitamin D 4.
- The kidney is the main site for the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D 4.
- 25-hydroxyvitamin D is measured to determine vitamin D status, while 1,25-dihydroxyvitamin D is involved in the activation of the vitamin D receptor (VDR) to induce/repress genes that maintain mineral homeostasis and skeletal integrity 4.
Clinical Significance
- Vitamin D deficiency is a recognized risk factor for all-cause mortality in normal individuals and in chronic kidney disease (CKD) patients 4.
- The symptoms of vitamin D deficiency are unspecific and very common, and physicians may easily suspect vitamin D deficiency and measure 25-hydroxyvitamin D levels 5.
- Treatment with either vitamin D(2) or vitamin D(3) is recommended for deficient patients, and the measurement of serum 25-hydroxyvitamin D level is suggested as the initial diagnostic test in patients at risk for deficiency 6.