Does vitamin D3 (Cholecalciferol) increase phosphorus levels?

Vitamin D3 and Phosphorus Levels

Yes, vitamin D3 (cholecalciferol) increases phosphorus levels through its active metabolite 1,25-dihydroxyvitamin D3, which enhances intestinal phosphate absorption.

Mechanism of Action

• Vitamin D3 must be metabolized to 25-hydroxyvitamin D3 in the liver and subsequently to 1,25-dihydroxyvitamin D3 (calcitriol) in the kidney before it can function to regulate mineral metabolism 1
• Active vitamin D (calcitriol or alfacalcidol) increases phosphate absorption from the gut, which can lead to elevated serum phosphorus levels 2
• 1,25-dihydroxyvitamin D3 specifically stimulates the active transport of phosphate in the intestine through the sodium-phosphate cotransporter NaPi-IIb/Slc34a2 3
• The effect of vitamin D3 on phosphate absorption is primarily on the active transcellular pathway, while the paracellular pathway appears not to be affected 3

Clinical Evidence

• In patients with X-linked hypophosphataemia (XLH), active vitamin D is given with oral phosphate supplements to increase phosphate absorption from the gut 2
• Administration of 1,25-dihydroxyvitamin D3 to mice results in increased active transport of phosphate in the jejunum 3, 4
• In hypoparathyroid patients, administration of 1-alpha-hydroxy-vitamin D3 or 1,25-dihydroxy-vitamin D3 leads to increases in urinary phosphorus excretion and variable changes in serum phosphate concentration 5
• The effect of vitamin D on phosphate absorption varies by intestinal region, with the jejunum showing the most consistent increase in phosphate absorption in response to 1,25-dihydroxyvitamin D3 in both mice and rats 4

Clinical Considerations and Monitoring

• When therapy with vitamin D sterols is initiated or the dose is increased, serum levels of calcium and phosphorus should be monitored at least every 2 weeks for 1 month and then monthly thereafter 2
• Treatment with vitamin D should not be undertaken or continued if serum phosphorus levels exceed 6.5 mg/dL, because of the risk of further elevating serum phosphorus levels 2
• The serum calcium-phosphorus product should be maintained at <55 mg²/dL² to prevent complications 2
• Vitamin D supplementation can lead to hyperphosphaturia in addition to increased intestinal phosphate absorption 3

Potential Adverse Effects

• A major side effect of vitamin D treatment is increased intestinal absorption of calcium and phosphorus, which can worsen hyperphosphatemia in patients with impaired kidney function 2
• In patients with chronic kidney disease, conventional treatment with phosphate supplementation and active vitamin D might increase calciuria and thereby promote nephrocalcinosis 2
• Several reports suggest positive associations between daily oral phosphate doses and the risk of developing nephrocalcinosis, whereas the relationship with active vitamin D therapy has been observed less frequently 2

Special Populations

• In patients with chronic kidney disease, vitamin D analogs such as paricalcitol or doxercalciferol may be considered when serum calcium and/or phosphorus levels are above the target range 2
• In patients with X-linked hypophosphataemia, the optimal dose of active vitamin D varies from patient to patient, with requirements generally higher during early childhood and puberty (growth phases) 2
• In vitamin D-deficient rats, dietary phosphorus restriction leads to malabsorption of calcium that can be corrected by the administration of either vitamin D3 or 1,25-dihydroxyvitamin D3, despite hypophosphatemia 6

In conclusion, vitamin D3 supplementation increases phosphorus levels primarily through enhancing intestinal phosphate absorption, with the active metabolite 1,25-dihydroxyvitamin D3 playing the key role in this process.