Can vitamin D supplements increase serum calcium levels, potentially leading to hypercalcemia?

From the Guidelines

Vitamin D supplements can increase serum calcium levels, as evidenced by studies showing a notable increase in serum calcium levels in patients taking vitamin D analogues. The use of calcitriol or vitamin D analogues has been shown to increase serum calcium levels, with a mean increase of 0.08 mmol/L (0.32 mg/dL) in the paricalcitol group compared to a decrease of 0.06 mmol/L (0.25 mg/dL) in the placebo group 1. This increase in serum calcium levels can lead to episodes of hypercalcemia, which were more common in the paricalcitol group (22.6%) than the placebo group (0.9%) 1. Some key points to consider when evaluating the effect of vitamin D supplements on serum calcium levels include:

• The risk of hypercalcemia is higher in patients taking vitamin D analogues, particularly when combined with calcium-based phosphate binders 1
• The increase in serum calcium levels can be corrected by stopping the use of calcium-based phosphate binders without changing the vitamin D analogue dose 1
• The use of vitamin D analogues should be reserved for severe and progressive secondary hyperparathyroidism (SHPT) due to the risk-benefit ratio 1
• Patients with certain conditions, such as chronic kidney disease, are at higher risk for developing hypercalcemia with vitamin D supplementation 1.

From the FDA Drug Label

Excessive administration of vitamin D compounds, including paricalcitol capsules, can cause over suppression of PTH, hypercalcemia, hypercalciuria, hyperphosphatemia, and adynamic bone disease. Concomitant administration of high doses of calcium-containing preparations or thiazide diuretics with paricalcitol may increase the risk of hypercalcemia. High intake of calcium and phosphate concomitant with vitamin D compounds may lead to serum abnormalities requiring more frequent patient monitoring and individualized dose titration Yes, vitamin D supplements can increase serum calcium, as evidenced by the risk of hypercalcemia associated with excessive administration of vitamin D compounds 2.

• Key factors that may contribute to this risk include:
  • Concomitant administration of high doses of calcium-containing preparations or thiazide diuretics
  • High intake of calcium and phosphate concomitant with vitamin D compounds

From the Research

Vitamin D Supplements and Serum Calcium

• Vitamin D supplements can increase serum calcium levels, as evidenced by studies that have shown a link between vitamin D supplementation and hypercalcemia 3, 4.
• The ingestion of excessive amounts of vitamin D can result in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] 3.
• Vitamin D plays an essential role in calcium homeostasis, and its active form, calcitriol (1,25(OH)2D), increases intestinal calcium absorption and facilitates renal reabsorption, leading to elevated serum calcium levels 5.
• However, it is important to note that vitamin D supplementation can precipitate hypercalcemia and nephrolithiasis in individuals with altered vitamin D catabolism, highlighting the importance of monitoring serum calcium levels in patients being supplemented with vitamin D 4.

Mechanisms and Interactions

• The interaction of 1,25(OH)2D with its receptor (VDR) increases the efficiency of intestinal absorption of calcium, leading to elevated serum calcium levels 5.
• Serum phosphate levels can also influence 1,25(OH)2D and fibroblast growth factor 23 (FGF23) levels, and higher phosphate concentrations can suppress vitamin D activation and stimulate parathyroid hormone (PTH) release 5.
• New vitamin D receptor activators (VDRAs) have been developed to treat high serum PTH levels with a reduced risk of hypercalcemia and hyperphosphatemia, such as paricalcitol, which suppresses PTH secretion with minimal increases in serum calcium and phosphate 6.

Clinical Implications

• Vitamin D supplementation can increase the risk of hypercalcemia, particularly in individuals with altered vitamin D catabolism or those taking excessive amounts of vitamin D 3, 4.
• Monitoring serum calcium levels is crucial in patients being supplemented with vitamin D to prevent hypercalcemia and its sequelae 4.
• The use of VDRAs, such as paricalcitol, may be a safer alternative to traditional vitamin D supplementation in certain patient populations, such as those with secondary hyperparathyroidism 6.