What causes elevated vitamin D levels?

From the Guidelines

Elevated vitamin D levels are primarily caused by excessive supplementation, typically above 10,000 IU daily for extended periods, rather than from diet or sun exposure alone. The causes of elevated vitamin D levels can be broken down into several categories, including:

• Excessive supplementation: Taking high-dose vitamin D supplements is the most common cause of elevated vitamin D levels, as noted in a study published in Autoimmunity Reviews 1.
• Medical conditions: Certain medical conditions like granulomatous disorders (sarcoidosis, tuberculosis), some lymphomas, and primary hyperparathyroidism can increase vitamin D activation.
• Medications: Some medications, such as certain antifungals like ketoconazole and some anticonvulsants, may also raise vitamin D levels.
• Manufacturing errors: Rarely, vitamin D toxicity can occur from manufacturing errors in supplements or fortified foods.
• Genetic conditions: People with specific genetic conditions affecting vitamin D metabolism may also develop elevated levels.

It's essential to note that sunbathing can produce vitamin D doses equivalent to an oral vitamin D intake of up to 20,000 IU per day, but in healthy subjects who have spent prolonged periods in a sunny environment, measured 25(OH)D concentrations rarely exceed 100 ng/mL, suggesting that this level may be considered as a safe upper limit for serum 25(OH)D levels 1. The safety limit for vitamin D levels is considered to be 100 ng/mL, and intake above 100,000 IU daily or 25(OH)D levels exceeding 100 ng/mL can lead to hypercalcemia in generally healthy adults 1.

Symptoms of elevated vitamin D levels may include nausea, vomiting, weakness, and kidney problems, and blood tests measuring 25-hydroxyvitamin D can confirm elevated levels, with values above 100 ng/mL generally considered excessive. Treatment involves stopping vitamin D supplements, limiting calcium intake, increasing fluid consumption, and in severe cases, medication to lower calcium levels.

From the Research

Causes of Elevated Vitamin D Levels

Elevated vitamin D levels can be caused by various factors, including:

• Excessive intake of vitamin D supplements, which can lead to hypercalcemia, hypercalciuria, and hyperphosphatemia 2
• Granulomatous diseases such as sarcoidosis, which can cause overproduction of the active metabolite of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) 3, 4
• Lymphomas, which can produce 1,25(OH)2D3, leading to hypercalcemia 5
• Other conditions such as primary hyperparathyroidism, malignancy, and genetic disorders 6

Specific Conditions Associated with Elevated Vitamin D Levels

• Sarcoidosis: patients with sarcoidosis who receive vitamin D supplementation are at increased risk of developing hypercalcemia, with 42.3% of patients developing hypercalcemia compared to 18.3% of those who did not receive vitamin D 4
• Lymphoma: nearly one-half of all hypercalcemic patients with lymphoma present with inappropriately elevated circulating concentrations of 1,25(OH)2D3, which can be produced by tumor-adjacent macrophages 5
• Primary hyperparathyroidism: approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy, and elevated vitamin D levels can be associated with PHPT 6

Mechanisms of Elevated Vitamin D Levels

• Overproduction of 1,25(OH)2D by granulomatous tissue or tumor-adjacent macrophages, leading to increased intestinal absorption of calcium and hypercalcemia 3, 5
• Excessive intake of vitamin D supplements, which can lead to hypercalcemia, hypercalciuria, and hyperphosphatemia, even without developing hypervitaminosis D 2