What are the side effects of excessive vitamin D (Vitamin D) intake?

Side Effects of Excessive Vitamin D Intake

Excessive vitamin D intake can cause toxicity leading to hypercalcemia with symptoms including fatigue, weakness, altered mental status, nausea, vomiting, constipation, polyuria, polydipsia, and kidney injury, with toxicity typically occurring when 25(OH)D levels exceed 150 ng/mL. 1

Clinical Manifestations of Vitamin D Toxicity

Vitamin D toxicity affects multiple body systems and presents with various symptoms:

Generalized Symptoms

• Fatigue and weakness
• Confusion
• Weight loss 2

Neurological Symptoms

• Altered mental status
• Irritability
• Potential progression to coma
• Pseudotumor cerebri 1

Gastrointestinal Symptoms

• Nausea and vomiting
• Constipation
• Abdominal pain
• Pancreatitis 2, 3

Renal and Endocrine Symptoms

• Polyuria and polydipsia
• Acute kidney injury
• Kidney stones
• Hypercalciuria 1

Other Manifestations

• Bone abnormalities
• Dermatitis and skin disorders
• Alopecia
• Muscle pain
• Cheilitis
• Hepatocellular necrosis
• Hyperlipidemia 1

Laboratory Findings

Key laboratory findings in vitamin D toxicity include:

• Elevated serum 25(OH)D levels >150 ng/mL (375 nmol/L) - the hallmark of vitamin D toxicity 1
• Hypercalcemia (elevated serum calcium)
• Hyperphosphatemia
• Suppressed parathyroid hormone (PTH) levels
• Elevated urinary calcium excretion 1

Risk Factors and Causes

Vitamin D toxicity typically occurs due to:

• Excessive supplementation with daily doses >10,000 IU for prolonged periods
• Accidental overdose or prescription of mega-doses (as seen in cases with cumulative doses of 3,600,000 IU) 2
• Manufacturing errors in vitamin D preparations 4
• Individual variation in vitamin D metabolism (some people may experience toxicity at doses safe for others) 1

Cardiovascular Risks

Excessive vitamin D may have significant cardiovascular implications:

• Increased risk of cardiovascular calcification
• Potential acceleration of atherosclerosis
• Stimulation of smooth muscle cell proliferation
• Induction of fibroblast growth factor-23 (FGF-23), linked to adverse cardiovascular events 5
• U-shaped relationship between vitamin D levels and cardiovascular risk (both low and high levels increase risk) 1

Prevention and Safety Guidelines

To prevent vitamin D toxicity:

• The upper limit of safety for vitamin D intake is generally considered to be 4,000 IU daily 5, 1
• Risk of harm increases significantly above 10,000 IU daily for prolonged periods 1
• Monitor serum calcium and phosphorus every 3 months during high-dose supplementation 1
• Be aware that individual variation exists in vitamin D metabolism 1

Management of Vitamin D Toxicity

If vitamin D toxicity is suspected:

1. Immediately discontinue all vitamin D supplements
2. Increase oral fluid intake
3. Consider IV hydration with normal saline for severe hypercalcemia
4. Use loop diuretics to enhance calcium excretion
5. Consider bisphosphonates in severe cases (pamidronate has shown efficacy) 6
6. Restrict dietary calcium intake temporarily
7. Monitor serum calcium and vitamin D levels every 2-4 weeks initially 1

Important Caveats

• Recovery from vitamin D toxicity may take months as vitamin D has a long half-life (vitamin D levels may take 18 months to normalize) 7
• Even standard doses may cause toxicity in individuals with genetic variations affecting vitamin D metabolism 1
• Vitamin D toxicity was once considered rare but is becoming more common due to increased supplementation practices 2
• Self-administration of high-dose vitamin D without medical supervision increases risk of toxicity 3

Clinicians should maintain awareness of the toxic potential of high-dose vitamin D and use supplements cautiously, particularly when treating vitamin D deficiency 2.