Vitamin d supplement side effects
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Side Effects of Vitamin D Supplementation
Hypercalcemia and Hypercalciuria
One of the primary concerns with long-term vitamin D supplementation is its impact on calcium metabolism. Studies have shown that vitamin D supplementation can lead to an increased risk of hypercalcemia (elevated calcium levels in the blood) and hypercalciuria (elevated calcium levels in the urine) 12. Specifically, a meta-analysis of 48 studies found that participants taking vitamin D supplements had a higher risk of developing hypercalcemia and hypercalciuria compared to those taking a placebo 1. Another study confirmed these findings, indicating a trend towards increased hypercalcemia with high-dose vitamin D supplementation over a year or more 2.
Kidney Stones
The relationship between vitamin D supplementation and kidney stones is less clear. While some studies suggest a potential increase in kidney stone risk with vitamin D and calcium co-supplementation, the overall evidence does not strongly support this association. For instance, a systematic review found no significant increase in kidney stone risk among participants taking vitamin D supplements compared to those on a placebo 12. This suggests that while hypercalcemia and hypercalciuria are concerns, they do not necessarily translate into a higher incidence of kidney stones.
Noncalcemic Adverse Effects
Vitamin D supplementation has also been investigated for noncalcemic adverse effects, such as gastrointestinal and dermatological symptoms. A systematic review of randomized controlled trials (RCTs) found that long-term vitamin D supplementation did not significantly increase the risk of these noncalcemic adverse effects 3. Additionally, the review noted that vitamin D did not lead to higher withdrawal rates from studies, indicating that it is generally well-tolerated 3.
Impact on Mental Health and Inflammation
Interestingly, vitamin D supplementation has shown some beneficial effects on mental health and inflammation markers. A meta-analysis of RCTs found that vitamin D supplementation significantly reduced depression scores and improved sleep quality in patients with psychiatric disorders 9. Furthermore, it also led to a reduction in inflammatory markers such as C-reactive protein (CRP) 9. These findings suggest that while there are some risks associated with vitamin D supplementation, there are also potential benefits, particularly in mental health and inflammation.
Conclusion
In summary, long-term vitamin D supplementation is associated with an increased risk of hypercalcemia and hypercalciuria, but not necessarily with kidney stones. Noncalcemic adverse effects are generally not increased with vitamin D supplementation, and there may be beneficial effects on mental health and inflammation. As with any supplement, it is important to balance the potential benefits and risks and to consult healthcare providers for personalized advice.
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Most relevant research papers on this topic
Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis.
Long-term vitamin D supplementation increases risks of hypercalcemia and hypercalciuria, but does not increase kidney stone risk.
Meta-Analysis
Very Rigorous Journal
Highly CitedAdverse events from large dose vitamin D supplementation taken for one year or longer
Long-term high-dose vitamin D supplementation did not significantly increase the risk of total adverse events or kidney stones, but there was a trend towards increased hypercalcemia and possibly hypercalciuria.
Systematic ReviewNoncalcemic adverse effects and withdrawals in randomized controlled trials of long-term vitamin D2 or D3 supplementation: a systematic review and meta-analysis
Long-term vitamin D supplementation does not increase the risk of noncalcemic adverse effects, as reported in randomized controlled trials.
Meta-AnalysisThe Effect of Vit-D Supplementation on the Side Effect of BioNTech, Pfizer Vaccination and Immunoglobulin G Response Against SARS-CoV-2 in the Individuals Tested Positive for COVID-19: A Randomized Control Trial
Vitamin D supplementation of 600 IU daily can reduce post-vaccination side effects and increase IgG levels in COVID-19 patients.
RCT
Large Human TrialThe effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis.
Vitamin D supplementation with or without calcium does not significantly reduce skeletal or non-skeletal outcomes in unselected community-dwelling individuals by more than 15%.
Meta-AnalysisHighly CitedRelation between Vitamin D and COVID-19 in Aged People: A Systematic Review
Vitamin D deficiency is associated with an increased risk of COVID-19 in aged people, and supplementation may improve clinical outcomes.
Systematic ReviewVery Rigorous JournalNon-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data
Vitamin D supplementation shows no significant benefits on cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases, but may have beneficial effects on depression, blood pressure, respiratory tract infections, and mortality.
Meta-Analysis
Rigorous JournalHighly CitedSupplementation with 1000 IU vitamin D/d leads to parathyroid hormone suppression, but not increased fractional calcium absorption, in 4-8-y-old children: a double-blind randomized controlled trial.
Vitamin D3 supplementation at 1000 IU/d increases 25(OH)D and decreases parathyroid hormone in children with average vitamin D intake below dietary recommendations, but does not significantly affect calcium absorption.
RCTVery Rigorous JournalThe effects of vitamin D supplementation on mental health, and biomarkers of inflammation and oxidative stress in patients with psychiatric disorders: A systematic review and meta-analysis of randomized controlled trials
Vitamin D supplementation improves mental health and reduces inflammation in patients with psychiatric disorders, but does not affect other biomarkers of inflammation and oxidative stress.
Meta-AnalysisHighly CitedThe effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials.
Vitamin D supplementation has a small positive impact on muscle strength, but no significant effect on muscle mass or muscle power.
Meta-AnalysisRigorous JournalHighly Cited