Cholecalciferol side effects
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Cholecalciferol Side Effects: A Comprehensive Review
Introduction to Cholecalciferol
Cholecalciferol, also known as vitamin D3, is a form of vitamin D commonly used in supplements to treat or prevent vitamin D deficiency. While it is essential for bone health and calcium regulation, its supplementation can have various side effects, especially at high doses. This article synthesizes findings from multiple studies to provide a clear understanding of the potential side effects of cholecalciferol.
Common Side Effects of Cholecalciferol
Hypercalcemia and Mineral Imbalance
One of the primary concerns with high doses of cholecalciferol is the risk of hypercalcemia, a condition characterized by elevated calcium levels in the blood. However, studies have shown that even high doses of cholecalciferol do not necessarily lead to hypercalcemia. For instance, a study on patients with chronic kidney disease (CKD) stages 3-4 found that high daily doses of cholecalciferol did not cause hypercalcemia or other significant side effects1. Similarly, another study on multiple sclerosis (MS) patients reported that high-dose cholecalciferol was safe and well-tolerated without causing hypercalcemia2.
Increased Risk of Erythropoietin Resistance
In hemodialysis patients, cholecalciferol supplementation has been associated with increased erythropoietin resistance over the long term. This was observed in a study where cholecalciferol increased serum hepcidin levels initially but led to higher erythropoietin resistance after six months3. This suggests that while cholecalciferol can improve vitamin D levels, it may complicate anemia management in these patients.
Adverse Effects in Dairy Cows
Interestingly, a study on dairy cows revealed that high doses of cholecalciferol could lead to adverse health outcomes such as retained placenta and metritis, along with reduced milk production4. Although this study was conducted on animals, it highlights the potential for high doses of cholecalciferol to cause significant side effects.
Immunologic and Inflammatory Effects
Immunomodulatory Effects in MS Patients
Cholecalciferol has been shown to have immunomodulatory effects, particularly in MS patients. High doses of cholecalciferol reduced the proportion of pro-inflammatory T cells and increased the proportion of naive and central memory T cells, indicating a shift towards a less inflammatory immune profile2. This suggests potential benefits in autoimmune conditions, although the long-term implications need further study.
Inflammatory Markers in Hemodialysis Patients
In hemodialysis patients, cholecalciferol supplementation significantly reduced inflammatory markers such as high-sensitive C-reactive protein (hsCRP) and neutrophil-to-lymphocyte ratio (NLR)7. This indicates that cholecalciferol may have anti-inflammatory benefits in this population, potentially improving overall health outcomes.
Cardiovascular and Vascular Effects
Vascular Calcification
Cholecalciferol has been studied for its effects on vascular calcification, a common issue in hemodialysis patients. One study found that cholecalciferol significantly increased serum levels of 25-hydroxyvitamin D and fetuin-A, a protein that inhibits vascular calcification, without causing adverse effects5. However, another study reported no significant improvements in cardiovascular parameters such as blood pressure and pulse wave velocity after cholecalciferol supplementation10.
Cardiac Function
A study on dialysis patients found that cholecalciferol did not significantly improve cardiac function or reduce blood pressure, although it did increase left ventricular volume10. This suggests that while cholecalciferol may have some impact on heart structure, its benefits for cardiac function are limited.
Conclusion
Cholecalciferol supplementation, particularly at high doses, is generally safe and well-tolerated in various populations, including those with CKD and MS. However, it can lead to increased erythropoietin resistance in hemodialysis patients and has been associated with adverse effects in dairy cows. Its immunomodulatory and anti-inflammatory effects are promising, but its benefits for cardiovascular health remain inconclusive. As with any supplement, it is essential to monitor for potential side effects and adjust dosages accordingly.
Sources and full results
Most relevant research papers on this topic
High doses of cholecalciferol alleviate the progression of hyperparathyroidism in patients with CKD Stages 3–4: results of a 12-week double-blind, randomized, controlled study
High doses of cholecalciferol effectively halt the progression of secondary hyperparathyroidism in patients with chronic kidney disease Stages 3-4, without causing hypercalcaemia or other side effects.
RCTSafety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis
High-dose cholecalciferol supplementation is safe and well-tolerated in multiple sclerosis patients, exhibiting immunomodulatory effects.
RCT
Highly CitedEffect of cholecalciferol on serum hepcidin and parameters of anaemia and CKD-MBD among haemodialysis patients: a randomized clinical trial
Cholecalciferol supplementation increases serum hepcidin levels in haemodialysis patients, but may increase erythropoietin resistance in the long term.
RCT
Rigorous JournalRandomized clinical trial to evaluate the effects of a prepartum cholecalciferol injection on postpartum serum calcium dynamics and health and performance in early-lactation multiparous dairy cows.
Prepartum cholecalciferol injections in early-lactation multiparous dairy cows increased the risk of retained placenta and metritis, but did not significantly affect milk yield in the first 10 days after parturition.
RCTRigorous JournalThe impact of cholecalciferol on markers of vascular calcification in hemodialysis patients: A randomized placebo controlled study.
Cholecalciferol effectively and tolerably improves vitamin D deficiency and vascular calcification in hemodialysis patients without causing adverse effects.
RCTEffects of cholecalciferol on functional, biochemical, vascular, and quality of life outcomes in hemodialysis patients.
Cholecalciferol supplementation improves vitamin D levels in hemodialysis patients without increasing calcium or phosphorus levels, but does not affect muscle strength, functional capacity, or quality of life.
RCTHighly Cited#3706 EFFECT OF CHOLECALCIFEROL INTAKE ON NOVEL INFLAMMATORY INDICATORS IN HEMODIALYSIS PATIENTS
Weekly (50.000 IU) oral cholecalciferol effectively replenishes vitamin D levels and reduces inflammation in hemodialysis patients, with neutrophil-to-lymphocyte ratio being an effective, non-expensive inflammatory indicator.
RCTEffects of cholecalciferol supplementation on inflammatory markers and muscle damage indices of soccer players after a simulated soccer match.
Cholecalciferol supplementation for 8 weeks increased vitamin D levels without affecting muscle damage or inflammation, but increased interleukin-6 levels.
RCTThe effect of cholecalciferol supplementation on allograft function in incident kidney transplant recipients: A randomized controlled study
Cholecalciferol supplementation did not improve allograft function in incident kidney transplant recipients compared to placebo.
RCTCardiovascular effects of cholecalciferol treatment in dialysis patients – a randomized controlled trial
Cholecalciferol treatment for six months in chronic dialysis patients did not improve 24-hour blood pressure, arterial stiffness, or cardiac function.
RCTRigorous Journal