D2 vs d3
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Comparative Efficacy of Vitamin D2 vs. Vitamin D3
Introduction to Vitamin D Forms: D2 and D3
Vitamin D is essential for maintaining bone health and supporting the immune system. It exists in two primary forms: Vitamin D2 (ergocalciferol) and Vitamin D3 (cholecalciferol). Despite their structural similarities, these two forms exhibit different efficacies in raising and maintaining serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of vitamin D status.
Vitamin D3 Superior in Raising Serum 25(OH)D Levels
Multiple studies have consistently shown that Vitamin D3 is more effective than Vitamin D2 in increasing serum 25(OH)D levels. A randomized controlled trial involving 335 women demonstrated that Vitamin D3 increased vitamin D status by 74%-75%, compared to a 33%-34% increase with Vitamin D2 over 12 weeks2. Similarly, a systematic review and meta-analysis confirmed that Vitamin D3 supplementation had a significantly greater effect on raising serum 25(OH)D concentrations than Vitamin D2, particularly when administered as a bolus dose3.
Long-term Efficacy: D3 Maintains Higher 25(OH)D Levels
Long-term studies further support the superiority of Vitamin D3. Research conducted over the winter months showed that daily supplementation with Vitamin D3 was more effective in maintaining serum 25(OH)D levels compared to Vitamin D2. Participants receiving Vitamin D3 had stable 25(OH)D levels, whereas those on Vitamin D2 experienced a significant decline9. Another study found that Vitamin D3 increased both total and free 25(OH)D levels more effectively than Vitamin D2, suggesting better bioactivity10.
Metabolic Pathways and Hydroxylation Differences
The metabolic pathways of Vitamin D2 and D3 also differ. Vitamin D2 has been shown to suppress the serum concentrations of various vitamin D metabolites, including 25(OH)D3 and 1α,25-dihydroxyvitamin D3, while increasing the ratio of 24R,25-dihydroxyvitamin D3 to 25(OH)D3. In contrast, Vitamin D3 supplementation increases these metabolites, indicating a more favorable metabolic profile1.
Clinical Implications and Recommendations
Given the evidence, Vitamin D3 appears to be the preferred form for supplementation. It is more potent, maintains higher serum 25(OH)D levels over time, and has a more favorable impact on vitamin D metabolism. This has significant implications for public health recommendations and clinical practices, particularly in populations at risk of vitamin D deficiency.
Conclusion
In summary, Vitamin D3 is more effective than Vitamin D2 in raising and maintaining serum 25(OH)D levels. Its superior efficacy and favorable metabolic effects make it the preferred choice for vitamin D supplementation. Further research may continue to elucidate the specific mechanisms and long-term benefits of Vitamin D3 over Vitamin D2.
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Most relevant research papers on this topic
Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial
Oral bolus vitamin D2 is less effective than vitamin D3 in elevating total serum 25(OH)D concentration, and may have different effects on vitamin D metabolism.
RCT
Rigorous JournalVitamin D2 vs. vitamin D3: They are not one and the same
Vitamin D3 is more than twice as effective as vitamin D2 at raising vitamin D levels, when given at a low dose in a physiologically relevant and public health-friendly manner.
Meta-AnalysisComparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis
Vitamin D3 supplementation is more effective at raising serum 25-hydroxyvitamin D concentrations than vitamin D2, potentially making it the preferred choice for supplementation.
Meta-Analysis
Very Rigorous Journal
Highly CitedVitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D.
Vitamin D2 is as effective as vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and does not negatively influence D3 levels.
RCTRigorous JournalHighly CitedVitamin D3 seems more appropriate than D2 to sustain adequate levels of 25OHD: a pharmacokinetic approach
D3 is more effective than D2 in maintaining adequate levels of 25-hydroxy vitamin D in the long term, potentially impacting both classic and non-classic effects of vitamin D.
RCTRigorous JournalVitamin D(3) is more potent than vitamin D(2) in humans.
D3 is 87% more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than equimolar D2, making it the preferred treatment option for vitamin D deficiency.
RCTVery Rigorous JournalHighly CitedDaily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial.
Vitamin D3 is more effective than vitamin D2 in increasing serum 25(OH)D in wintertime, making it a preferential form for optimizing vitamin D status in the general population.
RCT
Large Human TrialVery Rigorous JournalHighly CitedClinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients
Continued vitamin D3 supplementation beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity in critically ill pediatric burn patients.
RCTLong-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months
Daily vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over winter months in healthy adults.
RCTVery Rigorous JournalHighly CitedEffects of High-Dose Vitamin D2 Versus D3 on Total and Free 25-Hydroxyvitamin D and Markers of Calcium Balance.
D3 increases total and free 25-hydroxyvitamin D levels more effectively than D2, with free 25D potentially being a better marker of vitamin D bioactivity.
Non-RCTRigorous JournalHighly Cited