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Primary Research · 2012

Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis

Tripkovic L, Lambert H, Hart K, et al. · American Journal of Clinical Nutrition, 2012

Key finding

D3 (cholecalciferol) raised serum 25(OH)D significantly more effectively than D2 (ergocalciferol) at equivalent doses, supporting D3 as the preferred form.

BACKGROUND: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. DESIGN: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. RESULTS: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. CONCLUSIONS: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3) could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.

Abstract sourced from PubMed, a database of the U.S. National Library of Medicine. Displayed in the authors’ own words for context; our critique is in the sections below.

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How to read a study like this

The same questions worth asking about any research paper, not just this one. Worth a minute even if you trust the grade.

Who was studied, and do you resemble them?

Supplement effects often depend on baseline status. Vitamin D helps people who are deficient; iron helps people who are anemic. A result in people unlike you may not apply to you.

What was measured, and does it matter in daily life?

A study that shows a blood marker moved isn't the same as a study that shows people felt or functioned better. Ask what the outcome means in practice.

How large was the effect — not just whether it was significant.

'Statistically significant' only means the effect is unlikely to be zero. It doesn't tell you the effect is large enough to notice. Look for effect sizes, not just p-values.

Who paid for the trial, and what did they stand to gain?

Industry-funded trials are several times more likely to report positive results than independent ones. It's not usually fraud — it's subtle design and reporting choices. Weight accordingly.

Has anyone else replicated this?

Single positive trials are hypotheses. Replication by independent groups is what turns a hypothesis into reliable evidence. If the only positive trial is the one you're reading, wait.

Does the dose in the trial match what's being sold?

Supplement marketing routinely cites trials that used 5–10× the dose in the product. If the effective dose was 2 g/day and the capsule has 200 mg, expect roughly no effect.

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