The liposomal form of Vitamin D had the best response - RCT
Vitamin D supplementation and bone health in post-menopausal women: a 24-month randomized controlled intervention with enhanced bioavailability formulations
Eur J Clin Nutr. 2026 Aug 7. doi: 10.1038/s41430-026-01789-0. PDF behind paywall
Nauman Rasool 1 2, Yusra Munir 3
Background: Postmenopausal osteoporosis is a major public health issue affecting over one billion people worldwide. However, limited evidence exists on how different formulations with enhanced bioavailability compare in clinical outcomes with one another, even if there is extensive research on vitamin D tablets.
Objective: Post-menopausal women's bone mineral density (BMD), bone turnover markers, and fracture risk over a 24-month period were evaluated using regular cholecalciferol, micronized cholecalciferol, and liposomal vitamin D3 combined with calcium supplements.
Methods: Using age and baseline 25-hydroxyvitamin D [25(OH)D] levels, 612 post-menopausal women (ages 50-75 years) with T-scores ranging from -1.5 to -2.5 on dual-energy X-ray absorptiometry (DXA) were randomly assigned to one of four groups:
- regular cholecalciferol (1200 IU/day + 1000 mg calcium, n = 153),
- micronized cholecalciferol (1200 IU/day + 1000 mg calcium, n = 153),
- liposomal vitamin D3 (800 IU/day + 1000 mg calcium, n = 153), or
- placebo (n = 153).
Other results were changes in femoral neck, lumbar spine, total hip bone mineral density (BMD), bone-specific alkaline phosphatase (BSAP), C-terminal telopeptide of type I collagen (CTX), serum 25(OH)D levels, and incidence of new fragility fractures.
Results: Mean serum 25(OH)D levels were substantially higher (p = 0.003) in the liposomal group (38.2_ ± 7.5 ng/mL)_ than those in the control cholecalciferol group (28.5 ± 6.8 ng/mL).
The liposomal vitamin D3 group exhibited somewhat higher femoral neck BMD (2.8% ± 1.2%; p = 0.012) and lumbar spine BMD (2.8% ± 1.2%; p = 0.008) enhancement than did the placebo group (1.1% ± 0.9%).
The liposomal form showed the highest ratio (2.4 ± 0.6 versus 1.8 ± 0.5 placebo; p = 0.001); hence, BSAP/CTX ratios were significantly better in all the active treatment groups.
- Eight patients (5.2%) in the placebo group had fresh fragility fractures; two (1.3%),
- three (2.0%) in the conventional, and
- one (0.7% micronized, and liposomal groups, respectively; χ² = 7.42; p = 0.059.
Conclusions: Greater success in raising bone mineral density and lowering indicators of bone turnover with recent bioavailability-enhanced vitamin D3 formulas was observed in post-menopausal women, especially those on liposomal delivery systems. These results suggest that public health guidelines and clinical practice have to take into account a rather important element impacting the efficacy of vitamin D supplements: formulation technology.
Trial registration: ClinicalTrials.gov identifier: NCT04987654.
Response comparison assuming both groups started at 20 ng/mL
Conventional: 1.42 X increase ( 20 ng ==> 28.5 ng) Liposomal: 1.91 X increase ( 20 ng ==> 38.2 ng)
Even more response because Conventional IU = 1200, Liposomal only 800 IU (3/2)
Increased response: 2.86
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