Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis
Lancet DOI: 10.1016/S2213-8587(18)30265-1
Mark J Bolland, PhD; Andrew Grey, MD; Alison Avenell, MD
- Only 6% of the trials were done in populations with vitamin D deficiency ( < 10 ng), who would stand to benefit most from supplementation.
- Only 40% of the people who were supplemented achieved > 30 ng of vitamin D
- Typically need > 40 ng and other nutrients (e.g. Vitamin K), exercise to help
- Suspect that many of the trials did not wait for 4+ months for vitamin D level to plateau before counting falls and fractures
- Interestingly, Dr. Bolland published another study in BMC (Oct 2018) pointing out that many Vitamin D trials are worthless because they were performed on populations which had enough vitamin D doi: 10.1186/s12874-018-0555-1
- Ignored the additional items proven to needed for strong (not just more dense) bones
- Magnesium Vitamin K, Boron, Silica, Calcium, Protein, and exercise
- Postmenopausal women need Vitamin D, protein and exercise to prevent loss of muscle and bone – Aug 2018
- They did not look at bone strength, but only bone density, a poor proxy
- They did not look at the items proven to improve fragility and decrease falls
- They considered high-dose to be > 800 IU, 50,000 IU is high dose, not 800 IU
- Often a person needs much more than 800 IU to measurably increase vitamin D levels in the blood
- Falls reduced by a third if achieved 40 ng level vitamin D– RCT Sept 2018
- They are totally unaware that the Vitamin D receptor can limit the vitamin D getting to tissues such as bone and muscle
- Note: There are 7 ways to improve the Vitamin D receptor
- Bone density improved with resveratrol (which improves Vitamin D Receptor) – RCT Sept 2018
- Vitamin D receptor (TT), which restricts Vit D to cells, is associated with balance problems in seniors – June 2018
- One researcher noticed the long dosing intervals in several of the studies (interval was not mentioned in meta-analysis)
- Sanders 2010 used 12 month dosing - which has been known for a long time to not be useful
- Smith 2007 used 12 month dosing of Vitamin D2
- Law 2006 used 3 month dosing of Vitamin D2
- Khaw 2017 used 1 month dosing
- Trivedi 2003 used 4 month dosing
- Note: A decrease in response to Vitamin D doses starts at about 1/2 month
- Fractures not reduced by small amounts of vitamin D - meta-analysis Dec 2017
- Preventing Falls in Older Adults – Vitamin D combination is the best - JAMA Meta-analysis Nov 2017
- Hip fracture 58 percent more likely if low vitamin D – meta-analysis March 2017
- Vitamin D prevents falls – majority of meta-analyses conclude – meta-meta analysis Feb 2015
- Vitamin D and fractures – 24 meta-analyses and counting – Dec 2014
- Countries which have increased Vitamin D have decreased bone problems (Japan, Australia)
- Bone STRENGTH improved by 2800 IU of Vitamin D (not bone density) – RCT Oct 2018
Strong bones need more than just vitamin D
- Healthy bones need: Calcium, Vitamin D, Magnesium, Silicon, Vitamin K, and Boron – 2012
- Bone formation in the lab is aided by Vitamin D, Vitamin K1, and Vitamin K2 – meta-analysis Nov 2017
- Bone density improved with resveratrol (which improves Vitamin D Receptor) – RCT Sept 2018
- Resveratrol gets more vitamin D to the cells, without raising measure vitamin D levels
- Postmenopausal women need Vitamin D, protein and exercise to prevent loss of muscle and bone – Aug 2018
- Adding just vitamin D again failed to add bone density (also need Magnesium, Vitamin K, etc) – RCT Aug 2018
Falls and Fractures category contains the following summary
258 items in FALLS and FRACTURES - Vitamin D and Calcium cost-effectively reduce falls and fractures – April 2019
- see also Overview Seniors and Vitamin D
Falls
- Fall prevention - Vitamin D is one of the ways - umbrella review Jan 2024
- Deaths due to falls doubled in just a decade (age-adjusted, perhaps decreased vitamin D) – June 2019
- Preventing Falls in Older Adults – Vitamin D combination is the best - JAMA Meta-analysis Nov 2017
- Falls cut in half by 100,000 IU vitamin D monthly - RCT 2016
- Falls reduced by a third if achieved 40 ng level vitamin D– RCT Sept 2018
- Note: It took 6 months to get to that level. Most trials last only 3 months
- Vitamin D prevents falls – majority of meta-analyses conclude – meta-meta analysis Feb 2015
- Falls reduced by Vitamin D: 13 percent reduction if more than 700 IU – review of 38 trials – Aug 2022
Fracture
- Hip fractures are predicted by 10 factors – low Vitamin D is the biggest – Aug 2023
- Vitamin D and fractures – 24 meta-analyses and counting – Dec 2014
- Low trauma bone fractures in seniors – considering Vitamin D loading dose for all, without testing – Nov 2019
- Vitamin K (any amount and any kind) reduced bone fractures by 24 percent – meta-analysis – May 2019
- 75+ Hip fracture items in VitaminDWiki title Click here for details
Study ignored Sarcopenia
muscle loss, fraility, falling,... which is helped by Vitamin D etc.
Many experts said why the study should be ignored
- expert reaction to study on vitamin D supplementation and bone health in adults Oct 5
- New study does not change current advice on vitamin D supplementation, say osteoporosis experts Oct 5
- Vitamin D – to supplement or not to supplement - comment on Lancet article - Oct 2018 in VitaminDWiki
- Professor raises concerns over flaws in anti-vitamin D study
"...criticised the research for “lumping together” studies of high- and low-dose vitamin D, and those investigating vitamin D in people with and without adequate calcium intake."
"She also criticised the mix of studies in the review, which included trials of vitamin D alone, and trials with vitamin D plus calcium. "
"“This is a problem because several earlier meta-analyses also showed that where it works, it is vitamin D plus calcium, not vitamin D alone, that reduced fractures and falls,” she said."
"A further limitation of the study was that only four trials were undertaken in populations with a deficiency..."
PDF is available free at Sci-Hub 10.1016/S2213-8587(18)30265-1
Background
The effects of vitamin D on fractures, falls, and bone mineral density are uncertain, particularly for high vitamin D doses. We aimed to determine the effect of vitamin D supplementation on fractures, falls, and bone density.Methods
In this systematic review, random-effects meta-analysis, and trial sequential analysis, we used findings from literature searches in previously published meta-analyses. We updated these findings by searching PubMed, Embase, and Cochrane Central on Sept 14, 2017, and Feb 26, 2018, using the search term “vitamin D” and additional keywords, without any language restrictions. We assessed randomised controlled trials of adults (>18 years) that compared vitamin D with untreated controls, placebo, or lower-dose vitamin D supplements. Trials with multiple interventions (eg, co-administered calcium and vitamin D) were eligible if the study groups differed only by use of vitamin D. We excluded trials of hydroxylated vitamin D analogues. Eligible studies included outcome data for total or hip fractures, falls, or bone mineral density measured at the lumbar spine, total hip, femoral neck, total body, or forearm. We extracted data about participant characteristics, study design, interventions, outcomes, funding sources, and conflicts of interest. The co-primary endpoints were participants with at least one fracture, at least one hip fracture, or at least one fall; we compared data for fractures and falls using relative risks with an intention-to-treat analysis using all available data. The secondary endpoints were the percentage change in bone mineral density from baseline at lumbar spine, total hip, femoral neck, total body, and forearm.Findings
We identified 81 randomised controlled trials (n=53 537 participants) that reported fracture (n=42), falls (n=37), or bone mineral density (n=41). In pooled analyses, vitamin D had no effect on total fracture (36 trials; n=44 790, relative risk 1·00, 95% CI 0·93–1·07), hip fracture (20 trials; n=36 655, 1·11, 0·97–1·26), or falls (37 trials; n=34 144, 0·97, 0·93–1·02). Results were similar in randomised controlled trials of high-dose versus low-dose vitamin D and in subgroup analyses of randomised controlled trials using doses greater than 800 IU per day. In pooled analyses, there were no clinically relevant between-group differences in bone mineral density at any site (range −0·16% to 0·76% over 1–5 years). For total fracture and falls, the effect estimate lay within the futility boundary for relative risks of 15%, 10%, 7·5%, and 5% (total fracture only), suggesting that vitamin D supplementation does not reduce fractures or falls by these amounts. For hip fracture, at a 15% relative risk, the effect estimate lay between the futility boundary and the inferior boundary, meaning there is reliable evidence that vitamin D supplementation does not reduce hip fractures by this amount, but uncertainty remains as to whether it might increase hip fractures. The effect estimate lay within the futility boundary at thresholds of 0·5% for total hip, forearm, and total body bone mineral density, and 1·0% for lumbar spine and femoral neck, providing reliable evidence that vitamin D does not alter these outcomes by these amounts.Interpretation
Our findings suggest that vitamin D supplementation does not prevent fractures or falls, or have clinically meaningful effects on bone mineral density. There were no differences between the effects of higher and lower doses of vitamin D. There is little justification to use vitamin D supplements to maintain or improve musculoskeletal health. This conclusion should be reflected in clinical guidelines.Funding: Health Research Council of New Zealand.
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