The team concludes from the 54 randomised controlled trials involving 8,747 individuals that no benefits were observed from taking vitamin D to improve muscle function, strength, or mass even at doses exceeding 2,800 IU/day.
“We find it fair to conclude that the common statement that vitamin D protects muscle health lacks clinical evidence,” concludes the team from Denmark’s Aarhus University Hospital and Aarhus University.
“Adverse effects may even be present. Given the enormous public interest in vitamin D supplementation, we need to be aware of uncritical use of vitamin D. Identifying safe repletion regimens is warranted,” add the group, led by Dr Lise Sofie Bislev, Senior Registrar at the hospital.
The review and meta-analysis of placebo-controlled trials involved a search of randomised controlled trials published until October 2020 using Medline, Embase, and Google Scholar.
The team used human studies (except athletes) on supplementation with vitamin D2 or D3 vs. placebo, regardless of administration via daily, bolus, and duration with or without calcium co-supplementation.
Predefined endpoints included timed up and go test (TUG; seconds), chair rising test (seconds), 6-minute walking distance (m), and Short Physical Performance Battery (SPPB; points).
Other endpoints included maximum muscle strength (Newton) measured at handgrip, elbow flexion, elbow extension, knee flexion, and knee extension, as well as muscle (lean tissue) mass (kg).
Findings revealed vitamin D vs. placebo was linked with a significantly longer time spent performing the TUG and a significant lower maximum knee flexion strength.
In addition, total score in the SPPB showed a tendency toward worsening in response to vitamin D compared with placebo. Other measures of muscle health did not show between-group differences.
In subgroup analyses, including studies with low vitamin D levels, effects of vitamin D supplementation did not differ from placebo.
In discussing the findings, the team pointed out that RCTs have reported more ambiguous results, including both beneficial and harmful effects.
“Our findings are in contrast with most observational studies,” they wrote. “Observational studies do, however, not prove causative effects of vitamin D, and findings may be prone to reverse causality.
“Vitamin D is synthesised in the skin in response to sunlight exposure,” they continue. “People with open-air activities may have increased 25(OH)D levels due to exposure of their skin to sunlight, and physical efforts related to outdoor activities may improve muscle function.
“Placebo-controlled RCTs are needed, as investigation of muscle function demands cooperation from the patients and may show improvement of results over time, a well-described phenomenon called learning effect.
“This is a systematic bias in the interpretation of beneficial effects of vitamin D on muscles if no control group is included.”
Effects of high dose vit D
Addressing vitamin D’s possible negative effect from high doses, the team acknowledged impaired muscle function and increased risks of falls and fractures had been observed but could not make any firm conclusions.
“Whether the increased risk of falls and fractures is caused by impaired muscle health is currently unknown,” they said.
“For some effect parameters (elbow and knee extension/flexion and 6MWD), at least half of the included participants used moderate to high dosages of vitamin D (over 2800 IU/d). It is possible that the negative finding on knee flexion is due to the dosage used.
“The subgroup analysis showing reduced elbow flexion with an end-of-study 25(OH)D level above 100 nmol/L supports this hypothesis.
“Subgroup analyses in the studies reporting negative effects on the TUG or the SPPB do, however, not support this theory, as the dosages used were substantial lower.”
Source: Journal of Bone and Mineral Research
Published online: DOI: 10.1002/jbmr.4412
“Vitamin D and Muscle Health: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.”
Authors: Lise Sofie Bislev