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Older adults treated with high-dose vitamin D as part of a double-blind, randomized clinical trial achieved target 25-hydroxyvitamin D levels at 6 and 12 months, but did not achieve the primary endpoint of improved lower extremity function.
In fact, the highest dose used in the study – 60,000 IU of vitamin D3 monthly – was associated with an increased risk of falls, according to Dr. Heike A. Bischoff-Ferrari of University Hospital Zurich, and her colleagues.
In the 200 home-dwelling adults aged older than 70 years who participated in the 1-year study, monthly doses of 60,000 IU of vitamin D3 and 24,000 IU of vitamin D3 plus 300 mcg of calcifediol were significantly more likely than a 24,000 IU dose of vitamin D3 alone to result in 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months, but lower extremity function did not differ among the groups, the investigators reported in a study published online Jan. 4 in JAMA Internal Medicine.
For example, the adjusted changes in Short Physical Performance Battery scores – a measure of walking speed, successive chair stands, and balance – were 0.17, 0.16, and 0.16 at 6 months in the 24,000 IU, 60,000 IU, and 24,000 IU plus calcifediol groups, respectively, and 0.38, 0.10, and 0.11 at 12 months (JAMA Intern Med. 2016 Jan 4. doi: 10.1001/jamainternmed.2015.7148).
However, the incidence of falls was 66.9%, 66.1%, and 47.9% in the groups, respectively, and the mean number of falls was higher in the 60,000 IU group (1.47) and 24,000 IU plus calcifediol group (1.24) than in the 24,000 IU group (0.94), they said, noting that a similar pattern was observed during study months 0-6 and months 7-12.
Study subjects had a mean age of 78 years, 58% were vitamin D deficient with levels of less than 20 ng/mL at baseline, and 13% were severely deficient (levels less than 10 ng/mL). All had experienced a low-trauma fall in the previous 12 months and were thus considered a high-risk group for vitamin D deficiency and functional decline. Vitamin D supplementation was given via one 5-mL drink solution each month that provided 24,000 IU of vitamin D3 – equivalent to the current recommendation of 800 IU/day – plus three placebo capsules; a 5-mL drink solution that provided 60,000 IU of vitamin D3 – the equivalent of 2,000 IU/day – plus three placebo capsules; or a 5-mL placebo drink, two capsules containing 12,000 IU of vitamin D3 each, and one capsule containing 300 mcg of calcifediol, which is a potent liver metabolite of vitamin D.
Although vitamin D supplementation has been proposed as a possible strategy for delaying functional decline because of its effects on muscle strength, the current findings, which are consistent with some prior studies, suggest that high-doses of vitamin D confer no benefit with respect to function decline, compared with a standard-of-care dose of 24,000 IU of D3, and that high doses may increase falls in those with a prior fall event. Further research is needed to confirm the findings for daily dosing regimens, as well as to explore the physiology behind a possible detrimental effect of a high monthly bolus dose of vitamin D on muscle function and falls, they concluded.
This study was funded by the Swiss National Science Foundation and the VELUX Foundations, as well as by investigator-initiated funds from Merck Sharp & Dohme AG, WILD, and DSM Nutritional Products. Dr. Bischoff-Ferrari reported receiving speaker fees from and serving on advisory boards for Merck Sharp & Dohme AG, Amgen, WILD, DSM Nutritional Products, Roche Diagnostics, Nestle, Pfizer, and Sanofi.
The vitamin D storyline may be similar to that of antioxidant vitamins, Dr. Steven R. Cummings and his colleagues wrote in an editorial.
“Enthusiasm for the health benefits of vitamin supplements is coupled with the belief that ‘vitamins’ are inherently safe and reinforced by observational studies showing, essentially, that healthy people have higher vitamin levels. Then [randomized, controlled trials] and meta-analyses proved that the supplements in fact increase mortality (beta carotene, vitamin E), or have no health benefits (vitamin A, vitamin C),” they wrote (JAMA Intern Med. 2016 Jan 4. doi: 10.1001/jamainternmed.2015.7568).
The strategy of supplementation with vitamin D to achieve serum levels of at least 30 ng/mL to reduce the risk of falls and fractures has not been established, and according to the findings by Bischoff-Ferrari et al., it may increase the risk of falling.
“Until that approach is supported by randomized trials with updated meta-analyses, it would be prudent to follow recommendation from the Institute of Medicine (IOM) that people 70 years or older have a total daily intake of 800 IU of vitamin D without routine measurement of serum 25(OH)D levels,” they wrote, adding that recommended intakes are best achieved through a balanced diet.
Dr. Cummings is with the California Pacific Medical Center Research Institute, San Francisco, and the University of California, San Francisco. He and his coauthors reported having no disclosures.
The vitamin D storyline may be similar to that of antioxidant vitamins, Dr. Steven R. Cummings and his colleagues wrote in an editorial.
“Enthusiasm for the health benefits of vitamin supplements is coupled with the belief that ‘vitamins’ are inherently safe and reinforced by observational studies showing, essentially, that healthy people have higher vitamin levels. Then [randomized, controlled trials] and meta-analyses proved that the supplements in fact increase mortality (beta carotene, vitamin E), or have no health benefits (vitamin A, vitamin C),” they wrote (JAMA Intern Med. 2016 Jan 4. doi: 10.1001/jamainternmed.2015.7568).
The strategy of supplementation with vitamin D to achieve serum levels of at least 30 ng/mL to reduce the risk of falls and fractures has not been established, and according to the findings by Bischoff-Ferrari et al., it may increase the risk of falling.
“Until that approach is supported by randomized trials with updated meta-analyses, it would be prudent to follow recommendation from the Institute of Medicine (IOM) that people 70 years or older have a total daily intake of 800 IU of vitamin D without routine measurement of serum 25(OH)D levels,” they wrote, adding that recommended intakes are best achieved through a balanced diet.
Dr. Cummings is with the California Pacific Medical Center Research Institute, San Francisco, and the University of California, San Francisco. He and his coauthors reported having no disclosures.
The vitamin D storyline may be similar to that of antioxidant vitamins, Dr. Steven R. Cummings and his colleagues wrote in an editorial.
“Enthusiasm for the health benefits of vitamin supplements is coupled with the belief that ‘vitamins’ are inherently safe and reinforced by observational studies showing, essentially, that healthy people have higher vitamin levels. Then [randomized, controlled trials] and meta-analyses proved that the supplements in fact increase mortality (beta carotene, vitamin E), or have no health benefits (vitamin A, vitamin C),” they wrote (JAMA Intern Med. 2016 Jan 4. doi: 10.1001/jamainternmed.2015.7568).
The strategy of supplementation with vitamin D to achieve serum levels of at least 30 ng/mL to reduce the risk of falls and fractures has not been established, and according to the findings by Bischoff-Ferrari et al., it may increase the risk of falling.
“Until that approach is supported by randomized trials with updated meta-analyses, it would be prudent to follow recommendation from the Institute of Medicine (IOM) that people 70 years or older have a total daily intake of 800 IU of vitamin D without routine measurement of serum 25(OH)D levels,” they wrote, adding that recommended intakes are best achieved through a balanced diet.
Dr. Cummings is with the California Pacific Medical Center Research Institute, San Francisco, and the University of California, San Francisco. He and his coauthors reported having no disclosures.
Older adults treated with high-dose vitamin D as part of a double-blind, randomized clinical trial achieved target 25-hydroxyvitamin D levels at 6 and 12 months, but did not achieve the primary endpoint of improved lower extremity function.
In fact, the highest dose used in the study – 60,000 IU of vitamin D3 monthly – was associated with an increased risk of falls, according to Dr. Heike A. Bischoff-Ferrari of University Hospital Zurich, and her colleagues.
In the 200 home-dwelling adults aged older than 70 years who participated in the 1-year study, monthly doses of 60,000 IU of vitamin D3 and 24,000 IU of vitamin D3 plus 300 mcg of calcifediol were significantly more likely than a 24,000 IU dose of vitamin D3 alone to result in 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months, but lower extremity function did not differ among the groups, the investigators reported in a study published online Jan. 4 in JAMA Internal Medicine.
For example, the adjusted changes in Short Physical Performance Battery scores – a measure of walking speed, successive chair stands, and balance – were 0.17, 0.16, and 0.16 at 6 months in the 24,000 IU, 60,000 IU, and 24,000 IU plus calcifediol groups, respectively, and 0.38, 0.10, and 0.11 at 12 months (JAMA Intern Med. 2016 Jan 4. doi: 10.1001/jamainternmed.2015.7148).
However, the incidence of falls was 66.9%, 66.1%, and 47.9% in the groups, respectively, and the mean number of falls was higher in the 60,000 IU group (1.47) and 24,000 IU plus calcifediol group (1.24) than in the 24,000 IU group (0.94), they said, noting that a similar pattern was observed during study months 0-6 and months 7-12.
Study subjects had a mean age of 78 years, 58% were vitamin D deficient with levels of less than 20 ng/mL at baseline, and 13% were severely deficient (levels less than 10 ng/mL). All had experienced a low-trauma fall in the previous 12 months and were thus considered a high-risk group for vitamin D deficiency and functional decline. Vitamin D supplementation was given via one 5-mL drink solution each month that provided 24,000 IU of vitamin D3 – equivalent to the current recommendation of 800 IU/day – plus three placebo capsules; a 5-mL drink solution that provided 60,000 IU of vitamin D3 – the equivalent of 2,000 IU/day – plus three placebo capsules; or a 5-mL placebo drink, two capsules containing 12,000 IU of vitamin D3 each, and one capsule containing 300 mcg of calcifediol, which is a potent liver metabolite of vitamin D.
Although vitamin D supplementation has been proposed as a possible strategy for delaying functional decline because of its effects on muscle strength, the current findings, which are consistent with some prior studies, suggest that high-doses of vitamin D confer no benefit with respect to function decline, compared with a standard-of-care dose of 24,000 IU of D3, and that high doses may increase falls in those with a prior fall event. Further research is needed to confirm the findings for daily dosing regimens, as well as to explore the physiology behind a possible detrimental effect of a high monthly bolus dose of vitamin D on muscle function and falls, they concluded.
This study was funded by the Swiss National Science Foundation and the VELUX Foundations, as well as by investigator-initiated funds from Merck Sharp & Dohme AG, WILD, and DSM Nutritional Products. Dr. Bischoff-Ferrari reported receiving speaker fees from and serving on advisory boards for Merck Sharp & Dohme AG, Amgen, WILD, DSM Nutritional Products, Roche Diagnostics, Nestle, Pfizer, and Sanofi.
Older adults treated with high-dose vitamin D as part of a double-blind, randomized clinical trial achieved target 25-hydroxyvitamin D levels at 6 and 12 months, but did not achieve the primary endpoint of improved lower extremity function.
In fact, the highest dose used in the study – 60,000 IU of vitamin D3 monthly – was associated with an increased risk of falls, according to Dr. Heike A. Bischoff-Ferrari of University Hospital Zurich, and her colleagues.
In the 200 home-dwelling adults aged older than 70 years who participated in the 1-year study, monthly doses of 60,000 IU of vitamin D3 and 24,000 IU of vitamin D3 plus 300 mcg of calcifediol were significantly more likely than a 24,000 IU dose of vitamin D3 alone to result in 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months, but lower extremity function did not differ among the groups, the investigators reported in a study published online Jan. 4 in JAMA Internal Medicine.
For example, the adjusted changes in Short Physical Performance Battery scores – a measure of walking speed, successive chair stands, and balance – were 0.17, 0.16, and 0.16 at 6 months in the 24,000 IU, 60,000 IU, and 24,000 IU plus calcifediol groups, respectively, and 0.38, 0.10, and 0.11 at 12 months (JAMA Intern Med. 2016 Jan 4. doi: 10.1001/jamainternmed.2015.7148).
However, the incidence of falls was 66.9%, 66.1%, and 47.9% in the groups, respectively, and the mean number of falls was higher in the 60,000 IU group (1.47) and 24,000 IU plus calcifediol group (1.24) than in the 24,000 IU group (0.94), they said, noting that a similar pattern was observed during study months 0-6 and months 7-12.
Study subjects had a mean age of 78 years, 58% were vitamin D deficient with levels of less than 20 ng/mL at baseline, and 13% were severely deficient (levels less than 10 ng/mL). All had experienced a low-trauma fall in the previous 12 months and were thus considered a high-risk group for vitamin D deficiency and functional decline. Vitamin D supplementation was given via one 5-mL drink solution each month that provided 24,000 IU of vitamin D3 – equivalent to the current recommendation of 800 IU/day – plus three placebo capsules; a 5-mL drink solution that provided 60,000 IU of vitamin D3 – the equivalent of 2,000 IU/day – plus three placebo capsules; or a 5-mL placebo drink, two capsules containing 12,000 IU of vitamin D3 each, and one capsule containing 300 mcg of calcifediol, which is a potent liver metabolite of vitamin D.
Although vitamin D supplementation has been proposed as a possible strategy for delaying functional decline because of its effects on muscle strength, the current findings, which are consistent with some prior studies, suggest that high-doses of vitamin D confer no benefit with respect to function decline, compared with a standard-of-care dose of 24,000 IU of D3, and that high doses may increase falls in those with a prior fall event. Further research is needed to confirm the findings for daily dosing regimens, as well as to explore the physiology behind a possible detrimental effect of a high monthly bolus dose of vitamin D on muscle function and falls, they concluded.
This study was funded by the Swiss National Science Foundation and the VELUX Foundations, as well as by investigator-initiated funds from Merck Sharp & Dohme AG, WILD, and DSM Nutritional Products. Dr. Bischoff-Ferrari reported receiving speaker fees from and serving on advisory boards for Merck Sharp & Dohme AG, Amgen, WILD, DSM Nutritional Products, Roche Diagnostics, Nestle, Pfizer, and Sanofi.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Older adults treated with high-dose vitamin D as part of a double-blind, randomized clinical trial achieved target 25-hydroxyvitamin D levels at 6 and 12 months, but did not achieve the primary endpoint of improved lower extremity function.
Major finding: Fall incidence was 66.9%, 66.1%, and 47.9% with vitamin D3 at doses of 24,000 IU, 60,000 IU, and 24,000 IU, respectively, plus 300 mcg calcifediol.
Data source: A double-blind, randomized trial involving 200 patients.
Disclosures: This study was funded by the Swiss National Science Foundation and the VELUX Foundations, as well as by investigator-initiated funds from Merck Sharp & Dohme AG, WILD, and DSM Nutritional Products. Dr. Bischoff-Ferrari disclosed ties with Merck Sharp & Dohme AG, Amgen, WILD, DSM Nutritional Products, Roche Diagnostics, Nestle, Pfizer, and Sanofi.
