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High-Dose Vitamin D: No Help for Bone Health

Vitamin D might not be much help for strengthening bones among healthy adults without osteoporosis, Canadian researchers reported, even at doses far higher than recommended daily allowances.

In a clinical trial assessing three levels of daily vitamin D supplementation -- 400 IU, 4,000 IU, and 10,000 IU -- radial volumetric bone mineral density (BMD) was significantly lower among those (ages 55-70) taking higher doses for 3 years, according to Steven Boyd, PhD, of the University of Calgary in Canada, and colleagues:

  • 400 IU: reference
  • 4,000 IU: -3.9 mg calcium hydroxyapatite (HA)/cm3 (95% CI -6.5 to -1.3)
  • 10,000 IU: -7.5 mg HA/cm3 (95% CI -10.1 to -5.0)

No dose of vitamin D supplementation was able to prevent bone loss, as each dose saw a drop in the percentage of radial volumetric BMD over 3 years, they reported in JAMA:

  • 400 IU: -1.2%
  • 4,000 IU: -2.4%
  • 10,000 IU: -3.5%

Boyd's group explained that the findings were unexpected, and that the outcomes were in fact the opposite of what they were anticipating. But they cautioned that "this evidence of high-dose vitamin D having a negative effect on bone should be regarded as hypothesis generating, requiring confirmation with further research. Therefore, the appropriate interpretation of this study is that for maintenance of bone quality in healthy vitamin D-sufficient adults, these results do not support a skeletal benefit of vitamin D doses well above the recommended dietary allowance."

Similar outcomes were noted with tibial BMD, with people on higher doses seeing a larger drop-off after 3 years. Compared with those on a 400 IU/day dose, the 4,000 IU dose group saw a -1.8 mg HA/cm3 (95% CI -3.7 to 0.1) difference in tibial volumetric BMD, while the 10,000 IU group saw a -4.1 mg HA/cm3 (95% CI -6.0 to -2.2) difference.

However, people on every dose saw a drop in average tibial density over the course of the trial compared with baseline values (-0.4% with 400 IU, -1.0% with 4,000 IU, and -1.7% with 10,000 IU).

One possible explanation for these findings could be related to an increase in plasma marker of bone resorption (CTx) paired with suppression of parathyroid hormone. This was particularly true among the highest 10,000 IU/day group who saw sharp decline in parathyroid hormone levels, as well as a sharp increase in plasma CTx levels during the first 18 months of being on high-dose vitamin D, according to the authors.

"High-dose vitamin D without extra calcium supplementation has been associated with increased levels of the active vitamin D metabolite 1, 25(OH)2 vitamin D (calcitriol), and an increase in CTx," they explained. On the other hand, high doses of vitamin D can also suppress parathyroid hormone levels either by directly impacting parathyroid cells or also by bolstering intestinal calcium absorption.

A total of 311 Canadian adults were included in the randomized trial, all of whom were free of osteoporosis at baseline and were ages 55-70. All participants had baseline serum 25-hydroxyvitamin D levels between 12-50 ng/mL (30-125 nmol/L) and baseline serum calcium levels between 8.4-10.2 mg/dL (2.10-2.55 mmol/L).

Vitamin D supplements were provided in the form of drops, and all participants were instructed to take no more than 200 IU of additional vitamin D each day, such as in the form of a multivitamin. Only those who weren't taking in the recommended level of calcium (1,200 mg/day) were provided calcium citrate tablets.

Volumetric BMD was measured with high-resolution peripheral quantitative CT. DXA scans were also used to measure the total hip areal BMD, which showed no changes over time among any of the vitamin D dosage groups.

As for adverse events, people on the highest dose of vitamin D experienced the most instances of hypercalciuria and hypercalcemia -- a serum calcium level more than 10.22 mg/dL (2.55 mmol/L). Other adverse events, such as renal or hepatic dysfunction, falls, low-trauma fractures, and cancer, didn't differ among the dosage groups.

Study limitations included the exclusion of people with osteoporosis or with 25(OH)D levels of <30 nmol/L, who may respond differently to high-dose vitamin D supplementation. Also, the study did not include a placebo control group.

The author has no conflicts of interest to disclose related to this subject

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