ORLANDO, Florida — Supplementation with high-dose, daily vitamin D does not prevent bone loss or benefit bone structure over 2 years, or reduce the risk of falls over 5 years versus placebo, according to two subanalyses of a large nationwide study of healthy men and women without vitamin D insufficiency at baseline.

"This is the largest randomized controlled trial in healthy women and men of supplemental vitamin D3 alone versus placebo on spine and hip areal bone mineral density (BMD) and measures of bone structure," lead author Meryl LeBoff, MD, chief, Calcium and Bone Section, Endocrinology Diabetes and Hypertension Division at Brigham and Women's Hospital, and professor of medicine, Harvard Medical School, in Boston, Massachusetts, told Medscape Medical News.

She presented the findings here at the American Society for Bone and Mineral Research (ASBMR) 2019 Annual Meeting.

"We were surprised that, contrary to our hypotheses, in the general healthy population in the United States who were not selected for low vitamin D levels, high-dose, daily vitamin D supplements did not improve measures of bone health (bone density or structure) or reduce the risk of falls," she noted.

Felicia Cosman, MD, professor of clinical medicine at Columbia University College of Physicians and Surgeons, New York City — who comoderated the session — said this latest research adds to the evidence that "vitamin D supplements are not going to improve BMD unless a person is deficient in this nutrient."

"I think the take-home message is that many healthy ambulatory people 55 years of age and older do not need supplemental vitamin D, certainly not 2000 IU daily, so people should not routinely take this," Cosman told Medscape Medical News.

Indeed, one recently published study has even suggested that high-dose vitamin D may be detrimental to bone health, although the authors did say the findings require confirmation.

Cosman stressed, however, that the message is very different for those with osteoporosis.

"Many patients with osteoporosis and fractures do need supplemental vitamin D, and in these patients, evidence suggests a benefit against fractures and a small improvement in BMD," she said.

Further Analyses of VITAL Trial

The known role of vitamin D in increasing the absorption of calcium and phosphate, which are incorporated in the mineral of bone, has long driven interest in its potential preventive benefits for bone health.

Vitamin D supplements are widely used in the general population to promote bone health, even though evidence supporting their use has been "inconclusive," said LeBoff.

At ASBMR, she reported that the new findings are from two further analyses of the large Vitamin D and Omega-3 Trial (VITAL), which enrolled 25,871 participants, including men aged 50 and older and women aged 55 and older, in 50 US states who were followed for a median intervention of 5.3 years.

The parent study was designed to investigate whether daily supplemental vitamin D 3 (2000 IU) and/or omega-3 fatty acids (fish oil 1 g) reduced the risk of developing cancer or cardiovascular disease.

LeBoff noted that the 2000 IU dose of vitamin D was used to provide the best balance of efficacy and safety, and to provide the mean achieved 25(OH)D level of approximately 40 ng/mL in the active treatment group.

For the subanalysis on bone health, LeBoff and colleagues investigated the effects of high-dose vitamin D supplementation on BMD among 771 VITAL participants in New England, including 46.7% women and 53.2% men who were taking no bone active medications.

They were a mean age of 63 years, about 9% were black, mean body mass index (BMI) was about 27.2 kg/m2, and baseline vitamin D supplement use was reported in 42.3% of participants.

At the 2-year follow-up, there were no significant increases in vitamin D levels or BMD changes in the placebo group (n = 383).

But in the vitamin D supplementation group (n = 388), total 25(OH)D levels increased from a mean of 27.0 ng/mL at baseline to 39.5 ng/mL at year 2, for a 46% increase (P < .001).

Despite the increases in total 25(OH)D levels in the vitamin D supplement group, however, the primary outcomes of changes in areal BMD bone measures, after adjusting for age, sex, baseline use of supplemental vitamin D and race, were not significantly different from placebo, including for spine (P = .55), femoral neck hip (P = .16), total hip (P = .23), and whole body (P = .60).

For the secondary outcomes of change in volumetric BMD, there were likewise no significant differences in any of the radius or tibia measures at 2 years in the supplemental vitamin D group, again, after adjusting for multiple confounders.

No Effect of Vitamin D on Falls Either in Overall VITAL Cohort

For the second analysis, researchers evaluated falls in the overall VITAL study, specifically characterized as two or more falls, injurious falls, or those resulting in a doctor's visit or hospital visit.

LeBoff and colleagues found that over 6000 of the 25,871 participants logged a total of more than 13,000 falls on questionnaires.

But no significant difference between the vitamin D and placebo groups was seen in rates of self-reported falls.

"This large well-controlled trial, consistent with some other large studies, suggests that supplemental vitamin D3 is not effective in the primary prevention of falls in the generally healthy US population not selected for low vitamin D levels," LeBoff said.

She noted that key limitations of both analyses are that "results from both studies are not generalizable to young men and women, or older adults with vitamin D deficiency who warrant treatment, or women and men with osteoporosis."

Benefits Not Likely if Vitamin D Levels Are Sufficient

LeBoff said these latest findings are consistent with the concept that once a sufficient level of a nutrient is reached, there are no longer benefits from further supplementation.

Notably, the Institute of Medicine (IOM) has concluded that a 25(OH)D level of 20 ng/mL is sufficient for 97.5% of the US population, corresponding to a recommended dietary allowance for adults of 600 IU/day and of 800 IU/day for those aged 71 years or older.

The vitamin D level of the VITAL subcohort was 27 ng/mL at baseline and increased to 40 ng/mL after the intervention.

So "participants may have already reached the vitamin D level needed for bone health," she explained.

"We explored possible thresholds, but we did not see additional benefit at extremely low levels of vitamin D (< 12 ng/mL)," although the number of participants with these low levels was small, she noted.

"Thus, in the United States, with fortification of milk and some other food sources, sun exposure, and 42% of adults in this study at baseline taking supplemental vitamin D (< 800 IU/day), additional vitamin D is of no benefit to bone density or structural measures," she said.

LeBoff added that the findings likely do not apply to other countries where individuals may have more significant vitamin D deficiency.

Benefits for Those With Low Bone Mass, but Ideal Vitamin D Goal Disputed

Cosman stressed to Medscape Medical News that "Doctors should not be dissuaded from recommending vitamin D supplements to patients who have a proven need."

"I believe that patients with osteoporosis and low bone mass should have a vitamin D level measured," she asserted.

"They should take the dose of vitamin D that is needed to attain the desired target level, though the actual target is somewhat controversial," Cosman acknowledged.

"The IOM says 20 ng/mL, but again, this is for all individuals, not those with a diagnosis of osteoporosis," she said

Many bone specialists recommend that a serum 25(OH)D level of ≥ 30 ng/mL is the target for patients with osteoporosis, noted Cosman

The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. The VITAL trial was supported by grants from the National Cancer Institute; National Heart, Lung, and Blood Institute; Office of Dietary Supplements; National Institute of Neurologic Disorders and Stroke; and National Center for Complementary and Integrative Health. Cosman has reported being a consultant, advisor, grant recipient, and speaker for Amgen and an advisor and speaker for Radius Health. She is a consultant for Tarsa/R-Pharma. Within the last 3 years, Cosman has been an advisor, consultant, and speaker for Eli Lilly and consultant/advisor for Merck.

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