High-Dose Vitamin D Supplementation in Healthy Adults Linked to Bone Thinning

Peer Reviewed

For healthy adults without vitamin D deficiency or osteoporosis, taking high-dose vitamin D (≥4000 IU/day) appears to not have additional benefit over recommended doses, and may in fact result in a small degree of bone thinning, according to a randomized controlled study that followed nearly 300 healthy adults between the ages of 55 and 70 years.

vitamin D capsules spill out of a bottleIt was surprising to find a negative effect on bone density as a function of taking high doses of vitamin D. Photo Source: 123RF.com.

The study found that participants who took 4000 or 10,000 IU/day for 3 years showed significantly greater decreases in total bone mineral density at the radius compared with those who took 400 IU/day (−2.4%, –3.5%, and –1.2%, respectively; P<.001). Total tibial bone mineral density (BMD) was significantly lower only with the 10,000 IU/day dose compared with the 400 IU/day dose (−1.7% versus –0.4%; P<.001). However, no significant difference in bone strength was observed at either the radius or tibia with either of the higher doses compared with the 400 IU/day dose.

To better understand the findings, which were reported in the August 27 issue of JAMA, SpineUniverse spoke with co-principal investigators Steven Boyd, PhD, and David Hanley, MD, FRCPC. Dr. Boyd is Professor in the Department of Radiology and Director for the McCaig Institute for Bone and Joint Health at the University of Calgary, and Dr. Hanley is Professor Emeritus in the Departments of Medicine, Oncology, and Community Health Sciences at the University of Calgary.

Funding for the study was provided by Pure North S'Energy Foundation.

What are the clinical implications of these findings for normal healthy adults?

A: In these healthy subjects, who had normal bone density and did not have vitamin D deficiency, 400 IU vitamin D daily maintained a normal blood 25-OH vitamin D, and the use of vitamin D doses of 4000 or 10,000 IU/day did not offer any additional bone health benefit.

It was surprising to find a negative effect on bone density as a function of taking high doses of vitamin D in this cohort of healthy adults, but it is important to keep things in perspective. Part of the reason we could detect this effect is our use of the latest in medical imaging technology, called high-resolution peripheral quantitative computed tomography (HR-pQCT), but known more colloquially as “XtremeCT.” The effect we measured was scientifically significant, but small in magnitude. Instead of the hypothesized benefit, both the 4000 and 10,000 IU groups had a greater loss of volumetric bone density as measured by HR-pQCT than the 400 IU group. This increased rate of bone loss was significant for the 10,000 IU group at both the radius and tibia, and for the 4000 IU group only at the radius. Actual rates of change in volumetric density over 3 years were modest: mean percent changes in volumetric BMD at the radius were -1.2% (400 IU group), -2.4% (4000 IU group) and -3.5% (10,000 IU group); and at the tibia, -0.4% (400), -1.0% (4000) and -1.7% (10,000).

While many are picking up on the decreased HR-pQCT measurements of bone mineral density with increased vitamin D supplementation, it is important to also note that we found no significant effect on bone strength. Also, there was no difference between the groups with respect to dual x-ray absorptiometry (DXA) bone density. Therefore, in our study participants, with normal bone density, it is unlikely the bone loss we measured would lead to increased fracture risk. In older individuals with osteoporosis and at much higher risk of fracture, an increased rate of bone loss with high doses of vitamin D might be of more clinical importance.

The 3 doses of vitamin D were generally well tolerated. Hypercalciuria was seen in all groups, but there was a relationship to vitamin D dose, with the greatest frequency in the 10,000 IU group.

The takeaway message is that, for healthy adults who are vitamin D sufficient while taking 400 IU daily, there is no further bone benefit to be derived by increasing the vitamin D dose. In this study, 400 IU vitamin D per day for 3 years maintained a serum 25-OH vitamin D well above the 20 ng/mL (50 nmol/L) level that the Institute of Medicine (IOM [now known as The Academy of Medicine]) report has suggested would represent adequate vitamin D nutrition for 97.5% of the population.

Were you surprised by the findings?

A: Our starting hypothesis was that increased vitamin D supplementation would lead to HR-pQCT measurable increases in bone density and strength. At the time that we were planning the study, there was debate as to the potential benefits of higher than standard Health Canada recommendations for vitamin D intake established by the 2011 IOM report on Dietary Reference Intakes for calcium and vitamin D. Some experts advocated higher doses for optimal skeletal benefits as well as nonskeletal benefits such as prevention of autoimmune disorders and cancers.

Why did you choose healthy adults to study, rather than patients with vitamin D deficiency or osteoporosis?

A: It has been reported that 3% of Americans consume daily doses greater than the IOM’s tolerable upper intake level (TUL) of 4000 IU/day. A TUL may be defined as the maximum dose that can be considered to be safe for the majority of the population—ie, can be taken without medical monitoring. Some experts had suggested that the TUL for vitamin D should be 10,000 IU/day.

Can you comment on how the findings do or do not pertain to patients with vitamin D deficiency who do not respond to recommended doses of vitamin D supplementation or patients with osteoporosis?

A: We are quite concerned that people recognize that our findings do not suggest stopping vitamin D supplementation, but rather that we strongly recommend that people follow the guidelines provided by organizations such as The Academy of Medicine, Health Canada or Osteoporosis Canada. It is unfortunate that splashy headlines about bone and vitamin D sometimes miss important information—that vitamin D is important for a healthy skeleton.

Our study was not designed to determine whether vitamin D was beneficial for people with osteoporosis or who had vitamin D deficiency. In fact, it is clear that maintaining adequate vitamin D levels is very important for skeletal health. Rather, our goal was to understand whether otherwise healthy adults (nonosteoporotic, adequate vitamin D levels) benefited by taking vitamin D supplementation over and above the recommendations by national health organizations.

Is there anything else you would like to emphasize to our readers?

A: This study did not address any of the other postulated nonskeletal benefits of vitamin D, such as reduced risk of auto-immune diseases or some cancers. It is possible that these benefits, if present, might require higher doses of vitamin D than the amount that seems to be adequate for bone.

Furthermore, we focused on older adults (55 to 70 years of age), and we don’t know whether the same effect of vitamin D supplementation we found would be true for a younger population. It would be very interesting to study because the growing skeleton (into your 20’s) has significant potential for effective intervention. The interaction of nutrient supplementation and physical exercise would also be very interesting to explore since we know that mechanical loads also play an important role in bone health. Perhaps supplementation with vitamin D and/or exercise would affect young and middle-aged people differently—we simply don’t know.

Dr. Boyd reported other (co-owner of software company that performs finite element analysis; the software was used to analyze the data in this study, but it was provided at no cost and no compensation was received for this work) from Numerics88 Solutions and other (for panel participation honorarium) from Amgen outside the submitted work.

Dr. Hanley reported receipt of grants and personal fees (for speaker honorarium) from Amgen and grants from Eli Lilly outside the submitted work.

Updated on: 09/18/19
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Cervical Total Disc Replacement and Routine Osteoporosis Screening
Steven Boyd, PhD
Professor, Department of Radiology
Director, McCaig Institute for Bone and Joint Health
Cumming School of Medicine
University of Calgary
David A. Hanley, MD, FRCPC
Departments of Medicine, Oncology, and Community Health Sciences
University of Calgary

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