Comment on USTSPF drafted research plan

Posted on: April 19, 2016   by  Amber Tovey

img

The U.S. Preventive Services Task Force (USPSTF) recently posted their draft research plan on vitamin D and/or calcium supplementation for primary prevention of fractures in adults, and requested the Vitamin D Council’s feedback.

The USPSTF is a panel of physicians and epidemiologists appointed by the US Department of Health and Human Services. They publish recommendations for a variety of different things after evaluating the effectiveness of interventions, screening and other clinical practices.

The draft research plan on vitamin D and/or calcium supplementation  purpose is to gather comments from the public before releasing a finalized recommendation six months later. It identifies study characteristics and criteria that they will use to find  studies to be included in their review.

The Vitamin D Council was more than happy to use this opportunity for our voices to be heard. Take a look below to read our response.

April 14, 2016

Dear Sir or Madam:

The Vitamin D Council believes that in 2013, the USPSTF overlooked a few crucial studies that illustrate the significant role vitamin D plays in fracture prevention. In 2013, the USPSTF concluded that there is inadequate research to support vitamin D supplementation among post-menopausal women, premenopausal women and men. This year, the Vitamin D Council hopes that the USPSTF will take the following recommendations into consideration before making their final statement.

As the USPSTF is well aware, clinical trials provide the strongest findings due to their ability to prove causation. However, when one evaluates the quality of a clinical trial, there are several things to keep in mind. First, are all subjects enrolled into the trial considered vitamin D deficient? What is the point in giving vitamin D to a treatment group that is already sufficient? Second, is the dosage large enough to make a significant impact on their vitamin D levels? In order to evaluate the effectiveness of supplementation, the majority of the participants must reach a sufficient vitamin D status by the end of the study. Normally, this requires a dosage equivalent of at least 800 IU daily. Lastly, the study’s population should be at risk for the outcome that the study is evaluating. In order to produce significant results, a proportion of the study population must experience the outcome, such as fractures. Researchers are unable to compare two groups if neither experience the outcome.

This leads me to request the inclusion of several relevant clinical trials into USPSTF’s research analysis:

  • Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial[1]
  • Vitamin D3 and calcium to prevent hip fractures in the elderly women[2]
  • Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomized double blind controlled trial[3]

These studies consist of experimental groups that were given the equivalent of at least 800 IU daily and control groups that were given a matching placebo. All studies concluded that vitamin D supplementation prevented fractures. However, all study populations involved an elderly population, because as explained earlier, the study population must be at risk for the outcome to produce significant results. Because of the difficulty in conducting a well-designed clinical trial using a population not at risk for fractures, researchers have not investigated the effects of vitamin D supplementation for prevention of fractures in younger populations. The Vitamin D Council believes the lack of clinical trials for younger populations led the USPSTF to recommend against vitamin D supplementation in premenopausal women, post-menopausal women and men. Though, the USPSTF should consider the results from observational studies that include these specific study populations, such as the following:

Women during menopausal transition

Serum 25 Hydroxyvitamin D, Bone Mineral Density and Fracture Risk Across the Menopause[4]

Post-menopausal women

Serum levels of 25-hydroxyvitamin D and functional outcome among postmenopausal women with hip fracture[5]

General Population (mean age 43)

Association of Vitamin D With Stress Fractures: A Retrospective Cohort Study[6]

The observational studies noted found a significant inverse relationship between vitamin D levels and fractures, indicating low vitamin D levels are associated with an increased risk for fractures.

In summary, clinical trials have determined that vitamin D supplementation reduces fracture risk in the elderly if adequate doses are used. Clinical trials have yet to determine the effects of vitamin D supplementation in populations who are not at risk for fractures. Though, current evidence from observational studies suggests that low vitamin D levels are associated with higher risk of fractures in younger populations. The Vitamin D Council, therefore, believes if the USPSTF recommends against vitamin D supplementation for the prevention of fractures, they may be doing more harm than good. Vitamin D supplementation is generally safe when used in appropriate dosages. A recent study illustrated the safety of vitamin D in comparison to Tylenol, showing vitamin D is much less harmful than Tylenol.[7]

It is important to remember that vitamin D and calcium are not the sole factors in the prevention of fractures, although some research suggests that vitamin D supplementation alone will likely aid in fracture prevention. But vitamin D does not work in a vacuum. For example, magnesium was found in a controlled trial to increase bone density.[8] Likewise, vitamin K has favorable effects on bone.[9] Silicon and boron are also found in bone. Higher dietary intake of vitamins A, C and E, β-carotene, and Se are associated with reduced fracture risk.[10]

Thus, the Vitamin D Council predicts studies using only one nutrient, vitamin D, in a low dose, will not reduce fractures.

We suggest you use the Heaney criteria[11] in evaluating studies, which are the population studied must be at an elevated risk for fracture, baseline vitamin D must be below 20 ng/ml, placebo group must remain below 20 ng/ml during the trial, final 25(OH)D should exceed 40 ng/ml in the treatment group, baseline and final 25(OH)D must be obtained in all subjects, and the nutrient’s co-factors should be given with the nutrient.

Citation

Tovey, A. & Cannell, JJ. Comment on USTSPF drafted research plan. The Vitamin D Council Blog & Newsletter, 2016.

References

[1]Flicker L, MacInnis RJ, Stein MS, et al. Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. J Am Geriatr Soc. 2005;53(11):1881-1888. doi:10.1111/j.1532-5415.2005.00468.x.

[2] Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992;327(23).

[3] Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326(7387):469. doi:10.1136/bmj.326.7387.469.

[4] Cauley J a., Greendale G a, Ruppert K, et al. Serum 25 Hydroxyvitamin D, Bone Mineral Density and Fracture Risk Across the Menopause. J Clin Endocrinol Metab. 2015;(March):jc.2014-4367. doi:10.1210/jc.2014-4367.

[5] Liu L-M, Wang S-H, Fu C-S, Han X-Z, Wei B-F. Serum levels of 25-hydroxyvitamin D and functional outcome among postmenopausal women with hip fracture. PLoS One. 2015;10(1):e0116375. doi:10.1371/journal.pone.0116375.

[6] Miller JR, Dunn KW, Ciliberti LJ, Patel RD, Swanson B a. Association of Vitamin D With Stress Fractures: A Retrospective Cohort Study. J Foot Ankle Surg. 2015:1-4. doi:10.1053/j.jfas.2015.08.002.

[7] Spiller H, Good T, Spiller N, Aleguas  a. Vitamin D exposures reported to US poison centers 2000-2014: Temporal trends and outcomes. Hum Exp Toxicol. 2015:1-5. doi:10.1177/0960327115595685.

[8] Stendig-Lindberg G, Tepper R, Leichter I.Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnes Res. 1993 Jun;6(2):155-63.

[9] Sun LL et al. Associations between the dietary intake of antioxidant nutrients and the risk of hip fracture in elderly Chinese: a case-control study. Br J Nutr. 2014 Nov 28;112(10):1706-14.

[10] Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013 Sep;24(9):2499-507.

[11] Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev. 2014 Jan;72(1):48-54.

5 Responses to Comment on USTSPF drafted research plan

  1. hlahore@gmail.com

    Link to the draft policy
    http://is.gd/uspstfvitd

    • Amber Tovey

      Thanks Henry! Anyone can post a comment. If any of our readers have an opinion on the matter or any helpful suggestions for USPSTF, please post a comment. As it states on their website, the opportunity for public comment expires on April 27, 2016 at 8:00 PM EST.

  2. Rita Celone Umile

    Hi Amber,

    Thank you for sharing this item with the readership here. I am concerned about the following statement in the above blog:

    “In order to evaluate the effectiveness of supplementation, the majority of the participants must reach a sufficient vitamin D status by the end of the study. Normally, this requires a dosage equivalent of at least 800 IU daily.”

    Will a dosage of 800 iu D3 daily really bring most folks up to sufficiency? I think not, and furthermore, I think this might be misleading to folks wondering what their daily dosage of D3 should be…. Certainly, they won’t get good advice (most likely) from their mainstream family practitioner, and I do not think I”m being jaded in my thoughts here.

    Please allow me also state that I think any study utilizing 400 iu to 800 iu (or even 2,000 iu 😉 ) D3 daily is doomed for failure. Why not treat a strep throat infection with 5 mg of penicillin daily for 10 days? Because it won’t cure the infection. A dose of 500 mg is required daily for 10 days.

    I also wonder if a 25(OH)D sufficiency level of around 45 ng/ml is satisfactory only if one is fortunate enough to have had an entire lifetime of vitamin D sufficiency. In other words, for the very vast majority of us, who have been at insufficient levels for most of our lives, indeed perhaps we would benefit from keeping our 25(OH)D levels closer to the top of optimal range…..What number would that be? I come here to this website for just that sort of information. Where else can folks go to get the honest information they need regarding the healthy benefits of vitamin D3 (and of course sunshine). 🙂

    In conclusion, I am puzzled recently regarding if unbiased information = honest information….. It’s a philosophical question for sure, but one that is now nagging at me constantly.

    🙂

    Thanks for your hard work and fine efforts.

    Warmly,
    Rita

    • Amber Tovey

      Hi Rita,

      I agree that, ideally, studies should use a daily dosage of 5000 IU. Unfortunately, the clinical trials that use this dosage are limited. In fact, I could not find a single study regarding the effects of vitamin D supplementation on fractures that used 5000 IU daily. Therefore, I only assessed the available studies. Even the studies that used dosages as small as 800 IU found significant effects on fractures. I believe that the USPSTF should consider these significant findings rather than ignore them. The studies that did not find effects of vitamin D supplementation on fractures used smaller dosages. For example, the Women’s Health Initiative used a daily vitamin D supplement of 400 IU and did not find significant effects on fractures. This would lead one to believe that vitamin D does produce beneficial effects, but must be administered in amounts greater than or equal to 800 IU. I believe a study that administers a larger dosage, near 5000 IU of vitamin D3, will find greater effects. Hopefully randomized controlled trials using a dosage of 5000 IU will be conducted in the future.

      Thank you, as always, for your thoughtful input. As I mentioned already, the research draft plan is open for public comment. Please share your thoughts with the USPSTF!

      Best,

      Amber Tovey

  3. rcbaker200@comcast.net

    I don’t have any formal study to quote. But one of the doctors I worked for since 2005 ran a lot of DEXA scans in post-menopausal women and of the ones who only took vitamin D (5000 units a day) because they couldn’t tolerate other medications, I saw almost all of them improve their bone density after 2 years. The usual improvement was 20%. I saw it in dozens of women.
    Robert Baker MD

Test Your Vitamin D Levels at Home!

Our in-home Vitamin D Test Kit is easy, affordable, and an accurate way to find out your Vitamin D status.

order NOW

We need your help!

We're spreading awareness on Vitamin D Deficiency
Donate NOW
Latest Articles
img
Vitamin D supplementation may provide relief for patients with atopic dermatitis

A recently published meta-analysis proves that vitamin D supplementation is a safe and effective treatment for atopic dermatitis.

Weekly Newsletter