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Open Access 01-12-2022 | Research

The effects of vitamin D supplementation on frailty in older adults at risk for falls

Authors: Yurun Cai, Amal A. Wanigatunga, Christine M. Mitchell, Jacek K. Urbanek, Edgar R. Miller III, Stephen P. Juraschek, Erin D. Michos, Rita R. Kalyani, David L. Roth, Lawrence J. Appel, Jennifer A. Schrack

Published in: BMC Geriatrics | Issue 1/2022

Abstract

Background

Low serum 25-hydroxyvitamin D [25(OH)D] level is associated with a greater risk of frailty, but the effects of daily vitamin D supplementation on frailty are uncertain. This secondary analysis aimed to examine the effects of vitamin D supplementation on frailty using data from the Study To Understand Fall Reduction and Vitamin D in You (STURDY).

Methods

The STURDY trial, a two-stage Bayesian, response-adaptive, randomized controlled trial, enrolled 688 community-dwelling adults aged ≥ 70 years with a low serum 25(OH)D level (10–29 ng/mL) and elevated fall risk. Participants were initially randomized to 200 IU/d (control dose; n = 339) or a higher dose (1000 IU/d, 2000 IU/d, or 4000 IU/d; n = 349) of vitamin D3. Once the 1000 IU/d was selected as the best higher dose, other higher dose groups were reassigned to the 1000 IU/d group and new enrollees were randomized 1:1 to 1000 IU/d or control group. Data were collected at baseline, 3, 12, and 24 months. Frailty phenotype was based on number of the following conditions: unintentional weight loss, exhaustion, slowness, low activity, and weakness (≥ 3 conditions as frail, 1 or 2 as pre-frail, and 0 as robust). Cox proportional hazard models estimated the risk of developing frailty, or improving or worsening frailty status at follow-up. All models were adjusted for demographics, health conditions, and further stratified by baseline serum 25(OH)D level (insufficiency (20–29 ng/mL) vs. deficiency (10–19 ng/mL)).

Results

Among 687 participants (mean age 77.1 ± 5.4, 44% women) with frailty assessment at baseline, 208 (30%) were robust, 402 (59%) were pre-frail, and 77 (11%) were frail. Overall, there was no significant difference in risk of frailty outcomes comparing the pooled higher doses (PHD; ≥ 1000 IU/d) vs. 200 IU/d. When comparing each higher dose vs. 200 IU/d, the 2000 IU/d group had nearly double the risk of worsening frailty status (HR = 1.89, 95% CI: 1.13–3.16), while the 4000 IU/d group had a lower risk of developing frailty (HR = 0.22, 95% CI: 0.05–0.97). There were no significant associations between vitamin D doses and frailty status in the analyses stratified by baseline serum 25(OH)D level.

Conclusions

High dose vitamin D supplementation did not prevent frailty. Significant subgroup findings might be the results of type 1 error.

Trial registration

ClinicalTrials.gov: NCT02166333.

Available only for authorised users

Fried LP, Cohen AA, Xue Q-L, Walston J, Bandeen-Roche K, Varadhan R. The physical frailty syndrome as a transition from homeostatic symphony to cacophony. Nat Aging. 2021;1(1):36–46. https://doi.org/10.1038/s43587-020-00017-z.CrossRefPubMedPubMedCentral

Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. Journals Gerontol Ser A-Biological Sci Med Sci. 2001;56A(3):M146–56. https://doi.org/10.1093/gerona/56.3.M146.CrossRef

Bandeen-Roche K, Seplaki CL, Huang J, et al. Frailty in older adults: a nationally representative profile in the United States. Journals Gerontol - Ser A Biol Sci Med Sci. 2015;70(11):1427–34. https://doi.org/10.1093/gerona/glv133.CrossRef

Gregorevic KJ, Hubbard RE, Lim WK, Katz B. The clinical frailty scale predicts functional decline and mortality when used by junior medical staff: a prospective cohort study. BMC Geriatr. 2016;16:117. https://doi.org/10.1186/s12877-016-0292-4.CrossRefPubMedPubMedCentral

Ensrud KE, Ewing SK, Taylor BC, et al. Frailty and risk of falls, fracture, and mortality in older women: the Study of Osteoporotic Fractures. Journals Gerontol Ser A. 2007;62(7):744–51. https://doi.org/10.1093/gerona/62.7.744.CrossRef

Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL. Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int. 2011;22(3):859–71. https://doi.org/10.1007/s00198-010-1407-y.CrossRefPubMed

Rosendahl-Riise H, Spielau U, Ranhoff AH, Gudbrandsen OA, Dierkes J. Vitamin D supplementation and its influence on muscle strength and mobility in community-dwelling older persons: a systematic review and meta-analysis. J Hum Nutr Diet. 2017;30(1):3–15. https://doi.org/10.1111/jhn.12394.CrossRefPubMed

Muir SW, Montero-Odasso M. Effect of Vitamin D Supplementation on Muscle Strength, Gait and Balance in Older Adults: A Systematic Review and Meta-Analysis. J Am Geriatr Soc. 2011;59(12):2291–300. https://doi.org/10.1111/j.1532-5415.2011.03733.x.CrossRefPubMed

Beaudart C, Buckinx F, Rabenda V, et al. The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2014;99(11):4336–45. https://doi.org/10.1210/jc.2014-1742.CrossRefPubMed

10.

Zhu K, Austin N, Devine A, Bruce D, Prince RL. A randomized controlled trial of the effects of vitamin D on muscle strength and mobility in older women with vitamin D insufficiency. J Am Geriatr Soc. 2010;58(11):2063–8. https://doi.org/10.1111/j.1532-5415.2010.03142.x.CrossRefPubMed

11.

Ensrud KE, Blackwell TL, Cauley JA, et al. Circulating 25-hydroxyvitamin D levels and frailty in older men: the Osteoporotic Fractures in Men study. J Am Geriatr Soc. 2011;59(1):101–6. https://doi.org/10.1111/j.1532-5415.2010.03201.x.CrossRefPubMed

12.

Ju SY, Lee JY, Kim DH. Low 25-hydroxyvitamin D levels and the risk of frailty syndrome: a systematic review and dose-response meta-analysis. BMC Geriatr. 2018;18(1):1–11. https://doi.org/10.1186/s12877-018-0904-2.CrossRef

13.

Buta B, Choudhury PP, Xue Q-L, et al. The association of vitamin D deficiency and incident frailty in older women: the role of cardiometabolic diseases. J Am Geriatr Soc. 2017;65(3):619–24. https://doi.org/10.1111/jgs.14677.CrossRefPubMed

14.

Wong YYE, McCaul KA, Yeap BB, Hankey GJ, Flicker L. Low vitamin D status is an independent predictor of increased frailty and all-cause mortality in older men: the Health in Men Study. J Clin Endocrinol Metab. 2013;98(9):3821–8. https://doi.org/10.1210/jc.2013-1702.CrossRefPubMed

15.

Bolzetta F, Stubbs B, Noale M, et al. Low-dose vitamin D supplementation and incident frailty in older people: an eight year longitudinal study. Exp Gerontol. 2017;2018(101):1–6. https://doi.org/10.1016/j.exger.2017.11.007.CrossRef

16.

Appel LJ, Michos ED, Mitchell CM, et al. The effects of four doses of vitamin D supplements on falls in older adults. Ann Intern Med. 2020;174(2):145–56. https://doi.org/10.7326/M20-3812.CrossRefPubMedPubMedCentral

17.

Michos ED, Mitchell CM, Miller ER III, et al. Rationale and design of the Study To Understand Fall Reduction and Vitamin D in You (STURDY): A randomized clinical trial of Vitamin D supplement doses for the prevention of falls in older adults. Contemp Clin Trials. 2018;73:111–22. https://doi.org/10.1016/j.cct.2018.08.004.CrossRefPubMedPubMedCentral

18.

Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56. https://doi.org/10.1093/gerona/56.3.m146.CrossRefPubMed

19.

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81. https://doi.org/10.1056/NEJMra070553.CrossRefPubMed

20.

Wilhelm-Leen ER, Hall YN, DeBoer IH, Chertow GM. Vitamin D deficiency and frailty in older Americans. J Intern Med. 2010;268(2):171–80. https://doi.org/10.1111/j.1365-2796.2010.02248.x.CrossRefPubMedPubMedCentral

21.

Vaes AMM, Brouwer-Brolsma EM, Toussaint N, et al. The association between 25-hydroxyvitamin D concentration, physical performance and frailty status in older adults. Eur J Nutr. 2019;58(3):1173–81. https://doi.org/10.1007/s00394-018-1634-0.CrossRefPubMed

22.

Pfeifer M, Begerow B, Minne HW. Vitamin D and muscle function. Osteoporos Int. 2002;13(3):187–94. https://doi.org/10.1007/s001980200012.CrossRefPubMed

23.

Rejnmark L. Effects of vitamin D on muscle function and performance: a review of evidence from randomized controlled trials. Ther Adv Chronic Dis. 2010;2(1):25–37. https://doi.org/10.1177/2040622310381934.CrossRef

24.

Pfeifer M, Begerow B, Minne HW, Suppan K, Fahrleitner-Pammer A, Dobnig H. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Osteoporos Int. 2009;20(2):315–22. https://doi.org/10.1007/s00198-008-0662-7.CrossRefPubMed

25.

Gowda U, Mutowo MP, Smith BJ, Wluka AE, Renzaho AMN. Vitamin D supplementation to reduce depression in adults: Meta-analysis of randomized controlled trials. Nutrition. 2015;31(3):421–9. https://doi.org/10.1016/j.nut.2014.06.017.CrossRefPubMed

26.

Shaffer JA, Edmondson D, Wasson LT, et al. Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosom Med. 2014;76(3):190–6. https://doi.org/10.1097/PSY.0000000000000044.CrossRefPubMedPubMedCentral

27.

Havdahl A, Mitchell R, Paternoster L, Davey SG. Investigating causality in the association between vitamin D status and self-reported tiredness. Sci Rep. 2019;9(1):2880. https://doi.org/10.1038/s41598-019-39359-z.CrossRefPubMedPubMedCentral

28.

Nowak A, Boesch L, Andres E, et al. Effect of vitamin D3 on self-perceived fatigue: a double-blind randomized placebo-controlled trial. Medicine. 2016;95(52). https://journals.lww.com/md-journal/Fulltext/2016/12300/Effect_of_vitamin_D3_on_self_perceived_fatigue__A.2.aspx.

29.

Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. https://doi.org/10.1210/jc.2011-0385.CrossRefPubMed

30.

Wanigatunga AA, Sternberg AL, Blackford AL, et al. The effects of vitamin D supplementation on types of falls. J Am Geriatr Soc. 2021;n/a(n/a). https://doi.org/10.1111/jgs.17290

31.

Grant WB, Karras SN, Bischoff-Ferrari HA, et al. Do studies reporting ’U’-shaped serum 25-hydroxyvitamin D-health outcome relationships reflect adverse effects? Dermatoendocrinol. 2016;8(1):e1187349–e1187349. https://doi.org/10.1080/19381980.2016.1187349.CrossRefPubMedPubMedCentral

32.

Davis CD. Vitamin D and health: can too much be harmful? Am J Lifestyle Med. 2009;3(5):407–8. https://doi.org/10.1177/1559827609338154.CrossRef

33.

Melamed ML, Michos ED, Post W, Astor B. 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168(15):1629–37. https://doi.org/10.1001/archinte.168.15.1629.CrossRefPubMedPubMedCentral

34.

Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503–11. https://doi.org/10.1161/CIRCULATIONAHA.107.706127.CrossRefPubMed

35.

Bislev LS, Langagergaard Rødbro L, Rolighed L, Sikjaer T, Rejnmark L. Effects of vitamin D3 supplementation on muscle strength, mass, and physical performance in women with vitamin D insufficiency: a randomized placebo-controlled trial. Calcif Tissue Int. 2018;103(5):483–93. https://doi.org/10.1007/s00223-018-0443-z.CrossRefPubMed

36.

Zhou J, Huang P, Liu P, et al. Association of vitamin D deficiency and frailty: a systematic review and meta-analysis. Maturitas. 2016;94:70–6. https://doi.org/10.1016/j.maturitas.2016.09.003.CrossRefPubMed

37.

Houston DK, Cesari M, Ferrucci L, et al. Association between vitamin D status and physical performance: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2007;62(4):440–6. https://doi.org/10.1093/gerona/62.4.440.CrossRefPubMed

Title: The effects of vitamin D supplementation on frailty in older adults at risk for falls
Authors: Yurun Cai
Amal A. Wanigatunga
Christine M. Mitchell
Jacek K. Urbanek
Edgar R. Miller III
Stephen P. Juraschek
Erin D. Michos
Rita R. Kalyani
David L. Roth
Lawrence J. Appel
Jennifer A. Schrack
Publication date: 01-12-2022
Publisher: BioMed Central
Published in: BMC Geriatrics / Issue 1/2022
Electronic ISSN: 1471-2318
DOI: https://doi.org/10.1186/s12877-022-02888-w

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