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Frailty is associated with low Vitamin D

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Less frail if more vitamin D – meta-analysis July 2020

Low Vitamin D Levels and Frailty Status in Older Adults: A Systematic Review and Meta-Analysis
Review Nutrients. 2020 Jul 30;12(8):E2286. doi: 10.3390/nu12082286.
Diego Marcos-Pérez 1 2, María Sánchez-Flores 1 3 4, Stefania Proietti 5, Stefano Bonassi 6 7, Solange Costa 3 4, Joao Paulo Teixeira 3 4, Juan Fernández-Tajes 8 9, Eduardo Pásaro 1 2, Vanessa Valdiglesias 2 4 10, Blanca Laffon 1 2
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Serum vitamin D deficiency is widespread among older adults and is a potential modifiable risk factor for frailty. Moreover, frailty has been suggested as an intermediate step in the association between low levels of vitamin D and mortality. Hence, we conducted a systematic review of the literature and meta-analysis to test the possible association of low concentrations of serum 25-hydroxyvitamin D (25(OH)D), a marker of vitamin D status, with frailty in later life. We reviewed cross-sectional or longitudinal studies evaluating populations of older adults and identifying frailty by a currently validated scale. Meta-analyses were restricted to cross-sectional data from studies using Fried's phenotype to identify frailty. Twenty-six studies were considered in the qualitative synthesis, and thirteen studies were included in the meta-analyses. Quantitative analyses showed significant differences in the comparisons of frail (standardized mean difference (SMD)-1.31, 95% confidence interval (CI) (-2.47, -0.15), p = 0.0271) and pre-frail (SMD-0.79, 95% CI (-1.58, -0.003), p = 0.0491) subjects vs. non-frail subjects. Sensitivity analyses reduced heterogeneity, resulting in a smaller but still highly significant between-groups difference. Results obtained indicate that lower 25(OH)D levels are significantly associated with increasing frailty severity. Future challenges include interventional studies testing the possible benefits of vitamin D supplementation in older adults to prevent/palliate frailty and its associated outcomes.


All studies of fraility found association with low vitamin D - Oct 2016

Relevance of vitamin D in the pathogenesis and therapy of frailty.
Curr Opin Clin Nutr Metab Care. 2016 Oct 1 DOI: 10.1097/MCO.0000000000000334
Bruyère O1, Cavalier E, Buckinx F, Reginster JY.
1aResearch Unit in Public Health, Epidemiology and Health Economics, University of Liège bDepartment of Clinical Chemistry, University of Liège, CHU Sart-Tilman, Liège, Belgium.

PURPOSE OF REVIEW:
This article reviews recently published evidence regarding the role of vitamin D in the physiopathology of physical frailty in elderly populations and its role in the management of this geriatric condition.
RECENT FINDINGS:
Some recent studies have found a low level of 25-hydroxyvitamin D, considered the best marker of vitamin D status, in frail individuals.
All prospective studies consistently report that low vitamin D status is associated with an increased risk of becoming frail. Recent studies also suggest that the relationship between vitamin D status and frailty is largely mediated by the development of sarcopenia. Very few well designed randomized controlled trials are available that assess the effectiveness of vitamin D supplementation in the prevention or management of frailty. In the absence of specific guidelines, a minimal serum 25-hydroxyvitamin D level of 75 nmol/l is proposed for frail elderly patients by some scientific societies. The doses necessary to reach this target are between 800 and 2000 IU/day.
SUMMARY:
Several studies suggest a potential effect of vitamin D on physical frailty but large clinical trials are lacking at this time to provide solid evidence of clinical benefit.

Fraility scale 55% more likely if low vitamin D - meta-analysis 2016

Association of vitamin D deficiency and frailty: A systematic review and meta-analysis.
Maturitas. 2016 Dec;94:70-76. doi: 10.1016/j.maturitas.2016.09.003. Epub 2016 Sep 13.
Zhou J1, Huang P2, Liu P3, Hao Q3, Chen S4, Dong B5, Wang J6.

There is a biologically plausible association between low vitamin D, specifically serum 25-hydroxyvitamin D 25(OH)D level, and frailty. We conducted a systematic review and meta-analysis to describe the association between low 25(OH)D level and frailty. We searched literature in OVID (Medline), EMBASE, Web of Knowledge and Cochrane CENTRAL Library Issue in May 2016, for cohort studies evaluating association of low 25(OH)D level with the risk of frailty. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines. A total of seven studies(17,815 participants)were eligible in our study.
The prevalence of frailty ranged from 3.9% to 31.9%. The pooled OR of frailty for the lowest versus the highest level of vitamin D was 1.27 (95% CI=1.17-1.38, I2=59%), suggesting that low level of vitamin D was significantly associated with the risk of frailty. In addition, results of subgroups analysis indicated that low level of vitamin D was significantly associated with the risk of frailty in female (pooled OR=1.27, 95% CI=1.15-1.40).
Similar result was also found when frailty was defined by the Fried criteria or the modified Fried criteria (pooled OR=1.25, 95% CI=1.14-1.37), and FRAIL scale (pooled OR=1.55, 95% CI=1.07-2.25). Compared to the highest level of 25(OH)D, the association between frailty and the lowest level of 25(OH)D was significant in our study.
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The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men - 2012

Age Ageing (2012) doi: 10.1093/ageing/afs162
First published online: October 30, 2012 Abdelouahid Tajar1,†, David M. Lee2,†?, Stephen R. Pye3, Matthew D. L. O'Connell3, Rathi Ravindrarajah3, Evelien Gielen4, Steven Boonen4, Dirk Vanderschueren4, Neil Pendleton5, Joseph D. Finn3, György Bartfai6, Felipe F. Casanueva7, Gianni Forti8, Aleksander Giwercman9, Thang S. Han10, Ilpo T. Huhtaniemi11, Krzysztof Kula12, Michael E. J. Lean13, Margus Punab14, Frederick C. W. Wu15 and Terence W. O'Neill16
Address correspondence to: D. M. Lee. Tel: (+44) 01612757380; Fax: (+44) 01612755043. Email: david.m.lee at manchester.ac.uk
Received April 27, 2012. Accepted August 23, 2012.

Vitamin D Life Summary

1500 Men in Spain
5% frail: 1 standard deviation lower in vitamin D level = 1.45X more likely to be frail
37% prefrail: 1 standard deviation lower in vitamin D level = 1.89X more likely to be prefrail

Background: the link between the vitamin D endocrine axis and frailty remains undefined, with few studies examining the joint effect of vitamin D and parathyroid hormone (PTH) levels. Our objective was to determine the association of frailty with serum 25-hydroxyvitamin D (25(OH)D) and PTH.

Setting: cross-sectional analysis within the European Male Ageing Study (EMAS).

Participants: a total of 1,504 community-dwelling men aged 60–79 years.

Methods: frailty was classified using a frailty phenotype (FP) and frailty index (FI). The association of frailty with 25(OH)D and PTH was examined using multinomial logistic regression; individual FP criteria with 25(OH)D and PTH using binary logistic regression. Results were expressed as relative odds ratios (ROR) and 95% confidence intervals (CIs) for multinomial; odds ratios (OR) and 95% CIs for binary models.

Results: using the FP, 5.0% of subjects were classified as frail and 36.6% as prefrail. Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: ROR = 1.45; 95% CI: 1.26–1.67) and frail (ROR = 1.89; 95% CI: 1.30–2.76), after adjusting for age, centre and health and lifestyle confounders (robust group = base category). Higher levels of PTH were associated with being frail after adjustment for confounders (per 1 SD increase: ROR = 1.24; 95% CI: 1.01–1.52). Comparable results were found using the FI. Among the five FP criteria only sarcopenia was not associated with 25(OH)D levels, while only weakness was associated with PTH.

Conclusion: lower 25(OH)D and higher PTH levels were positively associated with frailty in older men. Prospective data would enable the temporal nature of this relationship to be explored further.


Frailty in seniors 2.3 X more likely in next 8 years if have low vitamin D levels – Dec 2016

The Association of Vitamin D Deficiency and Incident Frailty in Older Women: The Role of Cardiometabolic Diseases
Journal of the American Geriatrics Society. First published: 23 Dec 2016, DOI: 10.1111/jgs.14677

Objectives: Evidence suggests vitamin D deficiency is associated with developing frailty. However, cardiometabolic factors are related to both conditions and may confound and/or mediate the vitamin D–frailty association. We aimed to determine the association of vitamin D concentration with incidence of frailty, and the role of cardiometabolic diseases (cardiovascular disease, diabetes, hyperlipidemia, hypertension) in this relationship.

Design: Prospective longitudinal cohort study (7 visits from 1994–2008).

Setting: Baltimore, Maryland.

Participants: Three hundred sixty-nine women from the Women's Health and Aging Study II aged 70–79 years, free of frailty at baseline.

Measurements: Serum circulating 25-hydroxyvitamin D (25OHD) concentration was assessed at baseline and categorized as: <10; 10–19.9; 20-29.9; and =30 ng/mL.
Frailty incidence was determined based on presence of three or more criteria:

  • weight loss,
  • low physical
  • weakness, and
  • slowness.

Cardiometabolic diseases were ascertained at baseline. Analyses included Cox regression models adjusted for key covariates.

Results: Incidence rate of frailty was 32.2 per 1,000 person-years in participants with 25(OH)D < 10 ng/mL, compared to 12.9 per 1,000 person-years in those with 25(OH)D = 30 ng/mL (mean follow-up = 8.5 ± 3.7 years). In cumulative incidence analyses, those with lower 25(OH)D exhibited higher frailty incidence, though differences were non-significant (P = .057). In regression models adjusted for demographics, smoking, and season, 25(OH)D < 10 ng/mL (vs =30 ng/mL) was associated with nearly three-times greater frailty incidence (hazard ratio (HR) = 2.77, 95% CI = 1.14, 6.71, P = .02). After adjusting for BMI, the relationship of 25(OH)D < 10 ng/mL (vs =30 ng/mL) with incident frailty persisted, but was attenuated after further accounting for cardiometabolic diseases (HR = 2.29, 95% CI = 0.92, 5.69, P = .07).

Conclusion: Low serum vitamin D concentration is associated with incident frailty in older women; interestingly, the relationship is no longer significant after accounting for the presence of cardiometabolic diseases. Future studies should explore mechanisms to explain this relationship.

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Sarcopenia in Vitamin D Life

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