Frailty and Vitamin D - many studies

17+ VitaminDWiki pages with FRAILTY in title

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< 4% of US elderly who have had 3 fragility fractures are prescribed to take Vitamin D - March 2024

Forgetting the Frail: National Trends in Vitamin D Prescription After Fragility Fracture-A Large Insurance Claims Database Study
J Am Acad Orthop doi: 10.5435/JAAOS-D-23-00932 PDF behind paywall 39 references online
Suspect that prescriptions of 800 IU (RDA for seniors) were found to not help, so doctors have given up prescribing

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The elderly have a higher risk of Frailty, etc. if low vitamin D - Jan 2024

Vitamin D insufficiency and disease risk in the elderly
J Clin Biochem Nutr. 2024 Jan;74(1):9-16. doi: 10.3164/jcbn.23-59
Kiyoshi Tanaka 1, Misora Ao 2, Junko Tamaru 3, Akiko Kuwabara 4

Vitamin D insufficiency, milder than deficiency, is common, and a risk of various diseases. Since vitamin D exert diverse actions, both skeletal and non-skeletal, its insufficiency is a risk of various diseases including osteoporosis, sarcopenia, cardiovascular disease, cancer, and even mortality. Regarding the association of vitamin D status and disease risk, a marked discrepancy exists between the results from the observational studies and intervention studies, mostly yielding the positive and negative results in the former and latter, respectively. Such inconsistency probably arises from methodological problems, of which the baseline vitamin D status would be the most important. Vitamin D intervention would be effective in the deficient/insufficient subjects, but not in sufficient subjects. Since the elderly subjects, especially the institutionalized people, are mostly vitamin D deficient/insufficient, they are likely to benefit from improvement of vitamin D status. Vitamin insufficiency is a risk of various diseases, and correcting the vitamin status alone would reduce the risk of many diseases, and favorable to avoid the undesirable consequences of polypharmacy in the elderly. Additionally, disease prevention by nutritional improvement is cheap and free from side effects, and suited for the primary prevention of diseases.
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VitaminDWiki

• Overview Seniors lack Vitamin D
• Fraility 9X more likely if low vitamin D – Nov 2015
• Overview: Bone fractures and vitamin D
• All items in mortality and vitamin D 320 items
• Seniors were 2X more likely to have functional limitation in 3 years if vitamin D deficient – Sept 2013
• Added 1 lb of muscle to sarcopenia adults in 13 weeks with just 800 IU vitamin D and protein – RCT Jan 2017
• Frailty and Vitamin D – with influence diagram Miller Oct 2010 which has the following chart

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Frail were 9X more likely to have low vitamin D - June 2022

Components of frailty, sarcopenia and their association with vitamin D deficiency. Cross-sectional, analytical study
Gac Med Mex . 2022;158(6):343-348. doi: 10.24875/GMM.M22000711.
Karla B Carrazco-Peña 1, Katia Farías-Moreno 2, Mario Del Toro-Equihua 3, Zahira C Aguilar-Mancilla 4, Mariana Trujillo-Magallón 5, Miguel A Solórzano-Rodríguez 6, Benjamín Trujillo-Hernández 1

Introduction: In older adults, the association of frailty and sarcopenia with vitamin D deficiency is well known, but the association of the components of frailty syndrome has been poorly studied.

Objective: To determine the association of the components of frailty and sarcopenia with vitamin D insufficiency in older adults.

Methods: Adults were studied, in whom age, education, marital status, history of fractures, hospitalizations, anthropometric indicators, sarcopenia, Charlson index, polypharmacy, Fried's frailty phenotype, and plasma vitamin D were recorded; figures < 30 ng/mL were considered indicative of vitamin D insufficiency. Descriptive and inferential statistics were used for statistical analysis. The association was determined by binary logistic regression.

Results: One-hundred and seventy-five adults with a mean age of 71.7 ± 6.7 years (95% CI = 60-90 years) were studied.
Binary logistic regression showed that the variables associated with vitamin D deficiency were

• exhaustion (OR = 2.6, 95% CI = 1.0-6.5, p = 0.03),
• frailty (OR = 9.2, 95% CI = 2.5-34.1, p = 0.001) and
• pre-frailty (OR = 4.6, 95% CI = 2.1-10.0, p < 0.001).

Conclusion: The frail and pre-frail phenotypes, as well as exhaustion, are associated with vitamin D insufficiency.
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Risk of prefrailty reduced 40% by 2,000 IU of Vitamin D + Omega-3 + Exercise: RCT - Judy 2022

Effects of Vitamin D, Omega-3 Fatty Acids and a Home Exercise Program on Prevention of Pre-Frailty in Older Adults: The DO-HEALTH Randomized Clinical Trial
The Journal of Frailty & Aging volume 12, pages71–77 (2023)
Michael Gagesch, M. Wieczorek, B. Vellas, R. W. Kressig, R. Rizzoli, J. Kanis, W. C. Willett, A. Egli, W. Lang, E. J. Orav & H. A. Bischoff-Ferrari

Background
The benefits of supplemental vitamin D3, marine omega-3 fatty acids, and a simple home exercise program (SHEP) on frailty prevention in generally healthy community-dwelling older adults are unclear.

Objective
To test the effect of vitamin D3, omega-3s, and a SHEP, alone or in combination on incident pre-frailty and frailty in robust older adults over a follow-up of 36 months.

Methods
DO-HEALTH is a multi-center, double-blind, placebo-controlled, 2x2x2 factorial randomized clinical trial among generally healthy European adults aged 70 years or older, who had no major health events in the 5 years prior to enrollment, sufficient mobility and intact cognitive function. As a secondary outcome of the DO-HEALTH trial, among the subset of participants who were robust at baseline, we tested the individual and combined benefits of supplemental 2,000 IU/day of vitamin D3, 1 g/day of marine omega-3s, and a SHEP on the odds of being pre-frail and frail over 3 years of follow-up.

Results
At baseline, 1,137 out of 2,157 participants were robust (mean age 74.3 years, 56.5% women, mean gait speed 1.18 m/s). Over a median follow-up time of 2.9 years, 696 (61.2%) became pre-frail and 29 (2.6%) frail. Odds ratios for becoming pre-frail were not significantly lower for vitamin D3, or omega 3-s, or SHEP, individually, compared to control (placebo for the supplements and control exercise).
However, the three treatments combined showed significantly decreased odds (OR 0.61 [95% CI 0.38–0.98; p=0.04) of becoming pre-frail compared to control. None of the individual treatments or their combination significantly reduced the odds of becoming frail.]

Conclusion
Robust, generally healthy and active older adults without major comorbidities, may benefit from a combination of high-dose, supplemental vitamin D3, marine omega-3s, and SHEP with regard to the risk of becoming pre-frail over 3 years.
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Frailty 2.3 X more likely if low vitamin D - June 2022

Mediating Effect of Physical Activity in the Association between Low 25-Hydroxyvitamin D and Frailty Trajectories: The English Longitudinal Study of Ageing
Nutrients . 2022 May 30;14(11):2292. doi: 10.3390/nu14112292.
Zaixing Shi 1 2 3, Kanglin Shi 1, Zeyun Zhang 1, Jianlin Lin 1, Ya Fang 1 2 3

Background: Frailty is associated with adverse health outcomes, and vitamin D (VD) deficiency may be a risk factor. We aimed to identify frailty trajectories and examine the mediating effect of physical activity (PA) on the association between VD deficiency and frailty trajectories.

Methods: We included 2997 participants aged 60 to 85 years from ELSA. VD was measured using serum 25-hydroxyvitamin D [25(OH)D (sufficient: >;50; insufficient: 30-50; deficient: <30 nmol/L). Frailty was assessed by a 60-item frailty index, and PA was measured on the basis of total energy expenditure. Frailty trajectories were identified using group-based trajectory modeling, and the mediation effect of PA was tested using causal mediation analysis.

Results: Three distinct frailty trajectories emerged: "Non-frail" (66.48%), "Pre-frail to frail" (25.67%) and "Frail to severely frail" (7.85%). VD deficiency was associated with the "Pre-frail to frail" (OR = 1.51, 95% CI: 1.14, 1.98) and "Frail to severely frail" trajectories (OR = 2.29, 95% CI: 1.45, 3.62). PA only mediated 48.4% (95% CI: 17.1%-270.8%) of the association between VD deficiency and the "Pre-frail to frail" trajectory.

Conclusions: Vitamin D deficiency is associated with the onset and worsening of frailty in older adults, and reduced PA may mediate its impact on the transition from pre-frailty to frailty.
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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.

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All studies of frailty 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.

Frailty 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.

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.

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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 the 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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17+ VitaminDWiki pages with SARCOPENIA in title

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