Elucidating the Link Between Hypovitaminosis D and Sarcopenia: New Insights into Mechanisms and Threshold from the Evidence of NHANES 2011-2018

doi:10.21203/rs.3.rs-3428086/v1

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Elucidating the Link Between Hypovitaminosis D and Sarcopenia: New Insights into Mechanisms and Threshold from the Evidence of NHANES 2011-2018

https://doi.org/10.21203/rs.3.rs-3428086/v1

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Background:

Sarcopenia is most common in older adults and is defined as a decrease in skeletal muscle muscle mass, which can cause impaired mobility and increased risk of physical disability. The role of Vitamin D is well known for its classical effects on bone health, and growing evidence also suggests its beneficial effects on muscle function and metabolism. Our study aimed to explore the association between vitamin D and sarcopenia/low muscle mass by using statistic approaches.

Methods:

In this study, 7217 participants aged 18–60 years in the nationally National Health and Nutrition Examination Survey (NHANES)2011–2018 were included finally. Multivariable logistic regression was used to assess the the potential and deeper connection of vitamin D and sarcopenia/low muscle mass. Restricted cubic splines (RCS) was used to explore their potential dose-response relationships and interactions. Mediation analysis was used to explore their potential mediated effects of neutrophils and calcium and phosphate product between vitamin D and sarcopenia/low muscle mass.

Results:

With increasing vitamin D, both the risk of sarcopenia and low muscle mass decreased significantly. The RCS showed the similar results. Mediation analysis suggested that neutrophils can be affected by mediations from vitamin D to sarcopenia/low muscle mass. Additionally, vitamin D may lead to low muscle mass by stimulating mechanisms calcium and phosphate product.

Conclusions:

Decreased serum vitamin D may be strongly associated with occurrence of sarcopenia/low muscle mass. This study provided important evidence for elucidating the relationships between vitamin D and skeletal muscle mass.

Vitamin D

skeletal muscle mass

sarcopenia

Sarcopenia, defined as the loss of skeletal muscle mass and function, is increasingly prevalent in aging populations. Sarcopenia can lead to impaired mobility, increased risk of physical disability and even mortality in older adults^[1]. The pathogenesis of sarcopenia is multifactorial, involving metabolic disorders, malnutrition, inflammation, and other factors^[2]. In recent years, the role of vitamin D in sarcopenia has received considerable research attention. Growing data indicates that vitamin D has additional positive benefits on muscular function and metabolism in addition to its well-known effects on bone health^[3–5].

Previous observational studies have reported significant associations between low serum 25-hydroxyvitamin D [25(OH)D] concentration and parameters of muscle impairment, including sarcopenia, muscle strength and physical performance^{[6, 7]}. Several mechanisms have been proposed regarding the positive influence of vitamin D on muscle^[8]. Firstly, vitamin D has direct effects on muscle tissue by activating vitamin D receptors and inducing gene expression related to muscle cell growth and proliferation^{[9, 10]}. Secondly, vitamin D helps maintain calcium homeostasis and promotes protein synthesis, both of which are important for preserving muscle mass^[5]. Moreover, the anti-inflammatory properties of vitamin D may also contribute to its protective effects against sarcopenia ^[11].

However, the nature of the relationship between vitamin D status and sarcopenia has not been fully established. Most published data came from observational studies, and the potential threshold and nonlinearity have not been well characterized. Using the large nationally representative sample from the 2011–2018 National Health and Nutrition Examination Survey (NHANES), this study sought to determine if blood 25(OH)D levels and the risks of reduced muscle mass and sarcopenia were related in a dose-response manner. We hypothesized a potential nonlinear relationship exist between vitamin D status and sarcopenia. Clarifying the role of vitamin D in sarcopenia may provide new insights into its prevention and treatment.

Study population

The study population was derived from the National Health and Nutrition Examination Survey (NHANES), which is a major program of the National Center for Health Statistics (NCHS) that assesses the health and nutritional status of the U.S. population. The Centers for Disease Control and Prevention (CDC) oversees NHANES data collection. A total of 19,331 NHANES participants from 2011–2018 were screened initially. After applying exclusion criteria, the final analysis included 7,217 adults aged 18 years and older.

Outcome variables

There were two outcome measures - sarcopenia status (sarcopenia/non-sarcopenia) and muscle mass status (normal/low muscle mass). Sarcopenia was defined using the FNIH criteria, requiring both low muscle strength and ow appendicular lean mass (low ALM). Muscle strength was assessed by grip strength measured in kg using a handgrip dynamometer (for details of the measurement, refer to https://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/MGX_G.htm). The maximum of six trials (three from each hand) was normalized by BMI to calculate grip strength/BMI. Appendicular lean mass (ALM) in kg was measured by dual energy X-ray absorptiometry (DXA) (for details of the measurement, refer to https://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/DXX_G.htm). Participants with grip strength/BMI < 1.0 for men and < 0.56 for women and ALM < 19.75 kg for men and < 15.02 kg for women were classified as having sarcopenia. Low muscle mass was defined as ALM < 19.75 kg for men and < 15.02 kg for women.

Hematological indicators

Blood vitamin D in this study included 25-Hydroxyvitamin D2, 25-Hydroxyvitamin D3, and 3-epi-25-Hydroxyvitamin D3 in nmol/L. Blood vitamin D was quantified by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Serum samples are first treated by the addition of an ethanolic solution containing three internal standards and a solution of 69–72% methanol followed by the addition of hexane. Analytes are extracted from the aqueous phase Analytes are extracted from the aqueous phase into the hexane layer (liquid-liquid extraction) which is dried under vacuum. The extract is re-dissolved with 69–72% methanol. extract is injected onto the PFP column for the separation of 25OHD3, epi-25OHD3, 25OHD2, and the internal standards (IS), 26,27-hexadeuterium-25- hydroxyvitamin D3, 6,19,19-trideuterium-3-epi-25-hydroxyvitamin D3 and 6,19,19-trideuterium-25-hydroxyvitamin D2. Detection is performed by Detection is performed by MS-MS on a Thermo TSQ Vantage system using atmospheric pressure chemical ionization in the positive ion mode. Groupings were made based on quartiles in nmol/L, with Q1 (< 42.1), Q2 (42.1–57.9), Q3 (57.9–74.4), and Q4 (> 74.4). Specific measurements can be obtained on the website of https://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/VID_G.htm. Calcium (mmol/L) and phosphate (mmol/L) can also be found on the website of https://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/BIOPRO_G.htm. Calcium and phosphate products was finally used for the mediation analysis.

Variables

All analyses in this study (including multivariate logistic regression analyses, restricted cubic spline plots, and mediation analysis) were conducted after adjusting for the covariates of age (18–30,30–40,40–50,50–60), gender (female, male), race (Mexican American, Non-Hispanic Black ,Non-Hispanic White, Other Hispanic, Other Race - Including Multi-Racial), education (low high school, High school, College or above), income to poverty index(< 1, 1–3, ≥ 3), smoking status (former, never, now), drinking status (former drinker, heavy drinker, mild drinker, moderate drinker, never drinker).

Statistical analysis

All analyses were performed applying R project for Statistical Computing (version 4.0.5). Categorical variables were expressed as number (%). Statistical differences in general and demographic characteristics between the two groups of patients were separately assessed using chi-square tests and independent samples t-tests. Covariate-adjusted multivariate logistic regression analyses were performed to assess the association between vitamin D and sarcopenia/low muscle mass, and odds ratios (ORs) and 95% confidence interval (95% CI) were obtained. Non-linear relationships and dose-response relationships between blood vitamin D levels and sarcopenia/low muscle mass were analyzed using restricted cubic spline (RCS) plots. Mediated relationships were used to characterize the role of neutrophils and calcium and phosphorus product in mediating the relationship between blood vitamin D and sarcopenia/low muscle mass.

Participant Distribution

A total of 19331 NHANES 2011–2018 participants were included in the study, 11977 participants aged less than 18 years were excluded, 1073 participants who were unable to obtain vitamin D and 3687 participants who could not be assessed for sarcopenia were excluded, and finally 7217 participants were included in the study of which 3549 were males and 3668 were females (for details in Fig. 1).

Baseline Characterization

Baseline characteristics of participants can be seen in Table 1. Participants were categorized according to different criteria sarcopenia/non-sarcopenia group and normal muscle mass/low muscle mass group. In the grouping based on the criteria of sarcopenia, 54 participants were assessed as sarcopenia and 7163 as non-sarcopenia, 36 males in sarcopenia group were about 66.67% while 49.04% males were in the non-sarcopenia group, the number of participants in the sarcopenia group who were in the age group of 50–60 years was 28 (51.86%), while in the non-sarcopenia group, there was a larger percentage of about 31.06% in the age group of 18–30 years. About approximately 50% of the patients in the sarcopenia group had income to income to poverty indexof 1–3, while the income to poverty indexin the non-sarcopenia group was more evenly distributed among the three groups. Non-Hispanic White had the largest proportion in both the sarcopenia and non-sarcopenia groups, with 37.58% and 40.74%, respectively, and 50% or more of the participants in both groups had College or above, and more than 60% of the participants in the non-sarcopenia group had a higher income to poverty indexthan in the sarcopenia group. Over 60% of participants had never smoked, and over 80% of participants in both groups had a history of alcohol consumption. In the non-sarcopenia group, the number of people in the Vitamin D four groups was about the same, while in the sarcopenia group, the Q1 percentage was larger, about 37.04%. Overall, only gender and age were significantly different in the two groups, while vitamin D, poverty index, race, education, smoking history, and drinking history were not significantly different.

Table 1

Baseline characteristics of participants in standardized by sarcopenia and low muscle mass
Characteristics	Non-Sarcopenia	Sarcopenia	P	Normal muscle mass	Low muscle mass	P
	N = 7163	N = 54		N = 5645	N = 438
Vitamin D (%)			0.2297			0.0155
Q1	1793 (25.03)	20 (37.04)		1399 (24.78)	122 (27.85)
Q2	1796 (25.07)	12 (22.22)		1395 (24.71)	129 (29.45)
Q3	1780 (24.85)	12 (22.22)		1421 (25.17)	97 (22.15)
Q4	1794 (25.05)	10 (18.52)		1430 (25.33)	90 (20.55)
Sex (%)			0.0145			0.3844
Female	3650 (50.96)	18 (33.33)		2784 (49.32)	226 (51.60)
Male	3513 (49.04)	36 (66.67)		2861 (50.68)	212 (48.40)
Age			< 0.0001			< 0.0001
18–30	2225 (31.06)	11 (20.37)		1850 (32.77)	74 (16.89)
30–40	1685 (23.52)	6 (11.11)		1318 (23.35)	93 (21.23)
40–50	1678 (23.43)	9 (16.67)		1333 (23.61)	100 (22.83)
50–60	1575 (21.99)	28 (51.85)		1144 (20.27)	171 (39.04)
Income to Poverty index (%)			0.3474			0.006
< 1	1752 (26.41)	11 (22.45)		1326 (25.24)	119 (29.38)
[1, 3)	2447 (36.88)	23 (46.94)		1930 (36.73)	164 (40.49)
≥ 3	2436 (36.71)	15 (30.61)		1998 (38.03)	122 (30.12)
Race/ethnicity (%)			0.193			< 0.0001
Mexican American	928 (12.96)	12 (22.22)		696 (12.33)	125 (28.54)
Non-Hispanic Black	1622 (22.64)	11 (20.37)		1286 (22.78)	35 (7.99)
Non-Hispanic White	2692 (37.58)	22 (40.74)		2167 (38.39)	144 (32.88)
Other Hispanic	672 (9.38)	4 (7.41)		508 (9.00)	63 (14.38)
Other Race	1249 (17.44)	5 (9.26)		988 (17.50)	71 (16.21)
Education (%)			0.4323			< 0.0001
Low high school	1424 (19.88)	14 (25.93)		1073 (19.01)	124 (28.31)
High school	1581 (22.07)	13 (24.07)		1236 (21.90)	115 (26.26)
College or above	4157 (58.04)	27 (50.00)		3335 (59.09)	199 (45.43)
Smoke status (%)			0.7207			0.0013
Former	1108 (16.06)	10 (19.23)		864 (15.98)	87 (20.00)
Never	4201 (60.88)	32 (61.54)		3265 (60.40)	276 (63.45)
Now	1591 (23.06)	10 (19.23)		1277 (23.62)	72 (16.55)
Alcohol status (%)			0.0931			< 0.0001
Former drinker	731 (11.11)	8 (15.38)		531 (10.00)	67 (16.18)
Heavy drinker	1668 (25.36)	13 (25.00)		1379 (25.97)	98 (23.67)
Mild drinker	1983 (30.15)	20 (38.46)		1642 (30.93)	110 (26.57)
Moderate drinker	1187 (18.05)	2 (3.85)		984 (18.53)	40 (9.66)
Never drinker	1008 (15.33)	9 (17.31)		773 (14.56)	99 (23.91)
Categorical variables were presented as n (%).

In the groupings based on individual muscle mass criteria, there were 5,645 in the normal muscle mass group and 438 in the low muscle mass group. There was a more even distribution of men and women in both groups. The normal muscle mass group had a higher number of people aged 18–30 years (32.77%), while the low muscle mass group was mostly aged 50–60 years (39.04%). The normal muscle mass group had a larger number of people with the income to poverty index of ≥ 3, about 38.03%, while the low muscle mass group had mostly 1–3 points of poverty (40.49%). There were more Non-Hispanic White in the normal muscle mass group than the low muscle mass group (38.39% vs 32.88%), more people in both groups had College or above education (59.09% vs 45.43%) and more people had no smoking history (60.40% vs 63.45%). Among the four vitamin D groups, the normal muscle mass group had even numbers in all four groups and the low muscle mass group had more people in Q2 (29.45%). In contrast to age, poverty index, race, education, alcohol history, and smoking history, which were all significantly different between the two groups, neither gender nor vitamin D differed significantly.

Association of blood vitamin D and sarcopenia/low muscle mass

We evaluated whether or not there was a correlation between serum vitamin D levels and sarcopenia using multivariate covariate adjusted logistic regression. (Table 2). It showed that higher vitamin D levels were associated with a lower risk of sarcopenia, and the ORs for Q2, Q3, and Q4 were all less than 1 and significantly different compared with Q1 (Q2: OR 0.37, 95%CI 0.15–0.84, P = 0.022; Q3: OR 0.42, 95%CI 0.18–0.93, P = 0.036; Q4: OR 0.36, 95%CI 0.15–0.85, P = 0.022) (see Table 2 and Supplementary Fig. 1). S Likewise, a noteworthy distinction existed regarding the correlation between vitamin D and low muscle mass. with the Q3 and Q4 groups with low vitamin D having a higher risk of developing low muscle mass compared to Q1 (Q3: OR 0.57, 95%CI 0.41–0.78, P < 0.01; Q4: OR 0.46, 95%CI 0.32–0.64, P < 0.01). The Q2 group did not show a significant difference, but the OR was also less than 1, somewhat reflecting the consistent findings (see Table 2 and Supplementary Fig. 2).

Table 2

Associations of vitamin D and sarcopenia/low muscle mass.
Vitamin D	OR	95%CI	P
Sarcopenia
Q1	Reference
Q2	0.37	0.15–0.84	0.022
Q3	0.42	0.18–0.93	0.036
Q4	0.36	0.15–0.85	0.022
Low muscle mass
Q1	Reference
Q2	0.77	0.57–1.03	0.079
Q3	0.57	0.41–0.78	< 0.001
Q4	0.46	0.32–0.64	< 0.001
The multivariate logistic model was adjusted for sex, age, race/ethnicity, education, poverty ratio, smoking status, drinking alcohol status.

Table 3

The indirect effect and direct effect of neutrophils/calcium and phosphate product between vitamin D and sarcopenia/low muscle mass by mediation analysis.
Mediators	Total effect		Indirect effect		Direct effect		Proportion Mediated(%)
Mediators	Conefficient(95%CIs)	P	Conefficient(95%CIs)	P	Conefficient(95%CIs)	P	Proportion Mediated(%)
Neutrophils
Sarcopenia	-0.000097(-0.000171, 0.000022)	0.013	0.000007(0.000002, 0.000014)	0.031	-0.000104(-0.000180, -0.000029)	0.008	6.7%
Low muscle mass	-0.001159(-0.002164, -0.000510)	0.006	-0.000056(-0.000109, -0.000015)	0.016	-0.001103(-0.002063, -0.000469)	0.008	5.1%
Calcium and phosphate product
Low muscle mass	-0.000328(-0.000566, -0.000071)	0.020	-0.000027(-0.000049, − .0000007)	0.012	-0.000301(-0.000536, -0.000040)	0.018	9.0%
The mediation analysis was adjusted for sex, age, race/ethnicity, education, poverty ratio, smoking status, drinking alcohol status.

Restricted cubic spline (RCS) plots

RCS plots were applied to assess the dose-response relationships and nonlinear relationships between vitamin D and sarcopenia/low muscle mass, and all analyses were performed after adjustment for covariates (Fig. 2). It is evident that the danger of sarcopenia was present at vitamin D levels below around 50 and that it progressively increased as vitamin D levels decreased, whereas the curve was essentially flat at higher vitamin D levels, with an OR close to 1 and a significant difference (P = 0.0292) and a nonlinear relationship (P = 0.1115). The RCS plot showed a clear S-shaped curve, roughly reflecting a nonlinear relationship with increasing vitamin D content, the lesser the chance of low muscle mass.

Mediation analysis

In assessing vitamin D for sarcopenia as well as low muscle mass, mediation analyses suggested that vitamin D appeared to mediate the development of sarcopenia through neutrophils, with an indirect effect of 6.7%, while the same conclusion was obtained for the development of low muscle mass, with an indirect effect of 5.1%, and both were significantly different. Continuing to analyze the mediating effect of the calcium-phosphorus product, it was found that vitamin D could mediate low muscle mass through the calcium and phosphate products, with an indirect effect of 9.0% (see Fig. 3 and Supplementary Table 3).

This extensive research of the US adult population offers strong evidence of a substantial negative relationship between vitamin D level and the risk of sarcopenia and poor muscle mass. Our dose-response analysis indicates the relationship is nonlinear, with sarcopenia risk escalating substantially only below vitamin D levels of 50 nmol/L. We also present novel findings suggesting the vitamin D-sarcopenia link may be partly mediated by suppressing neutrophil-driven inflammation and proteolysis.

Several mechanistic explanations may underlie the apparent protective effect of vitamin D against sarcopenia. In skeletal muscle tissue, the active vitamin D metabolite 1,25-dihydroxyvitamin D binds to intranuclear vitamin D receptors and exerts genomic effects by modulating gene transcription^[10]. Vitamin D responsive genes in muscle include those regulating proliferation and differentiation of muscle progenitor cells, such as IGF-1, myogenesis, myosin heavy chain, and follistatin^{[12, 13]}. Vitamin D was also shown to induce cell cycle arrest prior to myogenic initiation and stimulate muscle cell fusion^[14]. Additionally, vitamin D may promote muscle anabolism by suppressing myostatin, a negative regulator of muscle mass^[15]. Through these genomic mechanisms, vitamin D signaling directly stimulates muscle protein synthesis and generation of new muscle fibers.

Vitamin D also has non-genomic actions in muscle independent of regulating gene expression^[16]. By maintaining calcium and phosphorus homeostasis through coordinated interactions between vitamin D, parathyroid hormone, and calcitriol, vitamin D helps preserve the calcium signaling and mitochondrial energetics crucial for optimal muscle contraction and metabolism^{[10, 17]}. These combined genomic and non-genomic mechanisms likely underlie the observed association between lower vitamin D status and higher sarcopenia risk.

Significantly, our research has shown oxidative damage and neutrophil-driven proteolysis as a major mediator between vitamin D deficiency and increased risk of sarcopenia. Neutrophils potentiate muscle breakdown by releasing proteases like elastase and gelatinase, as well as reactive oxygen species and myeloperoxidase^[18–20]. Vitamin D is known to have immunosuppressive effects by inhibiting neutrophil recruitment, degranulation, and superoxide production^[21–23]. By dampening neutrophil-mediated inflammation and proteolysis, vitamin D may mitigate sarcopenia progression. This represents an intriguing indirect mechanism that warrants further investigations. The pathway involving neutrophils, calcium, and phosphate product in relation to vitamin D and reduced muscle mass was shown in Fig. 4.

Furthermore, our mediation analysis indicates that vitamin D may lower the incidence of sarcopenia by preserving the equilibrium of calcium and phosphate. One finding linked vitamin D insufficiency with reduced muscle mass was the presence of elevated calcium-phosphate product as a mediator. Vitamin D is crucial in calcium homeostasis through coordinated interactions with parathyroid hormone and calcitriol^{[10, 17]}. Calcium signaling and mitochondrial calcium utilization are vital for muscle excitation-contraction coupling and metabolism^[24]. Dysregulated calcium homeostasis can activate proteases and impair energetics^[24]. By preserving calcium balance, vitamin D helps maintain muscle mass and function.

From a nutritional perspective, vitamin D deficiency may exacerbate sarcopenia by hindering optimal response to protein intake. Adequate vitamin D status enhances the anabolic effects of dietary protein on muscle, allowing greater muscle protein synthesis^[12]. Older adults require higher protein intake to offset sarcopenia^[25]. Vitamin D deficiency may blunt this response, worsening muscle loss. Optimizing vitamin D status synergizes the benefits of protein intake on preserving muscle mass.

Notably, the dose-response relationship in our study suggests a nonlinear threshold effect, with sarcopenia risk escalating substantially only below vitamin D levels around 50 nmol/L. This implies 50 nmol/L may be the minimal threshold required to confer protective effects against sarcopenia, at least with regards to systemic vitamin D status. Clinical implications include setting this as the potential target level for vitamin D repletion in treatment or prevention of sarcopenia. Our finding aligns with existing guidelines stating vitamin D levels above 50 nmol/L are optimal for musculoskeletal health in the general adult population^[8].

Some limitations should be acknowledged when interpreting our results. The cross-sectional nature limits causal inference. Misclassifications of sarcopenia status based on algorithm-defined criteria may exist. Information on vitamin D supplementation was unavailable, which may confound the association. Nonetheless, our study provides compelling evidence from a sizable nationally representative sample supporting vitamin D insufficiency as an independent risk factor for sarcopenia and low muscle mass. The revealed nonlinear relationship and potential threshold effect have clinical relevance for guiding vitamin D therapeutic targets. The findings also advance mechanistic understanding by implicating neutrophil-mediated proteolysis and calcium homeostasis as potential mediators.

In summary, Vitamin D deficiency has been shown to increase the risk of sarcopenia in a nonlinear, threshold-dependent manner, as shown by this population-based research.. Vitamin D may confer protection by coordinated genomic up-regulation of muscle anabolism and non-genomic maintenance of calcium homeostasis. Our data newly implicate dampening of neutrophil-driven proteolysis and oxidative damage as a contributing mechanism. These results support optimizing vitamin D status for sarcopenia prevention and inform clinical guidelines for targeted vitamin D therapy. Further research should investigate the intricate molecular interplay between vitamin D signaling, immunity and muscle metabolism. Elucidating these pathways may unveil new modalities for mitigating sarcopenia progression and preserving musculoskeletal function in aging populations.

Data sharing statement

The database of the National Health and Nutrition Examination Survey (NHANES) was downloaded on the website of https://www.cdc.gov/nchs/nhanes/index.htm.

Ethical approval and consent to participate

All participants in NHANES study provided consent of enrollment. The institutional review board of the National Center for Health Statistics, CDC approved the protocols of the National Health and Nutrition Examination Survey (NHANES). The National Center for Health Statistics (NCHS) Research Ethics Review Board approved the study protocol (Protocol#2011-17 and #2018-01) on the website of https://www.cdc.gov/nchs/nhanes/irba98.htm.

Authors’ contributions

Yuwei He, Yuguang Li and Yining Liu performed the experiment, conducted.the data analysis and drafted the manuscript. Yixin Zhao, Fangqi Li, Xinqiao Chen and Jia Song contributed to the literature search and data anlysis. Jiuwei Cui, Xiangliang Liu and Wei Ji designed the study, revised the manuscript, perform the analysis with constructive discussions. All authors critically revised of the manuscript for important intellectual content.

Funding

This work was supported by Doctor of excellence program, The First Hospital of Jilin University (JDYY-DEP-2022024).

Declaration of Interest

The authors declare no conflict of interest.

Declaration of the financial disclosure

Non declared.

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Elucidating the Link Between Hypovitaminosis D and Sarcopenia: New Insights into Mechanisms and Threshold from the Evidence of NHANES 2011-2018

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Introduction

Methods

Study population

Outcome variables

Hematological indicators

Variables

Statistical analysis

Results

Participant Distribution

Baseline Characterization

Association of blood vitamin D and sarcopenia/low muscle mass

Restricted cubic spline (RCS) plots

Mediation analysis

Discussion

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1