Vitamin D, Muscle Strength and Cardiorespiratory Fitness – An Evidence-based Review

*Amin Mirrafiei, Mahsa Firouzi, Nadia Babaee, Samira Davarzani and Sakineh Shab-Bidar*

## **Abstract**

Recent evidence reported that a higher concentration of 25-hydroxyvitamin D [25[OH] D] has been associated with greater cardiorespiratory fitness [CRF] and muscle strength in both sexes. Low levels of 25[OH]D may be related to hypertrophy of myocardial, high blood pressure, and endothelial dysfunction, which is related to decreased amino acid uptake, prolonged time to peak muscle contraction and relaxation, dysregulation of intracellular Ca2+, muscle weakness, myalgia, impaired neuromuscular function, and hypotonia. Because CRF is defined as a function of maximal cardiac output and maximal arteriovenous oxygen difference, low levels of 25[OH]D may lead to deleterious effects on CRF. Recent findings also indicated vitamin D3 supplementation that leads to an increase in muscle fiber especially type 2, the cross-sectional area of muscle fibers, and improved muscle strength. In this chapter, we will systematically review the observational studies and randomized controlled trials that evaluated the association of vitamin D with CRF and muscle strength.

**Keywords:** vitamin D, 25-hydroxyvitamin D, Vo2 max, fitness, muscle strength

## **1. Introduction**

Vitamin D deficiency has become a major public health issue around the world affecting approximately 1 billion individuals worldwide. Vitamin D has long been known to play a role in the performance of many organs and tissues throughout the human body [1]. A low serum vitamin D level has been linked to an increased risk of diabetes, hypertension, and cardiovascular disease [CVD], as well as obesity, hyperlipidemia, and poor physical fitness, particularly low cardiorespiratory endurance and muscle strength [2, 3]. It has been documented in medical guidelines that vitamin D enhances muscular function in poor vitamin D conditions [4].

Cardiorespiratory fitness [CRF] is a physiologic fitness definition that refers to the circulatory and respiratory systems' ability to deliver oxygen during prolonged physical activity. It is partially determined by several non-modifiable characteristics such as gender, age, and hereditary factors. CRF also has been used to analyze the

association between physical activity and health status in recent years as a mediator [5]. In addition, muscle strength is a marker of the quality of functional performance. A decline in muscle strength leads to physical malfunction and disability in parallel to age and is associated with mobility restriction [6]. It has been debated that greater muscular strength may improve exercise performance by allowing for higher levels of cardiorespiratory stress [7].

A higher quantity of 25-hydroxyvitamin D [25[OH] D] has been linked to increased CRF and muscle strength in both sexes, according to accumulative research. Low amounts of 25[OH]D may have a negative influence on CRF. Furthermore, previous research has found a substantial link between serum vitamin D levels and physical fitness [8, 9]. The current chapter discusses the most recent knowledge about the link between vitamin D status, CRF, and muscle strength.

## **2. What is vitamin D?**

Vitamin D is a fat-soluble component that can be synthesized via sun exposure to the skin. The ultraviolet rays in sunlight make your skin make vitamin D [10]. Of course, the amount of production of this vitamin by your skin depends on various factors. For instance, what season of the year and what time of the day you are exposed to sunlight, is effective in the production of this vitamin by your skin. Note that usually, the sun's rays are less in the winter months. Also, the sun's rays are strongest between 10 am and 3 pm. The amount of cloud cover and air pollution and geographical location also have a significant effect on the production of vitamin D in the skin, as sites near the equator have higher levels of UV radiation. Vitamin D production in the skin is reduced by more than 95% when using sunscreen. To produce the same quantity of vitamin D as someone with white skin, someone with a naturally dark skin tone needs to be exposed to the sun for at least three to five times longer [11–14]. Furthermore, obesity is linked to vitamin D deficiency since there is an inverse relationship between serum 25[OH]D, activated in the liver, and a body mass index [BMI] of more than 30 kg/m2 [15]. The synthesized vitamin D in human skin is called D3, which is also found in salmon, sardine, mackerel, tuna, liver, egg yolk, and fortified foods like milk [16]. Another type of vitamin D, dubbed D2, is abundant in mushrooms [17]. The majority of the body's tissues and cells include the vitamin D receptor [VDR]. Numerous biological processes are influenced by 1,25[OH]2D, the active form of vitamin D that is transformed in the kidney, including the inhibition of cellular proliferation, induction of terminal differentiation, inhibition of angiogenesis, stimulation of insulin production, and inhibition of renin production [18]. Up to 200 genes that are thought to be involved in many of the health-related functions of vitamin D may be controlled by the local synthesis of 1,25[OH]2D [18]. The Institute of Medicine [IOM] recommends that vitamin D deficiency is defined as serum 25[OH]D concentration < 50 nmol/L and vitamin D sufficiency as 50 nmol/L, and optimal level is >75 nmol/L [1].

#### **2.1 Relationship with cardiorespiratory fitness**

Besides many biochemical and physiological properties of active vitamin D in the body, this vitamin can have huge effects on CRF, as recent research revealed a significant association between serum 25[OH]D levels and CRF. In a recent systematic review and meta-analysis [To find the answers to a particular topic, a systematic

### *Vitamin D, Muscle Strength and Cardiorespiratory Fitness – An Evidence-based Review DOI: http://dx.doi.org/10.5772/intechopen.106849*

review makes an effort to compile all accessible empirical studies. The statistical method of assessing and combining data from numerous related studies is called a meta-analysis [19].], our team that included both observational and interventional studies [up to October 2018, **Tables 1** and **2**] showed that in observational studies, serum 25[OH]D is directly related to CRF, as shown in **Figure 1,** with a significant increase in CRF in line with an increased 25[OH]D level [+0.65]. Furthermore, it was found through reanalysis of five clinical trials that vitamin D3 treatment raised CRF in comparison to placebo (**Figure 2**).

VO2 max, one of the most often used tests to quantify endurance capacity, is used to assess cardiorespiratory fitness. VO2 max stands for the maximal capacity to transport and utilize oxygen during exercise performed at increasing intensities. In other words, the maximum rate of oxygen consumption that may be achieved during intense activity is known as VO2 max [20]. It is used to describe the intensity of the aerobic process and displays the level of physical preparedness of an athlete. VO2 max is typically evaluated in laboratories on treadmills, cycling ergometers, or rowing ergometers by gradually increasing intensity over some time of more than 5 minutes [21]. Cardiac output, arterial oxygen content, the blood supply to active muscles, and oxygen use by muscles all contribute to VO2 max [3]. Through the action of vitamin D receptors, low serum 25[OH]D levels can result in cardiac hypertrophy, increased blood pressure, and endothelial dysfunction. It can, therefore, affect VO2 max by lowering cardiac output and raising peripheral vascular resistance [22]. Exercise raises VO2 max by boosting cardiac output. Those with modest levels of physical exercise may benefit more from vitamin D in terms of cardiac remodeling and VO2 max [23]. Furthermore, vitamin D insufficiency and physical inactivity can promote muscular atrophy and change the muscle fiber type [24].

The mechanisms behind Vitamin D's beneficial effects are the increased numbers of fast-twitch muscle fibers [IIa] in place of another type of fast-twitch muscle fibers [IIb], modification of maximum heart rate and stroke volume. In addition, because low levels of 25[OH]D affect bone mineralization and muscle function, they are linked to a decline in physical fitness. Vitamin D may have a function in lowering cortisol by preventing specific enzymes from working. High levels of cortisol boost antiinflammatory and calcification effects. By causing the dilatation of blood vessels, a decreased cortisol level frequently worsens blood pressure. By lowering blood cortisol levels, vitamin D aids in enhancing physical performance and lowering cardiovascular risk factors. Additionally, inflammation is decreased and interleukin-10 is produced by vitamin D. Thus, the probable mechanisms that define the effect of this vitamin on maximum oxygen intake are expanded airways, antimicrobial peptides, and greater air entry into the lungs by vitamin D [25–27].

### **2.2 Relationship with muscle strength**

Skeletal muscle helps organ systems maintain homeostasis. Muscle is malleable, adapting to physical activity, load, injury, sickness, and aging. The reduction of skeletal muscular strength, muscle mass, and physical performance as people get older has been linked to falls and fractures in elderly people, yet it is still a generally undetected disorder [28].

The presence of vitamin D3 metabolizing enzymes in skeletal muscle raises the possibility that vitamin D3 levels are locally regulated in this extrarenal tissue [28]. Total fat mass, lean mass, and balance are all physical fitness indices that are commonly influenced by vitamin D levels. Studies have demonstrated that severe


### *Vitamin D Deficiency - New Insights*


*Vitamin D, Muscle Strength and Cardiorespiratory Fitness – An Evidence-based Review DOI: http://dx.doi.org/10.5772/intechopen.106849*

**Table 1.**

*Characteristics of the included observational studies.*

**142**


*Vitamin D, Muscle Strength and Cardiorespiratory Fitness – An Evidence-based Review DOI: http://dx.doi.org/10.5772/intechopen.106849*

**Table 2.**

 *Characteristics of included randomized controlled trials.*

#### **Figure 1.**

*Forest plot of correlation between 25(OH) D and CRF.*

#### **Figure 2.**

*Forest plot for the effects of vitamin D3 supplementation on CRF.*

## *Vitamin D, Muscle Strength and Cardiorespiratory Fitness – An Evidence-based Review DOI: http://dx.doi.org/10.5772/intechopen.106849*

vitamin D deprivation can result in physiologic, histological, and electrophysiological alterations, supporting the role of vitamin D in maintaining muscle health. A strong resistance exercise's ability to restore strength may be predicted by a higher 25[OH] D concentration [29]. In younger adults, supplementing with vitamin D [4000 IU for 5 days] can increase muscle strength. However, it is important to note that the methodologies, dosages, participant characteristics, length of interventions, and findings of the research on the impact of vitamin D supplementation varied [30]. Both vitamin D insufficiency and vitamin D receptor [VDR] malfunction appear to have detrimental effects on the homeostasis of skeletal muscles. However, overexpression of VDR appears to have negative effects on skeletal muscle as well [31]. Although it has been demonstrated that vitamin D is also involved in the cellular metabolism of skeletal muscles, the precise molecular pathways that vitamin D activates in muscles are yet unknown. Vitamin D, through the activity of its active metabolite, 1,25[OH]2 D3, is crucial for normal calcium and phosphorus balance and the maintenance of skeletal health. The homeostasis of calcium involves vitamin D. Vitamin D controls the gut's absorption of calcium and maintains the levels of calcium and phosphate in the serum. It has been demonstrated to be crucial in controlling skeletal muscle tone and contraction [32]. The most recent study showed that treatment with 1,25[OH]2 D3 increased the oxygen consumption rate of skeletal muscle cells, demonstrating the role of vitamin D in the regulation of mitochondrial oxygen consumption and dynamics. An increase in respiration was associated with the production of ATP, suggesting that vitamin D improves the mitochondrial activity in muscle [33]. The hypothesis is that vitamin D can affect the blood supply to skeletal muscles and their ability to use oxygen due to the presence of the VDR in cardiac muscle, vascular tissue, and skeletal muscle. However, direct 1,25[OH]2 D3 administration of isolated mitochondria failed to increase oxygen consumption rate, indicating that 1,25[OH]2 D3's effects on oxygen consumption rate may be dependent on VDR or other extramitochondrial metabolic processes. People with lower vitamin D concentration get more benefits from vitamin D supplementation and more improvement in muscle strength [31, 33].

As a complementary basis to further strengthen the possible effect of vitamin D on muscle strength, numerous in vivo and in vitro experimental studies have demonstrated physiologic, histological, and electrophysiological alterations of skeletal muscle in severe vitamin D insufficiency, indicating a possible role for vitamin D in maintaining healthy muscles. As stated previously, it seems that the binding of vitamin D to its receptors promotes the absorption of inorganic phosphate needed for the production of energy-rich phosphate compounds [ATP] required for muscle cell contractility [34]. Additionally, high parathyroid hormone [PTH] has been proven to accelerate the breakdown of muscle proteins, and low vitamin D levels have been linked to secondary hyperparathyroidism [35]. Studies on muscle biopsies and electrophysiological tests further show the role of vitamin D in muscle cell activity. Treatment with vitamin D has been shown to reverse these changes, including an increased number of type II muscle fibers. Vitamin D deficiency has been linked to the atrophy of type II muscle fibers as well as nonspecific histological abnormalities like fatty infiltration, interstitial fibrosis, and sarcolemmal nuclear proliferation, all linking to lower muscle strength. Electrophysiological studies have connected low vitamin D levels to abnormal patterns, such as reduced motor unit potential length and amplitude, greater percentages of polyphasicity, and no concomitant denervation evidence [36].

## **3. Conclusion**

By calculating VO2 max, serum 25[OH]D is directly correlated with CRF. The most recent findings suggest that vitamin D supplementation may result in higher CRF improvements in men and younger adults. However, since science is constantly evolving and changing, and many facts are misunderstood or unknown, these findings might be modified over time. Furthermore, multiple lines of research have indicated that vitamin D supplementation has a positive impact on aged people's muscle function. An effect, however, is not always there as more studies demonstrating the absence of an effect than studies demonstrating positive benefits have been published. The lack of clear explanations for the discrepant findings is due to the fact that studies showing positive benefits from those showing no effect of an increased vitamin D level do not appear to share many common traits.

## **Conflict of interest**

The authors declare no conflict of interest.

## **Acronyms and abbreviations**


## **Author details**

Amin Mirrafiei, Mahsa Firouzi, Nadia Babaee, Samira Davarzani and Sakineh Shab-Bidar\* Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences [TUMS], Tehran, Iran

\*Address all correspondence to: s\_shabbidar@tums.ac.ir

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Vitamin D, Muscle Strength and Cardiorespiratory Fitness – An Evidence-based Review DOI: http://dx.doi.org/10.5772/intechopen.106849*

## **References**

[1] Greer FR. Defining vitamin D deficiency in children: Beyond 25-OH vitamin D serum concentrations. Pediatrics. 2009;**124**(5):1471

[2] Muscogiuri G et al. Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives. Nutrition, Metabolism and Cardiovascular Diseases. 2012;**22**(2):81-87

[3] Ardestani A et al. Relation of vitamin D level to maximal oxygen uptake in adults. The American Journal of Cardiology. 2011;**107**(8):1246-1249

[4] Owens DJ et al. "A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy." American Journal of Physiology-Endocrinology and Metabolism. 2015

[5] Blair SN et al. Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA. 1996;**276**(3):205-210

[6] Lauretani F et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. Journal of Applied Physiology. 2003;**95**(5):1851-1860

[7] Zoeller RF Jr, Riechman SE, Dabayebeh IM, Goss FL, Robertson RJ, Jacobs PL. Relation between muscular strength and cardiorespiratory fitness in people with thoracic-level paraplegia. Archives of Physical Medicine and Rehabilitation. 2005;**86**(7):1441-1446

[8] Bischoff HA et al. Muscle strength in the elderly: Its relation to vitamin D metabolites. Archives of Physical Medicine and Rehabilitation. 1999;**80**(1):54-58

[9] Eslami O, Shidfar F, Akbari-Fakhrabadi M. Vitamin D and cardiorespiratory fitness in the general population: A systematic review. International Journal for Vitamin and Nutrition Research. 2017;**87**(5-6):330-341

[10] Nair R, Maseeh A. Vitamin D: The "sunshine" vitamin. Journal of Pharmacology and Pharmacotherapeutics. 2012;**3**(2):118-126

[11] Holick MF. Environmental factors that influence the cutaneous production of vitamin D. The American Journal of Clinical Nutrition. 1995;**61**(3):638S-645S

[12] Diehl JW, Chiu MW. Effects of ambient sunlight and photoprotection on vitamin D status. Dermatologic Therapy. 2010;**23**(1):48-60

[13] Youl PH, Janda M, Kimlin M. Vitamin D and sun protection: The impact of mixed public health messages in Australia. International Journal of Cancer. 2009;**124**(8):1963-1970

[14] Libon F, Cavalier E, Nikkels A. Skin color is relevant to vitamin D synthesis. Dermatology. 2013;**227**(3):250-254

[15] Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. The American Journal of Clinical Nutrition. 2000;**72**(3):690-693

[16] Carlberg C. Nutrigenomics of vitamin D. Nutrients. 2019;**11**(3):676

[17] Jones K. Maitake: A potent medicinal food. Alternative and Complementary Therapies. 1998;**4**(6):420-429

[18] Robinson S, Canavan M, O'Donnell M, Mulkerrin E. Vitamin D supplementation-clarity required regarding treatment regimens and target plasma levels. QJM: An International Journal of Medicine. 2014;**107**(4):327-329

[19] Garg AX, Hackam D, Tonelli M. Systematic review and meta-analysis: When one study is just not enough. Clinical Journal of the American Society of Nephrology. 2008;**3**(1):253-260

[20] Hawkins MN, Raven PB, Snell PG, Stray-Gundersen J, Levine BD. Maximal oxygen uptake as a parametric measure of cardiorespiratory capacity. Medicine and Science in Sports and Exercise. 2007;**39**(1):103-107

[21] Beltz NM, Gibson AL, Janot JM, Kravitz L, Mermier CM, Dalleck LC. Graded exercise testing protocols for the determination of VO2max: Historical perspectives, progress, and future considerations. Journal of Sports Medicine (Hindawi Publ Corp). 2016;**2016**:3968393

[22] Min B. Effects of vitamin D on blood pressure and endothelial function. The Korean Journal of Physiology & Pharmacology. 2013;**17**(5):385

[23] D'Silva A et al. Cardiovascular remodeling experienced by real-world, unsupervised, young novice marathon runners. Frontiers in Physiology. 2020;**11**:232

[24] Moreira-Pfrimer LD, Pedrosa MA, Teixeira L, Lazaretti-Castro M. Treatment of vitamin D deficiency increases lower limb muscle strength in institutionalized older people independently of regular physical activity: A randomized doubleblind controlled trial. Annals of Nutrition and Metabolism. 2009;**54**(4):291-300

[25] Girgis CM, Clifton-Bligh RJ, Hamrick MW, Holick MF, Gunton JE. The roles of vitamin D in skeletal muscle: Form, function, and metabolism. Endocrine Reviews. 2013;**34**(1):33-83

[26] Marawan A, Kurbanova N, Qayyum R. Association between serum vitamin D levels and cardiorespiratory fitness in the adult population of the USA. European Journal of Preventive Cardiology. 2019;**26**(7):750-755

[27] Karefylakis C, Särnblad S, Ariander A, Ehlersson G, Rask E, Rask P. Effect of vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men—a randomized controlled trial. Endocrine. 2018;**61**(3):388-397

[28] Distefano G, Goodpaster BH. Effects of exercise and aging on skeletal muscle. Cold Spring Harbor Perspectives in Medicine. 2018;**8**(3)

[29] Polly P, Tan TC. The role of vitamin D in skeletal and cardiac muscle function. Frontiers in Physiology. 2014;**5**:145

[30] Hossein-nezhad A, Holick MF. Vitamin D for health: A global perspective. Mayo Clinic Proceedings (Elsevier). Jul 2013;**88**(7):720-755. DOI: 10.1016/j.mayocp.2013.05.011

[31] Dzik KP, Kaczor JJ. Mechanisms of vitamin D on skeletal muscle function: Oxidative stress, energy metabolism and anabolic state. European Journal of Applied Physiology. 2019;**119**(4):825-839

[32] Gil Á, Plaza-Diaz J, Mesa MD. Vitamin D: classic and novel actions. Annals of Nutrition and Metabolism. 2018;**72**(2):87-95

[33] Latham CM et al. Vitamin D promotes skeletal muscle regeneration and mitochondrial health. Frontiers in Physiology. 2021;**12**:660498

*Vitamin D, Muscle Strength and Cardiorespiratory Fitness – An Evidence-based Review DOI: http://dx.doi.org/10.5772/intechopen.106849*

[34] Mosekilde L. Vitamin D and the elderly. Clinical Endocrinology. 2005;**62**(3):265-281

[35] Ritz E, Boland R, Kreusser W. Effects of vitamin D and parathyroid hormone on muscle: Potential role in uremic myopathy. The American Journal of Clinical Nutrition. 1980;**33**(7):1522-1529

[36] Rejnmark L. Effects of vitamin D on muscle function and performance: A review of evidence from randomized controlled trials. Therapeutic Advances in Chronic Disease. 2011;**2**(1):25-37

## **Chapter 11**
