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

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.

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, 12, 13, 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 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).

Study first author	Country	Year	Journal	Study population	Sex	Sample size	Range age, or mean age	Assess vitamin D	Assess vo2 max	Correlation r	Adjusted
Al Asoom	KSA	2016	Journal of Taibah University Medical Sciences	Young Saudi females	Female	87	20.78	Liquid chromatography (HPLC)	Bruce treadmill protocol	0.259	Adjusted but Not reported
Mowry	USA	2009	J Am Osteopath Assoc	Adolescent girls and young women	Female	59	16_24	Chemiluminescent	Maximal-graded treadmill test	0.36	Not reported
Chang-Duk	Korea	2013	Med Sci Sports Exerce	Young and healthy college male student	Male	799	24.2; 24.2; 23.7	LIAISON 25(OH) vitamin D total assay (CLIA)	Maximal graded exercise test on a treadmill	0.4	Un adjusted
Valtuen˜a	Europe	2013	Qjm	Random sample of 3000 European adolescents	Male	470	12.5–17.5	ELISA	20 m shuttle run test	0.108	Not reported
Valtuen˜a	Europe	2013	Qjm	Random sample of 3000 European adolescents	Female	536	12.5–17.5	ELISA	20 m shuttle run test	0.022	Not reported
Ellis	USA	2014	Endocrine	Healthy women	Female	67	60–74	Immunoassay	Modified bruce graded treadmill protocol	0.344	Partial adjusted for percent fat
Serra	USA	2016	Hormone and Metabolic Research	Overweight and obese sedentary women with history of GDM	Female	51	38–65	By RIA (DiaSorin, Still water MN)	Graded exercise test on a treadmill	0.26	Not reported
Koundourakis	Greece	2014	PLoS One	Members of two teams and one Football team	Male	67	25.6	DiaSorin25 hydroxy vitamin D	Motorizetreadmill using an automated gas-analysis system	0.436	Not reported
Dong	USA	2010	J Exerc Nutrition Biochem	Adolescents from high schools,	Male and female	559	14–18	Liquid chromatography−mass spectroscopy	Multi stage treadmill test	0.1	For age, sex, race, sexual maturation, height, and season
Waschbisch	Switzerland	2012	Eur Neurol	Patients with relapsing–remitting disease	Male and female	42	39; 36	ELISA	Bicycle ergometer	0.4	Not reported
Park	Korea	2013	J Exerc Nutrition Biochem	Male students in the university of S in Jangan-gu, Suwon, Gyeonggi	Male	593	24.2; 24.2; 23.7	DiaSorin LIAISON automated analyzer	Bruce treadmill protocol	0.326	Not reported
Sun	Japan	2014	Nutrients	One hundred and seven Japanese men	Male	107	40–79	Immunosorbent assay	Graded exercise test on cycle ergometer	0.34	Age, season, VFA
Sun	Japan	2015	J Atheroscler Thromb	136 healthy Japanese men	Male	136	20–79	Semi-automated device	Cycle ergometer	0.361	Age adjusted
Ardestani	USA	2011	Am J Cardiol	Adults free of overt cardiovascular and metabolic disease	Male and female	200	40	ELISA immunoassay protocol	Modified Balke treadmill test	0.29	Not reported
. Fitzgerald	USA	2014	Journal of Strength and Conditioning Research	Fifty-seven Caucasian male competitive ice hockey players	Male	52	18–23	Liquid chromatography- spectrometry	During a skate treadmill GXT.	0.052
Saponaro	Italy	2017	Endocrine	Consecutive patients diagnosed with heart failure	Male and female	261	65	HPLC-MS/MS	Electronically braked cycle-ergometer by a ramp protocol	0.16	Un adjusted
Marawan	USA	2018	European Journal of Preventive Cardiology	Adult population of the USA	male and female	1995	20–49	Diasorin 25-hydroxyvitamin D assay.	Using submaximal exercise test protocols.	0.1	Un adjusted
Książek	Poland	2016	Journal of Human Kinetics	43 Polish premier league soccer players	male and female	43	22.7	Electrochemil-uminescence (ECLIA) using the Elecsys system	During exercise testing with increasing loads were determined with a portable system K4 b2	0.02	Un adjusted
Pandey	USA	2018	The American Journal of Medicine	Older Patients with Heart Failure with Preserved Ejection Fraction	Male and female	112	70	Dia Sorin radioimmunoassay	Electronically braked cycle ergometer in the upright position	0.26	Season
Pandey	USA	2018	The American Journal of Medicine	37 healthy age-matched controls	Male and female	37	70	Dia Sorin radioimmunoassay	Electronically braked cycle ergometer in the upright position	0.077	Season

Table 1.

Characteristics of the included observational studies.

First author	Location	Population study	Subjects in/pl.*	Mean age in/pl	Mean bmi baseline in/pl	25(OH)D mean baseline in/pl	25(OH)D mean final in/pl	Duration in week	Dose vitamin D weekly (iu)	Mean change Vo2 max in/pl
Todd	UK	Healthy male and female athlete	22/20	20/20	23.89/22.31	44.49/40.93	81.77/46.33	12	21,000 Oral spray	_0.64/_2
Scholten	USA	Physically active males	14/14	32.8/29.9	23.4 /26.2	67.7/67.7	126.2/72.91	8	28,000Cap	_0.69/_0.29
Scholten	USA	Physically active males	6/6	32.2/30.3	23.1/25.9	87.92/75.66	118.24/79.64	8	28,000Cap	1.52/_0.86
Carrillo	USA	Overweight and obese adults during resistance training	10/13	26.2/26	30.6/31.9	20.8/18.1	33.4/23.5	12	28,000 CAP	6/5.7
Boxer	USA	Patients with heart failure (HF).	24/23	65.8/66	34.8/31.3	19.1/17.8		24	50,000 CAP	_0.17/_0.68
Singla	India	Adults with (T2DM)performed moderate-intensity aerobic exercise	9/9	41.5/39.3	28.1/27.9	9.8/10.9	38/10	12	60,000 CAP	_0.85/_8.63
Karefylakis	Sweden	Over weight/obese men with vitamin D deficiency	17/18	49.8/49.4	31.5/31.2	44.3/44.2	70.5/49.8	24	14,000 Drop	0.4/0.6

Table 2.

Characteristics of included randomized controlled trials.

In/pl.: intervention/placebo.

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.

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 anti-inflammatory 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, 26, 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 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 extra-mitochondrial 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

CVD

cardiovascular disease

CRF

cardiorespiratory fitness

25[OH]D

25-hydroxyvitamin D

UV

ultraviolet

BMI

body mass index

VDR

vitamin D receptor

IOM

Institute of Medicine

IU

international unit