Role of Vitamin D in Athletes and Their Performance: Current Concepts and New Trends

are currently experiencing a vitamin D (VITD) de ciency pandemic across the world. Athletes have the same predisposition to low levels of vitamin D, the majority of its concentrations being below 20 ng/mL in a wide range of sports, especially in the winter months. Vitamin D is important in bone health, but recent research also points out its essential role in extraskeletal functions, including skeletal muscle growth, immune and cardiopulmonary functions and in ammatory modulation, which in uence athletic performance. Vitamin D can also interact with extraskeletal tissues to modulate injury recovery and also in uence the risk of infection. The data presented in this paper has triggered investigations in relation to the importance of maintaining adequate levels of vitamin D and to the possible positive in uence supplementation has on immune and musculoskeletal functions in athletes, bene ting their performance and preventing future injuries. The objective of this review is to describe the latest research conducted on the epidemiology of vitamin D de ciency and its e ects on sports performance and musculoskeletal health. Keywords:vitamin D; athletic performance; 25(OH)D; supplementation; de ciency; athlete 1. Introduction Over the past decade, interest in research in relation to vitamin D (VITD) has been growing exponentially, partly due to the increased prevalence of its de ciency in the population and the association between the de ciency of VITD and a wide range of diseases [1–3]. The importance and versatility of vitamin D in the organism is becoming increasingly evident. VITD plays an active role in immune function, protein synthesis,

vitamin D (VITD) has been growing exponentially, partly due to the increased prevalence of its de ciency in the population and the association between the de ciency of VITD and a wide range of diseases [1–3]. The importance and versatility of vitamin D in the organism is becoming increasingly evident. VITD plays an active role in immune function, protein synthesis, muscle function, cardiovascular function, in ammatory response, cell growth and musculoskeletal regulation [2–5]. In relation to vitamin D and its role in athletes, an important eld of research on its in uence on bone balance, muscle resistance and athletic performance is currently underway [6–10]. A priori, athletes might seem to have su cient levels of VITD. However, the latest research shows that this assumption is wrong. In the last decade, the scienti c community has conducted studies on VITD levels in various groups of athletes including runners, basketball players, jockeys, gymnasts and even dancers, showing that these levels in athletes are comparable to those of the general population. However, recent publications show that these levels will considerably depend on geographical location, and on the type of sport, whether it is indoor or outdoor, etc. A line of special interest is the in uence of VITD de ciency on athlete morbidity [8–12]. The de ciency of this vitamin is generally widespread in the athletic population with an increase in morbidities associated with it, and the appearance of osteomalacia and osteoporosis [10–12]. Given the high prevalence of its de ciency and its negative Nutrients2020,12, 579; doi:10.3390 /nu12020579 /journal/nutrients

Nutrients2020,12, 579 2 of 17 potential on morbidity, the possible determination of VITD levels in athletes is considered part of the screening routine [7,10]. In relation to VITD supplementation in athletes with de ciency, several studies have shown that this increases muscle strength. Higher serum levels of vitamin D are associated with reduced injury rates and better sports performance. It is important to correctly identify people with vitamin D de ciency who need supplements to help optimize their performance and prevent future injuries [1,10,11]. Finally, it seems that there is a paradoxical relationship between ethnicity and VITD concentration. As an example, white-skinned subjects generally have lower levels of VITD but higher bone mineral density and decreased risk of fracture [6,12]. This review was prepared by searching available medical and scienti c literature from PubMed, EMBASE and Cochrane Library. Nutrition, endocrinology, biochemistry, orthopedics, sports and toxicology journals, among others, were analyzed as well as by reviewing several books, conference proceedings, government publications. 2. Synthesis and Metabolism of Vitamin D On the one hand, VITD is a micronutrient, since its de ciency can be treated by supplementation, and it is also a prohormone, seeing that its precursors are transformed into active metabolites. It comes in two biologically inactive forms, cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) [2,4,13]. Vitamin D is mostly synthesized in the skin. Cholecalciferol, or vitamin D3, is the primary source of endogenous VITD and is formed through the interaction of ultraviolet B (UVB) radiation after sun exposure with 7-dehydrocholesterol, which is stored inside the plasma membrane of every skin cell. Ergocalciferol, or vitamin D2, represents a small percentage and has its origin in exogenous dietary intake [14–16]. Vitamin D is di cult to obtain through diet because very few foodstu s contain the vitamin naturally, the exceptions being the liver of fatty sh, mushrooms and eggs, among others. Supplementation or forti cation with vitamin D2 and D3, such as milk and other dairy products, cereals, etc., currently implies an exogenous supply [14,16]. The VITD obtained from sun exposure, food or supplementation is biologically inert and must undergo two hydroxylations

foodstu s contain the vitamin naturally, the exceptions being the liver of fatty sh, mushrooms and eggs, among others. Supplementation or forti cation with vitamin D2 and D3, such as milk and other dairy products, cereals, etc., currently implies an exogenous supply [14,16]. The VITD obtained from sun exposure, food or supplementation is biologically inert and must undergo two hydroxylations in the organism to become active, the rst being performed in the liver by the CYP2R1 enzyme where it is converted to 25-hydroxyvitamin D3 (calcidiol). The second being performed in the kidney and other tissues by the CYP27B1 enzyme to form 1.25-dihydroxyvitamin D3 (calcitriol) that is the biologically active form. The active metabolite of vitamin D is transported through the bloodstream by the binding protein vitamin D (BPD), reaching numerous skeletal and extraskeletal target organs. In fact, the CYP27B1 enzyme is present in many target cells in the body to allow local synthesis of calcitriol. In addition, vitamin D receptors (VDR) are present in most tissues [15–18]. The metabolism of VITD and its functions in di erent systems of the human body are shown in Figure14].

Nutrients2020,12, 579 3 of 17Nutrients 2019, 11, x FOR PEER REVIEW 3 of 17 Figure 1. Vitamin D metabolism and its action in the body. Source of Figure 1: Mulligan, M.L.; Felton, S.K.; Riek, A.E.; Bernal - Mizrachi, C. Implications of vitamin D deficiency in pregnancy and lactation. Am J Obstet Gynecol 2010, 202 (5), 429 [14]. PTH (Parathyroid Hormone). DPB (Vitamin D-Binding Protein) DM (Diabetes Mellitus) SGA (Small for Gestational Age). 3. Vitamin D Mechanism of Action The functions of VITD are performed in the body via two pathways through endocrine and autocrine mechanisms [19–23]. The endocrine mechanism is the most studied and works by increasing intestinal calcium absorption and osteoclastic activity. Vitamin D is essential in bone growth, density and remodeling [13,18,21–23]. When vitamin D levels decrease below normal limits, PTH increases bone resorption to meet the body’s demands for calcium. This means that low levels of VITD lead to an increase in bone turnover with an added risk of bone injury such as stress fractures, which are very common in athletes. The second mechanism of action of vitamin D involves an autocrine pathway. Although it is not so well known, this pathway is essential since it hosts many of the organism’s key metabolic processes, such as signaling processes, expression and genetic response, hormone protein synthesis, Figure 1. Vitamin D metabolism and its action in the body. Source of Figure: Mulligan, M.L.; Felton, S.K.; Riek, A.E.; Bernal - Mizrachi, C. Implications of vitamin D de ciency in pregnancy and lactation. Am J Obstet Gynecol 2010, 202 (5), 429 [14]. PTH (Parathyroid Hormone). DPB (Vitamin D-Binding Protein) DM (Diabetes Mellitus) SGA (Small for Gestational Age). 3. Vitamin D Mechanism of Action The functions of VITD are performed in the body via two pathways through endocrine and autocrine mechanisms [19–23]. The endocrine mechanism is the most studied and works by increasing intestinal calcium absorption and osteoclastic activity. Vitamin D is essential in bone growth, density and remodeling [13,18,21–23]. When vitamin D levels decrease below normal limits, PTH increases bone resorption to meet the body's demands for calcium. This means that

body via two pathways through endocrine and autocrine mechanisms [19–23]. The endocrine mechanism is the most studied and works by increasing intestinal calcium absorption and osteoclastic activity. Vitamin D is essential in bone growth, density and remodeling [13,18,21–23]. When vitamin D levels decrease below normal limits, PTH increases bone resorption to meet the body's demands for calcium. This means that low levels of VITD lead to an increase in bone turnover with an added risk of bone injury such as stress fractures, which are very common in athletes.

Nutrients2020,12, 579 4 of 17 The second mechanism of action of vitamin D involves an autocrine pathway. Although it is not so well known, this pathway is essential since it hosts many of the organism's key metabolic processes, such as signaling processes, expression and genetic response, hormone protein synthesis, immune/in ammatory response, turnover and cell synthesis. Without VITD, the ability to e ectively respond to physiological and pathological symptoms would be totally altered [19–22]. This vitamin works as a modulator of up to 2000 genes involved in cell growth, immune function and protein synthesis [15,21,23]. The autocrine pathway seems to be the most important in relation to the action of vitamin D on skeletal muscle function. Targets for the VITD receptor have been identi ed in almost every body tissue. VDR regulates expression in hundreds of genes that perform essential bodily functions. The discovery of VDR in muscle suggests the importance of the role of VITD in muscle tissue [19–23]. At present, the existing theory is that an adequate concentration of vitamin D in the blood is necessary to optimize the function of genomics [9]. This role as a genetic modulator explains how vitamin D can a ect a variety of physiological functions, such as bone health, muscle function, in ammation and immunity, all important for health, training and performance [19,21]. In the article published by Owens and collaborators in 2016 [4], there is an excellent schematic representation in which the above can be observed [4]. 4. Prevalence of De ciency and Insu ciency of Vitamin D in Athletes Not only is it estimated that 1 billion people in the world currently have VITD de ciency, but the progressive increase in its prevalence worldwide is also worrying [5,9,24–28]. Most articles evidence that VITD de ciency is widespread across the world and at prevalence rates that meet the criteria of a pandemic (de nition of a pandemic: “an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually a ecting a large number of people”) [5,14,25]. However other authors questioned this sentence [28]. VITD de ciency is

evidence that VITD de ciency is widespread across the world and at prevalence rates that meet the criteria of a pandemic (de nition of a pandemic: “an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually a ecting a large number of people”) [5,14,25]. However other authors questioned this sentence [28]. VITD de ciency is a frequent nding among the American population, so much so that 36% to 57% of adults are de cient [27–29]. This de ciency is also common in Europe mostly countries in Northern European latitudes (>35 N) such as the UK, Ireland, Denmark, France, Germany, etc. [5,25,29]. A similar prevalence has been found even in areas where there is greater sun exposure, such as Australia, the USA and Saudi Arabia [8,27–29]. In Canada, 30–50% of children and adults have VITD de ciency. Similar data has been found in other countries, see Africa, New Zealand, Brazil, etc., evidencing a high risk of VITD de ciency in both adults and children [24,25,27,29]. The main factors for VITD de ciency are cultural and environmental in uences. The major cause for the VITD de ciency pandemic is the lack of awareness of the population that sun exposure is the main source of vitamin D. In relation to food sources of VITD, it is di cult to obtain vitamin D through the diet because very few foods naturally contain the vitamin, exceptions being the liver of fatty sh such as salmon, sardines, herring and red meat. Actually, diet source includes forti ed foods such as milk, fat spreads and cereals. Due to the critical role played by exposure to sunlight and, in particular, to ultraviolet radiation in the synthesis of VITD, any factor that alters this mechanism will contribute to VITD de ciency, such as the decrease of UVB radiation reaching the earth's surface, the use of sunscreens, melanin that diminishes the e ectiveness of sun in producing VITD, polluting atmospheric particles, latitude, weather, lifestyles, etc. [8,9,12,19,22,24,25,29]. In addition, numerous endogenous factors can alter the production of vitamin D and can induce its de ciency, such

mechanism will contribute to VITD de ciency, such as the decrease of UVB radiation reaching the earth's surface, the use of sunscreens, melanin that diminishes the e ectiveness of sun in producing VITD, polluting atmospheric particles, latitude, weather, lifestyles, etc. [8,9,12,19,22,24,25,29]. In addition, numerous endogenous factors can alter the production of vitamin D and can induce its de ciency, such as its altered metabolism, malabsorption or insu cient intake in one's diet [24,25,29]. Current strategies in Public Health include dietary supplementation with VITD and education of young children and adolescents. Such initiatives have an important e ect on the decrease in the prevalence of developmental problems such as rickets and stunting [2,3,5,8,9]. Other strategies support no need to perform screening everyone for the VITD status. It is more cost-e ective to increase food forti cation with VITD [29]. However, symptoms of VITD de ciency in adults, osteoporosis, osteomalacia and immune de ciencies are ignored in most cases. Patients with VITD de ciency have

Nutrients2020,12, 579 5 of 17 musculoskeletal pains that are often misdiagnosed as bromyalgia, chronic fatigue syndrome and myositis, among others [30–37]. In relation to athletes, VITD de ciency within the global athletic population also follows the same patterns [7,10,12,30–37]. When VITD levels in professional athletes are analyzed, we observe that they are all a ected in a similar way. The di erent studies present the following results: among basketball professionals, 32% of the athletes were found to be de cient and 47% had VITD insu ciency. Among National American Football League players, 26% had VITD de ciency and 42% to 80% showed levels of insu ciency. Of Liverpool's professional football players, 36% showed de ciency or insu ciency [30–36]. De ciencies or insu ciencies have been found in most dancers, swimmers, volleyball players, taekwondo ghters, jockeys, runners, weightlifters, etc. [31–37]. Furthermore, multiple studies have shown that dark-skinned athletes have a higher risk of su ering from secondary alterations due to VITD de ciency [26,28,34,35]. One study showed that athletes with high concentrations of melanin in their skin need up to 10 times longer exposure to ultraviolet (UVB) radiation to generate the same reserves of VITD as light-skinned athletes. A study by Mehran et al. on professional hockey players in which vitamin D de ciency was 0% and insu ciency only appeared as 13% should be noted. The authors attributed this low frequency to race, since 96.2% of the players were Caucasians [34,37]. In relation to the degree of solar exposure and athleticism, the distance to the equator, season and weather will dictate the source of solar VITD. The production of VITD from the solar source will obviously be in uenced by hours of sunshine, pollution, sun block, skin pigment, age, etc. During the summer months and/or countries with more hours of sunshine, UVB radiation from the sun can be absorbed in su cient amounts to synthesize VITD [4,6,19,32]. However, during the winter months, the angle of the sun prevents UVB radiation from reaching latitudes above 35–37 degrees. When analyzing levels of VITD in athletes, it should be taken into account

etc. During the summer months and/or countries with more hours of sunshine, UVB radiation from the sun can be absorbed in su cient amounts to synthesize VITD [4,6,19,32]. However, during the winter months, the angle of the sun prevents UVB radiation from reaching latitudes above 35–37 degrees. When analyzing levels of VITD in athletes, it should be taken into account that these can vary according to the season, place of training, type of sport and skin color [4,6,30,35]. According to some authors, the levels of vitamin D are generally lower in the winter months [30, 31,33,34]. However, suboptimal vitamin D levels occur even in sunny countries near the equator when the sun is avoided or the skin is protected. Despite all the factors mentioned above, a high prevalence of vitamin D de ciency has been documented in athletes in both outdoor and indoor sports [3,6,25,35–37]. A recent meta-analysis that groups together 23 studies composed of 2313 athletes found that 56% had insu cient levels of vitamin D [23]. Koundourakis et al. [11,12] showed that professional Greek football players who trained at a latitude of 35.9 did not have insu cient levels of vitamin D. Almost identical levels were reported in players of the National Football League, in elite gymnasts in Australia and in young Hawaiian skaters and a variety of other athletes around the world. These ndings were observed regardless of sun exposure. In a recent study conducted in Israel at a favorable latitude (31.8 N) for sunshine, 73% of athletes were de cient in vitamin D [1,3,6,25,35,37]. Finally, in relation to dietary recommendations, studies nd that athletes do not come close to meeting these in most countries. One study found that only 5% of college athletes met the US Recommended Dietary Allowance (RDA) [32]. 5. Assessment of Vitamin D Status Determination of 25-OHVITD Status of levels of insu ciency or de ciency of VITD can be de ned by using an indicator to determine the blood level of total 25-hydroxy vitamin D (25-OHVITD). This indicator is currently considered as the most quali ed to show the body store of

Recommended Dietary Allowance (RDA) [32]. 5. Assessment of Vitamin D Status Determination of 25-OHVITD Status of levels of insu ciency or de ciency of VITD can be de ned by using an indicator to determine the blood level of total 25-hydroxy vitamin D (25-OHVITD). This indicator is currently considered as the most quali ed to show the body store of vitamin D [38–40]. The measurement of blood levels of 25-OHVITD will show us the cutaneous production of VITD that is obtained from food and supplements. It should be noted that the plasma average life is approximately 15–20 days and is recognized as a biomarker of exposure. However, it is controversial whether blood levels of 25-OHVITD could be considered as a biomarker of e ect (e.g., relationship

The paper discusses vitamin D's role in athletic performance and health.