204

International Journal of Sport Nutrition and Exercise Metabolism, 2008, 18, 204-224
2008 Human Kinetics, Inc.
The authors are with the Dept. of Family and Consumer Sciences, University of Wyoming, Laramie,
WY 82071.
Should We Be Concerned About
the Vitamin D Status of Athletes?
Kentz S. Willis, Nikki J. Peterson, and D. Enette Larson-Meyer
A surprisingly high prevalence of vitamin D insufciency and deciency has
recently been reported worldwide. Although very little is known about vitamin D
status among athletes, a few studies suggest that poor vitamin D status is also a
problem in athletic populations. It is well recognized that vitamin D is necessary
for optimal bone health, but emerging evidence is nding that vitamin D deciency
increases the risk of autoimmune diseases and nonskeletal chronic diseases and
can also have a profound effect on human immunity, inammation, and muscle
function (in the elderly). Thus, it is likely that compromised vitamin D status can
affect an athletes overall health and ability to train (i.e., by affecting bone health,
innate immunity, and exercise-related immunity and inammation). Although
further research in this area is needed, it is important that sports nutritionists
assess vitamin D (as well as calcium) intake and make appropriate recommenda-
tions that will help athletes achieve adequate vitamin D status: serum 25(OH)D
of at least 75 or 80 nmol/L. These recommendations can include regular safe sun
exposure (twice a week between the hours of 10 a.m. and 3 p.m. on the arms
and legs for 530 min, depending on season, latitude, and skin pigmentation) or
dietary supplementation with 1,0002,000 IU vitamin D
3
per day. Although this is
signicantly higher than what is currently considered the adequate intake, recent
research demonstrates these levels to be safe and possibly necessary to maintain
adequate 25(OH)D concentrations.
Keywords: exercise, training, health, exercise performance, nutrition, physical
performance
Vitamin D deciency is currently considered an epidemic for all age groups in
the United States (Calvo & Whiting, 2003; Chen et al., 2007; Hanley & Davison,
2005; Holick, 2003; Nesby-ODell et al., 2002) and worldwide (Glerup et al., 2000;
Isaia et al., 2003; Lips, 2007; Zittermann, 2003). It is widely accepted that vitamin
D is necessary for proper bone formation (Holick, 2006c), but emerging evidence
is also nding that vitamin D deciency increases the risk of nonskeletal chronic
diseases including cardiovascular disease, diabetes, hypertension, and certain types
of cancer (Chiu, Chu, Go, & Saad, 2004; Garland et al., 2006; Holick, 2003, 2004),
Vitamin D and Athletes 205
as well as autoimmune disorders such as multiple sclerosis, rheumatoid arthritis,
systemic lupus erythematosus (Kamen et al., 2006), and inammatory bowel disease
(Cantorna, Munsick, Bemiss, & Mahon, 2000). In addition, several recent studies
have found that vitamin D status has a profound effect on human immunity (Can-
nell et al., 2006) and helps control inammation (Cannell et al.; Moore, Piazza,
McCartney, & Lynch, 2005). There is also some thought that low vitamin D status
might be linked to back pain and suboptimal athletic performance (Cannell, 2006).
Despite these wide-ranging health benets, very little is known about vitamin D
status among athletes and tness enthusiasts. Considering the potential for signi-
cant effects on an athletes overall health and ability to train (i.e., by affecting bone
health, innate immune response, and exercise-related immunity and inammation),
this is an area that warrants further research and demands the attention of the ath-
letic community. This article reviews what is known about the vitamin D status of
athletes and whether vitamin D deciency or insufciency is likely to affect the
short- and long-term health and performance of athletes. Current implications for
sports dietitians and areas of future research are also discussed.
Vitamin D Synthesis and Sources
Vitamin D is a unique nutrient in that physiological sufciency can be met entirely
through endogenous synthesis (Holick, 2006a; Hollis, 2005). When the skin is
exposed to ultraviolet B (UVB) radiation (wavelength range of 290315 nm),
the 7-dehydrocholesterol in the plasma membranes of the epidermis and dermis
is converted to precholecalciferol (previtamin D
3
). This previtamin D
3
is quickly
converted to the more thermodynamically stable vitamin D
3
(cholecalciferol) and
moves from the plasma membrane to the dermal capillary bed, pulled into cir-
culation by vitamin-D-binding protein. Once synthesized, vitamin D
3
undergoes
obligate hydroxylations, rst in the liver to 25-hydroxyvitamin D, or 25(OH)D, and
then in the proximal kidney tubules (as well as other extrarenal tissues) to create
the biologically active form, 1,25-dihydroxyvitamin D, or 1,25(OH)
2
D. Because
sunlight is necessary to activate this process, any factor that limits the amount or
quality of sun exposure can compromise vitamin D status. Such factors include the
following (adapted from Webb, 2006; Whiting & Calvo, 2005b):
Aging (impairs synthesis capacity)
Skin pigmentation (melanin absorbs UVB photons)
Regular sunscreen use (SPF 15)
Clothing
Cloud cover, atmospheric pollution
Time of day
Wintertime latitude >35 N or S
This includes the winter season in northern or southern locales distant from the
equator (latitude >~35 N or S; Kimlin, Olds, & Moore, 2007) because the solar
zenith angle during these months is large and UVB photons are absorbed by the
atmosphere and therefore cannot stimulate endogenous synthesis (Kimlin et al.;
Webb, 2006).
206 Willis, Peterson, and Larson-Meyer
Vitamin D can also be obtained in the diet from limited natural and fortied
sources that include fatty sh, fortied milk, margarine, and ready-to-eat cereal
(Table 1). Dietary vitamin D includes vitamin D
3
(cholecalciferol) and vitamin D
2

(ergocalciferol), which is derived from UVB radiation of the plant and yeast sterol
ergosterol. After absorption, dietary vitamin D is transported to the liver and sub-
sequently hydroxylated as previously described. Once it reaches this point, dietary
vitamin D
3
is metabolized essentially the same as endogenously synthesized vitamin
D
3
. Vitamin D
2
, however, appears to be only about 2040% as effective as D
3
at
increasing and maintaining endogenous 25(OH)D concentrations (Armas, Hollis,
& Heaney, 2004; Houghton & Vieth, 2006; Trang et al., 1998).
Assessment of Vitamin D Status
The biologically active form of vitamin D, 1,25(OH)
2
D, is a result of hydroxylation
on the 25th carbon by the kidneys. The active 1,25(OH)
2
D and parathyroid hormone
(PTH) function to maintain intracellular and extracellular calcium concentrations
within a physiologically acceptable range (Holick, 2005; Lips, 2006). Inadequate
vitamin D concentrations result in decreased intestinal absorption of calcium. This
creates a small decrease in serum calcium concentrations that stimulates PTH
secretion. The increase in PTH mobilizes calcium and phosphorus from bone to
restore serum calcium concentrations to normal. The latter effect is a result of
vitamin-D-induced expression of calbindin (an intestinal calcium-binding protein)
Table 1 Dietary Sources of Vitamin D
Food Serving size Vitamin D (IU)
Cod-liver oil
a
1 Tbsp 1,360
Wild salmon
b
3.5 oz 981
Sun-dried shiitake mushrooms
c
1 oz 400500
Canned sardines
a
3.5 oz 270
Farmed salmon
b
3.5 oz 249
Tuna ahi-YT
b
3.5 oz 164
Milk, fortied
a,e
8 oz 100
Orange juice, fortied
a
8 oz 100
Cod
b
3.5 oz 80
Yogurt, fortied
d
46 oz 880
Margarine, fortied
d
1 Tbsp 60
Kraft 2% milk singles (American)
d
1 slice (21 g) 40
Cereal, fortied (10% DV)
d
3/41 cup 40
Egg yolk
a
1 18
a
USDA national nutrient database for standard reference: www.nal.usda.gov/fnic/foodcomp/search.
b
Chen et al., 2007.
c
Holick, 2005.
d
Food-label values.
e
Murphy et al. (2001) found that only 47.7% of
648 samples of milk collected over a 4-year period in New York State were within the acceptable range
for vitamin D (400600 IU/quart). Most milk samples that were out of compliance were underfortied.
Chen, Shao, Heath, and Holick (1993) found that 49% of 173 milk samples collected in the United
States and Canada contained less than 80% of the recommended vitamin D content.
Vitamin D and Athletes 207
and an epithelial calcium-channel protein (Holick, 2005), which increases the
efciency of calcium and phosphorus absorption by active transport across the
intestinal mucosa.
The inactive but major circulating form of the vitamin, 25(OH)D, is used as
the clinical measure of vitamin D status because it provides a more stable and
meaningful measure of vitamin D status than does the biologically active form
(Holick, 2005; Lips, 2004) for several reasons. First, as stated earlier, compromised
vitamin D status will trigger an increase in PTH. The increased PTH concentration
signals the kidney to increase production of 1,25(OH)
2
D. This serves to maintain
normal, or even slightly elevated, 1,25(OH)
2
D concentrations when vitamin D
status is in fact compromised. Second, 1,25(OH)
2
D has a relatively short half-
life (<4 hr; Holick, 1990), and its concentrations are ~1,000 times lower than its
precursor, 25(OH)D. With a reported half-life of 28 weeks (Holick, 2004; Vieth,
1999), 25(OH)D concentrations are much more stable than 1,25(OH)
2
D. Finally,
25(OH)D is also used as a substrate for most extrarenal tissues, which have the
capacity to synthesize 1,25(OH)
2
D for their own use but depend on adequate serum
concentration of 25(OH)D (Whiting & Calvo, 2005b).
Prevalence of Vitamin D Defciency
in the General Population
A surprisingly high prevalence of vitamin D insufciency and deciency (Calvo &
Whiting, 2003), along with the reemergence of pediatric rickets (Weisberg, Scanlon,
Li, & Cogswell, 2004), has recently been reported in the United States and Canada
and is also thought to be an issue worldwide (Calvo, Whiting, & Barton, 2005;
Glerup et al., 2000; Isaia et al., 2003; Lips, 2007; Zittermann, 2003). Although
results from the National Health and Nutrition Examination Survey (NHANES III)
suggest that Americans consume more than the recommended intake of vitamin D
(group mean >280 IU/day; Calvo et al.), many studies indicate that serum 25(OH)D
concentrations are often decient. One study of 165 young adults age 1829 years
living in Boston found that of 36% were vitamin D decient at the end of winter,
with 25(OH)D concentrations 50 nmol/L (Tangpricha, Pearce, Chen, & Holick,
2002). Another study of otherwise healthy individuals (age 1065 years) who had
persistent nonspecic musculoskeletal-pain syndromes found that 93% had some
degree of vitamin D deciency (serum concentration 50 nmol/L) and 28% had
severe deciency25(OH)D concentrations 20nmol/L (Plotnikoff & Quigley,
2003). In addition, a very recent study of 307 urban adolescents living in Massa-
chusetts who were screened during their annual physical examinations found that
24% were decient, 25(OH)D 37.5 nmol/L, and 4.6% were severely decient,
25(OH)D 20 nmol/L (Gordon, DePeter, Feldman, Grace, & Emans, 2004). Given
these and other recent ndings, many experts feel that the recommended adequate
intake and tolerable upper limit for vitamin D might be too low to maintain bone
health and reduce chronic-disease risk (Bischoff-Ferrari, Giovannucci, Willett,
Dietrich, & Dawson-Hughes, 2006; Cannell, 2006; Chen et al., 2007; Dawson-
Hughes et al., 2005; Heaney, 2005; Vieth, 2006; Whiting & Calvo, 2005b). One
current difculty in assessing vitamin D status, however, is that exact thresholds
for serum concentrations of 25(OH)D that dene deciency, insufciency, and
208 Willis, Peterson, and Larson-Meyer
adequacy have not been uniformly agreed on (Hollis, 2005; Lips, 2004; Whiting &
Calvo, 2005a). In most cases serum concentrations of 25(OH)D of <2025 nmol/L
are dened as decient (Heaney, 2004) or severely decient (Vieth, 1999) because
of their association with clinical osteomalacia among adults, whereas serum con-
centrations of 2025 nmol/L and the lower end of the typical reference (37.550
nmol/L) are dened as insufciency (Heaney, 2004; Snijder et al., 2005) or marginal
deciency (Vieth, 1999), but the terms are also used interchangeably (Tangpricha
et al., 2002). Insufciency, however, appears to be the currently favored term for
the range of marginal deciency and is the theoretical serum concentration that
is not high enough to protect against certain chronic diseases (Whiting & Calvo,
2005a). As indicated in Table 2, circulating concentrations of 2029 nmol/L will
prevent rickets, but concentrations of at least 7580 nmol/L are needed to support
optimal health and disease prevention (Chen et al., 2007; Dawson-Hughes et al.;
Heaney, 2005; Vieth, 2006; Whiting & Calvo, 2005b).
Although vitamin D insufciency appears to be problematic in the general
population, studies are also nding that individuals of certain ethnic and racial
groups (Calvo & Whiting, 2003; Harris & Dawson-Hughes, 1998; Harris, Sote-
riades, Coolidge, Mudgal, & Dawson-Hughes, 2000; Looker, Dawson-Hughes,
Calvo, Gunter, & Sahyoun, 2002; Nesby-ODell et al., 2002; Plotnikoff & Quigley,
2003) and those with specic dietary patterns (Calvo et al., 2005; Davey et al.,
2003; Outila, Karkkainen, Seppanen, & Lamberg-Allardt, 2000; Whiting & Calvo,
2005b) might be at even greater risk. The prevalence of vitamin D insufciency,
for example, is found to be higher in Black men and women living in the United
States and Canada (Calvo & Whiting; Harris & Dawson-Hughes; Harris et al.,
2000; Nesby-ODell et al.) and in Canadian Aboriginal women (Weiler, Leslie,
Krahn, Steiman, & Metge, 2007) than in similar-age light-skinned individuals.
Although some of these differences might result from reduced vitamin D intake
Table 2 Vitamin D Recommendations
Source
Recommended serum
25(OH)D (nmol/L)
a
Recommended
intake (IU/day)
b
Recommended
tolerable upper
limit (IU/day)
b
Bischoff-Ferrari et al., 2006 90100 >1,000
Cannell, 2006 125 Up to 5,000
Dawson-Hughes et al., 2005 7080 8001,000
Hathcock, Shao, Vieth,
and Heaney, 2007 10,000
Heaney, 2005 80 2,600 10,000
Chen et al., 2007 75150 8001,000
Hollis, 2005 80 Possibly >2,000
Lips, 2004 50
Vieth, 2006 75 2,000
a
To convert these values to ng/mL, divide by ~2.5.
b
Recommendations are for vitamin D
3
, cholecalciferol.
Vitamin D and Athletes 209
(Calvo & Whiting; Calvo et al.; Weiler et al.), reduced endogenous synthesis from
the high-melanin pigment in the skin might be the most important factor (Webb,
2006). Recent analysis of the NHANES III data indicates that >50% of African
American women have hypovitaminosis D (vitamin D insufciency) in the winter
months (Nesby-ODell et al.), which researchers dened as 25(OH)D 37.5
nmol/L. Because of the nature of NHANES data collection, all the surveys in the
north were taken during the summer, so these ndings are likely to underestimate
the prevalence of vitamin D insufciency in this population. It also appears that
vitamin D deciency in some dark-pigmented groups seems to differentially affect
bone-fracture risk, which is known to be low in African Americans (Holick, 2004;
Whiting & Calvo, 2005a) and elevated in Aboriginal women (Leslie et al., 2004)
relative to the general population. Concerning dietary practices, vitamin D intake
appears to be lower in some vegetarians (Davey et al.) and vegans (Outila et al.) and
in those who consume few dairy products or fortied foods (Calvo et al.; Whiting
& Calvo, 2005b). The high phytate and ber content of vegetarian diets might also
decrease vitamin D absorption or increase vitamin D loss by impairing interhepatic
vitamin D circulation (Batchelor & Compston, 1983). In contrast, consuming sh
at least four times per week achieved mean vitamin D concentrations of 65 nmol/L
(Nakamura, Nashimoto, Hori, & Yamamoto, 2000).
Vitamin D Intake and Status in Athletes
Vitamin D appears to be a largely ignored nutrient in sports nutrition. Very few
investigations and reviews focusing on the micronutrient status of athletes and their
potential performance implications have even included discussions of vitamin D.
Of the studies that have assessed vitamin D intake (Table 3), it has been found that
athletes in general report consuming far less than the current daily recommenda-
tion for vitamin D despite presumably having higher energy needs than the general
population (which should also presumably result in higher energy and nutrient
intakes). It is important to note, however, that the nutrient-composition databases
used to quantify vitamin D intake (including the USDA national nutrient database)
do not have current data on the vitamin D content of many foods (Calvo et al.,
2005). A current and comprehensive database is necessary to properly evaluate
dietary intake. Although research has demonstrated that African American men
and women in the general population have a lower intake of vitamin D from milk
and ready-to-eat cereals than do Whites, comparative data are not available for
athletes (Calvo et al.).
Even less appears to be known about the prevalence of vitamin D insuf-
ciency in athletes. In our review of the literature, we were able to locate only three
published studies reporting the vitamin D status of athletic populations (Bannert,
Starke, Mohnike, & Frohner, 1991; Lehtonen-Veromaa et al., 1999; Maimoun et
al., 2006). In one study of young Finnish female athletes (runners and gymnasts)
and nonathletes, age 915 years, nearly 68% were vitamin D insufcient, serum
25(OH)D <37.5 nmol/L, in the winter months, and 13% of those were decient,
serum 25(OH)D <10 nmol/L. The prevalence of vitamin D insufciency and de-
ciency, however, was not different in the athletes than in the nonathletes. Although
the investigators found that the mean 25(OH)D concentration in the group was
210 Willis, Peterson, and Larson-Meyer
drastically improved at the end of the summer, they were not signicantly affected
by 3 months of supplementation of 400 IU of vitamin D (Lehtonen-Veromaa et
al.). In another study of 85 athletes age 827 in intensive training in the former
East Germany, 37% were vitamin D decient, serum 25(OH)D <25 nmol/L. The
decreased serum 25(OH)D concentrations, nevertheless, did not appear to correlate
with the retarded bone maturation also noted in a large number of the children,
particularly the gymnasts (Bannert et al.). In a third recently published study, 7
male competitive road cyclists living around Montpellier, France, and training an
average of 16 hr/week had serum 25(OH)D concentrations indicative of adequate
status (81 16 nmol/L; M SD); however, the group mean was surprisingly
(considering their outdoor training schedules) only borderline sufcient, and the
number with insufcient status was not reported (Maimoun et al., 2006). In agree-
ment with these studies, preliminary results from our laboratory found that 40%
of a small group (N = 20) of distance runners age 1945 residing in Baton Rouge,
LA (latitude 30 N), were vitamin D insufcient, 25(OH)D <80 nmol/L, despite
training outdoors and living at a latitude where endogenous vitamin D synthesis
is possible throughout the year (Willis, Peterson, & Larson-Meyer, 2007). In this
study, however, there were no signicant relationships between vitamin D status
and season tested, sex, weekly training, or vitamin supplementation.
Table 3 Vitamin D Intake of Athletes
Study Participants
Assessment
index
Vitamin D
intake
Rankinen et al.,
1998
21 Finnish elite male ski jump-
ers, age 19.7 3.6 years; %BF
16.1 7.2
4-day food
recall: 3
weekdays and
Sunday
100 72 IU,
density 0.33
0.20
Ziegler, Nelson,
Barratt-Fornell,
Fiveash, and
Drewnowski,
2001
41 U.S. national gure skaters
(21 males, 20 females), males
age 16.5 1.6 years, %BF 5.8
2.1; females age 14.1 1.7
years, %BF 12.5 2.2
4-day food
recall: 2 non-
consecutive
weekdays, both
weekend days
Male 140
188 IU,
female 108
220 IU
Clark, Reed,
Crouse, and
Armstrong,
2003
13 female NCAA Division 1
soccer players, age 19.7 0.7
years, %BF 16.4 2.4
3-day food
recall: 2 week-
days, 1 week-
end day
Preseason
96 6.8 IU,
postseason
100 104 IU
Bergen-Cico
and Short, 1992
44 junior high and high school
female cross-country runners,
age 13.9 1.1 years, %BF 18.9
4
3-day food
recall: 3 con-
secutive week-
days
182 78 IU
Lehtonen-
Veromaa et al.,
1999
66 competitive runners, 65 com-
peting gymnasts, and 60 nonath-
letic controls, age 915 years
FFQ: 3 week-
days, 1 week-
end day
172 84
FFQ, 116
60 food
recall
Note. FFQ = food-frequency questionnaire.
Vitamin D and Athletes 211
Potential Impact of Vitamin D Status
on Health and Performance
Because vitamin D plays an important role in bone health and the prevention of
autoimmune and chronic diseases, it is also likely that this vitamin affects health
and performance in athletes. Specically, adequate vitamin D status might increase
an athletes chance of maintaining good health during training by reducing risk
of stress fractures and keeping the immune system and inammatory responses
in check. There is also some evidence that vitamin D status might affect athletic
performance. The following section will review the potential impact of vitamin D
on the health and performance of athletes.
Impact of Vitamin D Status on Bone Health in Athletes
The classic function of vitamin D is its inuence on bone health through its regula-
tion of calcium homeostasis. The rst-discovered and most well-known symptoms
of vitamin D deciency are diseases such as rickets in children and osteomalacia
and osteoporosis in adults. Although athletes are at a low risk for such diseases, a
less severe deciency can still negatively affect bone health. In fact, serum con-
centrations of 25(OH)D have been found to be related to bone-mineral density
(Bischoff-Ferrari et al., 2006; Valimaki et al., 2004), with the greatest density
observed at 25(OH)D concentrations nearing 100 nmol/L (Bischoff-Ferrari et al.,
2006). These associations have been observed in younger (2049 years), as well
as older (>50 years), individuals.
Stress fractures are a common problem for many athletes and can represent a
serious obstacle to training. Although reports vary, some studies of track and eld
athletes demonstrate cumulative annual incidences as high as 21% (Snyder, Koes-
ter, & Dunn, 2006). Studies of other college athletes report much lower incidences
of 13%. Fortunately, some of these cases might be preventable. In one study, an
increased risk of fracture in young males was signicantly associated with decreased
serum 25(OH)D concentrations (Ruohola et al., 2006). In another, stress fractures
were associated with higher PTH concentrations (which are directly inuenced by
calcium intake and vitamin D status), even though 25(OH)D concentrations were
not directly related (Valimaki et al., 2005). Furthermore, supplementation with
vitamin D has been shown to decrease incidence of fractures in older populations
(Bischoff-Ferrari et al., 2006) and is of great interest in athletic populations. In fact,
preliminary data from a Creighton University study indicate a signicant decrease
in stress-fracture incidence among female naval recruits supplemented with vita-
min D and calcium when compared with a control (Lappe, Cullen, Thompson, &
Ahlf, 2007). From these ndings it is evident that compromised vitamin D status
can diminish bone health, even in otherwise healthy athletes. This compromised
status might increase stress-fracture risk, an undesirable outcome for an athlete
in training.
Impact of Vitamin D on Gene Expression and Cell Growth
Our understanding of the noncalcitropic functions of vitamin D has increased dra-
matically over the past 25 years. Although it has long been recognized that vitamin
212 Willis, Peterson, and Larson-Meyer
D inuences bone health by up-regulating the expression of genes that enhance
calcium absorption and bone deposition, vitamin D also functions as a modulator
of the expression of many other genes involved in cell growth and immunity. In
this role the hormonally active form, 1,25(OH)
2
D, interacts with its nuclear vitamin
D receptor, which is present in most tissues and cells in the human bodyinclud-
ing intestine and bone, as well as brain, heart, immune cells (Stumpf, Sar, Reid,
Tanaka, & DeLuca, 1979), and skeletal muscle (Bischoff-Ferrari et al., 2004;
Simpson, Thomas, & Arnold, 1985). The vitamin Dvitamin D receptor complex
subsequently bonds with the retinoic acid x-receptor, which is then recognized by
specic gene sequences known as vitamin D response elements to regulate the
expression of specic genes involved in cell growth, immune function, and protein
synthesis. In immune cells, the vitamin Dvitamin D receptor complex appears to
regulate T- and B-lymphocyte function, cytokine production, macrophage activation,
and monocyte maturation (Adorini, 2002; Deluca & Cantorna, 2001). In skeletal
muscle, the vitamin Dvitamin D receptor complex is hypothesized to regulate
protein synthesis, although its specic action is not yet known (Costa, Blau, &
Feldman, 1986; Simpson et al.). Higher concentrations of 25(OH)D in circula-
tion are imperative to this function because 25(OH)D is used directly by the cell
(which contains 1--hydroxylase) to make 1,25(OH)
2
D. These specic functions
of vitamin D represent a small, albeit vital, piece of its involvement in the innate
immune response and possibly also physical performance.
Impact of Vitamin D Status on Immunity
In addition to its direct functions in immune-cell proliferation, vitamin D is also
involved in another important aspect of the innate immune system. Recent research
has uncovered a direct link between vitamin D status and the release of disease-
ghting antimicrobial peptides (AMPs; Gombart, Borregaard, & Koefer, 2005;
Liu et al., 2006; Wang et al., 2004). AMPs can be secreted by many components of
the innate immune system, including (but not limited to) neutrophils, natural killer
cells, macrophages, monocytes, mast cells, and epithelial cells in the respiratory
tract (Cannell, 2007; Gombart et al.). Generally these AMPs exert their effects
by compromising the integrity of the cell membrane of invading pathogens (De
Smet & Contreras, 2005). The release of AMPs such as cathelicidin (CAMP) is
triggered when invading pathogens are recognized by toll-like receptors. Liu et
al. demonstrated that stimulation of the toll-like receptors triggers a conversion of
25(OH)D
3
to the active 1,25(OH)
2
D
3
and induces the expression of the vitamin D
receptor that promotes the release of CAMP.
Considering that vitamin D is such a potent stimulator of human AMPs, vitamin
D status can potentially have signicant effects on innate immunity. In fact, Liu et
al. (2006) discovered that African Americans with reduced 25(OH)D concentra-
tions exhibit a decreased ability to synthesize CAMP. These ndings might help
explain the increased susceptibility to tuberculosis observed in populations that
exhibit lower 25(OH)D concentrations (Sita-Lumsden, Lapthorn, Swaminathan, &
Milburn, 2007). Furthermore, it has been demonstrated that a single dose of vitamin
D
3
(100,000 IU) can enhance innate immune response and restrict the growth of
mycobacteria (Martineau et al., 2007). Cannell et al. (2006) also suggest that the
ability of vitamin D to regulate the expression of AMPs in the epithelial cells of the
respiratory tract could inuence an individuals susceptibility to the inuenza virus.
Vitamin D and Athletes 213
In fact, preliminary data have suggested that 3 years of supplementation with vitamin
D
3
(800 IU for 2 years and 2,000 IU for 1 additional year) reduced self-reported
incidence of inuenza and the common cold and abolished the seasonality of these
infections (Aloia & Li-Ng, 2007). In this manner, seasonal uctuations in vitamin
D status could, in part, explain the seasonality of viral respiratory infections.
These ndings in a normal population might be directly applicable to athletes
who are at similar or increased risk for infection and illness. Although not all stud-
ies are in agreement, some research suggests that prolonged intense training has a
suppressive effect on innate immune function and increases risk of upper respiratory
tract infection (Nieman, 2000; West, Pyne, Renshaw, & Cripps, 2006). A specic
mechanism has yet to be elucidated but would likely involve multiple aspects of
the immune system. Although there are currently no published studies addressing
the effects of exercise on AMP function, suppressed CAMP activity resulting from
decreased vitamin D status could certainly affect an athletes immune status. Further
research is necessary to determine the effect (if any) that vitamin D supplementa-
tion might have on infection and illness in athletes in training.
Impact of Vitamin D Status on Exercise-Related Infammation
Vitamin D might also work through the immune system to control inammation,
which results from the accumulation of uid and immune cells in injured tissue.
Vitamin D has been shown to increase the production of anti-inammatory cyto-
kines, transforming growth factor, and interleukin-4 (IL-4; Cantorna, Woodward,
Hayes, & DeLuca, 1998) and reduce production of the proinammatory cytokines
interleukin-6 (IL-6), interferon, interleukin-2 (IL-2), and tumor necrosis factor
(Lemire, 1992; Muller, Diamant, & Bendtzen, 1991; Rigby, Denome, & Fanger,
1987; Rigby, Noelle, Krause, & Fanger, 1985; Rigby, Stacy, & Fanger, 1984; Zhu,
Mahon, Froicu, & Cantorna, 2005). Although there is no evidence to date that
directly links vitamin D insufciency to sports-related inammation, several of
the proinammatory cytokines, particularly IL-6, are elevated after a single bout
of exercise (Ostrowski et al., 1998), and this unexplainably occurs to a greater
degree in some well-trained athletes than in others (Edwards, Burns, Ring, & Car-
roll, 2006; Ostrowski et al.). The release of IL-6 also appears to be increased after
intensied periods of training (Robson-Ansley, Blannin, & Gleeson, 2007). Elevated
concentrations of the proinammatory cytokines are hypothesized to be involved in
the overreaching (or overtraining) syndrome associated with high-volume training
(Smith, 2000). In this cascade of events, muscle or skeletal trauma induces release
of the proinammatory cytokine IL-6, which activates conversion of circulating
monocytes to macrophages. Macrophages in turn produce large quantities of other
proinammatory cytokines including IL-1beta, tumor necrosis factor, and additional
IL-6. These elevated circulating cytokines might then coordinate a whole-body (or
systemic) inammatory response by communicating with the brain to alter mood
and behavior and with the liver to up-regulate gluconeogenesis and de novo syn-
thesis of acute phase proteins, both of which are classic symptoms of overreaching.
Although it is not completely known whether and how vitamin D inuences the
inammatory cascade, studies in mice have found that vitamin D supplementation
reduces the inammatory cycle in inammatory bowel disease and autoimmune
encephalomyelitis (an animal model of multiple sclerosis; Cantorna et al., 2000)
and could therefore also be involved in exercise-associated inammation.
214 Willis, Peterson, and Larson-Meyer
Based on our current understanding of the role that vitamin D plays in inam-
mation, it is possible that compromised vitamin D status increases the risk or sever-
ity of certain sports-related injuries, a possibility that was alluded to in a 1950s
German report (Spellerberg, 1952). In that report, athletes training at the Sports
College of Cologne experienced a signicant reduction in chronic pain from sports
injuries after an extensive 6-week program of irradiation (on both sides of their
bodies for up to 10 min twice a week) with a central sun lamp. The report also
stated that athletes experienced improved performance, but this was poorly dened.
Several large-scale studies have also found that adequate vitamin D status protects
against cartilage loss and disease progression in individuals with knee osteoarthritis
(McAlindon et al., 1996) and reduces disease risk in those with rheumatoid arthri-
tis (Merlino et al., 2004). In osteoarthritis, vitamin D most likely acts to prevent
softening of the joint cartilage, whereas in rheumatoid arthritis it most likely acts
to reduce immune response and inammation. In a small experimental study in
multiple sclerosis patients, 6 months of supplementation with 1,000 IU vitamin D
was also found to suppress serum concentrations of the anti-inammatory cytokine
transforming growth factor but did not conclusively alter concentrations of the
proinammatory cytokines interferon, IL-2, and tumor necrosis factor (Mahon,
Gordon, Cruz, Cosman, & Cantorna, 2003).
Impact of Vitamin D Status on Performance
A recent review in the Vitamin D Newsletter presented evidence that vitamin D
might benet athletic performance. According to the article, numerous studies were
performed in the early part of the 20th century, mostly by Russian and German
scientists, that indirectly suggested that vitamin D status might affect athletic perfor-
mance (Cannell, 2007). Specically, most of the evidence suggests that irradiation
with a sun lamp that provides articial UVB radiation (and increased endogenous
vitamin D synthesis) was associated with improved athletic performance and was
perhaps a well-kept secret of former Soviet and German athletic powers (Cannell,
2007). To our knowledge, however, current studies have investigated the effect of
vitamin D status on physical performance only in the elderly. These studies have
found that poor vitamin D status is signicantly associated with reduced muscle
strength and poor physical function (Houston et al., 2007; Mowe, Haug, & Bohmer,
1999; Wicherts et al., 2007). Physical function was assessed by evaluating grip
strength, stair-climbing ability, outdoor activity, and fall occurrence (Mowe et al.);
a short physical-performance battery (Houston et al.); and specic walking, stand-
ing, and balance movements (Wicherts et al.). Some (Bischoff et al., 2003; Dhesi
et al., 2004) but not all studies (Kenny, Biskup, Robbins, Marcella, & Burleson,
2003) have even demonstrated that vitamin D supplementation can improve muscle
function and lessen the risk of falling in older adults. In these studies, a single
high dose (600,000 IU ergocalciferol; Dhesi et al.) appeared to be more effective
at improving muscle function at 6 months than regular low-dose supplementation
(1,000 IU cholecalciferol plus 500 mg calcium/day; Kenny et al.). Furthermore,
Bischoff et al. were able to demonstrate a signicant decrease in falls after only 3
months of supplementation with vitamin D plus calcium (800 IU + 1,200 mg/day)
when compared with those supplemented with calcium (1,200 mg/day) alone.
Although the specic action of vitamin D is not known, Sato, Iwamoto, Kanoko, and
Satoh (2005) found that improvements in strength with vitamin D supplementation
Vitamin D and Athletes 215
(1,000 IU/day for 2 years) were correlated with increases in the relative number
and size of Type II muscle bers in female stroke survivors. In addition, patients
with vitamin D deciency often complain of aching bones and muscle discomfort,
which is thought to be caused by a mineralization defect that innervates pain bers
(Tangpricha et al., 2004; Whiting & Calvo, 2005a).
Vitamin D Requirements for Athletes
In the most recent revision of the dietary recommendations for Americans and
Canadians, the adequate daily intakes for vitamin D are 200 IU for children and
adults up to 50 years of age, 400 IU for adults age 5170, and 600 IU for adults
71 years of age or older. Most vitamin D experts agree, however, that the recom-
mended adequate intake falls short for optimizing health in todays sun-avoiding
societies (Glerup et al., 2000; Heaney, 2005; Hollis, 2005; Vieth, 2004; Whiting
& Calvo, 2005b). Many are also advocating for a U.S. governmental reevaluation
of the vitamin D requirements (Glerup et al.; Heaney, 2005; Holick, 2005; Hollis;
Vieth et al., 2007) that would include establishing an estimated average require-
ment (Whiting & Calvo, 2005a) from emerging evidence linking poor vitamin D
status to increased risk of chronic and autoimmune diseases. Although specic
recommendations of many of these experts vary from 1,000 to 4,000 IU/day
(Table 2), it is important to keep in mind that the oral requirement depends on both
endogenous synthesis and vitamin D storage (Calvo et al., 2005). As an example,
recent research has estimated that without adequate sun exposure, individuals of
all ages require at least 600 and 1,000 IU (Bischoff-Ferrari et al., 2006; Boonen
et al., 2006; Glerup et al.; Heaney, Davies, Chen, Holick, & Barger-Lux, 2003;
Holick, 2006b; Larsen, Mosekilde, & Foldspang, 2004), much higher than the
current recommended adequate intake.
Despite increased training, there is no evidence to suggest that the vitamin
D requirement for athletes is different than for the general population. Athletes at
risk of poor vitamin D status include those with low vitamin D intake or limited
sun exposure. The latter includes athletes who only practice indoors or those who
practice outdoors in the early mornings and late afternoons, as well as those who
diligently apply sunscreen, wear athletic clothing with sun-protection factors (which
is becoming increasingly available from many athletic clothing companies), or have
dark-pigmented skin. In addition, athletes with high or low body fat might also be at
increased risk for vitamin D insufciency during the winter months (or other periods
of reduced UVB exposure). In normal-weight individuals, vitamin D
3
synthesized
in the skin (or consumed in the diet) is stored in subcutaneous fat and released as
needed during the winter months (Chen et al., 2007; Glerup et al., 2000). There is
evidence to suggest, however, that this process is ineffective in obese individuals
with excess body fat because vitamin D
3
might be sequestered deep in the subcu-
taneous fat, decreasing its availability for conversion into 25(OH)D (Wortsman,
Matsuoka, Chen, Lu, & Holick, 2000). This is supported by the observations that
25(OH)D concentrations are inversely correlated with body-fat percentage (within
the typical range of sedentary individuals; Snijder et al., 2005) and are commonly
depressed with obesity (along with elevated PTH concentrations; Bell et al., 1985;
Hypponen & Power, 2007; Snijder et al., 2005; Yanoff et al., 2006). Athletes with
extremely low body fat, on the other hand, might also be at increased risk during
216 Willis, Peterson, and Larson-Meyer
the winter months simply because of a decreased ability to store vitamin D in
subcutaneous tissues, although this is currently purely speculation.
Vitamin D Intoxication
Although intoxication from excess intake or supplementation is extremely rare, it
can be caused by ingesting (intentionally or unintentionally) extremely high supple-
mental doses. Doses of 150,0002,604,000 IU per day for 2 years, for example,
have been found to raise 25(OH)D concentrations to 1,217 nmol/L and induce both
hypercalcemia and hyperphosphatemia (Koutkia, Chen, & Holick, 2001). Doses
of 10,000 IU per day for up to 5 months do not cause toxicity (Vieth, 2004) and
appear to be safe (Heaney et al., 2003). A recent report described a case of vitamin
D intoxication that was caused by manufacturer error in which 188,640 IU of vita-
min D
3
had been added to a vitamin supplement (serving size = six capsules/day)
instead of the intended 400 IU (Klontz & Acheson, 2007). In this case, the patient
was admitted (after 2 months of supplementation) with severe hypercalcemia (>3.75
mmol/L) and elevated serum 25(OH)D (1,171 nmol/L) concentrations and presented
with classic signs and symptoms of toxicity including fatigue, constipation, back
pain, forgetfulness, nausea, and vomiting. Prolonged hypercalcemia is known to
produce soft-tissue calcication, hypertension, and heart-rhythm abnormalities.
Possible vitamin D intoxication issues are important to consider in the athletic
population because many athletes, coaches, and trainers hold the philosophy that
if a little is good, more is better. Vitamin D intoxication from solar exposure, on
the other hand, does not lead to toxicity because excess previtamin D
3
(that does
not escape into the circulation) photoisomerizes to biologically inert photoproducts
with prolonged UV exposure (Holick, 1981).
Recommendations and Practical Applications
Clearly, additional research is needed to determine whether vitamin D can inuence
training and performance in athletes. Given its role in bone health and recently
recognized role in immunity, inammation, and chronic-disease prevention it is
important that sports nutritionists assess vitamin D, as well as calcium, intake and
evaluate potential risk for vitamin D insufciency (or deciency). Direct assess-
ment of vitamin D status via measurement of 25(OH)D concentrations might also
be helpful, but the assay is costly and not readily available to athletes. Assessment
of calcium intake is important because adequate calcium intake reduces vitamin
D turnover through suppression of PTH (Lips, 2004).
It is not known exactly how much vitamin D sports nutritionists should
recommend to their athletes and active clients. Individual researchers (Table
2) along with the Vitamin D Council (Cannell, 2006), however, are currently
recommending between 800 and 2,000 IU/day. Because it is very difcult to
regularly obtain that much vitamin D from food sources, sensible sun exposure
or vitamin D supplementation is required. Holick (2007) recently suggested that
exposing arms and legs to sunlight for 530 min (depending on season, latitude, and
skin pigmentation) between the hours of 10 a.m. and 3 p.m. twice a week without
sunscreen should be adequate to maintain vitamin D status (Chen et al., 2007).
Sunscreen with an SPF of at least 15 should then be applied to prevent damaging
Vitamin D and Athletes 217
effects of excessive sunlight exposure (Holick, 2005). During the winter months,
however, vitamin D supplementation is required for athletes living at northern and
southern latitudes distant from the equator (>35 N or S; Holick, 2005; Kimlin et
al., 2007).
The recommendation to obtain vitamin D via a dietary supplement is favored
by many experts because of the reported link between skin cancer and excessive
sunlight exposure, especially sunlight that causes sunburn (Kennedy, Bajdik, Wil-
lemze, De Gruijl, & Bouwes Bavinck, 2003; Wolpowitz & Gilchrest, 2006). To be
most effective, supplements should contain vitamin D
3
(cholecalciferol) rather than
vitamin D
2
(ergocalciferol) and should not contain vitamin A, which can interfere
with the function of vitamin D (Trang et al., 1998). It is also a good idea that supple-
ments be purchased from a reputable company. Keep in mind, however, that vitamin
D
3
is not acceptable to vegans and many vegetarians because it is commercially
synthesized from animal fat (Holick, 2005). Vitamin D
2
, the plant form acceptable to
vegetarians and the form used to fortify products targeted at vegetarians (including
rice and soy milks), is much less effective than vitamin D
3
at increasing concen-
trations of 25(OH)D (Armas et al., 2004; Houghton & Vieth, 2006; Trang et al.).
Vitamin D scientists are also questioning whether higher doses of vitamin D
2
offer
the same overall benets of vitamin D
3
in preventing bone fractures (and possible
other chronic conditions) and whether high doses might lead to a higher risk of
toxicity than vitamin D
3
(Houghton & Vieth). Because vitamin D supplements are
commonly available in 1,000-IU doses, sports nutritionists might want to consider
athletes dietary intake, frequency of sun exposure, skin color, body size, history
of stress fractures, occurrence of illness or bone and joint injury, and recent serum
25(OH)D concentration, if available, when making recommendations. Indeed, the
vitamin D content in a multivitamin (400 IU) is likely not sufcient.
Frequent use of tanning beds, which typically emit 26% UVB radiation, has
also been suggested as an alternative to meeting vitamin D needs (Chen et al.,
2007), but this recommendation meets with obvious controversy. Regular users of
tanning beds have been found to have robust serum concentrations of 25(OH)D
(approx 112 nmol/L) and higher bone density in the hip at the end of winter than
nontanners, who had concentrations of approximately 45 nmol/L (Tangpricha et
al., 2004). Exposure to a tanning bed for 3050% of the typical time recommended
with sunscreen on the face was found to be effective at maintaining vitamin D status
in patients with fat malabsorption (Koutkia, Lu, Chen, & Holick, 2001).
Conclusions
Given the known role of vitamin D in bone health and its recently recognized role
in chronic-disease prevention, immunity, and inammation, it is imperative that
sports nutritionists assess vitamin D status and make appropriate recommendations
that will help athletes achieve adequate vitamin D status. Careful attention should
be paid when assessing athletes with restrained eating patterns who also spend most
of their time indoors (gymnasts, ballet dancers, gure skaters, wrestlers) because
they might be at an even greater risk of insufciency. Considering the relative
inefciency of vitamin D
2
, strict vegetarian or vegan athletes who spend most of
their time indoors might also be at increased risk. Although the recommendation to
achieve adequate vitamin D status, 25(OH)D of at least 75 or 80 nmol/L, appears
218 Willis, Peterson, and Larson-Meyer
to be important for improving overall health and reducing risk of autoimmune and
chronic disease, athletes with a history of stress fracture, frequent illness, or bone
and joint injury are also likely to have more short-term benets. Research is needed,
however, to determine whether insufcient vitamin D status increases an athletes
risk of illness or injury and whether vitamin D supplementation can affect athletic
training and improve overall health and performance.
Acknowledgments
We thank Inga Harper at the National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases, Phoenix Epidemiology and Clinical Research Branch,
for assistance in interpreting References 4 and 99.
References
Adorini, L. (2002). 1,25-Dihydroxyvitamin D
3
analogs as potential therapies in transplan-
tation. Current Opinion in Investigational Drugs (London, England : 2000), 3(10),
14581463.
Aloia, J.F., & Li-Ng, M. (2007). Re: Epidemic inuenza and vitamin D. Epidemiology and
Infection, 135(7), 10951096.
Armas, L.A., Hollis, B.W., & Heaney, R.P. (2004). Vitamin D
2
is much less effective than
vitamin D
3
in humans. The Journal of Clinical Endocrinology and Metabolism, 89(11),
53875391.
Bannert, N., Starke, I., Mohnike, K., & Frohner, G. (1991). [Parameters of mineral metabo-
lism in children and adolescents in athletic training]. Kinderarztliche Praxis, 59(5),
153156.
Batchelor, A.J., & Compston, J.E. (1983). Reduced plasma half-life of radio-labelled
25-hydroxyvitamin D
3
in subjects receiving a high-bre diet. The British Journal of
Nutrition, 49(2), 213216.
Bell, N.H., Epstein, S., Greene, A., Shary, J., Oexmann, M.J., & Shaw, S. (1985). Evidence
for alteration of the vitamin Dendocrine system in obese subjects. The Journal of
Clinical Investigation, 76(1), 370373.
Bergen-Cico, D.K., & Short, S.H. (1992). Dietary intakes, energy expenditures, and anthro-
pometric characteristics of adolescent female cross-country runners. Journal of the
American Dietetic Association, 92(5), 611612.
Bischoff, H.A., Stahelin, H.B., Dick, W., Akos, R., Knecht, M., Salis, C., et al. (2003).
Effects of vitamin D and calcium supplementation on falls: A randomized controlled
trial. Journal of Bone and Mineral Research, 18(2), 343351.
Bischoff-Ferrari, H.A., Borchers, M., Gudat, F., Durmuller, U., Stahelin, H.B., & Dick, W.
(2004). Vitamin D receptor expression in human muscle tissue decreases with age.
Journal of Bone and Mineral Research, 19(2), 265269.
Bischoff-Ferrari, H.A., Giovannucci, E., Willett, W.C., Dietrich, T., & Dawson-Hughes,
B. (2006). Estimation of optimal serum concentrations of 25-hydroxyvitamin D for
multiple health outcomes. The American Journal of Clinical Nutrition, 84(1), 1828.
Boonen, S., Bischoff-Ferrari, H.A., Cooper, C., Lips, P., Ljunggren, O., Meunier, P.J., et al.
(2006). Addressing the musculoskeletal components of fracture risk with calcium and
vitamin D: A review of the evidence. Calcied Tissue International, 78(5), 257270.
Calvo, M.S., & Whiting, S.J. (2003). Prevalence of vitamin D insufciency in Canada and
the United States: Importance to health status and efcacy of current food fortication
and dietary supplement use. Nutrition Reviews, 61(3), 107113.
Calvo, M.S., Whiting, S.J., & Barton, C.N. (2005). Vitamin D intake: A global perspective
of current status. The Journal of Nutrition, 135(2), 310316.
Vitamin D and Athletes 219
Cannell, J. (2006). Dr. Cannell answers readers questions. Vitamin D Council Newsletter.
Retrieved July 21, 2006, from www.vitamindcouncil.org/PDFs/April2006-questions.pdf
Cannell, J. (2007). Peak athletic performance and vitamin D. The Vitamin D Newsletter.
Retrieved from www.vitamindcouncil.org/PDFs/March 2007.pdf
Cannell, J.J., Vieth, R., Umhau, J.C., Holick, M.F., Grant, W.B., Madronich, S., et al. (2006).
Epidemic inuenza and vitamin D. Epidemiology and Infection, 134(6), 11291140.
Cantorna, M.T., Munsick, C., Bemiss, C., & Mahon, B.D. (2000). 1,25-Dihydroxychole-
calciferol prevents and ameliorates symptoms of experimental murine inammatory
bowel disease. The Journal of Nutrition, 130(11), 26482652.
Cantorna, M.T., Woodward, W.D., Hayes, C.E., & DeLuca, H.F. (1998). 1,25-dihydroxyvi-
tamin D
3
is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta
1 and IL-4. Journal of Immunology (Baltimore, Md.: 1950), 160(11), 53145319.
Chen, T.C., Chimeh, F., Lu, Z., Mathieu, J., Person, K.S., Zhang, A., et al. (2007). Factors
that inuence the cutaneous synthesis and dietary sources of vitamin D. Archives of
Biochemistry and Biophysics, 460(2), 213217.
Chen, T.C., Shao, A., Heath, H., III, & Holick, M.F. (1993). An update on the vitamin D
content of fortied milk from the United States and Canada. The New England Journal
of Medicine, 329(20), 1507.
Chiu, K.C., Chu, A., Go, V.L., & Saad, M.F. (2004). Hypovitaminosis D is associated with
insulin resistance and beta cell dysfunction. The American Journal of Clinical Nutri-
tion, 79(5), 820825.
Clark, M., Reed, D.B., Crouse, S.F., & Armstrong, R.B. (2003). Pre- and post-season dietary
intake, body composition, and performance indices of NCAA Division I female soccer
players. International Journal of Sport Nutrition and Exercise Metabolism, 13(3), 303319.
Costa, E.M., Blau, H.M., & Feldman, D. (1986). 1,25-Dihydroxyvitamin D
3
receptors and
hormonal responses in cloned human skeletal muscle cells. Endocrinology, 119(5),
22142220.
Davey, G.K., Spencer, E.A., Appleby, P.N., Allen, N.E., Knox, K.H., & Key, T.J. (2003).
EPIC-Oxford: Lifestyle characteristics and nutrient intakes in a cohort of 33 883
meat-eaters and 31 546 non meat-eaters in the UK. Public Health Nutrition, 6(3),
259269.
Dawson-Hughes, B., Heaney, R.P., Holick, M.F., Lips, P., Meunier, P.J., & Vieth, R. (2005).
Estimates of optimal vitamin D status. Osteoporosis International, 16(7), 713716.
De Smet, K., & Contreras, R. (2005). Human antimicrobial peptides: Defensins, cathelicidins
and histatins. Biotechnology Letters, 27(18), 13371347.
Deluca, H.F., & Cantorna, M.T. (2001). Vitamin D: Its role and uses in immunology. The
FASEB Journal, 15(14), 25792585.
Dhesi, J.K., Jackson, S.H., Bearne, L.M., Moniz, C., Hurley, M.V., Swift, C.G., et al. (2004).
Vitamin D supplementation improves neuromuscular function in older people who fall.
Age and Ageing, 33(6), 589595.
Edwards, K.M., Burns, V.E., Ring, C., & Carroll, D. (2006). Individual differences in the
interleukin-6 response to maximal and submaximal exercise tasks. Journal of Sports
Sciences, 24(8), 855862.
Garland, C.F., Garland, F.C., Gorham, E.D., Lipkin, M., Newmark, H., Mohr, S.B., et al.
(2006). The role of vitamin D in cancer prevention. American Journal of Public Health,
96(2), 252261.
Glerup, H., Mikkelsen, K., Poulsen, L., Hass, E., Overbeck, S., Thomsen, J., et al. (2000).
Commonly recommended daily intake of vitamin D is not sufcient if sunlight exposure
is limited. Journal of Internal Medicine, 247(2), 260268.
Gombart, A.F., Borregaard, N., & Koefer, H.P. (2005). Human cathelicidin antimicrobial
peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-
regulated in myeloid cells by 1,25-dihydroxyvitamin D3. The FASEB Journal, 19(9),
10671077.
220 Willis, Peterson, and Larson-Meyer
Gordon, C.M., DePeter, K.C., Feldman, H.A., Grace, E., & Emans, S.J. (2004). Prevalence
of vitamin D deciency among healthy adolescents. Archives of Pediatrics & Adolescent
Medicine, 158(6), 531537.
Hanley, D.A., & Davison, K.S. (2005). Vitamin D insufciency in North America. The
Journal of Nutrition, 135(2), 332337.
Harris, S.S., & Dawson-Hughes, B. (1998). Seasonal changes in plasma 25-hydroxyvitamin
D concentrations of young American Black and White women [see comments]. The
American Journal of Clinical Nutrition, 67(6), 12321236.
Harris, S.S., Soteriades, E., Coolidge, J.A., Mudgal, S., & Dawson-Hughes, B. (2000).
Vitamin D insufciency and hyperparathyroidism in a low income, multiracial,
elderly population. The Journal of Clinical Endocrinology and Metabolism, 85(11),
41254130.
Hathcock, J.N., Shao, A., Vieth, R., & Heaney, R. (2007). Risk assessment for vitamin D.
The American Journal of Clinical Nutrition, 85(1), 618.
Heaney, R.P. (2004). Functional indices of vitamin D status and ramications of vitamin D
deciency. The American Journal of Clinical Nutrition, 80(6, Suppl.) 1706S1709S.
Heaney, R.P. (2005). The vitamin D requirement in health and disease. The Journal of Steroid
Biochemistry and Molecular Biology, 97(1-2), 1319.
Heaney, R.P., Davies, K.M., Chen, T.C., Holick, M.F., & Barger-Lux, M.J. (2003). Human
serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol.
The American Journal of Clinical Nutrition, 77(1), 204210.
Holick, M.F. (1981). The cutaneous photosynthesis of previtamin D3: A unique photoendo-
crine system. The Journal of Investigative Dermatology, 77(1), 5158.
Holick, M.F. (1990). The use and interpretation of assays for vitamin D and its metabolites.
The Journal of Nutrition, 120(Suppl. 11), 14641469.
Holick, M.F. (2003). Evolution and function of vitamin D. Recent Results in Cancer
Research. Fortschritte der Krebsforschung. Progres Dans les Recherches Sur le Cancer,
164, 328.
Holick, M.F. (2004). Sunlight and vitamin D for bone health and prevention of autoimmune
diseases, cancers, and cardiovascular disease. The American Journal of Clinical Nutri-
tion, 80(6, Suppl.) 1678S1688S.
Holick, M.F. (2005). The vitamin D epidemic and its health consequences. The Journal of
Nutrition, 135(11), 2739S2748S.
Holick, M.F. (2006a). High prevalence of vitamin D inadequacy and implications for health.
Mayo Clinic Proceedings, 81(3), 353373.
Holick, M.F. (2006b). Resurrection of vitamin D deciency and rickets. The Journal of
Clinical Investigation, 116(8), 20622072.
Holick, M.F. (2006c). The role of vitamin D for bone health and fracture prevention. Current
Osteoporosis Reports, 4(3), 96102.
Holick, M.F. (2007). Vitamin D deciency. The New England Journal of Medicine, 357(3),
266281.
Hollis, B.W. (2005). Circulating 25-hydroxyvitamin D levels indicative of vitamin D suf-
ciency: Implications for establishing a new effective dietary intake recommendation
for vitamin D. The Journal of Nutrition, 135(2), 317322.
Houghton, L.A., & Vieth, R. (2006). The case against ergocalciferol (vitamin D
2
) as a vitamin
supplement. The American Journal of Clinical Nutrition, 84(4), 694697.
Houston, D.K., Cesari, M., Ferrucci, L., Cherubini, A., Maggio, D., Bartali, B., et al. (2007).
Association between vitamin D status and physical performance: The InCHIANTI
Study. The Journals of Gerontology. Series A, Biological Sciences and Medical Sci-
ences, 62(4), 440446.
Hypponen, E., & Power, C. (2007). Hypovitaminosis D in British adults at age 45 y: Nation-
wide cohort study of dietary and lifestyle predictors. The American Journal of Clinical
Nutrition, 85(3), 860868.
Vitamin D and Athletes 221
Isaia, G., Giorgino, R., Rini, G.B., Bevilacqua, M., Maugeri, D., & Adami, S. (2003). Preva-
lence of hypovitaminosis D in elderly women in Italy: Clinical consequences and risk
factors. Osteoporosis International, 14(7), 577582.
Kamen, D.L., Cooper, G.S., Bouali, H., Shaftman, S.R., Hollis, B.W., & Gilkeson, G.S.
(2006). Vitamin D deciency in systemic lupus erythematosus. Autoimmunity Reviews,
5(2), 114117.
Kennedy, C., Bajdik, C.D., Willemze, R., De Gruijl, F.R., & Bouwes Bavinck, J.N. (2003).
The inuence of painful sunburns and lifetime sun exposure on the risk of actinic kera-
toses, seborrheic warts, melanocytic nevi, atypical nevi, and skin cancer. The Journal
of Investigative Dermatology, 120(6), 10871093.
Kenny, A.M., Biskup, B., Robbins, B., Marcella, G., & Burleson, J.A. (2003). Effects of
vitamin D supplementation on strength, physical function, and health perception in
older, community-dwelling men. Journal of the American Geriatrics Society, 51(12),
17621767.
Kimlin, M.G., Olds, W.J., & Moore, M.R. (2007). Location and vitamin D synthesis: Is the
hypothesis validated by geophysical data? Journal of Photochemistry and Photobiol-
ogy. B, Biology, 86(3), 234239.
Klontz, K.C., & Acheson, D.W. (2007). Dietary supplement-induced vitamin D intoxication.
The New England Journal of Medicine, 357(3), 308309.
Koutkia, P., Chen, T.C., & Holick, M.F. (2001). Vitamin D intoxication associated with an
over-the-counter supplement. The New England Journal of Medicine, 345(1), 6667.
Koutkia, P., Lu, Z., Chen, T.C., & Holick, M.F. (2001). Treatment of vitamin D deciency
due to Crohns disease with tanning bed ultraviolet B radiation. Gastroenterology,
121(6), 14851488.
Lappe, J.M., Cullen, D.M., Thompson, K., & Ahlf, R. (2007, February). Calcium and vita-
min D supplementation reduces incidence of stress fractures in Navy recruits. Paper
presented at the Orthopaedic Research Society 53rd annual meeting, San Diego, CA.
Larsen, E.R., Mosekilde, L., & Foldspang, A. (2004). Vitamin D and calcium supplementation
prevents osteoporotic fractures in elderly community dwelling residents: A pragmatic
population-based 3-year intervention study. Journal of Bone and Mineral Research,
19(3), 370378.
Lehtonen-Veromaa, M., Mottonen, T., Irjala, K., Karkkainen, M., Lamberg-Allardt, C.,
Hakola, P., et al. (1999). Vitamin D intake is low and hypovitaminosis D common in
healthy 9- to 15-year-old Finnish girls. European Journal of Clinical Nutrition, 53(9),
746751.
Lemire, J.M. (1992). Immunomodulatory role of 1,25-dihydroxyvitamin D
3
. Journal of
Cellular Biochemistry, 49(1), 2631.
Leslie, W.D., Derksen, S., Metge, C., Lix, L.M., Salamon, E.A., Wood Steiman, P., et al.
(2004). Fracture risk among First Nations people: A retrospective matched cohort study.
Canadian Medical Association Journal, 171(8), 869873.
Lips, P. (2004). Which circulating level of 25-hydroxyvitamin D is appropriate? The Journal
of Steroid Biochemistry and Molecular Biology, 8990(15), 611614.
Lips, P. (2006). Vitamin D physiology. Progress in Biophysics and Molecular Biology,
92(1), 48.
Lips, P. (2007). Vitamin D status and nutrition in Europe and Asia. The Journal of Steroid
Biochemistry and Molecular Biology, 103(3-5), 620625.
Liu, P.T., Stenger, S., Li, H., Wenzel, L., Tan, B.H., Krutzik, S.R., et al. (2006). Toll-like
receptor triggering of a vitamin D-mediated human antimicrobial response. Science,
311(5768), 17701773.
Looker, A.C., Dawson-Hughes, B., Calvo, M.S., Gunter, E.W., & Sahyoun, N.R. (2002).
Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopu-
lations from NHANES III. Bone, 30(5), 771777.
222 Willis, Peterson, and Larson-Meyer
Mahon, B.D., Gordon, S.A., Cruz, J., Cosman, F., & Cantorna, M.T. (2003). Cytokine prole
in patients with multiple sclerosis following vitamin D supplementation. Journal of
Neuroimmunology, 134(12), 128132.
Maimoun, L., Manetta, J., Couret, I., Dupuy, A.M., Mariano-Goulart, D., Micallef, J.P., et
al. (2006). The intensity level of physical exercise and the bone metabolism response.
International Journal of Sports Medicine, 27(2), 105111.
Martineau, A.R., Wilkinson, R.J., Wilkinson, K.A., Newton, S.M., Kampmann, B., Hall,
B.M., et al. (2007). A single dose of vitamin D enhances immunity to mycobacteria.
American Journal of Respiratory and Critical Care Medicine, 176(2), 208213.
McAlindon, T.E., Felson, D.T., Zhang, Y., Hannan, M.T., Aliabadi, P., Weissman, B., et
al. (1996). Relation of dietary intake and serum levels of vitamin D to progression
of osteoarthritis of the knee among participants in the Framingham Study. Annals of
Internal Medicine, 125(5), 353359.
Merlino, L.A., Curtis, J., Mikuls, T.R., Cerhan, J.R., Criswell, L.A., & Saag, K.G. (2004).
Vitamin D intake is inversely associated with rheumatoid arthritis: Results from the
Iowa Womens Health Study. Arthritis and Rheumatism, 50(1), 7277.
Moore, M.E., Piazza, A., McCartney, Y., & Lynch, M.A. (2005). Evidence that vitamin D
3

reverses age-related inammatory changes in the rat hippocampus. Biochemical Society
Transactions, 33(Pt. 4), 573577.
Mowe, M., Haug, E., & Bohmer, T. (1999). Low serum calcidiol concentration in older
adults with reduced muscular function. Journal of the American Geriatrics Society,
47(2), 220226.
Muller, K., Diamant, M., & Bendtzen, K. (1991). Inhibition of production and function of
interleukin-6 by 1,25-dihydroxyvitamin D
3
. Immunology Letters, 28(2), 115120.
Murphy, S.C., Whited, L.J., Rosenberry, L.C., Hammond, B.H., Bandler, D.K., & Boor,
K.J. (2001). Fluid milk vitamin fortication compliance in New York State. Journal
of Dairy Science, 84(12), 28132820.
Nakamura, K., Nashimoto, M., Hori, Y., & Yamamoto, M. (2000). Serum 25-hydroxyvitamin
D concentrations and related dietary factors in peri- and postmenopausal Japanese
women. The American Journal of Clinical Nutrition, 71(5), 11611165.
Nesby-ODell, S., Scanlon, K.S., Cogswell, M.E., Gillespie, C., Hollis, B.W., Looker, A.C.,
et al. (2002). Hypovitaminosis D prevalence and determinants among African American
and White women of reproductive age: Third National Health and Nutrition Examination
Survey, 19881994. The American Journal of Clinical Nutrition, 76(1), 187192.
Nieman, D.C. (2000). Special feature for the Olympics: Effects of exercise on the immune
system: Exercise effects on systemic immunity. Immunology and Cell Biology, 78(5),
496501.
Ostrowski, K., Hermann, C., Bangash, A., Schjerling, P., Nielsen, J.N., & Pedersen, B.K.
(1998). A trauma-like elevation of plasma cytokines in humans in response to treadmill
running. The Journal of Physiology, 513(Pt 3), 889894.
Outila, T.A., Karkkainen, M.U., Seppanen, R.H., & Lamberg-Allardt, C.J. (2000). Dietary
intake of vitamin D in premenopausal, healthy vegans was insufcient to maintain
concentrations of serum 25-hydroxyvitamin D and intact parathyroid hormone within
normal ranges during the winter in Finland. Journal of the American Dietetic Associa-
tion, 100(4), 434441.
Plotnikoff, G.A., & Quigley, J.M. (2003). Prevalence of severe hypovitaminosis D in patients
with persistent, nonspecic musculoskeletal pain. Mayo Clinic Proceedings, 78(12),
14631470.
Rankinen, T., Lyytikainen, S., Vanninen, E., Penttila, I., Rauramaa, R., & Uusitupa, M.
(1998). Nutritional status of the Finnish elite ski jumpers. Medicine and Science in
Sports and Exercise, 30(11), 15921597.
Vitamin D and Athletes 223
Rigby, W.F., Denome, S., & Fanger, M.W. (1987). Regulation of lymphokine production and
human T lymphocyte activation by 1,25-dihydroxyvitamin D
3
. Specic inhibition at the
level of messenger RNA. The Journal of Clinical Investigation, 79(6), 16591664.
Rigby, W.F., Noelle, R.J., Krause, K., & Fanger, M.W. (1985). The effects of 1,25-dihy-
droxyvitamin D
3
on human T lymphocyte activation and proliferation: A cell cycle
analysis. Journal of Immunology (Baltimore, Md.: 1950), 135(4), 22792286.
Rigby, W.F., Stacy, T., & Fanger, M.W. (1984). Inhibition of T lymphocyte mitogenesis by
1,25-dihydroxyvitamin D
3
(calcitriol). The Journal of Clinical Investigation, 74(4),
14511455.
Robson-Ansley, P.J., Blannin, A., & Gleeson, M. (2007). Elevated plasma interleukin-6
levels in trained male triathletes following an acute period of intense interval training.
European Journal of Applied Physiology, 99(4), 353360.
Ruohola, J.P., Laaksi, I., Ylikomi, T., Haataja, R., Mattila, V.M., Sahi, T., et al. (2006). Asso-
ciation between serum 25(OH)D concentrations and bone stress fractures in Finnish
young men. Journal of Bone and Mineral Research, 21(9), 14831488.
Sato, Y., Iwamoto, J., Kanoko, T., & Satoh, K. (2005). Low-dose vitamin D prevents mus-
cular atrophy and reduces falls and hip fractures in women after stroke: A randomized
controlled trial. Cerebrovascular Diseases (Basel, Switzerland), 20(3), 187192.
Simpson, R.U., Thomas, G.A., & Arnold, A.J. (1985). Identication of 1,25-dihydroxyvi-
tamin D
3
receptors and activities in muscle. The Journal of Biological Chemistry,
260(15), 88828891.
Sita-Lumsden, A., Lapthorn, G., Swaminathan, R., & Milburn, H.J. (2007). Reactivation
of tuberculosis and vitamin D deciency: The contribution of diet and exposure to
sunlight. Thorax, 62, 10031007.
Smith, L.L. (2000). Cytokine hypothesis of overtraining: A physiological adaptation to
excessive stress? Medicine and Science in Sports and Exercise, 32(2), 317331.
Snijder, M.B., van Dam, R.M., Visser, M., Deeg, D.J., Dekker, J.M., Bouter, L.M., et al.
(2005). Adiposity in relation to vitamin D status and parathyroid hormone levels: A
population-based study in older men and women. The Journal of Clinical Endocrinol-
ogy and Metabolism, 90(7), 41194123.
Snyder, R.A., Koester, M.C., & Dunn, W.R. (2006). Epidemiology of stress fractures. Clinics
in Sports Medicine, 25(1), 3752, viii.
Spellerberg, A.E. (1952). [Increase of athletic effectiveness by systematic ultraviolet irradia-
tion]. Strahlentherapie, 88(34), 567570.
Stumpf, W.E., Sar, M., Reid, F.A., Tanaka, Y., & DeLuca, H.F. (1979). Target cells for 1,25-
dihydroxyvitamin D
3
in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid.
Science, 206(4423), 11881190.
Tangpricha, V., Pearce, E.N., Chen, T.C., & Holick, M.F. (2002). Vitamin D insufciency
among free-living healthy young adults. The American Journal of Medicine, 112(8),
659662.
Tangpricha, V., Turner, A., Spina, C., Decastro, S., Chen, T.C., & Holick, M.F. (2004).
Tanning is associated with optimal vitamin D status (serum 25-hydroxyvitamin D
concentration) and higher bone mineral density. The American Journal of Clinical
Nutrition, 80(6), 16451649.
Trang, H.M., Cole, D.E., Rubin, L.A., Pierratos, A., Siu, S., & Vieth, R. (1998). Evidence that
vitamin D
3
increases serum 25-hydroxyvitamin D more efciently than does vitamin
D
2
. The American Journal of Clinical Nutrition, 68(4), 854858.
Valimaki, V.V., Alfthan, H., Lehmuskallio, E., Loyttyniemi, E., Sahi, T., Stenman, U.H., et
al. (2004). Vitamin D status as a determinant of peak bone mass in young Finnish men.
The Journal of Clinical Endocrinology and Metabolism, 89(1), 7680.
Valimaki, V.V., Alfthan, H., Lehmuskallio, E., Loyttyniemi, E., Sahi, T., Suominen, H., et al.
(2005). Risk factors for clinical stress fractures in male military recruits: A prospective
cohort study. Bone, 37(2), 267273.
224 Willis, Peterson, and Larson-Meyer
Vieth, R. (1999). Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and
safety. The American Journal of Clinical Nutrition, 69(5), 842856.
Vieth, R. (2004). Why the optimal requirement for vitamin D
3
is probably much higher than
what is ofcially recommended for adults. The Journal of Steroid Biochemistry and
Molecular Biology, 8990(15), 575579.
Vieth, R. (2006). What is the optimal vitamin D status for health? Progress in Biophysics
and Molecular Biology, 92(1), 2632.
Vieth, R., Bischoff-Ferrari, H., Boucher, B.J., Dawson-Hughes, B., Garland, C.F., Heaney,
R.P., et al. (2007). The urgent need to recommend an intake of vitamin D that is effec-
tive. The American Journal of Clinical Nutrition, 85(3), 649650.
Wang, T.T., Nestel, F.P., Bourdeau, V., Nagai, Y., Wang, Q., Liao, J., et al. (2004). Cutting
edge: 1,25-Dihydroxyvitamin D
3
is a direct inducer of antimicrobial peptide gene
expression. Journal of Immunology (Baltimore, Md.: 1950), 173(5), 29092912.
Webb, A.R. (2006). Who, what, where and whenInuences on cutaneous vitamin D
synthesis. Progress in Biophysics and Molecular Biology, 92(1), 1725.
Weiler, H.A., Leslie, W.D., Krahn, J., Steiman, P.W., & Metge, C.J. (2007). Canadian
Aboriginal women have a higher prevalence of vitamin D deciency than non-Aborigi-
nal women despite similar dietary vitamin D intakes. The Journal of Nutrition, 137(2),
461465.
Weisberg, P., Scanlon, K.S., Li, R., & Cogswell, M.E. (2004). Nutritional rickets among
children in the United States: Review of cases reported between 1986 and 2003. The
American Journal of Clinical Nutrition, 80(6, Suppl.), 1697S1705S.
West, N.P., Pyne, D.B., Renshaw, G., & Cripps, A.W. (2006). Antimicrobial peptides and
proteins, exercise and innate mucosal immunity. FEMS Immunology and Medical
Microbiology, 48(3), 293304.
Whiting, S.J., & Calvo, M.S. (2005a). Dietary recommendations for vitamin D: A critical
need for functional end points to establish an estimated average requirement. The
Journal of Nutrition, 135(2), 304309.
Whiting, S.J., & Calvo, M.S. (2005b). Dietary recommendations to meet both endocrine
and autocrine needs of vitamin D. The Journal of Steroid Biochemistry and Molecular
Biology, 97(12), 712.
Wicherts, I.S., van Schoor, N.M., Boeke, A.J., Visser, M., Deeg, D.J., Smit, J., et al. (2007).
Vitamin D status predicts physical performance and its decline in older persons. The
Journal of Clinical Endocrinology and Metabolism, 92(6), 20582065.
Willis, K.S., Peterson, N.J., & Larson-Meyer, D.E. (2007, April). Vitamin D status of distance
runners residing in the southern United States. Paper presented at the Sports Nutrition
Training Camp, SCANs 23rd annual symposium, Austin, TX.
Wolpowitz, D., & Gilchrest, B.A. (2006). The vitamin D questions: How much do you
need and how should you get it? Journal of the American Academy of Dermatology,
54(2), 301317.
Wortsman, J., Matsuoka, L.Y., Chen, T.C., Lu, Z., & Holick, M.F. (2000). Decreased
bioavailability of vitamin D in obesity. The American Journal of Clinical Nutrition,
72(3), 690693.
Yanoff, L.B., Parikh, S.J., Spitalnik, A., Denkinger, B., Sebring, N.G., Slaughter, P., et al.
(2006). The prevalence of hypovitaminosis D and secondary hyperparathyroidism in
obese Black Americans. Clinical Endocrinology, 64(5), 523529.
Zhu, Y., Mahon, B.D., Froicu, M., & Cantorna, M.T. (2005). Calcium and 1 alpha,25-dihy-
droxyvitamin D
3
target the TNF-alpha pathway to suppress experimental inammatory
bowel disease. European Journal of Immunology, 35(1), 217224.
Ziegler, P., Nelson, J.A., Barratt-Fornell, A., Fiveash, L., & Drewnowski, A. (2001). Energy
and macronutrient intakes of elite gure skaters. Journal of the American Dietetic
Association, 101(3), 319325.
Zittermann, A. (2003). Vitamin D in preventive medicine: Are we ignoring the evidence?
The British Journal of Nutrition, 89(5), 552572.