Metabolic Markers in Sports Medicine

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Metabolic markers in sports

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Article in Advances in clinical chemistry · December 2012

DOI: 10.1016/B978-0-12-394317-0.00015-7 · Source: PubMed
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ADVANCES IN CLINICAL CHEMISTRY, VOL. 56
METABOLIC MARKERS IN SPORTS MEDICINE

Giuseppe Banfi,*,†,1 Alessandra Colombini,* Giovanni
Lombardi,* and Anna Lubkowska‡,§
*IRCCS Istituto Ortopedico Galeazzi, Milano, Italy

†
School of Medicine, University of Milano, Milano, Italy
‡
Department of Physiology, Faculty of Natural Sciences,
Szczecin University, Szczecin, Poland
§
Chair and Department of Biochemistry and Medical Chemistry,
Pomeranian Medical University, Szczecin, Poland
1. Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3. Liver Metabolism Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.1. Aminotransferases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.2. Bilirubin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
4. Muscle Metabolism Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
4.1. Creatine Kinase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
4.2. Lactate Dehydrogenase and Other Markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
4.3. Myocardial Markers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
5. Kidney Parameters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
5.1. Creatinine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
5.2. Urea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.3. Cystatin C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
6. Uric Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
7. Glucose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
8. Lipid Profile. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
9. Bone Metabolism Markers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
10. Effect of Body-Mass Index on Laboratory Parameters. . . . . . . . . . . . . . . . . . . . . . . . . . 40
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
1
Corresponding author: Giuseppe Banfi, e-mail: [email protected]
0065-2423/12 $35.00 Copyright 2012, Elsevier Inc.

DOI: 10.1016/B978-0-12-394317-0.00015-7 All rights reserved.
2 BANFI ET AL.
1. Abstract
Physical exercise induces adaptations in metabolism considered beneficial

for health. Athletic performance is linked to adaptations, training, and
correct nutrition in individuals with genetic traits that can facilitate such
adaptations. Intense and continuous exercise, training, and competitions,
however, can induce changes in the serum concentrations of numerous labo-
ratory parameters. When these modifications, especially elevated laboratory
levels, result outside the reference range, further examinations are ordered or
participation in training and competition is discontinued or sports practice
loses its appeal. In order to correctly interpret commonly used laboratory
data, laboratory professionals and sport physicians need to know the behav-
ior of laboratory parameters during and after practice and competition. We
reviewed the literature on liver, kidney, muscle, heart, energy, and bone
parameters in athletes with a view to increase the knowledge about clinical
chemistry applied to sport and to stimulate studies in this field.
In liver metabolism, the interpretation of serum aminotransferases concen-
tration in athletes should consider the release of aspartate aminotransferase
(AST) from muscle and of alanine aminotransferase (ALT) mainly from the
liver, when bilirubin can be elevated because of continuous hemolysis, which is
typical of exercise. Muscle metabolism parameters such as creatine kinase (CK)
are typically increased after exercise. This parameter can be used to interpret the
physiological release of CK from muscle, its altered release due to rhabdomyol-
ysis, or incomplete recovery due to overreaching or trauma. Cardiac markers
are released during exercise, and especially endurance training. Increases in
these markers should not simply be interpreted as a signal of cardiac damage
or wall stress but rather as a sign of regulation of myocardial adaptation. Renal
function can be followed in athletes by measuring serum creatinine concentra-
tion, but it should be interpreted considering the athlete’s body-mass index
(BMI) and phase of the competitive season; use of cystatin C could be a reliable
alternative to creatinine. Exercise and training induce adaptations in glucose
metabolism which improve glucose utilization in athletes and are beneficial for
reducing insulin insensitivity in nonathletes. Glucose metabolism differs slightly
for different sports disciplines, as revealed in laboratory levels. Sport activities
induce a blood lipid profile superior to that of sedentary subjects. There are few
reports for a definitive conclusion, however. The differences between athletes
and sedentary subjects are mainly due to high-density lipoprotein cholesterol
(HDLC) concentrations in physically active individuals, although some differ-
ences among sport disciplines exist. The effect of sports on serum and urinary
markers for bone metabolism is not univocal; further studies are needed to
establish the real and effective influence of sport on bone turnover and especially
to establish its beneficial effect.
METABOLIC MARKERS IN SPORTS MEDICINE 3
2. Introduction
Physical activity is recommended for controlling weight, delaying the onset

of chronic disorders, and preventing various diseases; it has become a cor-
nerstone for well-being, fitness, and healthy lifestyle. With regular physical
activity, the body enhances fuel utilization by adapting its metabolism to
increased energy expenditure. The science of training studies the beneficial
adaptations the body makes to improve performance. Athletic performance
is linked to adaptation, training, and correct nutrition in individuals with
genetic traits which can facilitate such adaptations. Sports-induced metabolic
changes, however, can alter the serum concentrations of numerous laborato-
ry parameters. These modifications, especially increases, can often result
outside the normal range, leading to further examinations or discontinuation
of training and competition. Moreover, when apparently anomalous mod-
ifications are detected in an athlete practicing a specific competition or sport,
he/she will be warned about the potential dangers associated with physical
activity, creating a dilemma about the benefits and hazards of sport [1,2].
It is important, therefore, that clinical chemists and sport physicians know
the changes in metabolism in athletes, as disclosed through common labora-
tory parameters measured in the clinical laboratory or directly on the field [3]
in many cases.
The behavior of laboratory parameters in athletes, especially in profes-
sional athletes, has not been extensively studied and described. The length of
the various chapters of the present review is an approximate measure of the
interest in different parameters in sports medicine and applied physiology.
We reviewed the literature on liver, kidney, muscle, heart, energy, and bone
parameters in athletes with a view to increase current knowledge about clinical
chemistry applied to sports and to stimulate further studies in this field.
3. Liver Metabolism Parameters
3.1. AMINOTRANSFERASES
Aminotransferases (AST, ALT) are commonly analyzed in serum to assess
and monitor liver damage and possible viral infections of the liver. ALT is
found mainly in the liver but also in smaller amounts in the kidneys, heart,
muscles, and pancreas while AST is present in the liver but in considerable
amounts also in other tissues including the muscles.
Studies in the general population and blood donors have shown a clear
correlation between ALT concentrations and body weight and BMI (weight
in kilograms divided by height in meters squared [BMI]) [4–6]. A similar
correlation was also described for AST in two studies [5,7].
4 BANFI ET AL.
The resting aminotransferase concentrations and the BMI of 116 male

professional athletes from 7 different sport disciplines (rugby, triathlon,
soccer, sailing, cycling, basketball, alpine skiing) were measured before the
start of training and the competitive season. The average AST and ALT
concentration for the whole group was 24.4 10.5 and 23.6 6.5 U/L,
respectively. There was no statistically significant difference in concentra-
tions between the athletes and sedentary subjects. In the athletes, a positive
correlation was found between BMI and ALT and a very weak negative
correlation between BMI and AST. Assessment of elevated ALT concentra-
tions should therefore include BMI, while interpretation of high AST levels
should take into account the fact that AST is released from muscles during
physical exercise [8].
No differences in serum AST and ALT concentrations were found between
athletes (runners, hammer throwers, wrestlers, weightlifters) and age-
matched sedentary subjects. There were no differences in aminotransferase
concentrations between the athlete groups, except for the lower values in the
wrestlers [9].
Aminotransferases are also released from activated muscles, and levels can
increase after acute physical exercise. However, AST and ALT levels differ
during and after sport performances. After a marathon, for example, the
AST concentration in 37 runners rose significantly from a basal value of 29.3
to 51.6 U/L at 4 h after the end of race and to 106.9 U/L at 24 h, whereas ALT
did not increase significantly: basal 21.8 versus 24.8 and 29.8 U/L at 4 and
24 h after the end of the race [10]. Augmentation of aminotransferases is
linked to performance intensity and duration, as found for both enzymes in
ultraendurance events [11], whereas neither does practice, even when intense,
appear to modify serum AST and ALT concentrations [12] nor does mara-
thon running [10].
High AST and ALT values (> 30 U/L) in professional American football
players have been reportedly linked to liver involvement in the metabolic
syndrome, contrasting with the apparent health status of these athletes [13].
In American football players, AST and ALT values measured before and
after a game showed a significant increase in AST due to muscular damage
[14]; increased AST was also correlated with muscle cramps during twice-a-
day practices in training camp [15]. In elite road cyclists, who had increased
iron body stores and a liver overload of ferritin accumulation, serum AST
and ALT concentrations were not abnormally elevated and, consequently,
did not reveal liver damage [16].
Notably, high liver enzymatic levels can result from the abuse of anabolic–
androgenic steroids which are metabolized in the liver. ALT and AST were
two times higher in 17 steroid abuser bodybuilders than in 15 former abusers.
The aminotransferase concentrations were correlated with the extent
(duration and dosage) of steroid abuse; the mean hormone dosage was 1.03 g
per week for 33 weeks per year over 8 years [17]. Hormone dosage is crucial,
since liver enzymes can result within their reference range after low-dose
administration [18].
Accurate assessment and interpretation of ALT and AST concentrations
in professional and nonprofessional athletes are essential for diagnosis and
prevention.
In summary:
– interpretation of serum aminotransferase concentration in athletes
should consider the release of AST from muscles and the release of ALT
mainly from the liver.
3.2. BILIRUBIN
Bilirubin production closely depends on erythrocyte destruction and
physiological turnover and, in turn, on hemoglobin catabolism. Hemolysis
is highly increased in athletes. The principal source of increased red blood
cell (RBC) turnover is the intravascular hemolysis common in some sports
that is caused by impact with the ground (footstrike hemolysis), mechanical
damage to RBCs during continuous muscle contractions [19], continuous
exposure to high-oxygen flux which causes oxidative damage, and pertur-
bation of osmotic homeostasis which might render RBCs more susceptible
to membrane damage during their transit through the microcirculation.
Since sport-induced hemolysis has mainly been investigated in studies on
acute exercise [20], it is difficult to evaluate its influence over an entire
competitive season.
Because hemolysis is increased in intense exercise, serum concentrations of
total and indirect bilirubin are often high in athletes. For example, in 100 elite
athletes from 11 sports (56 males and 44 females; mean age 19 years, range
16–27), elevated bilirubin concentration was the second laboratory abnor-
mality found during screening, preceded only by increased AST. When the
test was repeated only on athletes with apparently abnormal values, bilirubin
ranked first. These data are limited because the phase of season and the
physical demand by practice and competition were not taken into account;
nonetheless, the results identify high bilirubin as common place among
athletes [3].
Variability of bilirubin concentration after acute exercise was described in
37 marathoners in which total bilirubin significantly increased from 0.5 to
0.8 mg/dL at 4 h and remained at 0.8 mg/dL at 24 h after the race. Direct
bilirubin increased from 0.2 to 0.3 and 0.4 mg/dL at the same time points. In
19/37 participants, the bilirubin level was higher than the reference interval:
6 BANFI ET AL.
the increase was explained by augmented hemolysis during the race [10]. In
an ultraendurance race (1600 km, 16 days duration), bilirubin rose from 1.1
to 1.9 mg/dL at day 4, but dropped to 0.9 at day 11, and remained at this level
after the race. The lowest haptoglobin concentration was reported at day 3 of
the race, demonstrating that hemolysis peaked during the early stage of the
event [21]. This result confirmed the early increase and subsequent stabiliza-
tion of bilirubin found in athletes during an extreme long-distance race [22]
and the marked increase from 1.0 0.1 to 3.1 0.4 mg/dL after an ultra-
endurance race (32–36-h duration) [23].
In a study involving 10 elite soccer players over a competition season,
blood samples were drawn at the end of the regular season (May), after the
recovery period (June), and then after the next preseason training (August).
Mean bilirubin values significantly increased at the end of the recovery
period (mean 1.05 mg/dL), and then returned to baseline (0.7 mg/dL) before
the start of the new season, that is, the values measured at the end of season
representing the phase of maximal exhaustion. The increase in bilirubin after
the recovery phase, in combination with the increase in granulocytes, inter-
leukin 8 (IL-8), serum nitrate, and ferritin, indicated a compensated hypo-
perfusion and a relative hypoxia during the season, followed by a reperfusion
during the recovery phase associated with muscle protein turnover and
inflammatory endothelial reaction [24]. In a study involving 20 elite soccer
players before the start of practice and competition, no difference in the mean
bilirubin concentration was found between athletes (0.89 0.36 mg/dL) and
controls (0.86 0.47 mg/dL) [25].
A relationship between bilirubin concentration and hemolysis over a
whole competition season was reported in 24 male rugby players (age
range 19–35 years) from the Italian National team. The blood drawings
were performed before the start of the training and competitive seasons in
August 2004 and at the end of the competitive season in May 2005. The
significant increase in bilirubin after the season (from a mean 0.4 to
0.6 mg/dL) was accompanied by a significant decrease in haptoglobin,
demonstrating the continuous, rising effect of hemolysis over time. More-
over, the mean sphered cell volume (MSCV), a hematological index of
erythrocytes, had significantly decreased by the end of the season. There-
fore, since the decrease in MSCV associated with an indirect increase in
bilirubin is a specific sign of erythrocyte destruction, specific training and
competition schemes and diet or therapy modifications should be decided
according to these values [26].
In summary:
– bilirubin could be elevated in athletes because of continuous hemolysis,
which is typical of exercise.
4. Muscle Metabolism Parameters
4.1. CREATINE KINASE

Strenuous overexertion exercise can result in muscle damage evidenced by
delayed-onset muscle soreness, strength loss, weakness, tenderness, and
increased blood levels of muscle proteins including CK, lactate dehydroge-
nase (LDH), and myoglobin (Mb) [27]. Exertional rhabdomyolysis is a
clinical condition in which excessive muscle damage can lead to renal failure
and is typically described in extreme, ultraendurance exercise [28]. CK and
other intramuscular proteins are cleared from the blood by the reticuloendo-
thelial system, while myoglobin is cleared by the kidneys. High blood myo-
globin levels induce a selective proteinuria into the urine, resulting in
myoglobinuria when the protein is not completely reabsorbed by the renal
tubules, and it can also precipitate in the kidney tubules, potentially resulting
in acute renal failure, especially in such environmental conditions as heat
stress and dehydration [27]. The release of proteins from myocells during
exercise is due to increased membrane permeability or membrane breakage
[29]. The increased permeability could be linked to the increase in oxidant
species typical of exercise which peroxidises membranes. Serum CK activity
has been studied extensively and is considered a qualitative marker for
skeletal muscle microtrauma [30]. The increase in serum CK during sport
performances depends on exercise duration, with peak values recorded after
endurance events [10]. Elevated CK is also typical of eccentric exercise.
Training induces CK augmentation, with higher values recorded for seden-
tary subjects than athletes, demonstrating the adaptive behavior of trained
muscles [31]. In a study involving track and field athletes in four running
workouts that differed in distance (300 vs. 400 m) and mode of execution
(continuous/single vs. intermittent), the increase in CK during training
depended on the intensity and not the type of regimen [32]. The combined
effect of resistance exercise and hydration state on muscle damage was
studied in seven healthy resistance-trained athletes who completed three
identical resistance exercise bouts (6 sets of up to 10 repetitions of the back
squat) in different hydration states: euhydrated, hypohydrated (approxi-
mately 2.5% body mass), and hypohydrated (approximately 5.0% body
mass). The CK concentrations remained within the normal resting range at
all time points, showing that hypohydration did not cause muscle damage
following the resistance exercise challenge [33].
The medium concentration and distribution of CK and the CK isoenzyme
MB levels in physically active subjects are significantly higher (nearly double)
than those of sedentary individuals matched for age and sex. This remarkable
difference with the sedentary population was observed in athletes who had
8 BANFI ET AL.
rested for a period of 24–48 h since the last training, and it was comparable
between athletes in medium- and high-workload endurance training [34]. In
athletes, CK should therefore be measured at 48 h after practice or competi-
tion [35]. CK levels should be monitored during and after exercise to evaluate
recovery, that is, to determine whether the levels return to basal, preexercise
values or high values persist which can be a signal of trauma, overtraining, or
muscular pathology. In rugby league players deliberately overreached
through intensive training, the mean serum CK concentration after the
programmed exercise cycle was significantly higher than that of normally
trained teammates (1402 vs. 664 U/L) [36]. Similar results were reported for
eight well-trained cyclists after 2 weeks of intense training, with a subsequent
reduction in CK activity after 7 days of recovery [37]. This demonstrated that
muscle recovery cannot be determined only from changes in serum CK levels,
as no correlation exists between serum enzyme leakage and muscular perfor-
mance impairment after exercise [38]. Persistently elevated CK accompanied
by reduced exercise tolerance is suggestive of overtraining.
Elevated CK is commonly encountered in athletes [39]. To calculate refer-
ence values, CK was assayed in serum samples from 483 male and 245 female
athletes (age range 7–44 years). The samples were collected throughout the
training and competition periods. All athletes were members of Greek sport
clubs and had been training for 2–25 years (median 8 years), undertaking
5–10 training sessions per week (median 6 sessions), and exercising 1–2 h per
training session (median 1.6 h). They practiced a wide variety of sports,
including both endurance and strength/power activities: running (sprint,
middle distance, and endurance); jumping; throwing; combined events
(triathlon, heptathlon, and decathlon); swimming (sprint and middle distance);
cycling; rowing; kayaking; football (soccer); basketball; volleyball; handball;
water polo; tennis; table tennis; gymnastics; judo; taekwondo; karate; boxing;
weightlifting; bodybuilding; diving; motocross; and snowboarding.
For comparison, CK was also assayed in a smaller number of nonathletes.
The reference intervals were nonparametrically calculated (2.5th–97.5th per-
centile): the reference intervals were 82–1083 U/L in the male and 47–513 U/L
in the female athletes. The upper reference limits were twice the limit reported
for moderately active nonathletes or as calculated in the nonathletes in this
study. The upper limits were up to six times higher than the limits reported for
inactive individuals in the literature. A limitation of the study was the recruit-
ment of athletes during various season phases, but a merit was the definition of
concentrations for specific sports. The lower reference limits were 83 U/L
(confidence interval [CI] 53–84) for the male football players and 70 U/L
(CI 61–89) for the male swimmers. The upper reference limits were 1492
(CI 924–1908) and 523 (CI 435–543) U/L, respectively. Reference intervals
are usually proposed for the general population.
Although CK concentrations have mainly been studied in individual,

endurance exercise performances, it is also interesting to evaluate this para-
meter in team sports, which are characterized by heavy, intense training and
competitions. Rugby is considered one of the most intense and physically
demanding field games in the world. CK was measured in 10 top-level rugby
players during an international rugby tournament. The samples were taken
on entry to the camp, the morning of the game (pre-), within 15 min of the
conclusion of the game (post-) and again the following two mornings (14 and
38 h postgame, respectively). The mean CK values were 497 U/L in the first
sample, 333 U/L in the pregame sample, 519 U/L in the postgame sample,
and 1182 U/L at 14 h and 750 U/L at 38 h postgame. The postgame values
were significantly higher than the entry values and were related to player
involvement in tackles and game contact events [40]. The same correlation
has been described in other collision-type sports such as boxing, rugby, and
American football [14,41,42].
Plasma CK leakage results from muscle damage due to continuous trauma
during game contact events. Although there is a similar rising trend of CK
after a match, there are important differences in absolute CK values: in
collegiate American football players, CK was about 150 U/L, but never
higher than 250, after a game, without significant differences from pregame
concentrations, whereas myoglobin increased about 20 times. The explana-
tion for this finding was that the experience level of the subjects probably
minimized disruption of the skeletal muscle membrane and that the smaller
myoglobin molecule would leak out of the membrane more readily than the
larger CK molecules. However, training and adaptation were not considered
to be a source of minimal changes in CK, while the CK concentration was
similar between the two groups of athletes, that is, a group of athletes who
trained and played and a group who trained but did not play, while myoglo-
bin concentration differed between them [14]. Time of sampling is crucial,
because CK release is quite slow, generally peaking at 24 h after game end,
whereas myoglobin peaked after 45 min in 15 amateur rugby players. CK
and myoglobin values were correlated with the number of tackles [41].
Serum CK concentrations were studied in rugby players to define the
effectiveness of different recovery methodologies. Rugby matches were
found to produce significant increases in interstitial CK concentration, as
measured by a transdermal method, from pre- to postcompetition, with levels
of 1023 and 2194 U/L, respectively. The peak CK value was recorded for the
sample taken immediately after the end of the game. Active recovery consisted
of cycling after the match, compressive garments, or water contrast treatment,
that is, the players immersed their body to the level of the anterior superior
iliac spine in one of two temperature-controlled water baths, alternating
between 1 min in cold water (8–10 C) and 2 min in hot water (40–42 C) for
10 BANFI ET AL.
approximately 9 min. As judged from CK levels, active recovery was more

effective than passive recovery [43]. The differences between professional, top-
level New Zealander and amateur Japanese rugby players in terms of training
and competition strength were demonstrated by CK basal concentrations,
which were three times lower in the latter [41,43]. The stabilization of CK
concentrations in top-level Italian rugby players by active recovery (cycling
followed by cold water immersion of legs for 10 min) was demonstrated by
measuring serum CK after intense training [44]. However, the effects of active
recovery were contentious.
CK concentration was not affected by cold water recovery in physically
active subjects, owing to eccentric exercise-induced muscle damage. In this
study, ice-water immersion offered no benefit for pain, swelling, isometric
strength, and function, and made muscles more sore the following day. CK
concentrations were lower than those found in professional rugby players
[45]. In a group of 38 trained subjects, significant reductions in CK were
observed at 24 and 72 h postexercise following contrast water immersion,
and 48 h postexercise following hot water immersion when compared to
passive recovery. However, hydrotherapy interventions did not influence
postexercise changes in LDH or myoglobin [46].
In summary:
– serum CK concentration is typically increased after exercise
– there is a correlation between CK concentration and exercise intensity
and duration
– extremely high CK concentrations are found in rhabdomyolysis
– incomplete recovery, that is, a return to basal values, signals the occur-
rence of trauma or overtraining
– CK concentration might be used to monitor return to activity of athletes
with muscular injury.
4.2. LACTATE DEHYDROGENASE AND OTHER MARKERS

The investigation of LDH and CK isoenzymes provides additional infor-
mation not only on the state of the muscle but also on its biochemical
adaptation to the physical load, since patients with persistently elevated
CK activity also have altered LDH profiles [47]. Markers of both skeletal
muscle and myocardial damage have been identified, including the CK-MB
isoenzyme, myoglobin, and cardiac troponins, and it has been shown that
exercise may also influence the results of these investigations in asymptomatic
healthy subjects, particularly if exercise is prolonged or strenuous [48].
Professional cyclists at rest showed higher values of LDH and CK in
comparison with sedentary subjects [49].
A significant increase in mean CK, LDH, and AST was noted in a group of
white male runners immediately after a 13-mile minimarathon, as well as a
significant incidence of postexertional values above normal limits for CK
(93%) and LDH (86%), whereas no athlete exhibited abnormal AST values
[50]. Postrun levels of CK, CK-MB, LDH, and myoglobin were significantly
higher than the prerun levels as the result of moderate (5–10-mile run)
exercise in the absence of myocardial damage: immediately after the run,
the values of CK, CK-MB, LDH, myoglobin were 1.2, 1.5, 1.2, and 4 times
higher, respectively, than the prerun values [51]. After a half-marathon run,
the time-to-peak value varied widely among the parameters tested: AST,
LDH, and myoglobin peaked 3 h after the run, whereas the levels of CK
and CK-MB were still increasing at 24 h after the run. CK-MB was still
increasing at 24 h after the run. The major increment over the prehalf
marathon value was recorded for myoglobin, which increased nearly three-
fold, whereas AST and LDH increased 1.1- and 1.3-fold, respectively; at 24 h
after the end of the run, the concentration of CK and CK-MB was still 1.8-
and 1.5-fold higher than that measured at baseline [52].
CK, CK-MB, and myoglobin were significantly increased after the fourth
stage of a 5-day stage cycling race, but the increase was far lower than that
described in marathons and half-marathons [53].
4.3. MYOCARDIAL MARKERS

Strenuous exercise can generate transitory ischemia, myocardial stress,
and diastolic left ventricular dysfunction, often inducing an increase in
biochemical parameter concentrations usually measured in the diagnosis of
heart diseases. There is a consistent literature on the alterations in cardiac
markers after intense and long-lasting exercise in particular. Interpretation of
the changes, that is, the often dramatic increases mimicking an anomalous
condition of cardiac markers, shifted from being taken as signal of heart
damage and danger to health to the understanding that they reflected a
common body response to heavy cardiovascular demand during exercise.
4.3.1. NT-proBNP
Brain natriuretic peptide (BNP) is produced by cardiomyocytes and released
into bloodstream where it can be measured; the cleaved form of the BNP
precursor (amino acids 1–76) is the N-terminal proB-type natriuretic peptide
(NT-proBNP), which can also be measured in blood, and is a proposed marker
for evaluating and monitoring heart conditions characterized by myocardial
wall stress. This counter-regulatory hormone reduces myocardial wall stress by
increasing natriuresis, vasodilation, and sympathoinhibitory effects as an
12 BANFI ET AL.
antagonist to the renin–angiotensin system. It is also cytoprotective and a

growth regulator of cardiac cells.
Cardiac damage during marathon running has been described in 60 non-
professional athletes who participated in the 2005 Boston Marathon: 60% of
recreational runners showed increased troponin T after the race; NT-proBNP
concentration roughly doubled. Left ventricular size and ejection fraction did
not change, but a reduced left ventricular compliance was echocardiographi-
cally demonstrated. Changes in biochemical signs of cardiac damage were
higher in the subjects who had a low training workload [54].
Increased NT-proBNP after physical exercise has been typically described
in endurance athletes.
In 15 mountain bikers and 5 marathoners, NT-proBNP increased after 1
and 3 h of exercise from 21 pg/mL before to 30 pg/mL after 1 h and decreased
to basal value at 3 h after exercise; no clinical or echocardiographic signs of
heart damage were reported [55]. However, the values measured in endurance
athletes (10 triathletes, 5 cyclists, 5 marathoners) were not found to differ from
those of healthy untrained control subjects with a normal-sized heart: the
median was 24.7 pg/mL in the athletes and 28.9 pg/mL in the controls [56].
Lippi et al. [49] also found lower mean NT-proBNP levels in 50 profes-
sional cyclists compared with 35 sedentary subjects (23.6 vs. 36.3 pg/mL).
Endurance and strenuous exercise induce an increase in NT-proBNP, but the
serum concentration is rarely higher than the upper reference limit estab-
lished for the general population. In 15 mountain marathoners, the median
NT-proBNP concentration before the race was 39.7 pg/mL (range 19.3–
84.1 pg/mL). The median concentration after the race was 97.6 pg/mL
(range 46.9–190 pg/mL). The concentrations were significantly different
(P < 0.001); only in two cases was the concentration higher (> 125 pg/mL),
which is usually considered the pathological threshold. Of note is that the
distribution of values before the race was not Gaussian, while it was normal
after the race (mean 102.7 45.5 pg/mL) [57].
NT-proBNP was measured in 15 male athletes involved in an ultramarathon,
entitled Spartathlon, characterized by extreme conditions (246 km in distance,
5–36 C environmental temperature, and 60–85% humidity). Blood drawings
were performed before the race, within 15 min of the end of the race, and 48 h
later. NT-proBNP showed a dramatic increase after the ultramarathon. The
mean was 1280.6 259 pg/mL versus a basal value of 38.1 4.8 pg/mL; but at
48 h after the end of the event, the concentration decreased to about twice the
basal value (89.8 13.6 pg/mL). The changes in NT-proBNP paralleled those
of other parameters, including growth differentiation factor-15 (GDF 15), a
stress-responsive member of the transforming growth factor (TGF) b cytokine
superfamily. In animal models, GDF 15 is induced in the heart in response to
ischemia and reperfusion, pressure overload, and heart failure. Also endoglin,
an accessory protein of the TGF b receptor system expressed on endothelial

cells, which is a marker of activated endothelium, showed an increase after the
race, promptly recovered after 48 h, and was quantitatively much lower than
that of the other two parameters. The prolonged strenuous exercise induced an
inflammatory response affecting the oxidation, endothelial, and ventricular
wall stress markers, as demonstrated by the increase in GDF 15, endoglin,
and NT-proBNP. Marker increase is a signal of protection of heart, tissues,
and vessels, because a transient endothelial dysfunction occurs during ultra-
endurance races [58]. The amount of NT-proBNP released into the bloodstream
seems to depend on exercise duration: in an ultraendurance marathon (160 km),
NT-proBNP increased from a mean of 28 to 725 pg/mL in 25 athletes who
finished the race [59], while after a marathon, it rose from a mean of 39 to 139 pg/
mL in 15 female runners [60] and from a mean of 48 to 183 pg/mL in 27 runners
(25 M, 2 F) [61]. The values measured in endurance runners could be compared
with those recorded in endurance cyclists. In 29 male amateur cyclists partici-
pating in the Ötztaler Radmarathon (230 km distance, 5500 m altitude differ-
ence), NT-proBNP increased from 28 21 to 278 152 pg/mL immediately
after the race [62]. In professional cyclists, it increased after the fourth stage of a
5-day stage race, but was lower than that in amateurs (from 47.5 37.5 to
75.3 55.3 pg/mL) [53].
Recovery, that is, a return to basal BNP and NT-proBNP after a mara-
thon, is typically quite slow, needing up to 3 days; the increase in BNP is a
delayed in comparison to NT-proBNP: BNP did not increase immediately
after a marathon in 15 amateur female runners, while NT-proBNP concen-
tration was three times higher over the basal value [60].
Athlete age is an important factor in interpreting the increased NT-proBNP
after endurance sport performance. The marker increased after a marathon
involving young and old athletes (age > 60 years), but its concentration was
significantly higher in the older runners, in which postrace levels were about
three times higher than basal levels. Interestingly, there was a difference in
NT-proBNP between the groups (84.3 37.0 vs. 38.3 39.3 pg/mL) before
the race, with a wide interindividual variability. However, marathon running
did not induce heart dysfunction in the well-trained older athletes. The con-
centration was similar to the basal level at assessment 2 weeks postrace. The
individual postrace NT-proBNP increase was not age-dependent. The runners
with elevated postmarathon NT-proBNP did not differ with regard to weekly
training, running time, and age or any electrocardiographic variable at base-
line, postrace, or follow-up. Running a marathon is not associated with
age-related myocardial damage [63].
Conversely, in athletes presenting with left ventricular hypertrophy,
abnormal NT-proBNP concentration is a signal of hypertrophic cardiomyop-
athy, whereas normal values deserve follow-up and further examinations [64].
14 BANFI ET AL.
The NT-proBNP or BNP values in nonendurance athletes at rest are

usually low and physiological in comparison with sedentary healthy subjects,
as demonstrated in professional football players [65].
The median NT-proBNP concentration in top-level rugby players at rest was
29.1 (range 15.1–70.1 pg/mL) versus 51.9 pg/mL (range 30.1–77.3 pg/mL) in
nonathletes (P < 0.001) and similar (P > 0.05) to that in 44 professional soccer
players (median 32.4 pg/mL; range 11.3–91.8 pg/mL). In these 30 elite rugby
players, NT-proBNP concentrations significantly increased during a training
session. The median after training was 57.1 (range 27.2–143.8 pg/mL) and
61.7 pg/mL (range 29.2–176.4 pg/mL) after recovery. Elevated posttraining
NT-proBNP levels were unaffected by the type of recovery (active: cycling plus
ice-water immersion of legs). The relatively high NT-proBNP levels after active
recovery, when psychophysical stress is higher because of cycling and cold water
immersion, suggest that not only endurance exercise but also strenuous stressful
short exercise can induce an increase in NT-proBNP concentrations [66].
Increased NT-proBNP is also linked to the different lifespan of the mole-
cule in comparison with intact BNP, which does not increase after endurance
sports performance [67].
The increase in NT-proBNP during and after exercise reflects the growth-
regulating properties of BNP, which regulates myocardial adaptation in
healthy athletes and is not simply a signal of damage or wall stress [55].
Notably, serum concentration of BNP and other cardiac markers is not linked
with echocardiographically measured left ventricular mass [65] but is corre-
lated with ejection fraction [68]. The increase in NT-proBNP in 17 recreational
marathoners from 37.4 5.9 to 59.310.5 pg/mL immediately after a run and
to 68.1 11 pg/mL at 6 h after the end of the run was not correlated with
anomalies in heart function, as evaluated by cardiovascular magnetic reso-
nance [69]. Therefore, elevated serum concentrations of the marker should not
be interpreted as a danger signal, but rather as a physiological response to
intense heart activity. It could be hypothesized that myocardial response
during exercise might be regulated by BNP production and release in athletes
[70]. The adaptation of the heart to training is followed by increased BNP, as
found in healthy male British Army recruits, who had high resting values after
10 weeks of exercise, accompanied by an increase in left ventricular mass [71].
Moreover, NT-proBNP values should be correctly interpreted by consid-
ering the glomerular filtration rate (GFR) [72].
In summary:
– NT-proBNP, a marker of heart wall failure, increases after exercise
– increased serum NT-proBNP concentration in athletes should not be
interpreted as a signal of damage or wall stress, but rather as a sign of
regulation of myocardial adaptation.
4.3.2. Troponins
The exercise-related increase in cardiac biomarkers, especially in cardio-
specific troponins (cTns), has been extensively described, but a definitive
pathophysiological explanation has not been forthcoming. Evidence for
apparently abnormal serum troponin concentration in athletes, especially
after endurance performance, is enormously magnified by the novel highly
sensitive (Hs) cTns assays [73]. The number of athletes with postexercise
values exceeding the 99th percentile threshold of a normal healthy popula-
tion and/or the recommended cut-off corresponding to an optimal precision
(coefficient of variation 10%) might now dramatically increase with the
introduction of last generation assays. The wide differences among the
results from numerous studies on this topic are summarized in Table 1.
A recent meta-analysis pooling 16 studies involving 939 participants
showed that there were only six premarathon cTn elevations (0.6%) but as
many as 579 postrace elevations (62%). The odds ratio for converting from a
normal prerace to an elevated postrace cTn was 51.8. Age and gender were
not associated with postrace increases, but study publication date and assay
sensitivity were indeed associated with cTn elevation. Cardiac TnI was also
less commonly elevated versus cardiac TnT, which can be explained by the
greater sensibility of the latter assay. Currently, available data are consistent
with the hypothesis that cTn levels might frequently increase after strenuous
exercise [87].
Cardiac troponins are present in high concentrations in the myocyte, in
both a cytosolic and a structurally bound protein pool. The detection and
(or) increase after physical exercise probably do not reflect clinically threat-
ening myocardial injury. It could be linked to increased cellular permeability
and early troponin release (leakage) from the cytosolic pool or from a
different readily accessible cell pool [88]. The release from the heart of a
measurable amount of troponins should be transient and recover promptly
without irreversible consequences. A possible explanation for troponin re-
lease during exercise, especially when intense, is the production of blebs
during myocardial ischemia [89]. Blebs refer to ‘‘bubbles’’ developing from
the plasma membrane in response to temporary ischemia, which can be either
reabsorbed or shed into the circulation when reoxygenation is not completely
assured. When ischemia is severe and prolonged, the blebs grow, collapse and
cell necrosis occur [90].
Data from a study on the comparison between serum troponin and func-
tional cardiac parameters measured by a gold standard imaging methodolo-
gy (i.e., cardiovascular magnetic resonance) demonstrated that the increase
in troponins and other cardiac biomarkers was unrelated to either alterations
in cardiac function or any detectable myocardial damage. The study involved
TABLE 1
CHANGES IN TROPONINS AFTER EXERCISE
Type of Distance or
Assay Study population exercise duration Sampling Results Reference
Triage cTnI (Biosite 37 amateur runners Running Marathon Baseline, 4, 24 h Postexercise levels exceeded [10]
Diagnostic; USA) (32 M, 5 F; age postexercise the URL in none of the
49 10 years) athletes
cTnT (Modular; Roche 11 professional cyclists Cycling 5-day cycling race Before and Postexercise levels exceeded [53]
Diagnostics, (all M; age 27 4 immediately after the URL in none of the
Germany) years) fourth stage of athletes
5-day cycling race
Elecsys cTnT STAT 29 amateur cyclists Cycling Endurance Baseline, Postexercise levels exceeded [62]
(Elecsys-2010; Roche (sex not specified; age mountain race immediately after, the URL in 45% of
Diagnostics, 34 8 years) 24 h, 1 week athletes; postexercise
Germany) postexercise levels after 1 day exceeded
the URL in none of the
athletes
AccuTnI Access, 20 elite mountain bikers Cycling 1-h or 3-h exercise Baseline, 1, 3 h Postexercise levels exceeded [55]
Beckman, USA; and runners (all M; and on track at 75% postexercise the URL in 35% (cTnI)
Elecsys cTnT, Roche age 36 7 years) running of individual and 30% (cTnT) of
Diagnostics, Germany anaerobic athletes
threshold
Elecsys cTnT STAT 27 amateur runners Running Marathon Baseline, Postexercise levels exceeded [61]
(Elecsys-2010; Roche (25 M and 2 F; age not immediately the URL in 33% of
Diagnostics, specified) postexercise, 1 day athletes; postexercise
Germany) after levels after 1 day exceeded
the URL in none of the
athletes
Elecsys cTnT STAT 10 amateur endurance Running Ultramarathon, Baseline, Postexercise levels exceeded [74]
(Elecsys-2010; Roche runners (all M; age 52 216 km immediately the URL in none of the
Diagnostics, [43–57])a postexercise athletes
Germany)
ACS:Centaur TnI (ACS: 482 amateur endurance Running Marathon Baseline, Postexercise levels exceeded [75]
Centaur, Bayer Labs, runners (318 M and immediately the URL in 68% of
USA) and Elecsys 164 F; age 39 10 postexercise athletes
cTnT STAT (Elecsys- years)b
2010; Roche
Diagnostics,
Germany)
Elecsys cTnT STAT 17 (all M; age 47 Running Half-marathon, Baseline, Postexercise levels exceeded [76]
(Elecsys-2010; Roche [37–64])c 21 km immediately and 3, the URL in none of the
Diagnostics, 6, 24 h postexercise athletes
Germany)
Elecsys cTnT STAT 9 amateur endurance Running Marathon on a Baseline, at 30-min During and immediately [77]
(Roche Diagnostics runners (all M; age motorized intervals during postexercise levels
Germany) unavailable) treadmill, 42 km exercise, exceeded the URL in
immediately, 3, 6, 100% and 89% of athletes,
12, and 24 h respectively; 24 h
postexercise postexercise levels
exceeded the URL in 56%
of athletes
cTnI (Architect 85 amateur endurance Running Marathon, 42 km Baseline, Postexercise levels exceeded [78]
i2000SR; Abbott runners (70 M and immediately, and the URL in 81% (Hs-
Diagnostics, USA); 15 F; age 47 [45–49])d 24 h postexercise cTnI), 86% (Hs-cTnT),
Elecsys cTnT STAT and 45% (cTnT) of
and hs-cTnT (Elecsys athletes
2010; Roche
Diagnostics,
Germany)
Elecsys cTnT STAT 25 subjects (20 M and 5 Running Ultramarathon, Baseline, Postexercise levels exceeded [59]
(Elecsys-1010; Roche F; age 41 5 years)b 160 km immediately the URL in 20% of
Diagnostics, postexercise athletes
Germany)
(continues)
TABLE 1 (Continued)
Type of Distance or
Assay Study population exercise duration Sampling Results Reference
Elecsys cTnT STAT 61 nonelite marathon Running Half-marathon, Baseline, Postexercise levels exceeded [79]
(Elecsys-2010; Roche runners (half- 21 km and full immediately, and the URL in 46% of
Diagnostics, marathon; 40 M and marathon, 1 h postexercise athletes (half-marathon)
Germany) 21 F; age 40 12 42 km and in 53% of athletes (full
years)b marathon)
68 nonelite marathon
runners (full
marathon; 44 M and
24 F; age 42 14
years)b
Elecsys cTnT STAT 13 adolescent endurance Running Two 45-min and Baseline, Postexercise levels exceeded [80]
(Elecsys-2010; Roche runners (all M; 14 2 two 90-min immediately, and the URL in 15%, 62%,
Diagnostics, years) constant-load 5 h postexercise and 92% of athletes
Germany) treadmill runs performing 90 min at 80%
ventilatory threshold
(Thvent), 45 min at 100%
Thvent, and 90 min 100%
Thvent
CTnI (not specified) 92 amateur endurance Running Marathon, 42 km Baseline, Postexercise levels exceeded [81]
runners (65 M and 27 immediately the URL in 32% of
F; age 43 10 years)b postexercise athletes
Hs-cTnT (Elecsys-2010; 10 amateur endurance Running Ultramarathon, Baseline, Postexercise levels exceeded [82]
Roche Diagnostics, runners (all M; age 52 216 km immediately the URL in 40% of
Germany) [43–57])a postexercise athletes
Elecsys cTnT STAT 14 amateur endurance Running Marathon, 42 km Baseline, Postexercise levels exceeded [83]
(Elecsys-2010; Roche runners (8 M, 6 F; age immediately, 3 the URL in 100% of
Diagnostics, 33 6 years)b days and 1 week athletes
Germany) postexercise
Hs-cTnT (Elecsys-2010; 78 M amateur endurance Running Marathon, 42 km Baseline and 20 min Postexercise levels exceeded [63]
Roche Diagnostics, runners (all M; age postexercise the URL in 39% of
Germany) 53 14 years)b athletes
AccuTnI (Access; 91 elite cyclists (all M; Cycling Cycle-touring Baseline and 20 min Postexercise levels exceeded [84]
Beckman Coulter, age 40 9 years)b event, 206 km postexercise the URL in 43% of
USA) athletes
Elecsys cTnT STAT 185 amateur endurance Running Cross-country Baseline and 45 min Postexercise levels exceeded [85]
(Elecsys-2010; Roche runners (132 M; age race, 30 km postexercise the URL in 41% of
Diagnostics, 62 5 years; 53 F; age athletes
Germany) 59 4 years)b
AccuTnI (Access; 21 amateur endurance Running 45, 90, and 180 min Baseline and 30 min Postexercise levels exceeding [86]
Beckman Coulter, runners (19 M; age and 3 h the URL nonsignificantly
USA) 38 8 years and 2 F; postexercise different from baseline
age 38 1 years)b (range 0–9%)
Vitros TnI (Johnson & 15 amateur mountain Running Mountain Baseline, Postexercise levels exceeded [57]
Johnson, USA) runners (13 M, 2 F; marathon immediately the URL in none of the
age 28 5 years) postexercise athletes
Advia cTnI (Siemens, 17 amateur runners (all Running Marathon Baseline, Postexercise levels exceeded [69]
USA) M; age 33.5 6.5 immediately, and the URL in 47%
years) 6 h postexercise immediately after
marathon and in 64%
after 6 h
Elecsys cTnT STAT and 78 amateur runners (all Running Marathon Baseline, Postexercise levels exceeded [86]
Hs-cTnT (Elecsys- M; age not specified) immediately, and the URL in 94%
2010; Roche 2 weeks immediately after
Diagnostics, postexercise marathon by Hs test
Germany)
URL, upper reference limit; cTnI, cardiac troponin I; cTnT, cardiac troponin T; Hs, highly sensitive.
a
Median and 25–75% percentiles.
b
Mean standard deviation.
c
Mean and range.
d
Mean and 95% confidence interval (95% CI).
20 BANFI ET AL.
17 recreational athletes before and after a marathon run. Troponin was

measured at an initial assessment 24 h before the exercise, immediately
after completion of the marathon, and again 6 h later. Postmarathon cardio-
vascular imaging was performed 6 h after the end of the marathon by
measuring ventricular volume, function, mass, and wall motion. This time
point was chosen based on the assumption that 6 h would allow a sufficient
amount of time for inflammation to develop and be detectable,
corresponding with the time when TnI is typically detectable in ischemic
models.
The criteria for myocardial inflammation or fibrosis following the mara-
thon run were not met by the recruited marathoners. This suggests that
elevated cardiac troponins indicate reversible cardiomyocyte membrane
damage that may reflect part of a remodeling process [69].
In summary:
– troponins are released into the bloodstream after strenuous exercise
– with the recently introduced commercial assays, because of their higher
analytical sensitivity, the number of apparently anomalous cases after
exercise may be seen to increase
– the presence of measurable troponin amounts in the blood should not be
interpreted as cardiac damage in the absence of clinical symptoms or
instrumental findings of myocardial disease.
5. Kidney Parameters
5.1. CREATININE
Serum creatinine concentration is the most widely used and commonly
accepted measure of renal function in clinical medicine. Reference values of
biochemical parameters specific for athletes have never been defined; those
used for the general population, including serum creatinine, are routinely
applied to athletes. The common reference range for creatinine in the general
population is 0.7–1.3 mg/dL (62–115 mmol/L) for adult males, by using Jaffé
reaction in automated systems.
In sports medicine, creatinine is used in the assessment of an athlete’s
general health status, particularly in events where hydroelectrolytic balance
is crucial. Study of the behavior of serum creatinine and its reference interval
is essential to avoid misinterpretation of values in athletes, which are some-
times higher than the thresholds established for the general population.
The reference values commonly used for athletes are those defined for the
general, sedentary population. By definition, athletes are considered physically
normal and healthy, but high training workloads and psychophysical stress
due to competitions can alter homeostasis, leading to apparently anomalous
biochemical and hematological values.
Creatinine is nonenzymatically derived from creatine. Creatine turnover
rates in normal men are constant, accounting for 1.6% of the total creatine
pool per day. It is clear that the creatinine concentration in blood, which is
used as a parameter of the GFR, is influenced by body mass, diet (dietary
meat content), and analytical methods. The Jaffe method, commonly used
for measuring creatinine, is simple, inexpensive, and easily adapted to auto-
mated systems. However, it is limited by interference from molecules other
than creatinine (up to 20% of the total amount). For this reason, enzymatic
methods and, recently, the calibration of all methods against gas
chromatography–isotope dilution mass spectrometry are recommended [91].
The different aspects of the relationship between creatinine values and
sport activities have been described in a review [92].
Serum creatinine concentration is higher in athletes than in sedentary
people. A large-scale study recruited 220 elite athletes: 15 triathletes from
the Italian National team, 29 basketball players from a Italian First Division
team, 35 cyclists from two professional teams, 13 racing motorcyclists from a
professional team, 27 soccer players from a Italian First Division team, 23
sailors from the crew of an America’s Cup yacht, 34 alpine skiers from the
Italian National team, and 44 rugby players from the Italian National team.
All athletes were males and the age range was 17–36 years.
The control group (100 subjects matched for age) was composed of seden-
tary, nonobese, apparently healthy males, without biochemical and hemato-
logical signs of diseases. The mean value was 1.1 0.2 mg/dL for the whole
group of athletes and 1.0 0.1 mg/dL for the controls. The mean values for the
different sports groups were 0.99 0.07 mg/dL (triathletes); 1.15 0.07 mg/
dL (basketball players); 0.93 0.07 mg/dL (cyclists); 0.92 0.09 mg/dL
(motorcyclists); 1.27 0.09 mg/dL (soccer players); 1.08 0.11 mg/dL (sai-
lors); 1.15 0.10 mg/dL (skiers); and 1.30 0.11 mg/dL (rugby players) [93].
Higher creatinine concentration in professional soccer players than in seden-
tary controls (1.11 0.11 vs. 0.88 0.15 mg/dL) was described elsewhere [25].
Differences in creatinine between physically active and inactive subjects
were demonstrated for professional athletes from eight different sports,
showing different characteristics of aerobic/anaerobic metabolism, different
training loads and frequency of competitions, different length of competi-
tions, and different periods of training and competitions throughout the
year. The distribution of the serum creatinine concentrations in the athlete
population showed mean concentrations characteristically lower than those
observed in the sedentary subjects (below a threshold of 1 mg/dL and much
higher above 1 mg/dL), that is, the distribution is not homogeneous.
22 BANFI ET AL.
The interpretation of creatinine values in athletes should take into account

that the behavior of this parameter can differ from the general population
and result apparently anomalous in some athletes, despite correct hydration
and diet.
The relationship between serum creatinine concentrations and the kind of
sport discipline has been studied in endurance athletes. In these sportsmen,
usually characterized by a low BMI, serum creatinine concentrations were
lower than those of sedentary controls: 0.79–0.98 mg/dL for Nordic skiers
(n ¼ 37) and 0.72–0.95 mg/dL for cyclists (n ¼ 80) against an interval of
0.82–1.06 mg/dL for controls (n ¼ 60) [94]. Serum creatinine concentrations
in cyclists lower than those in controls were confirmed in 50 professional
athletes in comparison with 35 sedentary subjects (0.93 0.14 vs.
0.98 0.10 mg/dL; P ¼ 0.044) [95].
The kind of sport and related anthropometrical characteristics of athletes
produce different ranges of creatinine concentrations. The creatinine level in
cyclists is very stable during the competitive season, while it may be altered in
athletes competing in other sports.
Altered serum creatinine values during training and acute exercise have
been reported. Generally, serum creatinine concentrations are not signifi-
cantly influenced by practice and competition [12], even in extreme sports
[21]. In marathoners, there was no evidence of a gender-related effect on
postrace values and no evidence of a significant correlation with change in
body weight [96]; a significant increase was described in 27 amateur runners,
accompanied by increased urea immediately after the race which normalized
1 day later [61].
In Thai boxers (n ¼ 20; age range 14–17 years), the creatinine values
during normal training, intensive training, and after a match were not
statistically different from those of the control group. No differences were
described for creatinine clearance, except for the significantly lower value
observed after a match compared with the control group and with the
previous values of the athletes recorded during the training period, probably
because of changes in renal hemodynamics (reduction in renal blood flow)
during the fight [12]. In 16 volunteers participating in the First Race Across
the Alps, an ultraendurance cycle race (509 km at an altitude of 300–2750 m),
over 11 mountain passes, there was a statistically significant increase in serum
creatinine immediately after the end of the event in comparison with the
values observed before the start of the race. The mean values, however,
always fell with the reference intervals (1.26 0.21 mg/dL postrace,
0.95 0.17 mg/dL prerace) and returned to baseline at 24 h after the end
of the race (0.94 0.17 mg/dL) [97].
A study reported the changes in creatinine values over a competitive
season in athletes from different sport disciplines (rugby, alpine skiing, and
cycling). Analysis of variance showed significant differences among groups of

athletes practicing different sports. The analysis for repeated measures
demonstrated significant differences for rugby (P < 0.005) and skiing
(P < 0.02) but not for cycling (P ¼ 0.25). Differences in training regimen
and sport characteristics are relevant for interpreting creatinine values. In
rugby players and skiers, the serum creatinine concentration was found to
decrease significantly when training regimens were heavier and competitions
more frequent [98].
The use of equations for estimating GFR (eGFR) has been recently
recommended [91]. The equations include creatinine concentrations as well
as additional variables known to influence creatinine measurement and
interpretation. The Cockcroft and Gault (CG) formula proposed some
years ago is still widely used, although the modification of diet in renal
disease (MDRD) formula is now recommended [91]. MDRD could be par-
ticularly useful in sports medicine because it is unaffected by body mass. The
GFR in cyclists was estimated by an equation: the creatinine clearance
calculated in ultramarathon cyclists by the CG formula showed a significant
decrease immediately after the race (85 19 mL/min) of eGFR compared to
the basal value (114 27 mL/min). The values returned to normal within
24 h of the end of the race (113 28 mL/min) [62].
The mean eGFR as evaluated by the MDRD equation was significantly
lower in the sedentary population (98 mL/min/1.73 m2; 95% CI 77–124) than
in the subgroups of amateur (109 mL/min/1.73 m2; 95% CI 79–149) and
professional cyclists (113 mL/min/1.73 m2; 95% CI 87–171); however, it
was not statistically different between amateur and professional cyclists.
On multivariable regression analysis, the average intensity of daily physical
exercise was significantly associated with serum creatinine and eGFR. The
observed GFR reduction seems limited to periods when athletes are unac-
customed to the training load. Thus, the MDRD equation should be used
with caution in athletes, and it should consider intensity and type of physical
exercise [99].
The differences in the GFR, as estimated by the MDRD, MCQE (Mayo
Clinic Quadratic Equation), and CG equations, in 60 professional male
cyclists at rest and 60 healthy sedentary matched controls were evaluated.
There was a significantly higher MDRD-estimated GFR in the athletes than
in controls (119 vs. 104 mL/min/1.73 m2), whereas the GFR estimated by
both the MCQE (137 vs. 135 mL/min/1.73 m2) and CG (127 vs. 127 mL/min/
1.73 m2) formulas did not differ significantly. As compared to the MDRD
values, the mean GFR calculated by the MCQE and CG formulas was
overestimated by 29% and 23% in the sedentary population, and by 17%
and 7% in the athletes, respectively. A lower bias was observed when the CG-
and the MCQE-estimated values in both the sedentary and athlete
24 BANFI ET AL.
populations were compared. The results showed that the three most widely
used creatinine-based formulas produce significant variations in the eGFR in
a population of endurance athletes at rest. The use of CG or MCQE formulas
is more suitable because they appear more robust against variations in
training regimen [100].
The eGFR was also evaluated in amateur runners participating in a half-
marathon. The mean eGFR at baseline was 76 mL/min/1.73 m2, decreased at
the end of the run (62 mL/min/1.73 m2) and over the following 3 h (68 mL/
min/1.73 m2) and 6 h (70 mL/min/1.73 m2), though a statistically significant
difference was achieved only immediately after the run (16% mean decrease;
P < 0.01). The decline in renal function observed after the half-marathon
was reversible in a population of middle-aged trained athletes; it confirmed
that medium-to-high intensity aerobic physical activity does not negatively
affect renal function in these subjects [101].
In summary:
– creatinine concentration should be interpreted considering athletes’
BMI and the phase of competitive season
– creatinine concentrations measured over a season should not be inter-
preted against reference intervals for the general population, but moni-
tored following an athlete’s consecutive values
– creatinine values fluctuate over the course of a competitive season
– creatinine-based equations should be used with caution in athletes; the
use of GC or MCQE formulas is more suitable because they appear more
robust against variations in training regimen.
5.2. UREA
Since urea specificity is low, creatinine should be the parameter of choice
for monitoring renal function. Some differences between the two renal
function parameters were reported. Urea increased at 4 and 24 h after a
marathon [10] and was still high at 24 h when creatinine had normalized [61];
during a 20-day ultralong race, urea increased after 4 and 11 days and
maintained high values after the end of the race, while creatinine did not
change from baseline concentration [21]. An increase was described also in
professional cyclists after a stage in a 5-day race [53].
5.3. CYSTATIN C
The use of parameters other than creatinine can aid in the assessment of
renal function in athletes. Cystatin C, a low-molecular-weight protein that is
freely filtered through the glomerulus and almost completely reabsorbed and
catabolized by tubular cells, has been proposed as a reliable marker of GFR.

This parameter is not influenced by some variables which confound creati-
nine measurement, for example, age, gender, and BMI.
The differences between the two renal function markers were clearly
depicted in a study on marathoners. Serum cystatin C and creatinine con-
centrations were elevated after a marathon in 26% and 46% of 70 recreational
male runners, respectively, possibly because of a reduction in renal blood
flow. The mean cystatin C increase was twice as low as compared to creati-
nine (21% and 41%, respectively), suggesting that cystatin C is indeed less
biased by muscle damage [102].
A study demonstrated that the cystatin C values in rugby players were
within the reference interval, while creatinine concentration was in many
cases higher than the upper reference limit, due to the high muscular mass of
the athletes. Moreover, the distribution of cystatin C was narrower than that
of creatinine [103]. It is attractive that the eGFR derived from cystatin
C values is not influenced by athlete’s age, as demonstrated in young and
old (> 60 years) marathon runners. In both groups, eGFR decreased after the
race (from 104 to 82 and to 77 mL/min in the younger and the older runners,
respectively, on average) [60]. Moreover, eGFR derived from the cystatin
C values appeared more sensitive than the creatinine-based equation MCQE
for defining the decrease in renal function during a mountain ascent from
base camp at 4497 m to a camp at 5533 m in 34 healthy mountaineers who
were randomized to two acclimatization protocols on an expedition to
Muztagh Ata Mountain (7549 m) in China [104].
In summary:
– Cystatin C is an attractive alternative to creatinine and their equations.
6. Uric Acid
Uric acid (UA) is important in sports medicine because it is the terminal

product of purine metabolism and the principal antioxidant in human plas-
ma. Purine metabolism is often increased in athletes due to the high animal
protein content in their diet and increased cell turnover.
UA is present in concentrations higher than those of ascorbate and
accounts for 60% of serum free radical scavenger capacity. During metabolic
stress, UA blocks peroxyl radicals and hydroxyl radicals and probably also
carbonate ions and nitrogen dioxide as well. Athletes are particularly prone
to the risk of oxidant increase and related potential cell and tissue damage:
UA serum concentrations could represent a level of antioxidant protection
against the possible harmful effects of oxidant species. However, a new
26 BANFI ET AL.
scenario involving UA and oxidative metabolism is emerging, wherein anti-

oxidant molecules may become pro-oxidant compounds when occurring in
high concentrations in the blood. Therefore, high UA concentrations are
associated with an increased risk of cardiovascular accidents, coronary dis-
ease, and stroke [105].
The increase in serum UA originates from the oxidation of hypoxanthine
in the liver, whereas the formation of UA in skeletal muscle seems to be
limited. UA in the blood may be utilized by muscles during exercise to
replenish muscle urate stores and block free radicals [106].
UA concentration in athletes is described in a few papers showing conten-
tious data. Lower UA concentrations were found in professional skiers and
cyclists than in sedentary controls [94]. Conversely, higher concentrations
were reported in professional soccer players in comparison with sedentary
controls; the high UA levels paralleled those of other antioxidants, including
ascorbic acid, a-tocopherol, and superoxidase dismutase activity [25].
UA concentrations can be modified by acute exercise: hypoxanthine, and
therefore UA as well, increases in athletes immediately after heavy exercise
[107]; hypoxanthine is considered a marker of muscle energy during exercise
[108]. Serum UA concentrations significantly increased from a mean of
4.5 0.3 to 5.4 0.3 mg/dL in 15 male runners who completed a 246-km
ultralong race, the Spartathlon, from Athens to Sparta, Greece. Interesting-
ly, the increased UA was concomitant with a decrease in reduced glutathione,
which is protective against oxidative attack, and a decrease in erythrocyte
glucose-6-phosphate dehydrogenase, a crucial enzyme for reducing oxidized
glutathione [23].
Possible changes in UA during a competition season were reported in elite
athletes from different disciplines. Resting serum UA levels in long-distance
runners were lowest during general preparation at low intensity and highest
during specific and intense preparation and during competition [106]. How-
ever, the changes in serum UA concentrations between training phases were
not significant. Conversely, significant differences were shown when pre- and
postexercise UA concentrations were compared in all phases of training and
competition.
Only a small increase ( 6%) has been reported in rugby players after the
intense training phase of a season [109], and a decrease from the precompeti-
tion to the competition phase (June) was found in elite kayakers [110].
In 18 alpine skiers from the Italian National team (10 males, 8 females)
followed over four consecutive competitive seasons, blood samples were
collected before the start of training (May), at the end of training and before
the start of competitions (October), and before the World Championships or
the Olympic Games, and toward the end of international competitions
(January); serum UA was a stable parameter at all four time points.
The variations in serum UA over various phases of a competitive season were

limited and lower than biological variability. High-intensity training and
high amounts of physical workload did not lead to significant changes in
serum UA, even between different seasons. A gender effect was reported,
with lower concentrations found in females than in males. The study con-
cluded that, although serum UA increases immediately after exercise, the
resting concentration is uninfluenced by sports activity, rendering this para-
meter of little use for marking high physical demand or overtraining [111].
In summary:
– UA is the major antioxidant in blood and increases after acute exercise
– UA concentration is stable during the competitive season.
7. Glucose
Physical exercise needs energy. The first source of energy is the glycogen
stored in the skeletal muscles and liver. Glycogen is enzymatically cleaved to
release glucose molecules which enter the glycolysis pathway. Aerobic and
anaerobic glycolysis produces adenosine triphosphate (ATP) utilized by the
muscles. Glucose is continuously consumed to supply energy, and its con-
centration must be maintained constant by glycogen demolition and the
intake of food and drink. Constant glucose levels are necessary to sustain
long-lasting exercise. Based on glucose availability, physical exercise is clas-
sified as aerobic or anaerobic or lactacid. Although glucose concentration is
necessarily reduced by exercise, the continuous intake of food and beverages
containing glucose or other carbohydrates to be transformed in glycogen is a
confounding factor in evaluating glucose levels during and after aerobic and
endurance exercise. The oral intake of glucose is widely studied for improv-
ing performance; for example, nutritional recommendations to improve
exercise performance and enhance exercise capacity are regularly based on
information related to the so-called glycemic index [112].
Only some specific aspects of glucose metabolism in athletes are mentioned
here; the regular physiological glucose concentration in fasting subjects is
generally taken for granted in athletes.
Physical training amplifies the effect of exercise on insulin sensitivity and
enhances glucose utilization and storage. Exercise upregulates insulin-
stimulated insulin receptor substrate 1 and Akt Ser473 phosphorylation,
increasing glucose disposal after insulin stimulation [113]. In this way, an
adaptive metabolism is stimulated by training in athletes who have increased
skeletal muscle glycogen and, if aerobically trained, increased recovery of
lactate to glycogen (lactate shuttle) [114]. The ability of insulin to stimulate
28 BANFI ET AL.
glucose uptake is markedly improved locally in previously active muscles.

Training improves insulin’s ability to stimulate the translocation of glucose
transporters (GLUT4) to the muscle membrane after exercise, because exer-
cise interacts with the insulin signaling pathway to GLUT4 translocation,
thus allowing for a more potent insulin response. Many studies have shown
that improved insulin action can occur independent of interactions with
proximal insulin signaling, although more recent observations indicate that
interactions exist at the distal signaling end of AS160, a protein involved in
the regulation of glucose transport into the cell, and atypical protein kinase
C [115].
In brief, a beneficial effect on glucose metabolism is derived from exercise:
physical exercise is recommended for preventing some chronic conditions
and for preventing and treating the metabolic syndrome.
In professional athletes (47 male road cyclists from 7 different teams), the
fasting glucose concentration was lower than that observed in sedentary
subjects (28 age-matched individuals), as also found in elite cyclists (72
males). Interestingly, glycated hemoglobin concentration, which is a measure
of erythrocyte hemoglobin glycation and reflects mean glycemia for the
previous 2–3 months, was higher in professional cyclists than sedentary
subjects (5.4% 0.2% vs. 5.2% 0.3%). The increased glycated hemoglobin
in athletes could be due to the persistent intake of carbohydrate during
exercise, to optimize performance and recovery [116].
Glycated hemoglobin concentration higher than the reference interval was
described in professional American football linemen who presented symp-
toms of the metabolic syndrome [117].
Fasting glycemic levels in professional athletes are low, but a relative
hyperglycemic status over long periods of the day, during training and
competition probably, causes increased glycation of hemoglobin. In fact,
the glucose concentrations were within the reference range at 4 and 24 h
after the end of a marathon: the range of concentration in amateur runners
was 47–151 mg/dL before the marathon, 63–158 mg/dL immediately after the
race, and 67–167 mg/dL 24 h later. Although there was no difference between
baseline and values at 4 and 24 h after the marathon, the range of concentra-
tion was wide [10]. During a 20-day ultralong race, an increase was noted at
day 11, but no difference versus the baseline value after the race was
reported, indicating a further adaptation during very long-endurance exer-
cise [21]. Exercise intensity and duration affect insulin release and serum
concentration. A load of 40% VO2max is sufficient to cause a drop in insulin
concentration, whereas a load of at least 70% is needed to stimulate other
hormones. Near-maximal exercise induces an increase in insulin, as occurs
after the cessation of exercise. The effect of exercise duration is commonly
more important than intensity in modifying hormonal status, but for insulin
the effect is mainly linked to glucose and carbohydrate availability [118].

During prolonged exercise without food intake, endurance athletes showed a
more pronounced decrease in insulin than sedentary subjects: this is a train-
ing-induced adaptation. The decrease in insulin is followed by a delayed
decrease in C-peptide and a concomitant increase in hyperglycemic hor-
mones such as growth hormone and adrenocorticotrophin [119]. Conversely,
after intake of a protein-rich diet, which is typical among many athletes,
plasma glucose concentrations were lower during recovery in elite female
cyclists [120].
Glucose concentration is the result of a delicate equilibrium between hyper-
glycemic and hypoglycemic hormones: it is not surprising, therefore, that
glycemic control differs between elite power and endurance athletes. Elite
power athletes (short-distance specialized track and field athletes and swim-
mers) exhibited a relatively lower insulin sensitivity than their endurance (long-
distance specialized track and field and swimming) counterparts [121]. These
data are of importance for the development of chronic diseases in later lifetime:
former elite power athletes have a significantly higher relative risk of diabetes
and the metabolic syndrome than endurance athletes [122].
In summary:
– plasma glucose concentration is not affected by exercise if food and
drink intakes are correct
– exercise and training induce adaptations in glucose metabolism which
improve glucose utilization in athletes and are beneficial for reducing
insulin insensitivity in nonathletes
– depending on the sport practiced, athletes have slightly different glucose
metabolism and, consequently, laboratory parameter levels.
8. Lipid Profile
The benefit of regular physical activity for fitness and prevention of the
metabolic syndrome and associated problems and diseases, including lipid
metabolism [123], is well established, although the extent of physical activity
required to improve general health status is not definitely determined [124].
Blood profile assessment in athletes and physically active subjects, as com-
pared with sedentary subjects, should illustrate the effective benefit of exer-
cise in preventing metabolic diseases. However, the use of simple lipid
metabolism parameters may not be sufficient, due to their dependence on
food intake, which is not easily scheduled or appropriately recorded. There-
fore, it is difficult to compare the numerous reports on professional athletes
and to determine the real usefulness of data for the general population.
30 BANFI ET AL.
Moreover, athletes are not always the best example for studying lipid
metabolism: of 70 elite American football athletes, 34 were identified as
having a metabolic syndrome according to measures of blood pressure,
waist circumference, fasting glucose, HDLC, and triglyceride levels [117].
The lipid profile of professional athletes (40 cross-country skiers and 102
cyclists) was compared to that of 50 sedentary subjects. Total cholesterol
(TC) was significantly lower in both groups of athletes, as were HDL and
low-density lipoprotein (LDL) cholesterol. Also, triglyceride (TG) levels
were lower in athletes. Interestingly, professional athletes generally met the
current desirable values for cardiovascular disease prevention recommended
by scientific associations. Total and fractioned cholesterol concentrations
were reportedly better in skiers than in cyclists, whereas the TG levels were
identical [125]. Lower HDLC was reported in professional as compared to
amateur cyclists [126]. Conversely, no difference in serum TG, TC, HDLC,
and LDLC was found between 14 endurance athletes and 14 sedentary men
who provided blood specimens at the beginning and the end of a week during
which they recorded physical activity and food intake; probably, the low
number of subjects and the high similarity between athletes and controls,
who had identical body fat percentage, can explain these data [127].
No difference in TC, LDLC, and TG concentrations was found between
sedentary subjects and two groups of athletes, one from a power discipline
(bodybuilding) and the other from an endurance discipline (long-distance
running); HDLC concentrations were higher in the athletes [128].
TG was found to be lower than the reference limits for the general popula-
tion in young distance runners, indicating that some lipid profile character-
istics in athletes are established early on. HDLC was higher in very young
runners (< 14 years of age), but with increasing age, the levels became similar
to those of sedentary age-matched subjects. The blood lipid profile is effec-
tively protective in younger athletes [129]. In particular, high HDLC con-
centrations seem to be typical of young athletes, as also reported in female
teenager gymnasts [130]. Different lipid profiles have been described in
female athletes who had different menstrual status. Nonprofessional athletes
in endurance sports (medium-and long-distance running, marathon, orien-
teering, cross-country skiing, and triathlon) were recruited and divided into
four groups on the basis of endurance training and menstrual status: 14 were
amenorrhoeic, 9 oligomenorrhoeic, and 12 regularly menstruating, as com-
pared with 12 regularly menstruating sedentary controls. TC was higher in
the amenorrhoeic athletes than in the other groups; the difference was mainly
due to high LDLC levels. No difference was found for HDLC. Amenorrhoea
in young endurance athletes is associated with endothelial dysfunction and
unfavorable lipid profile, with increased TC, LDLC, and apoprotein
B (Apo B), which are recognized risk factors for atherosclerosis [131].
No difference in TC, HDLC, LDLC, and TG concentrations was observed

when age-matched nonprofessional female athletes were compared with seden-
tary controls who did not differ in lifestyle or use of oral contraceptives [132].
There exist some differences among athletes from different sport disci-
plines. For example, a study on 10 middle-distance runners, 10 hammer
throwers, 10 wrestlers, and 8 weightlifters showed that TC and TG were
lower in athletes than in age-matched sedentary subjects. The HDL isolated
from the blood of runners had the highest antioxidant activity. Runners and
wrestlers had the most desirable lipoprotein function, as evaluated by size,
amount of apoprotein A1 (Apo A1), and associated enzyme activity. Athletes
practicing aerobic exercise exhibited better HDL profiles [9]. Short-distance
athletes specialized in two different sport disciplines (running and swimming)
had higher fasting LDLC and TG concentrations than those in long-distance
specialized athletes. Endurance training seems to be more protective [121].
The changes in lipid metabolism parameters in athletes after acute and
chronic exercise are summarized in Table 2. The data are controversial: lipid
parameters increased immediately after the effort in some exercises but
decreased in others. In all studies, however, the altered parameters returned
to normal, and the changes did not depend on exercise duration. The type of
exercise seems to have a different effect on acute lipid response: aerobic
exercise can modify blood lipid concentrations mainly with continuous exer-
cise, while intermittent exercise produces a greater increment in HDLC [139].
An increase in TC was observed in amateur cyclists after maximal and
submaximal exercise tests, but not in professional cyclists: this may be due
to changes in LDLC, which is decreased in professionals, or in HDLC, which
is increased in amateurs. Different mobilization of lipoprotein–cholesterol
can be expected, depending on exercise type [126].
A special topic concerning the lipid profile in physically active subjects is
the preservation of sport-induced benefits when activity is discontinued or
limited. Risk factors for cardiovascular accidents have been found to be
lower in former elite athletes followed for over 10 and 20 years after the
end of competitive sport cessation. Mean TC was lower in the former athletes
who maintained habitual exercise training for 10 and 20 years. The stability
of the beneficial effects of physical fitness over decades presupposes continu-
ous activity [140]. This conclusion was confirmed in former elite football
players who had lower TG and higher HDLC when compared with age-
matched subjects [141]. Detraining effects were extensively studied in 20
rowers. The recruited athletes had at least 10 years experience, with a mini-
mal training activity of eight training sessions per week for 45 weeks per year.
The athletes were divided in two groups: the first continued with regular
training and the second discontinued training; diet was controlled for both
groups. Continuing training induced a decrease in TG, TC, LDLC and an
TABLE 2
CHANGES IN CHOLESTEROL AND TRIGLYCERIDES AFTER ACUTE AND CHRONIC EXERCISE
Parameter Type of exercise Study population Results Reference
Total cholesterol Ultramarathon (100 km) 7 amateur runners (sex not Increase at 15 min after end of race; no [133]
specified; age 33 3.5 years) difference at 24 h after end of race
Triglycerides Ultramarathon (100 km) 7 amateur runners (sex not Decrease at 15 min and 24 h after end of [134]
specified; age 33 3.5 years) race
Total cholesterol Middle- and long-distance running 8 elite runners (all M) No difference after 14 days of training [135]
(4 weeks with increasing workload) regimen; decrease after 28 days of
training regimen
HDL cholesterol Middle- and long-distance running (4 8 elite runners (all M) No difference after 14 and 28 days of [135]
weeks with increasing workload) training regimen
LDL cholesterol Middle- and long-distance running (4 8 elite runners (all M) No difference after 14 days of training [135]
weeks with increasing workload) regimen; decrease after 28 days of
training regimen
Triglycerides Middle- and long-distance running (4 8 elite runners (all M) No difference after 14 days of training [135]
weeks with increasing workload) regimen; decrease after 28 days of
training regimen
Total cholesterol Triathlon (Ironman: 3.9 km 39 amateurs (26 M, 13 F, age Decrease after completion of triathlon [136]
swimming; 180 km cycling; 42 km 38 10 years)
running)
HDL cholesterol Triathlon (Ironman: 3.9 km 39 amateurs (26 M, 13 F, age No difference after completion of [136]
swimming; 180 km cycling; 42 km 38 10 years) triathlon
running)
LDL cholesterol Triathlon (Ironman: 3.9 km 39 amateurs (26 M, 13 F, age No difference after completion of [136]
swimming; 180 km cycling; 42 km 38 10 years) triathlon
running)
Triglycerides Triathlon (Ironman: 3.9 km 39 amateurs (26 M, 13 F, age Decrease after completion of triathlon [136]
swimming; 180 km cycling; 42 km 38 10 years)
running)
Total cholesterol Ultramarathon (1600 km, 20-day race) 9 amateur runners (7 M, 2 F) Decrease at 4 days after beginning of [21]
race; no difference at 11 days after
beginning of race and after end of race
Total cholesterol Marathon 37 amateur runners (32 M, 5 F; No difference at 4 h after end of race; [10]
age 49 10 years) decrease at 24 h after end of race
Total cholesterol Maximal and submaximal tests for 33 cyclists (all M; 17 amateurs, Increase after maximal and submaximal [126]
amateur cyclists; 180 km mountain age 23.3 2.0 years; 16 exercise; no difference after stage in
stage of cycling competition for professionals, age 23.8 0.9 cycling competition
professional cyclists years)
HDL cholesterol Maximal and submaximal tests for 33 cyclists (all M; 17 amateurs, Increase after maximal test; no difference [126]
amateur cyclists; 180 km mountain age 23.3 2.0 years; 16 after submaximal test and after stage
stage of cycling competition for professionals, age 23.8 0.9 in cycling competition
LDL cholesterol Maximal and submaximal tests for 33 cyclists (all M; 17 amateurs, No difference after maximal and [126]
amateur cyclists; 180 km mountain age 23.3 2.0 years; 16 submaximal exercise; decrease after
stage of cycling competition for professionals, age 23.8 0.9 stage in cycling competition
Triglycerides Maximal and submaximal tests for 33 cyclists (all M;17 amateurs, No difference after maximal and [126]
amateur cyclists; 180 km mountain age 23.3 2.0 years; 16 submaximal exercise; increase after
stage of cycling competition for professionals, age 23.8 0.9 stage in cycling competition
Total cholesterol Ultramarathon (246 km) 15 amateur runners (all M; age Decrease after race; no difference at 24 h [137]
range 31–46 years) after race
HDL cholesterol Ultramarathon (246 km) 15 amateur runners (all M; age No difference after race and at 24 h after [137]
range 31–46 years) race
LDL cholesterol Ultramarathon (246 km) 15 amateur runners (all M; age Decrease after race; no difference at 24 h [137]
range 31–46 years) after race
Triglycerides Ultramarathon (246 km) 15 amateur runners (all M; age No difference after race and at 24 h after [137]
range 31–46 years) race
Total cholesterol Live high-train low regimen (18-day 12 elite middle-distance runners Increase at 1 day after end of training [138]
period) (all M; age 23.9 4.8 years) regimen
(continues)
TABLE 2 (Continued)
Parameter Type of exercise Study population Results Reference
Triglycerides Live high-train low regimen (18-day 12 elite middle-distance runners No difference at 1 day after end of [138]
period) (all M; age 23.9 4.8 years) training regimen
Total cholesterol Continuous exercise at 44% VO2max or 15 elite runners (all M; age not Increase after exercise and no difference [139]
intermittent exercise at 39–72% specified) 24 h postexercise in both types of
VO2max exercise
HDL cholesterol Continuous exercise at 44% VO2max or 15 elite runners (all M; age not No difference after exercise and 24 h [139]
intermittent exercise at 39–72% specified) postexercise in continuous exercise;
VO2max increase after exercise and no
difference 24 h postexercise in
intermittent exercise
LDL cholesterol Continuous exercise at 44% VO2max or 15 elite runners (all M; age not Increase after exercise and no difference [139]
intermittent exercise at 39–72% specified) 24 h postexercise in continuous
VO2max exercise; no difference after exercise
and 24 h postexercise in intermittent
exercise
Triglycerides Continuous exercise at 44% VO2max or 15 elite runners (all M; age not No difference after exercise and 24 h [139]
intermittent exercise at 39–72% specified) postexercise in both types of exercise
VO2max
increase in HDLC. ApoB decreased, whereas ApoA1 was stable. Detraining,

conversely, induced an increase in TG, TC, and LDLC and a decrease in
HDLC. ApoB increased, whereas ApoA1 was still stable. Of note is that
during detraining the subjects increased their body fat mass by approximate-
ly 70% (12–20% of total body mass), although their caloric intake was 55%
less than that during the training regimen. Detraining induced a rapid loss of
endurance training benefits to lipid profile. Therefore, highly trained athletes
can experience lipid profile alterations at cessation of their sport activities,
unless they maintain a sufficient level of physical activity [142].
Athletes are characterized by high lipoprotein(a) concentrations [125,129].
An increase in plasma high lipoprotein(a) is regarded as a risk factor for
cardiovascular disease, but the atherogenic index in athletes is lower than in
sedentary controls, owing to the counterbalancing effect of the superior profile
of other lipid parameters [125].
An additional parameter which is an independent risk factor for cardio-
vascular accidents is homocysteine (Hcy). This marker is increased by physi-
cal exercise: for example, a significant increase in plasma Hcy concentrations
was demonstrated in 22 nonprofessional male athletes (age range 23–49
years) studied the day before and 24 h after finishing a marathon race.
Changes in plasma folate and plasma vitamin B12 concentrations were not
detected postrace, but Hcy increased by 19% at 24 h after the race. Before the
race, 20% of the subjects had a plasma Hcy concentration > 10 mmol/L
(usually 15 mmol/L, but taken as the threshold for cardiovascular risk in
this study), while 50% had a plasma Hcy concentration > 10 mmol/L after the
race [143]. In a study involving 82 nonprofessional athletes (59 males and 23
females) practicing different sports (mainly basketball, swimming, and soc-
cer) and 70 healthy age-matched subjects (40 males and 30 females) as a
control group, the prevalence of hyperhomocysteinemia (> 15 mmol/L) in
athletes and controls was 47% and 15%, respectively. No correlation was
found between Hyc and any of the other investigated variables, including
plasma folate, blood pressure, LDH, CK, total and HDLC, and IL-6. The
current data confirm that exercise induces hyperhomocysteinemia in athletes
participating in sports that require very different environmental training
conditions and with different levels of performance [144].
However, the effects of physical activity on Hcy are not completely defined.
Recreational physical activity in 124 twenty-three-year-old normal-weight
Italian nonprofessional athletes (8.7 2.46 h of exercise per week, mainly
volleyball, soccer, martial arts) and 116 sedentary controls revealed that
sport does not adversely impact homocysteine levels among young women
and that only low folate concentrations increase the risk of hyperhomocys-
teinemia. Physical activity may downregulate Hcy in females but not in males
[132]. The former athletes who had maintained physical activity had lower
36 BANFI ET AL.
Hcy levels than those who were becoming sedentary, indicating that physical
activity could also have a long-term positive effect on this parameter [145].
The presence of exercise-induced hyperhomocysteinemia in athletes should
be interpreted as a signal of adaptation to training, being an expression of
enhanced protein synthesis in muscle cells. The role of folate could be crucial
for defining altered Hcy.
In summary:
– sport activities induce a better blood lipid profile than that of sedentary
subjects; few reports, however, are available for drawing a definitive
conclusion
– differences between athletes and sedentary subjects are mainly due to
higher HDLC concentration in physically active individuals
– the benefits obtained from the superior lipid profile in athletes are
maintained over the entire lifespan only when training is continued after
cessation of the competitive period
– the acute effects of sport activities on blood lipid profile are not univocal
– the effects can widely depend on food intake, body fat mass, and type of
sport discipline practiced
– a beneficial and concordant effect of acute sport activities is increased in
HDLC
– return to basal values after acute exercise is always described, in all
performances with different intensity and duration
– different types of exercise can induce different lipid profile changes:
intermittent exercise induces greater increases in HDLC.
9. Bone Metabolism Markers
The behavior of bone metabolism markers in sports medicine has been

recently reviewed [146]. Bone metabolism markers are important in the study
of bone turnover in athletes and the general population, since physical
exercise is recommended for preventing osteoporosis and bone metabolism
disorders [147]. Although the use of serum or urinary markers is simpler and
safer than radiographic measurement of bone mass density (BMD), high
biological variability, analytical pitfalls, and various confounding factors
limit their usefulness and effectiveness. Bone mass refers to the net result of
the action of two counteracting metabolic processes, that is, bone formation
and bone resorption; the bone turnover in athletes is particularly high. The
commonly used biochemical markers for studying bone turnover are listed in
Table 3.
TABLE 3
BONE METABOLISM MARKERS
Acronym Bone formation markers
BAP or BALP Bone alkaline phosphatase

OC or BGP Osteocalcin (bone Gla-protein)
PICP Carboxyterminal propeptide of type I procollagen
Bone resorption markers
Pyr Pyridinoline (or pyridinium cross-links or simply cross-links)

Dpd or D-Pyr Deoxypiridinoline
ICTP Carboxyterminal cross-linked telopeptide of type I procollagen
CTx Carboxyterminal cross-linking telopeptide of type I collagen
NTx Amminoterminal cross-linking telopeptide of type I collagen
Acronyms are nonstandard.
There are many experiments on bone metabolism makers after acute

exercise, but none after long-term training or during and after a whole
competition season. Moreover, there are few studies on bone metabolism
markers in elite and top-level athletes, who have a higher bone turnover than
sedentary subjects do. The behavior of bone deposition and resorption
markers after acute exercise in professional and nonprofessional athletes
from different sport disciplines is summarized in Table 4. The data are
controversial; nonetheless, bone formation markers are generally more sen-
sitive to exercise than resorption markers. Short exercise is insufficient to
modify the serum concentrations of bone metabolism markers. The changes
in markers are usually more evident various hours or days after exercise and
apparently do not depend on exercise intensity.
Bone markers differ in sensitivity: bone alkaline phosphatase (BAP) is
sensitive to aerobic exercise; osteocalcin (OC) and cross-links to anaerobic
exercise; OC is the most sensitive bone formation marker following acute
exercise, while carboxyterminal cross-linking telopeptide of type I collagen
(CTx) appears to be the most sensitive resorption marker after acute exercise,
and aminoterminal cross-linking telopeptide of type I collagen (NTx), the
most sensitive over the competitive season.
During a training and competition season, professional athletes show
changes in bone formation markers depending on program intensity, while
bone resorption seems to be stable; the characteristics of exercise (e.g., weight
bearing, impact) are crucial [154,155].
There also exist differences among sport disciplines. Athletes who practice
weight-bearing sports have a BMD higher than those who practice
TABLE 4
CHANGES IN SERUM AND URINARY BONE BIOMARKERS DURING EXERCISE IN ATHLETES
Study population Sport discipline Bone formation markers Bone resorption markers Reference
19 (all F; 10 trained, 9 Volleyball players No differencea immediately after Not reported [148]
untrained; age (amateurs) exercise
range 20–24 years) Running ergometer for OC increased after 1 h in trained
30 min at 43–52% subjects
maximum OC unchanged in untrained subjects
23 (15 F, 8 M; age Marathon (amateurs) BAP decreased immediately after race Urinary hydroxyproline unchanged [149]
range 23–55 years) and at 1, 3, 5 days after race in F; OC
decreased immediately after race in
M (and at day 1 in F)
7 (all M; age range Ice hockey (national level) OC unchanged at 5 and 60 min after ICTP unchanged 5 and 60 min after [150]
19–26 years) Maximal work (Wingate exercise exercise
test) PICP unchanged at 5 and 60 min after
exercise
20 (10 M, 10 F; age Running (amateurs); 28 km BAP unchanged at 1 and 2 days after ICTP increased after 2 days in M [151]
range 22–53 years race for M and 15 km for race
[M], 22–55 years F OC decreased after 1 day in M; PICP
[F]) decreased after 1 day in F
17 (all M; age range Marathon (amateurs) PICP decreased immediately after race ICTP increased immediately after race; [152]
23–48 years) No difference after 1 and 2 days; no difference at 1, 2, 3, 4, 5, 6 days
increased after 3 days; no difference after race
after 4, 5, and 6 days
12 (all M; age range Triathlon (elite) BAP unchanged CTx increased 30, 60, 120 min after [153]
23–37 years) Ergometer cycle 80% exercise
VO2max for 1 h
7 (all M; age range Triathlon (national level) OC unchanged at 32 weeks after No difference in CTx 32 weeks after [154]
18–20 years) beginning of training, during beginning of training during
competitions; BAP decreased; CTx competitions
unchanged 32 weeks after beginning
of training during competitions
12 (all M, age range Rowing (international level) OC increased 6 months after beginning Not reported [155]
18–23 years) of training, during competitions
32 (15 M; 17 F; age 16 athletes from running, OC decreased at 75% AT at 3 and 24 h CTx increased at 95% and 110% AT [156]
range 17–39 years) soccer, cycling (amateurs) after exercise after 3 and 24 h in M athletes
16 sedentary; PINP decreased at 75% AT after 3 and TRAP unchanged in athletes
cycloergometer test for 60 24 h (both M and F athletes); OC
min at 75%, 95%, 110% increased at 95% AT after 3 h in
anaerobic threshold (AT) M athletes and 24 h in F athletes
16 (all M; age range Ultramarathon, 245 km BAP decreased immediately after race ICTP unchanged immediately after and [157]
25–48 years) (amateurs) and 1 day after race, no difference at 1, 3, 5 days after race;
3 and 5 days after race; OC decreased Hydroxyproline decreased
immediately after race and 1 day immediately after and increased at 1,
after race, no difference at 3 and 5 3, 5 days after race
days after race
PICP decreased immediately after race,
no difference at 1, 3, and 5 days after
race
15 (all M; age range Half-marathon, 21 km OC increased immediately after race, Not reported [158]
30–55 years) (amateurs) no difference at 3, 6, 24 h after race
a
Intended in comparison with baseline values measured before the exercise.
40 BANFI ET AL.
nonweight-bearing sports: in males, cycling is associated with lower bone

mineral density in comparison with running [159].
Urinary pyridinolines were higher in power track and field female athletes
than in endurance athletes; there was no difference between the same groups
of male athletes [160]. NTx was highest in collegiate athlete rowers and
higher in rowers and runners than in swimmers or controls. CTx was higher
in runners than in rowers, swimmers, or controls [161]. Increased bone
resorption was observed in 71 professional baseball players (age range
18–39 years), in which urinary NTx concentrations were measured; in this
study, serum biochemical markers and nutritional assessment in nine players
with high levels of urinary NTx (> mean þ 1 SD) revealed a concurrent
vitamin D insufficiency [162].
Bone resorption seems to be consistently higher in athletes, especially those
involved in endurance exercise: 25 females exhibited higher levels of bone
resorption marker CTx than controls [156]. Female athletes participating in
impact sports (volleyball, basketball) had a higher BMD and higher OC
concentrations than swimmers, whereas no differences were observed for
bone resorption, as measured by NTx concentration [163].
Also, the preservation of a theoretical sport-derived benefit for bone
metabolism is neither maintained after cessation of the competitive period,
as seen in former athletes who practiced professional soccer for almost
8 years [164], nor when physical activity is maintained in women athletes
(mean age 50 years, range 18–69; swimmers, triathletes, and runners): physi-
cal activity is unable to prevent the loss of bone with aging. BAP and
deoxypiridinoline (Dpd) did not differ from controls, and NTx was lower
in the athletes [165].
In summary, contentious data on bone metabolism in physically active
subjects need further study to establish the real and effective influence of
sport on bone turnover, and especially to establish its beneficial effect.
10. Effect of Body-Mass Index on Laboratory Parameters
Several metabolic parameters are related to BMI. The athletic population

is not homogeneous: its anthropometrical characteristics clearly differ by
type of sport practiced. Muscular mass is obviously a fundamental charac-
teristic of athletes, but BMI values range widely among athletes from various
disciplines. Therefore, the interpretation of certain laboratory parameters
should take into account the athlete’s BMI in order to avoid misclassification
and inappropriate further clinical and laboratory examinations.
A positive correlation between BMI and ALT was reported, while a very
weak negative correlation emerged between BMI and AST [8]. A correlation
TABLE 5
CHANGES IN LIVER AND MUSCLE METABOLISM PARAMETERS
Parameter Study population Type of exercise Results Reference
AST, ALT 37 amateur runners (32 M, 5 F; age Marathon AST increased from basal value at 4 h and further [10]
49 10 years) 3 h after the race; 11 increased at 24 h after race; ALT did not increased
runners (8 M, 3 F) 24 h after the race at 4 and 24 h after race
Bilirubin 37 amateur runners (32 M, 5 F; age Marathon Total bilirubin increased from basal value at 4 h and [10]
49 10 years) 3 h after the race; 11 no modifications were observed at 24 h after race.
runners (8 M, 3 F) 24 h after the race Direct bilirubin increased at the same time points
AST, ALT 10 professional boxers (all M; age range Boxing match Increased after match with respect to before match [12]
14–17 years) value
CK 10 professional boxers (all M; age range Boxing match Increased after match with respect to normal training [12]
14–17 years) period
CK 10 professional boxers (all M; age range Boxing match No modification after match with respect to normal [12]
14–17 years) training period
CK 21 footballers; 11 starters (all M; age Training camp and Increased from 1 day before the start of preseason [14]
20.6 1.0 years), 10 nonstarters competitive season training camp to the end of training camp (10 days
(all M; age 20.4 1.6 years) later) in both starters and nonstarters. Starters had
higher concentrations at the end of training camp
than nonstarters. Both groups returned to baseline
levels at week 3 of the competitive season and
remained constant for the rest of the season
AST, ALT 25 football players (all M; age Twice-a-day practices Increased postexercise AST and ALT with respect to [15]
25.2 2.7 years) in training camp basal value
AST, ALT 9 ultramarathon runners (7 M, 2 F; Ultraendurance race ALT increased with respect to prerace value at day 4 [21]
age 53 11.2 years) (1600 km, 16 days and was not different to the day 4 level on day 11
duration) and at the end of the run. AST levels increased with
respect to prerace value at day 4 and decreased with
respect to this value on day 11; both the day 11
value and that at the end of the run remained
increased compared with the level before the race
(continues)
TABLE 5 (Continued)
Bilirubin 9 ultramarathon runners (7 M, 2 F; age Ultraendurance race Increased with respect to prerace value at day 4, [21]
53 11.2 years) (1600 km, 16 days decreased to prerace value at day 11 and remained
duration) at this level after the race
CK 9 ultramarathon runners (7 M, 2 F; age Ultraendurance race Increased with respect to prerace value at day 4, [21]
53 11.2 years) (1600 km, 16 days decreased between days 4 and 11 and between day
duration) 11 and the end of the race; the value at the end of the
race remained above that measured before
LDH 9 ultramarathon runners (7 M, 2 F; age Ultraendurance race Increased at day 4 with respect to prerace value and [21]
53 11.2 years) (1600 km, 16 days was not different to the day 4 level on day 11 and at
duration) the end of the run
Bilirubin 15 runners (all M; median age 36.5 Ultraendurance race Increased values after the race with respect to value [23]
years) (32–36-h duration) measured before the race
Bilirubin 10 elite soccer players (all M; age Competitive season Increased at the end of the recovery period and then [24]
25.3 5.1 years) returned to baseline before the start of the new
season
Bilirubin 24 rugby players of the Italian National Competitive season Increased after the season with respect to value [26]
Team (all M; age range 19–35 years) measured before the start of the training and
competitive seasons
CK 10 top-level rugby players (all M; age International rugby Increased postgame value with respect to pregame [40]
26.4 0.7 years) tournament value
CK 15 elite amateur rugby players (all M; Competitive match Increased postgame value with respect to pregame [41]
age 26.6 0.7 years) value
CK 23 elite rugby players (all M; age 25 3 Competitive match Increased postgame value with respect to pregame [43]
years) value
AST Runners (all M; age range 23–47 years) 13-mile minimarathon Increased after marathon with respect to value [50]
measured before marathon
CK Runners (all M; age range 23–47 years) 13-mile minimarathon Increased after marathon with respect to value [50]
LDH Runners (all M; age range 23–47 years) 13-mile minimarathon Increased after marathon with respect to value [50]
CK 48 runners (all M; age range 19–58 Male 5–10-mile run; Increased postrun with respect to prerun value [51]
years); 23 runners (all F; age range female 5–10-mile
21–48 years); 13 runners (all M; age run; and male 15–55-
range 22–56 years) mile run
LDH 48 runners (all M; age range 19–58 Male 5–10-mile run; Increased postrun with respect to prerun value [51]
years); 23 runners (all F; age range female 5–10-mile
21–48 years); 13 runners (all M; age run; and male 15–55-
range 22–56 years) mile run
AST 15 trained subjects (all M; age range Half-marathon run Increased 3 h after the run with respect to prehalf [52]
37–64 years) (21 km) marathon value
CK 15 trained subjects (all M; age range Half-marathon run Increased 24 h after the run with respect to prehalf [52]
LDH 15 trained subjects (all M; age range Half-marathon run Increased 3 h after the run with respect to prehalf [52]
CK 11 professional road cyclists (all M; age One stage of a 5-day Increased after the fourth stage with respect to value [53]
27 4 years) professional cycling measured before race
race
TABLE 6
CHANGES IN KIDNEY PARAMETERS
Creatinine 37 amateur runners (32 M, 5 F; age 49 10 Marathon Increased from basal value at 4 and 24 h [10]
years) 3 h after the race; 11 runners (8 M, after race
3 F) 24 h after the race
Urea 37 amateur runners (32 M, 5 F; age 49 10 Marathon Increased from basal value at 4 and 24 h [10]
years) 3 h after the race; 11 runners (8 M, after race
3 F) 24 h after the race
Creatinine 10 professional boxers (all M; age range Boxing match No modification after match with respect [12]
14–17 years) to normal training period
Creatinine 9 ultramarathon runners (7 M, 2 F; age Ultraendurance race (1600 km, No modification with respect to value [21]
53 11.2 years) 16 days duration) measured before the race
Urea 9 ultramarathon runners (7 M, 2 F; age Ultraendurance race (1600 km, Increased after 4 and 11 days and [21]
53 11.2 years) 16 days duration) maintained high values after the end of
the race
Urea 11 professional road cyclists (all M; age One stage of a 5-day Increased after a stage with respect to value [53]
27 4 years) professional cycling race measured before race
Creatinine 27 amateur runners (25 M, 2 F; age range Marathon Increased after the race [61]
34–64 years)
Creatinine 16 ultramarathon cyclists (all M; age range First race across the Alps Increased after the end of the event with [97]
20–57 years) (525 km) respect to the value observed before the
race
Creatinine 18 rugbyists (all M; age 26 4 years), 13 Training and competition No modification in cyclists; decreased in [98]
skiers (all M; age 25 4 years), and 13 the first part of the season in rugby
cyclists (all M; age 27 5 years) players and in the last part of the season
in skiers
Cystatin C 70 recreational runners (all M; age range Marathon Increased after the run [102]
30–68 years)
with BMI was reported also for creatinine. Serum creatinine was measured in
151 professional athletes (age range 17–35 years): rugby (Italian National
team) (n ¼ 44); triathlon (Italian National team) (n ¼ 9); soccer (Italian
First Division team) (n ¼ 27); the America’s Cup yacht crew (n ¼ 22); alpine
skiing (Italian National team) (n ¼ 34); and the ProTour cycling team
(n ¼ 24) (Tables 5 and 6).
Blood drawings were performed before the start of training and competi-
tion season, strictly following preanalytical warnings. A positive correlation
was found between BMI and serum creatinine (r ¼ 0.48; P < 0.001). The
rugby players, who had the highest BMI values (28.83 2.41 kg/m2), also
had the highest values of serum creatinine (1.31 0.12 mg/dL). In contrast,
the cyclists, who had a low mean BMI (21.33 1.21 kg/m2), also had
correspondingly lower serum creatinine concentrations (0.91 0.07 mg/dL).
In some aerobic sports (cycling, triathlon), the BMI is highly homogeneous,
whereas in others (sailing, rugby), it is heterogeneous. Within these sports,
athletes have different anthropometric characteristics. In rugby, for example,
forwards generally have a higher BMI than backs; in soccer, goalkeepers have
a higher BMI than other players. Cyclists and triathletes, typically character-
ized by low fat tissue percentages, have the lowest creatinine values, whereas
rugby players, with their relatively high fat tissue percentage, have higher
values, confirming previous findings described for the general population
[166]. Taken together, the data show that the homeostatic values of creatinine
are related to not only to body size, but also to other physiological mechan-
isms, as an effect of increasing volume of distribution: it is known that total
body water is closely related to body mass [167].
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Metabolic Markers in Sports Medicine

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Metabolic markers in sports

Article in Advances in clinical chemistry · December 2012

Giovanni Lombardi Anna Lubkowska

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METABOLIC MARKERS IN SPORTS MEDICINE

*IRCCS Istituto Ortopedico Galeazzi, Milano, Italy

0065-2423/12 $35.00 Copyright 2012, Elsevier Inc.

Physical exercise induces adaptations in metabolism considered beneficial

Physical activity is recommended for controlling weight, delaying the onset

3. Liver Metabolism Parameters

The resting aminotransferase concentrations and the BMI of 116 male

4. Muscle Metabolism Parameters

4.1. CREATINE KINASE

Although CK concentrations have mainly been studied in individual,

approximately 9 min. As judged from CK levels, active recovery was more

4.2. LACTATE DEHYDROGENASE AND OTHER MARKERS

4.3. MYOCARDIAL MARKERS

antagonist to the renin–angiotensin system. It is also cytoprotective and a

an accessory protein of the TGF b receptor system expressed on endothelial

The NT-proBNP or BNP values in nonendurance athletes at rest are

17 recreational athletes before and after a marathon run. Troponin was

The interpretation of creatinine values in athletes should take into account

cycling). Analysis of variance showed significant differences among groups of

catabolized by tubular cells, has been proposed as a reliable marker of GFR.

Uric acid (UA) is important in sports medicine because it is the terminal

scenario involving UA and oxidative metabolism is emerging, wherein anti-

The variations in serum UA over various phases of a competitive season were

glucose uptake is markedly improved locally in previously active muscles.

the effect is mainly linked to glucose and carbohydrate availability [118].

No difference in TC, HDLC, LDLC, and TG concentrations was observed

Parameter Type of exercise Study population Results Reference

Parameter Type of exercise Study population Results Reference

increase in HDLC. ApoB decreased, whereas ApoA1 was stable. Detraining,

9. Bone Metabolism Markers

The behavior of bone metabolism markers in sports medicine has been

Acronym Bone formation markers

BAP or BALP Bone alkaline phosphatase

Bone resorption markers

Pyr Pyridinoline (or pyridinium cross-links or simply cross-links)

Acronyms are nonstandard.

There are many experiments on bone metabolism makers after acute

nonweight-bearing sports: in males, cycling is associated with lower bone

10. Effect of Body-Mass Index on Laboratory Parameters

Several metabolic parameters are related to BMI. The athletic population

Parameter Study population Type of exercise Results Reference

Parameter Study population Type of exercise Results Reference

Parameter Study population Type of exercise Results Reference

[62] G. Neumayr, R. Pfister, G. Mitterbauer, G. Eibl, H. Hoertnagl, Effect of competitive

[97] G. Neumayr, R. Pfister, H. Hoertnagl, G. Mitterbauer, W. Prokop, M. Joannidis, Renal

[135] M. Lehmann, H.H. Dickhuth, G. Gendrisch, W. Lazar, M. Thum, R. Kaminski, et al.,

[151] H. Brahm, K. Piehl-Aulin, S. Ljunghall, Biochemical markers of bone metabolism during

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