CE update [chemistry]

Effects Of Exercise On Laboratory Test

Results
Stacy E. Foran, MD, PhD, Kent B. Lewandrowski, MD, Alexander Kratz, MD, PhD, MPH
Division of Laboratory Medicine, Department of Pathology, Massachusetts General Hospital, and Harvard Medical School,
Boston, MA
DOI: 10.1309/3PDQ4AH662ATB6HM

After reading this article, the reader should understand the influence of exercise on laboratory parameters and the clinical
relevance of these changes.
Chemistry exam 20303 questions and the corresponding answer form are located after the “Your Lab Focus” section on p. 747.

왘 This report summarizes the literature
on the effects of different exercise
regimens on routine laboratory tests,
markers of vascular and cardiac
health and prostate specific antigen.
왘 Reports on the effects of exercise on
laboratory results in the literature are
scattered and inconsistent for many
analytes.
왘 Both short and long-term physical
activities alter a variety of laboratory
results, but it is important to
understand the difference between
“physiologic” and “pathologic” effects
of exercise.
The long-term positive effects of
physical activity on the incidence of coro-
nary artery disease, hypertension, dys-
lipoproteinemia, obesity, and life
expectancy are well known.1 This has led
to many official recommendations stress-
ing the importance of exercise to promote
optimal health.2,3 For example, the Amer-
ican College of Sports Medicine
(ACSM), the Center for Disease Control
(CDC), and the Surgeon General have
issued guidelines for sensible exercise
programs.
These exhortations have caused
736 many otherwise sedentary individuals to
adopt exercise regimens. Depending on
their intensity, duration, and frequency,
these regimens can have a variety of ef-
fects on laboratory test results. It is im-
portant for a physician to understand the
"physiologic" effects of exercise on labo-
ratory results and when the threshold to
pathological effects has been crossed. In
this article, we summarize the literature
on the effects of various forms of exercise
on many routine laboratory tests
performed in hospital laboratories.
In general, reports in the literature on
the effects of exercise on laboratory test
results are scattered and inconsistent. Inves-
tigations vary in the type, duration, and
intensity of exercise studied, sample num-
bers are often small, and biological, behav-
ioral, and experimental variables are not
always adequately controlled.4 Several
studies have shown a beneficial effect of
exercise on selected parameters such as
lipoproteins. However, few studies have
examined alterations in many common or
critical laboratory parameters such as elec-
trolytes and complete blood count that may
effect immediate patient management.
The effects of exercise on laboratory
tests can be conceptually divided into 2
major groups: 1) short-term effects of
strenuous exercise on laboratory values
reported in marathon runners and other
endurance athletes, and 2) long-term ef-
fects of exercise programs on laboratory
parameters. Frequently, it is difficult to
separate these 2 effects because partici-
pants in high-endurance sports undergo
training programs before participating in
competitive events.
Short-Term Effects of Exercise
on Routine Laboratory Tests
Biochemical and hematological tests
are performed on most hospitalized pa-
tients and many outpatients for diagnosis,
management, or screening of disease.
These tests include complete blood
counts (CBC), white cell differentials,
and determinations of glucose,
electrolytes, blood urea nitrogen (BUN),
creatinine, bilirubin, alanine aminotrans-
ferase (ALT), aspartate aminotransferase
(AST), albumin, total protein, uric acid,
and alkaline phosphatase levels.
Samples obtained from participants
in high endurance sports events such as
marathon running, have been frequently
used to determine the short-term effects of
exercise on laboratory tests [T1]. Blood is
usually obtained before and after exertion,
to document immediate changes caused
by endurance running. A reasonably large
study was recently reported on marathon
runners.5 Biological and hematological
parameters were measured in 37 runners
before a marathon and at 4 and 24 hours
after the race. An increase in glucose, total
protein, albumin, uric acid, calcium, phos-
phorous, BUN, creatinine, total and direct
bilirubin, ALT, AST and alkaline phos-
phatase was observed 4 hours post
marathon. No change was measured in
sodium, potassium, and osmolality after 4
hours, while magnesium, chloride, carbon
dioxide, and globulin decreased. BUN,
creatinine, uric acid, ALT, AST and direct
bilirubin remained elevated 24 hours after
the race, while glucose, total protein, albu-
min, globulin, calcium, phosphorous, total
bilirubin and alkaline phosphatase
returned to baseline. Dehydration and de-
creased renal perfusion may explain the
elevated BUN, creatinine, total protein,
and albumin. An increase in the white
blood cell count was also apparent along

Downloaded from https://academic.oup.com/labmed/article-abstract/34/10/736/2657269

by guest laboratorymedicine> october 2003> number 10> volume 34 ©
on 08 February 2018
 Reports in the Literature on Short-Term Effects of Exercise which argues against glomerular injury or
on Routine Laboratory Tests

Test Decrease No Change Increase

T1 trauma. The hematuria may be due to a
temporary hemodynamic impairment of
tubular function.22
Albumin 5 In the study of marathon runners by
Alkaline phosphatase 5
ALT 5,12
Kratz and co-workers cited above,5 many
AST 5,12 samples from trained runners obtained be-
Bilirubin 5 fore a marathon had laboratory results out-
BUN 5,11
Calcium 11 5,12
side of the standard reference range. The
Carbon dioxide 5,13,14 12 largest deviations were in myoglobin and
Chloride 5 11 cholesterol of which 89% and 49% of run-
Creatinine 12 5,9,13,14
Globulin 5,12
ners, respectively, were outside the stan-
Glucose 14 9 5,10,11,12 dard range. Differences were also noted
Hematocrit 5,14 15 11,12,13 for triglycerides (24% outside the range),
Hemoglobin 9,16 5,10,14
pH 11
glucose (22%), phosphorus (19%), RBC
Magnesium 5,11 count (19%), potassium (14%), AST
Osmolality 5 (11%), CK-MB (11%), ALT (5%), chloride
Platelets 5
Potassium 23 5,11,12 6,7,8,9,13,14
(5%), and white blood cell count (3%).
Sodium 8,11,18,23 5 6,7,9,12,13,14
Total protein 5,9,10 Long-Term Effects of Regular
Uric acid 12 5,9,13,14
WBC count 5,14,16
Exercise Programs on Routine
Laboratory Tests
Numbers refer to references Very few studies have been reported
comparing common laboratory results in
with neutrophilia, monocytosis, and de- Case reports have illustrated a tran- individuals who exercise regularly with
creased lymphocytes which is consistent sient increased risk of sudden cardiac those that do not follow a set exercise pro-
with an inflammatory reaction to tissue death in marathon runners.11 These run- gram [T2]. In a study by Seneczko,24 the
injury. Leukocytosis may be primarily due ners have severe hyponatremia in the ab- white blood cell count, which is an impor-
to the demargination of white blood cells sence of hypovolemia, which may be tant indicator of immune function, was
induced by increased blood flow. attributed to a high intake of free water. compared in 31 young healthy males who
Platelets, hemoglobin, MCH, MCHC, and In one runner, fatal hyponatremic played no sports and 32 football players
RDW were elevated at 4 and 24 hours, encephalopathy and acute cerebral edema after 1 year of training. The football play-
while hematocrit, RBC, and MCV occurred.17 It has been postulated that ers had an elevated white blood cell count
decreased. The hematocrit returned to rhabdomyolysis during marathons trig- with a differential that was shifted in favor
baseline at 24 hours. gers acute inflammation with release of of neutrophils, eosinophils, and
These results confirmed data from C-reactive protein and creatine kinase and monocytes at the expense of lymphocytes.
other marathon studies,6-12 except for the a neuroendocrine stress response with This implies that physical activity may
finding on sodium, potassium, and hema- release of IL-6. IL-6 may increase the boost the immune response. In the study
tocrit. Dancaster and colleagues8 and level of anti-diuretic hormone (ADH), by Boning, Tibes, and Schweigart,25 no
Kratz and colleagues5 found no change in despite a positive fluid balance, and pro- change in sodium, potassium, or magne-
sodium, but others have reported mote severe and occasionally fatal sium was seen after 10 to 15 minutes of
increases after marathon races.13,14 Dan- hyponatremia. During marathons or other
caster and colleagues measured elevations strenuous exercise, overhydration leading
in potassium, while Kratz and colleagues to obtundation or seizures may be as im- Reports in the Literature on Long-
Term Effects of Regular
found no difference. Reports regarding portant as dehydration. On-site point of Exercise Programs on
hematocrit after a marathon are also in-
consistent. Depending on the study,
care testing for serum chemistries in ill
patients may help in the diagnosis and
Routine Laboratory Tests T2
hematocrit can decrease,5,15 not change,16 rapid management of hyponatremia.18 Test No Change Increase 737
or increase11,13,14 after exercise. Sample Exercise induced hematuria or "ath- ALT 26
size, methodology or variations in fluid letic pseudonephritis" is a common be- AST 26
Chloride 25
intake may account for the differences. nign cause of discolored urine following pH 25
The discrepancies may also be due to dif- strenuous exercise.19-23 Nine of 50 Magnesium 25
ferences in timing of the samples, degree marathon runners (18%) had gross or mi- Sodium 25
WBC count 24
of fitness (training) or environmental croscopic hematuria following a race.19
(weather) factors. No red blood cell casts were found, Numbers refer to references

Downloaded from https://academic.oup.com/labmed/article-abstract/34/10/736/2657269

by guest © laboratorymedicine> october 2003> number 10> volume 34
on 08 February 2018
 Reports in the Literature on Short-Term Effects of Exercise pulmonary embolus. The balance
on Markers of Vascular and Cardiac Health

Test Decrease No Change Increase

T3 between clot formation and fibrinolysis
(or clot dissolution) may be tipped
towards fibrinolysis by exercise. Exercise
Fibrinolysis D-dimer 30,36 may promote the release of plasminogen
Fibrinogen 36 38 37
Lipids HDL 46,47 activators from the endothelium, enhance
LDL 46,47 45 conversion of plasminogen to plasmin,
TC 12,47 45,46 and lead to clot dissolution.31 D-dimer is
TG 12,45 47
Cardiac Markers AST 5,29 a degradation product of the enzymatic
CK 5,23,29 action of plasmin on crosslinked fibrin.
CK-MB 5,29 Increasing plasma levels of d-dimer have
Myoglobin 5,23,29,55
TnI 52 5,23,29,51,55 been investigated as a sensitive marker of
TnT 52 5,29,51,55 intravascular fibrin formation and the ex-
Cardiac Risk BNP 51 tent and severity of underlying atheroscle-
CRP 13,45 30
IMA 55 rosis.32 Plasma fibrinogen has also been
related to the incidence of coronary events
Numbers refer to references
in both healthy and nonhealthy popula-
Reports in the Literature on Long-Term Effects of Exercise tions.32,33 High fibrinogen is associated
on Markers of Vascular and Cardiac Health

Test Decrease No Change

T4
Increase
with coronary artery disease (CAD), obe-
sity, and a high body mass index. Some
evidence suggests that exercise decreases
Fibrinolysis D-dimer fibrinogen, but the mechanism for this is
Fibrinogen 33,32,35 34,37 unclear.33 Fibrinogen may decrease the
Lipids HDL 1,2,3,4,39,
40,41,42
risk of atherosclerosis and thrombosis by
LDL 2,43,39,44 favorably altering blood viscosity, platelet
TC 2,34,39,44 adhesion, and aggregation and by limit-
TG 2,34,39,44
Cardiac Markers AST 48
ing intravascular fibrin formation and
CK 48,49,50 deposition. Advancing age is associated
CK-MB 49,50 with an increased risk of CAD and ather-
LDH 48,49,50
Myoglobin 49,50
osclerosis. This may be due to increasing
TnI 49,50 concentrations of fibrinogen, d-dimer,
TnT 49,50 and reduced fibrinolytic activity.32
Cardiac Risk BNP 54,57 58,59
CRP 34
Whether moderate exercise can prevent
HCY 56 age-related changes in fibrinolysis is
Lp(a) 1,45 53 under investigation.
Numbers refer to references
Most studies examining fibrinogen,
fibrinolysis, and d-dimer have been done
on the fit population of both adults and
bicycle ergometer use in 6 untrained and 6 promote an imbalance in the prothrom- children [T4]. A study done in 193 chil-
trained adults. However, a decrease in pH botic and fibrinolytic systems that may dren and young adults aged 4 to 25 shows
and an increase in chloride levels were trigger an acute coronary syndrome an inverse relationship between fibrinogen
measured in untrained adults, which may (ACS) and sudden cardiac death.5,29,30 and fitness level as assessed by treadmill
have been due to a component of lactic aci- Several studies have investigated the ef- performance. The results remained signif-
dosis in the untrained probands. In 7 trained fects of low, moderate, and high inten- icant after adjusting for obesity and body
athletes and 15 healthy untrained athletes, sity exercise on fibrinogen, fibrinolysis, mass index.33 Sixty-nine adults aged 25 to
elevations in both ALT and AST were seen lipoproteins, and cardiac markers in an 69 participated in a 10-week fitness pro-
after 60 minutes of an ergometer test.26 attempt to determine how exercise mod- gram using a treadmill. Physical condi-
738 ulates laboratory parameters to alter car- tioning was associated with increased
Vascular and Cardiac Health diac risk [T3 and T4]. fibrinolysis that occurred in response to
Regular physical activity has been venous occlusion.31 In contrast, 74 obese
advocated for its cardioprotective Fibrinolysis teenagers were randomized to lifestyle
effects in both children and adults.27,28 Intravascular thrombus formation change or moderate to high intensity
In contrast, recent studies on marathon plays a role in the pathophysiology of physical training (5 days per week utiliz-
runners have shown that endurance run- several vascular diseases including stroke, ing 250 kcal/session). This study found no
ning may increase cardiac enzymes or myocardial infarction (MI), and change in fibrinogen or d-dimer when

Downloaded from https://academic.oup.com/labmed/article-abstract/34/10/736/2657269

by guest laboratorymedicine> october 2003> number 10> volume 34 ©
on 08 February 2018
 comparing the physically active and
lifestyle modification group, but this find-
ing may have resulted from lack of adher-
ence to the protocol.34 Exercise attenuated
the age related changes in fibrinogen, d-
dimer, and fibrinolysis, as measured in
healthy premenopausal and
postmenopausal women.32 Most studies
suggest that exercise promotes fibrinolysis.
One study stratified 4,075 physically ac-
tive men into low, moderate, or high fit-
ness groups based on a maximal treadmill
test. Not only did exercise lower fibrino-
gen, but the results suggest that within a fit
population, fibrinogen would continue to
decrease as a persons' fitness level
increased.35 The few studies done on
marathon runners are inconsistent [T3].
Results show increases, decreases, or no
change in fibrinogen and d-dimer after an
endurance race.36-38 In one study, d-dimer
remained elevated at 4 and 24 hours after
the race, while the increase in fibrinolytic
activity was seen only at 4 hours and re-
turned to baseline by 24 hours. This sug-
gested a preservation of balance between
thrombosis and fibrinolysis at 4 hours, but
a hemostatic balance toward clotting at 24
hours.30 Long-term exercise in the fit pop-
ulation appears to be more cardioprotec-
tive than excessive endurance training.
Lipids
Blood cholesterol and lipoprotein car-
riers are significantly involved in CAD and
are primary targets for pharmacological
intervention. LDL infiltrates the intimal
endothelial lining and is subsequently oxi-
dized which prevents its removal from the
circulation and augments plaque forma-
tion.39 On the other hand, studies have
shown that HDL has antiatherogenic prop-
erties with its concentration inversely re-
lated to the risk of CAD.4 A serum
concentration of HDL >60 mg/dL appears
to exert a protective effect against athero-
sclerosis.40 One of the possible
mechanisms by which physical activity
can decrease the risk of CAD is through
exercise induced increases in HDL.4 Total
cholesterol (TC), LDL, HDL and triglyc-
erides (TG) are frequently used to assess a
patient's cardiac risk and the observed al-
terations after exercise provide valuable
clinical information.
Downloaded from https://academic.oup.com/labmed/article-abstract/34/10/736/2657269
by guest
on 08 February 2018
Most articles show an increase in
HDL after bicycling, aerobics or running,
but the effect of exercise on TC, TG, and
LDL is controversial [T4].2-4,39-42 The ma-
jority of the literature finds no benefit of
exercise on TC, TG, or LDL.2,39,43-45 How-
ever, a study assigned 45 sedentary college
women to 8 weeks of step aerobics, aero-
bic dancing, or control. Both aerobic rou-
tines decreased total cholesterol.2 Seven
diabetic patients joined a 3-month physical
exercise program (1-hour sessions of
treadmill, bike, or walking). HDL
increased in type I diabetes mellitus and
LDL decreased in type II diabetes melli-
tus. The reason for this discrepancy is not
known.1 Lipoprotein values after marathon
training appear to change more
significantly when compared to the fit
population [T3]. Thirty marathon runners
were grouped as slow (fit), moderate (fit-
ter), or fast (fittest) based on their running
times. The elevation in HDL after the race
was inversely proportional to their running
time. The runners also exhibited a
decrease in LDL, but no change in choles-
terol.46 After a race, 12 females had lower
cholesterol for at least 5 days, decreased
LDL, and elevated HDL for up to 1 day
and a transient elevation of TG.47 Another
study found no difference in TG or choles-
terol after a marathon.45
Cardiac Markers
Patients who present with clinical
signs and symptoms of an ACS are usually
tested for their levels of cardiac markers
such as myoglobin, creatine kinase (CK),
CK-MB, troponin T or I. Traditional mark-
ers, including CK and CK-MB, increase 4
to 8 hours after the onset of acute symp-
toms and remain elevated for 48 to 72
hours. Newer markers include troponin T
(TnT) and troponin I (TnI), CK-MB iso-
forms, and myoglobin. Myoglobin is re-
leased before troponin and CK-MB. The
gold standards, TnT and TnI, peak at 1 day
and stay elevated for up to 1 week.
Only a few studies have been
performed in the fit asymptomatic popula-
tion regarding cardiac markers [T4]. Al-
though exercise is recommended to
maintain cardiovascular health and prevent
atherosclerosis, reports have shown that
moderate physical activity and marathon
© laboratorymedicine> october 2003> number 10> volume 34
running can cause elevations in cardiac
markers consistent with cardiac ischemia.
In a study by King and colleagues,48 4
males played a 1-hour game of handball
and elevations in CK, AST, and LDH were
measured up to 93 hours after exercise.
AST peaked at 5 hours, and CK peaked at
11 hours post exercise. In another study of
cycling and treadmill exercise, myoglobin,
LDH, and CK were all increased, but CK-
MB was elevated only after treadmill test-
ing. Neither study in the fit population
found a significant increase in TnT or
TnI.49,50 Nonspecific elevations in myoglo-
bin, AST, CK, and CK-MB are also noted
after marathon running and presumably
reflect exertional skeletal muscle
rhabdomyolysis [T3].5,29 It is also known
that the CK-MB content in skeletal muscle
of trained athletes is increased beyond the
normal 2% seen in untrained skeletal mus-
cle. Therefore in athletes with exertional
rhabdomyolysis, the elevation in CK-MB
may be more prominent and can exceed
cutoff values used to indicate acute my-
ocardial infarction. Troponin T and I are
more cardiospecific markers of cardiac
injury. Most studies in marathon runners
show a small increase in TnT and TnI in
some individual athletes that may persist
up to 24 hours after competition. However,
these slight elevations probably do not
represent microinfarction as documented
by negative SPECT sestamibi myocardial
scintigraphy in these subjects.5,29,51 In one
study of 22 runners at 6, 24, and 48 hours
after a marathon TnI and TnT were within
normal limits, but the number of partici-
pants was small.52 The elevations in myo-
globin, AST, CK, and CK-MB indicate
exertional rhabdomyolysis of skeletal
muscle. On the other hand, release of TnI
and TnT in some athletes suggest cardiac
dysfunction but this has not confirmed by
nuclear scintigraphic studies.
Consequently, the significance of small
elevations in troponin after competition
remains undetermined. 739
Cardiac Risk Profile
Recently, measurement of C-reactive
protein (CRP), lipoprotein (a) [Lp(a)],
brain natriuretic peptide (BNP), ischemia
modified albumin (IMA), and homocys-
teine (HCY) have been proposed to assess
 cardiac risk. CRP is a marker of inflam-
mation and recent studies have
investigated its utility in predicting the fu-
ture risk of CAD.34 Lp(a) is a macromole-
cular complex found in plasma, which is
formed when LDL is joined with
apolipoprotein (a), a unique glycoprotein.
Elevated concentrations of Lp(a) >300
mg/L are associated with an increased risk
of CAD.1 The exact mechanism is
unknown, but Lp(a) may inhibit fibrinoly-
sis or deposit cholesterol in arterial
walls.53 BNP is a neurohormone secreted
from the cardiac ventricles and reflects left
ventricle pressure. BNP levels are corre-
lated with the severity of cardiac disease
and the prognosis of congestive heart fail-
ure. Several groups have investigated the
ability of BNP to predict the extent of car-
diac dysfunction.54 IMA may indicate car-
diac ischemia before irreversible necrosis
in troponin-negative acute coronary syn-
dromes.55 Studies have also indicated that
elevated HCY levels increase the risk of
CAD. HCY should be maintained below
10 mg/dL to prevent adverse effects on the
vasculature.56
CRP has rarely been measured in
relation to exercise in the fit population
[T4]. Most results on CRP and its relation
to exercise were obtained during a stress
test after an MI. In one study, 8 months
of high intensity physical training had no
effect on the CRP level.34 With regards to
Lp(a), in 10 untrained volunteers, Lp(a)
level was decreased more than 72 hours
after bicycle ergometer.45 Lp(a) also de-
clined after physical activity in diabetic
patients, but it only decreased in patients
who had a Lp(a) greater than 300 mg/L.1
In another study with 140 participants,
who performed a graded exercise tread-
mill test, no difference was found in
Lp(a).53 BNP studies have shown both
elevations and no changes in BNP after
bicycle or treadmill exercises.54,57-59 After
maximal aerobic exercise in 11 trained
740 and 10 untrained subjects, BNP
elevations were obtained.58 Transient in-
creases in BNP were also noted in 23
healthy men 1 hour after treadmill exer-
cise that was not secondary to exercise
induced hemoconcentration.59 In contrast,
in 2 different studies no change in BNP
levels were noted after vigorous bicycle
Downloaded from https://academic.oup.com/labmed/article-abstract/34/10/736/2657269
by guest laboratorymedicine> october 2003> number 10> volume 34
on 08 February 2018
riding54 and a treadmill exercise test.57 A
literature search revealed no studies on
the effects of exercise on IMA in the fit
population. A single study on changes in
homocysteine was reported on 20 healthy
men aged 24 to 39 who ran on a treadmill
for 30 minutes. A nonsignificant increase
in HCY was observed secondary to he-
moconcentration.56
In marathon runners, CRP and Lp(a)
were found to decrease after marathon
training, but Lp(a) returned to baseline
after detraining [T3].13,45 In a different
study, CRP was acutely elevated after a
marathon.30 Elevations in BNP after a
marathon race have been reported.9 In run-
ners studied by our group, the increase in
BNP was seen only in athletes with a fall
in serum sodium levels (unpublished data).
In 19 marathon runners the level of IMA
remained within reference limits 30 min-
utes post-race but rose 24 to 48 hours
post-race. This suggests that IMA does not
increase in the short-term as a result of
acute cardiac ischemia, acute skeletal mus-
cle ischemia or gastrointestinal ischemia.55
The paucity and inconsistency of results
on cardiac risk profile make the effects of
exercise on CRP, Lp(a), BNP, IMA, and
HCY difficult to interpret. There is some
convincing evidence that exercise may
benefit Lp(a) levels.
Prostate Specific Antigen
Prostate cancer is the most frequently
diagnosed malignancy and second leading
cause of cancer death in males in the
United States. Screening for prostate can-
cer frequently includes digital rectal exam-
ination (DRE) and measurement of serum
prostate specific antigen (PSA). PSA is a
serine protease produced by prostatic ep-
ithelial cells. Assays for PSA are used for
the early detection of prostate cancer, but
the normal concentration of PSA depends
on several biological factors and an eleva-
tion of PSA does not necessarily indicate
cancer. For example, a common clinical
condition associated with elevations in
PSA is benign prostatic hyperplasia. Some
studies have also shown that physical ma-
nipulations such as DRE, biopsy, or trans-
rectal ultrasound can elevate PSA.
Elevations in PSA have also been re-
ported after different types and intensities
©
of exercise [T5].60,61 Most convincingly,
some data suggest that bicycle riding, be-
cause of its manipulation of the prostate,
may elevate PSA. In one case, a 70-year-
old man with prostate cancer lowered his
PSA when he stopped riding his bicycle.62
In a study of 301 healthy men, elevations
in PSA were observed after riding a bicy-
cle ergometer for 15 minutes. The eleva-
tion was age dependent and correlated
with the level of PSA before exercise.61
However, 2 other studies showed no effect
of long-term cycling on PSA.63,64 PSA
was not affected by running, speedskating,
waterskiing, or cross-country skiing as
seen in 2 small studies.65,66
In a recent study from our group,
PSA was assayed in 21 marathon runners.
Two runners had an elevation in PSA for
up to 24 hours after the race. These find-
ings suggest that selected patients should
refrain from PSA testing after exercise or
the measurement should be repeated if it is
elevated.60 More studies will be needed to
clarify the effects of various types of exer-
cise on PSA levels.
Conclusions
Daily exercise has been
recommended by the ACSM, CDC, and
Surgeon General for both its cardiopro-
tective effects and overall health benefits.
Physical activity has been shown to ele-
vate levels of HDL, but its effects on
other lipids and cardiac markers are in-
consistent. High intensity physical activ-
ity or marathon running may actually
elicit transient cardiac injury instead of
providing a benefit, so more research
needs to be done on the exact effects of
exercise on the heart. The increase in
BUN and creatinine after exercise are
probably transient secondary to dehydra-
tion and decreased renal perfusion, while
the increase in white blood cell count
may be due to demargination of white
blood cells induced by increased blood
flow. The effect of exercise on many
other laboratory parameters is largely un-
known and the results in the few available
reports are contradictory. Interestingly,
PSA may be elevated in selected patients
following exercise. This raises the ques-
tion whether or not other tumor markers
are affected by exercise. In some studies,
 Reports in Literature
on the Effects of Exercise
on PSA Level
Exercise Type No Change
T5
Increase
Short-Term 60
Long-Term 63,64,65,66 61,62
Numbers refer to references
Exercise Induced Disorders
Acute Coronary Syndrome
T6
Coagulopathy
Dehydration
Exertional Rhabdomyolysis
Hematuria
Hemolysis
Hyponatremia
trained athletes had laboratory values out-
side the normal reference range and new
ranges may need to be instituted to ade-
quately diagnose and treat athletes.
It is important to recognize specific
conditions that can occur after various
degrees of exercise [T6]. The line
between "physiologic" and "pathologic"
changes due to exercise is not well drawn
and ultimately clinicians must decide
which patients require medical expertise.
Post-exercise hematuria and other benign
conditions should be familiar to physi-
cians and patients should be spared inva-
sive and expensive testing. On the other
hand, severe hyponatremia can be fatal
and warrants immediate medical interven-
tion. Some conditions may progress from
self-limiting or benign (ie, "physiologic")
to those requiring treatment (ie, "patho-
logic") depending on the athlete, degree
of exercise and other variables. This point
of progression can be difficult to deter-
mine. As exercise-induced changes in
laboratory parameters become more de-
fined, the line between "physiologic" and
"pathologic" will become more apparent.
The variability in the data presented
may be due to biological, behavioral, or
experimental factors. Genetic factors, eth-
nicity, age, sex, hormonal status, and body
weight must be considered when design-
ing a study and interpreting results. Dif-
ferences in study design, exercise training
programs, sample size, type, volume, and
intensity of exercise, duration of training,
and adherence to the exercise program
Downloaded from https://academic.oup.com/labmed/article-abstract/34/10/736/2657269
by guest
on 08 February 2018
may also account for the variability in re-
sults. Behavioral characteristics such as
the use of tobacco, alcohol, hormones, or
medications will affect laboratory values.
Preanalytical factors such as timing of
blood draws, laboratory quality control,
and body position may also affect assay
results. The variability in these factors
makes the current studies difficult to in-
terpret. This review summarizes the ef-
fects of exercise on certain laboratory
parameters, but it also illustrates the need
for additional well controlled studies on
the changes in common laboratory pa-
rameters, as well as cardiac and tumor
markers, during and after exercise.
1. Rigla M, Sanchez-Quesada JL, Ordonez-Llanos J, et
al. Effect of physical exercise on lipoprotein(a) and
low-density lipoprotein modifications in type 1 and
type 2 diabetic patients. Metabolism. 2000;49:640-
647.
2. Kin Isler A, Kosar SN, Korkusuz F. Effects of step
aerobics and aerobic dancing on serum lipids and
lipoproteins. J Sports Med Phys Fitness.
2001;41:380-385.
3. Katzmarzyk PT, Leon AS, Rankinen T, et al.
Changes in blood lipids consequent to aerobic
exercise training related to changes in body fatness
and aerobic fitness. Metabolism. 2001;50:841-848.
4. Leon AS, Gaskill SE, Rice T, et al. Variability in the
response of HDL cholesterol to exercise training in
the HERITAGE Family Study. Int J Sports Med.
2002;23:1-9.
5. Kratz A, Lewandrowski KB, Siegel AJ, et al. Effect
of marathon running on hematologic and
biochemical laboratory parameters, including cardiac
markers. Am J Clin Pathol. 2002;118:856-863.
6. Roecker L, Kirsch KA, Heyduck B, et al. Influence
of prolonged physical exercise on plasma volume,
plasma proteins, electrolytes, and fluid-regulating
hormones. Int J Sports Med. 1989;10:270-274.
7. Cohen I, Zimmerman AL. Changes in serum
electrolyte levels during marathon running. S.A. Med
J. 1978;53:449-453.
8. Dancaster CP, Whereat SJ. Fluid and electrolyte
balance during the comrades marathon. S.A. Med J.
1971;45:147-150.
9. Nelson PB, Ellis D, Fu F, et al. Fluid and electrolyte
balance during a cool weather marathon. Am J
Sports Med. 1989;17:770-772.
10. Maron MB, Horvath SM, Wilkerson JE. Acute blood
biochemical alterations in response to marathon
running. Europ J Appl Physiol Occup Physiol.
1975;34:173-181.
11. Adner MM, Gembarowicz, R., Casey, J, et al. Point- 741
of-care biochemical monitoring of Boston marathon
runners. Point of Care: The Journal of Near-Patient
Testing & Technology. 2002;1:237-240.
12. Fallon KE, Sivyer G, Sivyer K, et al. The
biochemistry of runners in a 1600 km ultramarathon.
Br J Sports Med. 1999;33:264-269.
13. Boudou P, Fiet J, Laureaux C, et al. Variations de
quelques constituants plasmatiques et urinaires ches
les marathoniens. Ann Biol Clin. 1986;45:37-45.
© laboratorymedicine> october 2003> number 10> volume 34
 14. Kraemer RR, Brown BS. Alterations in plasma-
volume-corrected blood components of marathon
runners and concomitant relationship to
performance. Eur J Appl Physiol Occup Physiol.
1986;55:579-584.
15. Casoni I, Borsetto C, Cavicchi A, et al. Reduced
hemoglobin concentration and red cell
hemoglobinization in Italian marathon and
ultramarathon runners. Int J Sports Med.
1985;6:176-179.
16. Wells CL, Stern JR, Hecht LH. Hematological
changes following a marathon race in male and
female runners. Eur J Appl Physiol Occup Physiol.
1982;48:41-49.
17. The associated press. Road racing; Boston marathon
runner dies. New York Times. New York; 2002:7.
18. Siegel AJ. Role for on-site point-of-care testing in
the emergency care of athletes with exercise-
associated collapse. Point of Care: The Journal of
Near-Patient Testing & Technology. 2002;1:132-134.
19. Siegel AJ, Hennekens CH, Solomon HS, et al.
Exercise-related hematuria. Findings in a group of
marathon runners. JAMA. 1979;241:391-392.
20. Gambrell RC, Blount BW. Exercise-induced
hematuria. Am Fam Physician. 1996;53:905-911.
21. Alvarez C, Mir J, Obaya S, et al. Hematuria and
microalbuminuria after a 100 kilometer race. Am J
Sports Med. 1987;15:609-611.
22. Gilli P, De Paoli Vitali E, Tataranni G, et al.
Exercise-induced urinary abnormalities in long-
distance runners. Int J Sports Med. 1984;5:237-240.
23. Gerth J, Ott U, Funfstuck R, et al. The effects of
prolonged physical exercise on renal function,
electrolyte balance and muscle cell breakdown. Clin
Nephrol. 2002;57:425-431.
24. Seneczko F. White blood cell count and adherence in
sportsmen and non-training subjects. Acta Physiol
Pol. 1983;34:601-610.
25. Boning D, Tibes U, Schweigart U. Red cell
hemoglobin, hydrogen ion and electrolyte
concentrations during exercise in trained and
untrained subjects. Eur J Appl Physiol Occup
Physiol. 1976;35:243-249.
26. Koutedakis Y, Raafat A, Sharp NC, et al. Serum
enzyme activities in individuals with different levels
of physical fitness. J Sports Med Phys Fitness.
1993;33:252-257.
27. Sandvik L, Erikssen J, Thaulow E, et al. Physical
fitness as a predictor of mortality among healthy,
middle-aged Norwegian men. N Engl J Med.
1993;328:533-537.
28. Sallis JF, Patterson TL, Buono MJ, et al. Relation of
cardiovascular fitness and physical activity to
cardiovascular disease risk factors in children and
adults. Am J Epidemiol. 1988;127:933-941.
29. Siegel AJ, Lee-Lewandrowski E, Chun KY, et al.
Changes in cardiac markers including B-natriuretic
peptide in runners after the Boston marathon. Am J
Cardiol. 2001;88:920-923.
30. Siegel AJ, Stec JJ, Lipinska I, et al. Effect of
742 marathon running on inflammatory and hemostatic
markers. Am J Cardiol. 2001;88:918-920.
31. Williams RS, Logue EE, Lewis JG, et al. Physical
conditioning augments the fibrinolytic response to
venous occlusion in healthy adults. N Engl J Med.
1980;302:987-991.
32. DeSouza CA, Jones PP, Seals DR. Physical
activity status and adverse age-related differences
in coagulation and fibrinolytic factors in women.
Arterioscler Thromb Vasc Biol. 1998;18:362-368.
Downloaded from https://academic.oup.com/labmed/article-abstract/34/10/736/2657269
by guest laboratorymedicine> october 2003> number 10> volume 34
on 08 February 2018
33. Isasi CR, Starc TJ, Tracy RP, et al. Inverse
association of physical fitness with plasma
fibrinogen level in children: The Columbia
University BioMarkers Study. Am J Epidemiol.
2000;152:212-218.
34. Barbeau P, Litaker MS, Woods KF, et al.
Hemostatic and inflammatory markers in obese
youths: Effects of exercise and adiposity. J
Pediatr. 2002;141:415-420.
35. Church TS, Finley CE, Earnest CP, et al. Relative
associations of fitness and fatness to fibrinogen,
white blood cell count, uric acid and metabolic
syndrome. Int J Obes Relat Metab Disord.
2002;26:805-813.
36. Prisco D, Paniccia R, Bandinelli B, et al.
Evaluation of clotting and fibrinolytic activation
after protracted physical exercise. Thromb Res.
1998;89:73-78.
37. Ponjee GA, Janssen GM, van Wersch JW.
Prolonged endurance exercise and blood
coagulation: A 9 month prospective study. Blood
Coagul Fibrinolysis. 1993;4:21-25.
38. Mandalaki T, Dessypris A, Louizou C, et al.
Marathon Run III: Effects on coagulation,
fibrinolysis, platelet aggregation and serum
cortisol levels. A 3-year study. Thromb Haemost.
1980;43:49-52.
39. Leon AS, Rice T, Mandel S, et al. Blood lipid
response to 20 weeks of supervised exercise in a
large biracial population: the HERITAGE Family
Study. Metabolism. 2000;49:513-520.
40. Spate-Douglas T, Keyser RE. Exercise intensity:
Its effect on the high-density lipoprotein profile.
Arch Phys Med Rehabil. 1999;80:691-5.
41. Carroll S, Cooke CB, Butterly RJ, et al.
Associations of leisure-time physical activity and
obesity with atherogenic lipoprotein-lipid markers
among non-smoking middle-aged men. Scand J
Med Sci Sports. 2001;11:38-46.
42. Kumagai S, Shono N, Kondo Y, et al. The effect
of endurance training on the relationships between
sex hormone binding globulin, high density
lipoprotein cholesterol, apoprotein A1 and
physical fitness in pre-menopausal women with
mild obesity. Int J Obes Relat Metab Disord.
1994;18:249-254.
43. Tolfrey K, Jones AM, Campbell IG. The effect of
aerobic exercise training on the lipid-lipoprotein
profile of children and adolescents. Sports Med.
2000;29:99-112.
44. Hughes RA, Thorland WG, Housh TJ, et al. The
effect of exercise intensity on serum lipoprotein
responses. J Sports Med Phys Fitness.
1990;30:254-260.
45. Bonetti A, Tirelli F, Arsenio L, et al.
Lipoprotein(a) and exercise. J Sports Med Phys
Fitness. 1995;35:131-135.
46. Ketelhut RG, Ketelhut K, Messerli FH, et al.
Fitness in the fit: Does physical conditioning
affect cardiovascular risk factors in middle-aged
marathon runners? Eur Heart J. 1996;17:199-203.
47. Goodyear LJ, Van Houten DR, Fronsoe MS, et al.
Immediate and delayed effects of marathon
running on lipids and lipoproteins in women. Med
Sci Sports Exerc. 1990;22:588-592.
48. King SW, Statland BE, Savory J. The effect of a
short burst of exercise on activity values of
enzymes in sera of healthy young men. Clin Chim
Acta. 1976;72:211-218.
49. Bonetti A, Tirelli F, Albertini R, et al. Serum
cardiac troponin T after repeated endurance
exercise events. Int J Sports Med. 1996;17:259-262.
©
50. Shave R, Dawson E, Whyte G, et al. The
cardiospecificity of the third-generation cTnT
assay after exercise-induced muscle damage. Med
Sci Sports Exerc. 2002;34:651-654.
51. Ohba H, Takada H, Musha H, et al. Effects of
prolonged strenuous exercise on plasma levels of
atrial natriuretic peptide and brain natriuretic
peptide in healthy men. Am Heart J.
2001;141:751-758.
52. Lucia A, Serratosa L, Saborido A, et al. Short-
term effects of marathon running: no evidence of
cardiac dysfunction. Med Sci Sports Exerc.
1999;31:1414-1421.
53. Drowatzky KL, Durstine JL, Irwin ML, et al. The
association between physical activity,
cardiorespiratory fitness, and lipoprotein(a)
concentrations in a tri-ethnic sample of women:
The Cross-Cultural Activity Participation Study.
Vasc Med. 2001;6:15-21.
54. McNairy M, Gardetto N, Clopton P, et al. Stability
of B-type natriuretic peptide levels during exercise
in patients with congestive heart failure:
implications for outpatient monitoring with B-type
natriuretic peptide. Am Heart J. 2002;143:406-
411.
55. Apple FS, Quist HE, Otto AP, et al. Release
characteristics of cardiac biomarkers and
ischemia-modified albumin as measured by the
albumin cobalt-binding test after a marathon race.
Clin Chem. 2002;48:1097-1100.
56. Wright M, Francis K, Cornwell P. Effect of acute
exercise on plasma homocysteine. J Sports Med
Phys Fitness. 1998;38:262-265.
57. Onuoha GN, Nicholls DP, Patterson A, et al.
Neuropeptide secretion in exercise.
Neuropeptides. 1998;32:319-325.
58. Bentzen H, Pedersen RS, Nyvad O, et al.
Influence of training habits on exercise-induced
changes in plasma atrial and brain natriuretic
peptide and urinary excretion of aquaporin-2 in
healthy men. Scand J Clin Lab Invest.
2002;62:541-551.
59. Huang WS, Lee MS, Perng HW, et al. Circulating
brain natriuretic peptide values in healthy men
before and after exercise. Metabolism.
2002;51:1423-1426.
60. Kratz A, Lewandrowski KB, Siegel AJ, et al.
Effect of marathon running on total and free
serum prostate-specific antigen concentrations.
Arch Patholog Lab Med. 2003;127:345-348.
61. Oremek GM, Seiffert UB. Physical activity
releases prostate-specific antigen from the prostate
gland into blood and increases serum PSA
concentrations. Clin Chem. 1996;42:691-695.
62. Rana A, Chisholm GD. He sold his bike for a low
prostate specific antigen. J Urology.
1994;151:700.
63. Safford HR, Crawford ED, Mackenzie SH, et al. The
effect of bicycle riding on serum prostate specific
antigen levels. J Urology. 1996;156:103-105.
64. Swain RA, Monalto N, Ross D. The effect of
long-distance cycling on the prostate-specific
antigen level. Arch Fam Med. 1997;6:500-502.
65. Leventhal EK, Rozanski TA, Morey AF, et al. The
effects of exercise and activity on serum prostate
specific antigen levels. J Urology. 1993;150:893-894.
66. Banfi G, Pontillo M, Dolci A, et al. Prostate-
specific antigen is not increased in young men by
ultraendurance sport performances. Clin Chem.
1997;43:1465-1466.