CLINICAL COMMUNICATION TO THE EDITOR
Creatine Supplementation and
Venous Thrombotic Events
To the Editor:
Creatine is a naturally occurring compound that is pop-
ular as a sports nutrition supplement because it is believed to
improve exercise performance. We report 2 cases of venous
thrombosis occurring in otherwise healthy young men and
discuss their causal link to the consumption of creatine.
CASE 1
An 18-year-old student presented with a 1-week history of
headache that was associated with vomiting. Thrombosis of
the superior sagittal sinus, right transverse sinus, and right
internal jugular vein was demonstrated on magnetic reso-
nance imaging of the brain that was performed after his
admission to the hospital. There was no other significant
head and neck pathology detected. He had no personal or
family history of venous thromboembolism. Comprehensive
thrombophilia screening results were normal, which in-
cluded tests for protein C, protein S and antithrombin
III deficiencies, factor V Leiden and prothrombin gene
G20210A mutation, lupus anticoagulant and anticardiolipin
antibodies, Janus kinase 2 mutation for myeloproliferative
disorders, and paroxysmal nocturnal hemoglobinuria screen.
However, the patient was an active canoeist and had
been taking creatine as a sports nutrition supplement daily
for the last 3 months before his diagnosis. In further dis-
cussions, he recounted that he frequently felt thirsty and
had to drink more fluids during the time he was taking the
supplement.
He was anticoagulated for 6 months and has since
stopped taking creatine-containing products. At his most
recent review 6 months after cessation of anticoagulation, he
remains well with no recurrent thrombotic episode.
CASE 2
A 31-year-old man presented with a 5-day history of left
lower-limb swelling and pain and was diagnosed with
Funding: None.
Conflict of Interest: None.
Authorship: All authors had access to the data and played a role in
writing this manuscript.
Requests for reprints should be addressed to Chuen Wen Tan, MB BCh
BAO, MRCP (UK), Department of Hematology, Singapore General Hos-
pital, Outram Rd, Singapore 169608.
E-mail address: tan.chuen.wen@sgh.com.sg
0002-9343/$ -see front matter Ó 2014 Elsevier Inc. All rights reserved.
proximal left lower-limb deep vein thrombosis involving
the femoral and popliteal veins. He had no history of
recent surgery or immobilization but did travel approxi-
mately 3 weeks earlier on a flight lasting 5 hours. This
man led an active lifestyle and regularly exercised in a
gym. To boost his exercise performance, he also was
taking creatine supplements in the period leading to his
diagnosis.
There was no personal or family history of venous throm-
boembolism, and no other cause was evident. Catheter-guided
thrombolytic therapy was given, followed by 6 months of
anticoagulation treatment. He has since stopped the con-
sumption of creatine-containing supplement and has had no
venous thromboembolism recurrences.
DISCUSSION
Creatine is widely used by athletes to enhance sports per-
formances and increase muscle mass without significant
concern of adverse risk to health. However, creatine sup-
plementation could cause water to be drawn into the
muscles by the osmotic effect produced by an increase in
intracellular creatine.1 This could lead to dehydration,
especially in a hot environment, and cases of heat stroke
have been reported among users.2 To prevent this, many
creatine manufacturers advocate adequate hydration when
taking creatine. Dehydration also is a known precipitating
factor for venous thromboembolism.3 In the 2 cases
described, the young men were active athletes who spon-
taneously developed venous thromboembolism events that
were temporally related to the use of creatine supplements.
Having excluded other thrombophilic conditions, we
contend that dehydration associated with creatine use is
likely causal to these venous thromboembolism events.
Dehydration can be particularly acute in our humid tropi-
cal climate. The additional, albeit small risk of venous
thromboembolism associated with long-haul flights4 in the
second case can further enhance the dehydrating effects of
creatine.
CONCLUSIONS
As athletes continuously seek to improve their recreational
and professional performance goals through various means
including sports nutrition supplements, it is essential that we
warn them of the dehydrating potential of creatine and, by
extension, its thrombotic risk. Its consumption must be
accompanied by adequate and continuous rehydration dur-
ing sporting activities.
e8
Chuen Wen Tan, MB BCh BAO
Mya Hae Tha, MBBS
Heng Joo Ng, MBBS
Department of Hematology
Singapore General Hospital
Singapore, Republic of Singapore
http://dx.doi.org/10.1016/j.amjmed.2014.04.008
The American Journal of Medicine, Vol 127, No 8, August 2014
References
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