Accepted Manuscript

Creatine Supplementation and Venous Thrombotic Events

Chuen Wen TAN, MB BCh BAO, MRCP (UK) Mya Hae THA, MBBS, MRCP (UK)Heng Joo NG, MBBS, MRCP (UK), FRCPath (UK)

PII: S0002-9343(14)00345-3

DOI: 10.1016/j.amjmed.2014.04.008

Reference: AJM 12485

To appear in: The American Journal of Medicine

Received Date: 10 March 2014

Revised Date: 8 April 2014

Accepted Date: 8 April 2014

Please cite this article as: Wen TAN C, Hae THA M, Joo NG H, Creatine Supplementation and VenousThrombotic Events, The American Journal of Medicine (2014), doi: 10.1016/j.amjmed.2014.04.008.

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Creatine Supplementation and Venous Thrombotic Events

Tan CW, Tha MH, Ng HJ.

Department of Haematology, Singapore General Hospital, 20 College Road, Singapore

169856, Republic of Singapore

Authors and affiliations:

1) Chuen Wen TAN

MB BCh BAO, MRCP (UK)

Registrar, Department of Haematology,

Singapore General Hospital

2) Mya Hae THA

MBBS, MRCP (UK)

Associate Consultant, Department of Haematology,

Singapore General Hospital

3) Heng Joo NG

MBBS, MRCP (UK), FRCPath (UK)

Senior Consultant, Department of Haematology,

Singapore General Hospital

Corresponding author:

Chuen Wen Tan

Department of Haematology

Singapore General Hospital

Outram Road,

Singapore 169608

Tel: +65 92355860

Fax: +65 62260237

Email: tan.chuen.wen@sgh.com.sg

Funding: None

Conflict of interest: None for all authors

All authors contributed to the writing of the manuscript and approved this manuscript.

Article type: Clinical Communication to the Editor

Key words: Sports supplements, dehydration, thrombosis

Running head: Creatine and thrombosis

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To The Editor,

Creatine is a naturally occurring compound which is popular as 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 which was associated

with vomiting. Thrombosis of the superior sagittal sinus, right transverse sinus and right

internal jugular vein was demonstrated on MRI brain that was performed following 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 (VTE). Comprehensive

thrombophilia screening which included tests for protein C, protein S and anti-thrombin III

deficiencies, factor V Leiden and prothrombin gene G20210A mutation, lupus anticoagulant

and anti-cardiolipin antibodies, JAK-2 mutation for myeloproliferative disorders and

paroxysmal nocturnal hemoglobinuria screen were normal.

This young man was however an active canoeist and had been taking creatine as sports

nutrition supplement daily for the last 3 months prior to his diagnosis. In further discussions,

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.

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Case 2

A 31-year-old gentleman presented with a 5-day history of left lower limb swelling and pain

and was diagnosed with 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

approximately 3 weeks earlier on a flight lasting 5 hours. This gentleman led an active

lifestyle and regularly exercised in a gym. To boost his exercise performance, he was also

taking creatine supplements in the period leading to his diagnosis.

There was no personal or family history of VTE and no other cause was evident. Catheter-

guided thrombolytic therapy was given, followed by 6 months of anticoagulation treatment.

He had since stopped the consumption of creatine-containing supplement and has no VTE

recurrences.

Discussion

Creatine is a widely used by athletes to enhance sports performances and increase muscle

mass without significant concern of adverse risk to health. Creatine supplementation

however could cause water to be drawn into muscles by the osmotic effect produced by an

increase in intracellular creatine.1 This could lead to dehydration, especially in hot

environment and cases of heatstroke has been reported among users.2 To prevent this,

many creatine manufacturers therefore advocate adequate hydration when taking creatine.

Dehydration is also a known precipitating factor for VTE3. In the two cases described, the

young men were active athletes who spontaneously develop VTE events that were

temporally related to the use of creatine supplements. Having excluded other thrombophilic

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conditions, we contend that dehydration associated with creatine usage, is likely causal to

these VTE events. Dehydration can be particularly acute in our humid tropical climate. The

additional, albeit small risk of VTE associated with long haul flights4

in the second case can

further enhance the dehydrating effects of creatine. As athletes seek continuously 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 during sporting activities.

References

1. Graham AS, Hatton RC. Creatine: a review of efficacy and safety. J Am Pharm Assoc

(Wash). 1999;39(6):803-10.

2. Bailes JE, Cantu RC, Day AL. The neurosurgeon in sport: awareness of the risks of

heatstroke and dietary supplements. Neurosurgery. 2002;51(2):283-6.

3. Tait C, Baglin T, Watson H, et al, British Committee for Standards in Haematology:

Guidelines on the investigation and management of venous thrombosis at unusual

sites. Br J Haematol. 2012;159(1):28-38.

4. Watson HG, Baglin TP. Guidelines on travel-related venous thrombosis. Br J Haematol.

2011;152(1):31-34.