Allopurinol does not reduce

exercise induced muscle damage

in ultra-marathon runners.

DR PAUL R. MASON

MBBS (HONS), B. PHYSIO, MASTERS OCC. HEALTH

DR JONATHAN KING

FACSEP, FRACGP, MSC SPORT SCIENCE

Exercise induced muscle

damage. novel or unaccustomed exercise

soreness and swelling

reduced power

reduces ability to perform

subsequent bouts of exercise

Mechanisms of exercise

induced muscle damage.

Mechanical

muscle contraction

shock impulses

Reactive oxygen species

unbalanced valence shell

oxidise amino acids

oxidise cell membrane

damage of DNA / RNA

Biopsy findings in exercise

induced muscle damage. Structural changes

Cell necrosis

Serology of exercise

induced muscle damage. released intra-cellular elements

• Creatine Kinase

• Lactate Dehydrogenase

• Aspartate Aminotransferase

oxidised cell membranes

• Lipid peroxidation

• Produces malondialdehyde

Production of reactive oxygen species (1/2)

• ~2% of oxygen in ETC forms ROS

• by-product of oxygen

metabolism

Production of reactive oxygen species (2/2)

• Xanthine oxidase activity

• Purine metabolism

• Produces ROS

• Found in many tissues

• liver

• intestines

• endothelium

• lungs

• relative hypoxia

increases activity

Allopurinol

Active metabolite

oxypurinol• Inhibits xanthine oxidase

• Half life 23.3 +/- 6.0 hours

• Reduces ROS

production

Past research

Allopurinol and Markers of Muscle

Damage Among Participants in the

Tour de France

Significant differences

(placebo vs allopurinol)• CK (P=0.03)

• AST (P=0.02)

• Malondialdehyde (P=0.009)

Gómez-Cabrera, M.-C., Pallardó, F. V., Sastre, J., Viña, J., & García-del-Moral, L. (2003).

JAMA, 289(19), 2503–2504.

Allopurinol prevents cardiac and skeletal muscle damage in professional soccer players.

Significant differences (placebo vs

allopurinol)

CK (P<0.05)

LDH (P<0.05)

AST (P<0.05)

Myoglobin (P<0.05)

Malondialdehyde (P<0.05)

Sanchis-Gomar, F., Pareja-Galeano, H., Gomez-Cabrera, M. C., Candel, J., Lippi, G., Salvagno,

G. L., Viña, J. (2015). Scandinavian Journal of Medicine & Science in Sports, 25(1), e110–115.

Oxidative stress in marathon

runners: interest of antioxidant

supplementation. Placebo: increase in malondialdehyde (P<0.05)

Allopurinol: no significant change in malondialdehyde

Between group: no significant difference

Gomez-Cabrera, M.-C., Martínez, A., Santangelo, G., Pallardó, F. V., Sastre, J., & Viña, J.

(2006). The British Journal of Nutrition, 96 Suppl 1, S31–33.

Hypothesis

Prophylactic allopurinol may lead to

reduced exercise induced muscle damage

by reducing oxidative stress in ultra-

marathon runners.

Ultra-marathons

>42km

Often extreme conditions

>3,000 ultra-marathons annually

globally

Great North Walk 100’s

103.7 km

3,800m ascent/descent

22 hour limit

175.3 km

6,200m ascent/descent

36 hour limit

Check points ~25km apart

(eat, drink and rest)

Methodology

Recruitment via email

13 runners (8 male, 5 female)

Pre-event blood test

baseline renal/hepatic function

baseline uric acid levels

Test dose 300mg allopurinol/placebo

Dose night before event (300mg)

Dose on morning of event (300mg)

Post event blood test 48 hours post event

Results (1/2)

SexDistance

(km)Time Group

CK

(pre)

CK

(post)

LDH

(pre)

LDH

(post)

AST

(pre)

AST

(post)

Male 81.6 13:57:00 allopurinol 169 530 166 205 26 43

Male 175.3 35:37:00 allopurinol 205 1225 204 350 26 77

Male 103.7 16:07:00 allopurinol 159 601 183 268 23 40

Male 52.5 7:19:00 allopurinol 150 325 153 204 22 43

Female 175.3 35:41:00 allopurinol 175 1161 171 377 23 110

Female 28.6 6:15:00 allopurinol 133 146 193 205 22 22

Male 103.7 17:04:00 placebo 96 956 181 306 24 133

Male 85 15:00:00 placebo 96 191 181 189 24 33

Male 175.3 20:42:00 placebo 297 863 173 236 23 44

Male 175.3 35:15:00 placebo 110 773 174 233 25 54

Female 103.7 15:02:00 placebo 92 171 161 230 17 27

Female 175.3 33:42:00 placebo 69 355 159 266 22 59

Results (2/2)

Control (n = 6) Allopurinol (n = 6) Allopurinol vs. Control

Pre Post ∆ Pre Post ∆

Between-

condition changes

(Cohen’s d)

% Chances

Benefical/

Trivial/Harmful

CK

(U/L)

126.7

(57.2-196.2)

551.5

(261.1-841.9)

424.8

(161.2-688.5)

165.2

(145-185.3)

664.7

(302.9-1026.4)

499.5

(155.9-843.1)

-0.47

(-2.12 - 1.17)

24/15/62

LDH

(U/L)

171.5

(163.6-179.4)

243.3

(211-275.7)

71.8

(38.1-105.5)

178.3

(163-193.7)

268.2

(203.8-332.6)

89.8

(29.6-150.1)

0.43

(-2.25 - 3.11)

56/10/34

AST

(U/L)

22.5

(20.1-24.9)

58.3

(26.6-90)

35.8

(5-66.6)

23.7

(22.1-25.2)

55.8

(29.5-82.1)

32.2

(6.2-58.1)

-0.72

(-5.27 - 3.83)

36/6/58

Discussion

Shock impulses vs muscle contraction

Running vs. skiing

Event duration vs oxypurinol half life

4 runners >30 hours

Re-analysis did not change results

Conclusion

Premature to discount benefits of prophylactic allopurinol in

reducing oxidative stress

Malondialdehyde useful to assess oxidative stress directly

Future research should focus on

Low impact activities

Event duration <17 hours

Questions.

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Running Economy in Humans. The Scientific World Journal, 2013. https://doi.org/10.1155/2013/189149

Brancaccio, P., Lippi, G., & Maffulli, N. (2010). Biochemical markers of muscular damage. Clinical Chemistry and Laboratory Medicine,

48(6), 757–767. https://doi.org/10.1515/CCLM.2010.179

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Gomez-Cabrera, M.-C., Martínez, A., Santangelo, G., Pallardó, F. V., Sastre, J., & Viña, J. (2006). Oxidative stress in marathon runners:

interest of antioxidant supplementation. The British Journal of Nutrition, 96 Suppl 1, S31–33.

Gómez-Cabrera, M.-C., Pallardó, F. V., Sastre, J., Viña, J., & García-del-Moral, L. (2003). Allopurinol and markers of muscle damage

among participants in the Tour de France. JAMA, 289(19), 2503–2504. https://doi.org/10.1001/jama.289.19.2503-b

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