Session Title: Metabolic and Crystal Arthropathies: Mechanisms of Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose During acute gout attacks neutrophils are activated and release a number of pro-inflammatory cytokines and enzymes. One of these enzymes is myeloperoxidase (MPO), which we have previously shown to be elevated in the circulation of patients with acute gout. Furthermore, MPO was associated with increased oxidation of urate as demonstrated by the increased concentration of allantoin in the plasma of these patients. Thus, oxidative stress is a feature of acute attacks of gout. Allopurinol is the most commonly used urate lowering therapy. It is rapidly metabolised by aldehyde oxidase to oxypurinol as well as superoxide and hydrogen peroxide. Oxypurinol exerts most of its inhibitory effects on xanthine oxidoreductase. In our previous work, allopurinol use was also associated with an increase in allantoin, indicating that it increases oxidative stress. The aim of this study was to determine the effects of allopurinol on plasma ascorbate (vitamin C), because its levels are sensitive to oxidative stress.
Methods Patients with gout and a serum urate >0.36mmol/L were recruited. Twenty patients already receiving allopurinol were randomised to either increase the dose of allopurinol or commence vitamin C 500mg/d. Twenty patients not receiving urate lowering therapy were randomised to either start allopurinol or vitamin C 500mg/d. Plasma ascorbate, allantoin, myeloperoxidase, oxypurinol and serum urate were measured at day 0 and week 8.
Results As expected at day 0, the 20 patients receiving allopurinol had significantly lower serum urate compared to those not on allopurinol (0.44 vs 0.54 mM p<0.001). Use of allopurinol was also associated with significantly lower plasma ascorbate levels (38.8 vs 56.7 µM p=0.03) and higher MPO levels (29.4 vs 18.0 µM p<0.001) at day 0. There was a non-significant increase in serum allantoin.
In the 10 patients who commenced allopurinol there was a significant reduction between day 0 and week 8 in serum urate (0.57 vs 0.41 mM p=0.0003) and plasma ascorbate (54.2 vs 28.1 µM p=0.003) and an increase in plasma allantoin (2.6 vs 3.0 µM p=0.04). Plasma MPO was not affected by allopurinol. There was a significant negative correlation between plasma oxypurinol and plasma ascorbate concentrations (r=-0.54, p<0.0004). For the 10 patients who stayed on their original dose of allopurinol, supplementation with vitamin C increased plasma vitamin C (48.4 vs 68.1 µM p=0.01) but had no effect on either urate or allantoin levels.
Conclusion These results suggest that allopurinol promotes oxidative stress thereby depleting plasma ascorbate. Supplementation with vitamin C can increase plasma ascorbate in patients on allopurinol. The clinical significance of oxidative stress and low plasma ascorbate remains to be determined but our results indicate there may be a reason other than urate lowering for patients with gout to take vitamin C.
L. K. Stamp,
P. T. Chapman,
J. L. O’Donnell,
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/oxidative-stress-from-use-of-allopurinol-is-there-a-reason-for-patients-with-gout-to-take-vitamin-c/