Dr. Ron’s Research Review – March 13, 2013

© 2013

This week’s research review focuses on Uric Acid

Sweets

A marked increase in gout was observed in England during the 17th to 20th centuries, which is the marked increase in sugar intake. Sugar contains fructose, which raises uric acid and increases the risk for gout. Sugar intake increased markedly during this period due to its introduction in liquors, tea, coffee and desserts. (Rivard, Thomas et al. 2013)

Fructose

During the past few decades, the mean serum uric acid levels and the prevalence of hyperuricemia in the general population appear to have increased. Correspondingly, the prevalence and incidence of gout have doubled. The substantial increase in sugar-sweetened soft drinks and associated fructose consumption also has coincided with the secular trend of hyperuricemia and gout. (Rho, Zhu et al. 2011)

Vitamin C

A recent meta-analysis of randomized controlled trials found that oral vitamin C supplementation (median dose and duration: 500 mg/day and 30 days) significantly lowered serum uric acid. Pretreatment SUA values ranged from 2.9-7.0 mg/dl. The combined effect was a significant reduction in SUA of -0.35 mg/dl (95% confidence interval -0.66, -0.03; P = 0.032). (Juraschek, Miller et al. 2011)

Dr. Ron


Articles

Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials

         (Juraschek, Miller et al. 2011) Download

OBJECTIVE: To assess the effect of vitamin C supplementation on serum uric acid (SUA) by pooling the findings from published randomized controlled trials (RCTs). METHODS: A total of 2,082 publications identified through systematic search were subjected to the following inclusion criteria: 1) RCTs conducted on human subjects, 2) reported end-trial SUA means and variance, 3) study design with oral vitamin C supplementation and concurrent control groups, and 4) trial duration of at least 1 week. Trials that enrolled children or patients receiving dialysis were excluded. Two investigators independently abstracted trial and participant characteristics. SUA effects were pooled by random-effects models and weighted by inverse variance. RESULTS: Thirteen RCTs were identified in the Medline, EMBase, and Cochrane Central Register of Controlled Trials databases. The total number of participants was 556, the median dosage of vitamin C was 500 mg/day, trial size ranged from 8-184 participants, and the median study duration was 30 days. Pretreatment SUA values ranged from 2.9-7.0 mg/dl (Systeme International d'Unites [SI units]: 172.5-416.4 mumoles/liter). The combined effect of these trials was a significant reduction in SUA of -0.35 mg/dl (95% confidence interval -0.66, -0.03 [P = 0.032]; SI units: -20.8 mumoles/liter). Trial heterogeneity was significant (I(2) = 77%, P < 0.01). Subgroup analyses based on trial characteristics indicated larger reductions in uric acid in trials that were placebo controlled. CONCLUSIONS: In aggregate, vitamin C supplementation significantly lowered SUA. Future trials are needed to determine whether vitamin C supplementation can reduce hyperuricemia or prevent incident and recurrent gout.


The epidemiology of uric acid and fructose

         (Rho, Zhu et al. 2011) Download

During the past few decades, the mean serum uric acid levels and the prevalence of hyperuricemia in the general population appear to have increased. Correspondingly, the prevalence and incidence of gout have doubled. Potential reasons behind these trends include the increasing prevalence of obesity and metabolic syndrome, Western lifestyle factors, increased prevalence of medical conditions (eg, renal conditions, hypertension, and cardiovascular disorders), and use of medications that increase uric acid levels (eg, diuretics and low-dose aspirin). The substantial increase in sugar-sweetened soft drinks and associated fructose consumption also has coincided with the secular trend of hyperuricemia and gout. Recently, several large-scale epidemiologic studies have clarified a number of these long-suspected risk factors in relation with hyperuricemia and gout. Furthermore, recent studies have illuminated the substantial comorbidities of hyperuricemia and gout, particularly metabolic-cardiovascular-renal conditions. Although many prospective studies have suggested an independent association between serum uric acid levels and the future risk of cardiovascular-metabolic morbidities and mortality, only a limited number of randomized clinical trials and observational studies recently have shown that the use of allopurinol can be beneficial against these outcomes. Because these data are scarce and the effects of allopurinol might not be limited to decreasing serum uric acid levels, the potential causal role of uric acid on these outcomes remains to be clarified with further studies.

Sack and sugar, and the aetiology of gout in England between 1650 and 1900

         (Rivard, Thomas et al. 2013) Download

A marked increase in gout was observed in England during the 17th to 20th centuries. Many have ascribed this rapid increase in gout to the introduction of wines that were laced with lead. In this article, we suggest another likely contributor, which is the marked increase in sugar intake that occurred in England during this period. Sugar contains fructose, which raises uric acid and increases the risk for gout. Sugar intake increased markedly during this period due to its introduction in liquors, tea, coffee and desserts. We suggest that the introduction of sugar explains why gout was originally a disease of the wealthy and educated, but gradually became common throughout society.

References

Juraschek, S. P., E. R. Miller, 3rd, et al. (2011). "Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials." Arthritis Care Res (Hoboken) 63(9): 1295-306 PMID: 21671418

Rho, Y. H., Y. Zhu, et al. (2011). "The epidemiology of uric acid and fructose." Semin Nephrol 31(5): 410-9 PMID: 22000647

Rivard, C., J. Thomas, et al. (2013). "Sack and sugar, and the aetiology of gout in England between 1650 and 1900." Rheumatology (Oxford) 52(3): 421-6 PMID: 23175570