Elsevier

Seminars in Nephrology

Volume 31, Issue 5, September 2011, Pages 410-419
Seminars in Nephrology

The Epidemiology of Uric Acid and Fructose

https://doi.org/10.1016/j.semnephrol.2011.08.004Get rights and content

Summary

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.

Section snippets

Epidemiology of Uric Acid

According to the Third US National Health and Nutritional Examination Survey (NHANES III, 1988-1994) study (Table 1), the estimated mean serum uric acid concentration of the US population was 5.33 mg/dL (95% confidence interval [CI], 5.29-5.37 mg/dL). Overall, men had higher serum concentrations (6.06 mg/dL) than women (4.66 mg/dL) by approximately 1.4 mg/dL. The mean serum uric acid concentrations did not appear to differ significantly across race/ethnicity in this nationally representative

Demographics

Although hyperuricemia and gout historically have been considered conditions of men, and most research has focused on men, growing evidence suggests a substantial disease burden of gout among older women.14, 38 The difference in serum uric acid levels between the sexes10 likely is owing to the increased renal urate clearance by estrogen in women, particularly before menopause.39 A Japanese study showed a combination of estrogen and progesterone resulting in a significant decrease in serum uric

Trends in Fructose Consumption

The consumption of fructose in the United States has increased considerably since the introduction of high fructose corn syrup (HFCS) in 1967.25 HFCS is a product made from corn, and usually has a composition of 42% fructose (HFCS-42) or 55% fructose (HFCS-55).86 HFCS has several commercial advantages over crystalline sugar (sucrose), its predecessor sweetener, such as convenience to transport and use (because it is a transferable and easily mixable liquid), less dependence on foreign sources

Metabolic Syndrome and Diabetes

The metabolic syndrome affects more than 50 million Americans,107 and increases the risk for atherosclerotic cardiovascular disease and type 2 diabetes, as well as mortality.108 Insulin may enhance renal urate reabsorption via stimulation of urate-anion exchanger109 and/or the Na+-dependent anion co-transporter in brush-border membranes of the renal proximal tubule.85 Higher insulin levels are known to reduce renal excretion of uric acid.110, 111, 112 A close association between serum urate

Conclusions

During the past few decades, the mean serum uric acid levels and the prevalence of hyperuricemia in the general population appear to have increased. Potential reasons behind these trends include the increasing prevalence of obesity and metabolic syndrome, Western lifestyle factors, increased prevalence of medical conditions, and medication use that increase uric acid levels. In addition, the substantial increase in sugar-sweetened soft drinks and fructose consumption coincides with the secular

References (135)

  • D.R. Garrel et al.

    Milk- and soy-protein ingestion: acute effect on serum uric acid concentration

    Am J Clin Nutr

    (1991)
  • H.M. Loenen et al.

    Serum uric acid correlates in elderly men and women with special reference to body composition and dietary intake (Dutch Nutrition Surveillance System)

    J Clin Epidemiol

    (1990)
  • A. Kagan et al.

    Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: demographic, physical, dietary and biochemical characteristics

    J Chronic Dis

    (1974)
  • T.P. Torralba et al.

    The Filipino and gout

    Semin Arthritis Rheum

    (1975)
  • H.K. Choi et al.

    Alcohol intake and risk of incident gout in men: a prospective study

    Lancet

    (2004)
  • E.W. Campion et al.

    Asymptomatic hyperuricemiaRisks and consequences in the Normative Aging Study

    Am J Med

    (1987)
  • R.D. Abbott et al.

    Gout and coronary heart disease: the Framingham Study

    J Clin Epidemiol

    (1988)
  • W. Rathmann et al.

    Relations of hyperuricemia with the various components of the insulin resistance syndrome in young black and white adults: the CARDIA studyCoronary Artery Risk Development in Young Adults

    Ann Epidemiol

    (1998)
  • H.K. Choi et al.

    Coffee consumption and risk of incident gout in women: the Nurses' Health Study

    Am J Clin Nutr

    (2010)
  • U. Kela et al.

    Inhibitory effects of methylxanthines on the activity of xanthine oxidase

    Life Sci

    (1980)
  • H.J. Petrie et al.

    Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss

    Am J Clin Nutr

    (2004)
  • L. Berger et al.

    The effect of ascorbic acid on uric acid excretion with a commentary on the renal handling of ascorbic acid

    Am J Med

    (1977)
  • L.C. Lyu et al.

    A case-control study of the association of diet and obesity with gout in Taiwan

    Am J Clin Nutr

    (2003)
  • J.S. White

    Straight talk about high-fructose corn syrup: what it is and what it ain't

    Am J Clin Nutr

    (2008)
  • R. Murray et al.

    Are soft drinks a scapegoat for childhood obesity?

    J Pediatr

    (2005)
  • I.H. Fox et al.

    Studies on the mechanism of fructose-induced hyperuricemia in man

    Metab Clin Exp

    (1972)
  • H. Beck-Nielsen et al.

    Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects

    Am J Clin Nutr

    (1980)
  • A.W. Thorburn et al.

    Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats

    Am J Clin Nutr

    (1989)
  • D.S. Ludwig et al.

    Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis

    Lancet

    (2001)
  • H.K. Choi et al.

    Purine-rich foods, dairy and protein intake, and the risk of gout in men

    N Engl J Med

    (2004)
  • R. Roubenoff et al.

    Incidence and risk factors for gout in white men

    JAMA

    (1991)
  • H.K. Choi et al.

    Independent impact of gout on mortality and risk for coronary heart disease

    Circulation

    (2007)
  • H.K. Choi et al.

    Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile

    Rheumatology (Oxford)

    (2008)
  • H.K. Choi et al.

    Haemoglobin A1c, fasting glucose, serum C-peptide and insulin resistance in relation to serum uric acid levels—the Third National Health and Nutrition Examination Survey

    Rheumatology (Oxford)

    (2008)
  • H.K. Choi et al.

    Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey

    Arthritis Rheum

    (2007)
  • S.Y. Kim et al.

    Hyperuricemia and coronary heart disease: a systematic review and meta-analysis

    Arthritis Care Res (Hoboken)

    (2010)
  • S.Y. Kim et al.

    Gout and mortality

    Clin Exp Rheumatol

    (2008)
  • F.N. Brand et al.

    Hyperuricemia as a risk factor of coronary heart disease: the Framingham Study

    Am J Epidemiol

    (1985)
  • H.Y. Chang et al.

    Hyperuricemia and gout in Taiwan: results from the Nutritional and Health Survey in Taiwan (1993-96)

    J Rheumatol

    (2001)
  • R.J. Glynn et al.

    Trends in serum uric acid levels 1961-1980

    Arthritis Rheum

    (1983)
  • R.C. Lawrence et al.

    Estimates of the prevalence of arthritis and other rheumatic conditions in the United StatesPart II

    Arthritis Rheum

    (2008)
  • T.R. Mikuls et al.

    Gout epidemiology: results from the UK General Practice Research Database, 1990-1999

    Ann Rheum Dis

    (2005)
  • W. Rathmann et al.

    Ten-year change in serum uric acid and its relation to changes in other metabolic risk factors in young black and white adults: the CARDIA study

    Eur J Epidemiol

    (2007)
  • E. Roddy et al.

    The changing epidemiology of gout

    Nat Clin Pract Rheumatol

    (2007)
  • K.L. Wallace et al.

    Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population

    J Rheumatol

    (2004)
  • Q.Y. Zeng et al.

    Rheumatic diseases in China

    Arthritis Res Ther

    (2008)
  • Y. Zhu et al.

    Increasing gout prevalence in the US over the last two decades: the National Health and Nutrition Examination Survey (NHANES)

    (2010)
  • Y. Zhu et al.

    The serum urate-lowering impact of weight loss among men with a high cardiovascular risk profile: the Multiple Risk Factor Intervention Trial

    Rheumatology

    (2010)
  • Y. Zhu et al.

    Prevalence of hyperuricemia in the US general population: the National Health and Nutrition Examination Survey (NHANES) 1999-2008

    (2010)
  • J.J. Putnam et al.

    Food consumption, prices and expenditures, 1970-97US Department of Agriculture Economic Research Service Statistical Bulletin. No. 965

  • Cited by (131)

    • Musculoskeletal and immunological considerations

      2023, Ketogenic: The Science of Therapeutic Carbohydrate Restriction in Human Health
    • Sugar-sweetened soft drinks consumption and risk of hyperuricemia: Results of the ELSA-Brasil study

      2021, Nutrition, Metabolism and Cardiovascular Diseases
      Citation Excerpt :

      Other metabolic abnormalities induced by fructose seem to stimulate the synthesis of long-chain fatty acids leading to hypertriglyceridemia and insulin resistance [49], and both conditions have been associated with elevated serum uric acid levels [50]. In recent decades, increasing trends of hyperuricemia have been observed in several populations, mainly in western countries [21]. In Brazil, a population-based study that addressed the prevalence and epidemiological characteristics of hyperuricemia demonstrated an association between high levels of uric acid and cardiovascular risk factors (high BMI, abdominal obesity, and hypertriglyceridemia), and these being more pronounced in women [6].

    View all citing articles on Scopus
    View full text