Sugary drinks, fruit, and increased risk of gout

The accompanying prospective cohort study by Choi and Curhan adds dietary fructose intake to the list of possible risk factors for gout.1 Laboratory evidence that dietary fructose increases serum urate already exists, and recent epidemiological studies have found an association between dietary fructose and hyperuricaemia in the United States.2 3 4 5

The health professionals follow-up study was established in 1986 to examine the relation between nutritional factors and disease onset in later life in more than 50 000 American men.1 Previous analyses have looked at the association of obesity, alcohol, and diet with the onset of gout.

This new analysis looks at the role of non-alcoholic drinks and fruit on the first onset of gout. It finds a strong association between sugar sweetened soft drinks, usually containing fructose, and gout. Consuming two servings a day of a sugar sweetened soft drink increased the risk of developing gout by 85% (relative risk 1.85, 95% confidence interval 1.08 to 3.16). This compares with an increased risk of 49% from drinking 15-29.9 g/day of alcohol, 21% from eating an extra serving of meat a day, and 95% from having a body mass index of 25.0-29.9 versus 21.0-22.9; consuming 240 ml of skimmed milk a day decreased risk by 43%.6 A high intake of naturally occurring fructose also increased the risk of developing gout; consuming two or more glasses of fruit juice each day increased the risk by 81% (1.81, 1.12 to 2.93) and eating an apple or orange a day increased the risk by 64% (1.64, 1.05 to 2.56). These epidemiological data provide useful information for formulating appropriate dietary advice that might reduce recurrent gout.

These new data suggest that dietary fructose is an important factor in the development of gout. However, their importance for public health is context specific. In the US, soft drinks are usually sweetened with high fructose corn syrup (known in the European Union as isoglucose). In the rest of the world they are usually sweetened with sucrose—a disaccharide consisting of fructose and glucose. High fructose corn syrup is produced from corn syrups by enzymatic isomerisation. It is produced in preparations that contain 42%, 53%, and 90% of free fructose; the remainder is mainly glucose.7

Use of high fructose corn syrup and thus dietary intake of free fructose has increased dramatically in the US over the past 25 years.8 It is used in soft drinks and in a variety of other manufactured foods. Concerns exist that high fructose corn syrup has had a specific effect in promoting obesity in the US, as the rise in obesity corresponds with its use.7 8 One reason could be that fructose may have less effect on satiety than other sugars. However, some argue that because sucrose is rapidly broken down to glucose and fructose in the gut the effect of sucrose and high fructose corn syrup on obesity will be similar. An expert panel (supported by an unrestricted grant from Tate and Lyle Inc) that reviewed the evidence concluded that the “evidence is insufficient to implicate high-fructose corn syrup per se as a causal factor in the overweight and obesity problem in the United States.”7

The findings from Choi and Curhan’s study that unsweetened fruit juices and fruit increased the incidence of gout, and other recent epidemiological evidence that sweetened soft drinks increase serum urate, support the notion that free fructose intake has an adverse effect on urate metabolism.4 5 This might in turn have a causal effect on the development of the metabolic syndrome.3 This leads to an interesting paradox that on the one hand, fruit and fruit juices may increase serum urate—which in some studies seems to be an independent risk factor of cardiovascular disease—while on the other hand, increased fruit and vegetable intake is generally thought to reduce the risk of cardiovascular disease.9 These data do not support a change in current advice on fruit intake, but more work is needed to understand the association between the metabolic syndrome and dietary fructose.

Global differences in the use of sweeteners in soft drinks are driven primarily by economic factors. In the US, high fructose corn syrups are cheaper than sucrose because of high tariffs on imported sugar and other measures used to support domestic sugar production.10 The European Union has a quota for isoglucose production to protect the European sugar industry. The production quota for 2007-8 in the United Kingdom is 36 967 tonnes.11 In the US, 7881 000 tonnes were produced in 2006-7.12 Quotas are increasing in the EU, but the increase has levelled off in the US.12 The case against high fructose corn syrup as a cause of obesity is not proved, but evidence suggests an adverse effect on hyperuricaemia and gout. It would be ill advised for the EU to allow increased use of isoglucose until its safety has been confirmed. Perhaps liberalisation of the sugar trade will remove the demand for high fructose corn syrup; this would improve the health of consumers and the prosperity of countries that produce cane sugar.