In a recent study published in Nutrients, researchers evaluated the relationship between total carbohydrate intake and gout risk. They also investigated the influence of interactions between carbohydrate consumption and genomic vulnerability and explored mediating biomarkers.

Background

Gout is an inflammatory arthritic disorder characterized by elevated serum uric acid, urate saturation, and the deposition of monosodium urate crystals in the joints. It is associated with chronic diseases such as cardiovascular disease, venous thromboembolism, and metabolic syndrome. Diet is a crucial factor in gout etiology.

Low-carbohydrate weight-loss programs can lower urate levels, although the relationship between carbohydrate intake and gout risk is uncertain. Research suggests that certain types of carbohydrates, such as fructose, fruit juice, and sugar-sweetened drinks, enhance gout risk. The role of food and genetic variables in gout risk is understudied. Prospective studies indicate a considerable additive interaction impact between poor eating habits and genetic susceptibility to gout risk.

About the study

In the present study, researchers investigated the influences of carbohydrate quantity, type, and source combined with individual genetic vulnerability on gout development risk. They also explored urine and serum biomarkers that mediate the association between carbohydrate intake and the risk of gout.

The study included 187,387 United Kingdom Biobank participants aged 40 to 69 years who completed one or more dietary assessments. Exclusion criteria were individuals with gout or genetic kinship and those without adequate data on covariates, diet evaluations, and biomarkers. Trained professionals measured weight and height and collected serum and urine samples from 2006 to 2010. Self-reported digital questionnaires provided data on sociodemographic characteristics and lifestyle practices.

From 2009 to 2012, the Oxford online 24-hour dietary instrument obtained data on the intake of 206 foods and 32 beverages. The United Kingdom Nutrient Databank food composition tables provided nutritional composition information. Carbohydrate types analyzed included starch, fiber, and total sugars, divided into free and non-free (or added) types of sugars.

The researchers ascertained gout using the International Classification of Diseases, ninth revision (ICD-9) and ICD-10 codes. They genotyped the participants and calculated gout genetic risk scores (GRS) using 33 genetic susceptibility loci with genome-wide statistical significance. They evaluated the joint effects of carbohydrate intake and genetic susceptibility on gout risk.

Cox proportional hazard regression models estimated hazard ratios (HR) for the relationships between carbohydrate consumption and gout development risk, and restricted cubic splines evaluated dose-response associations between carbohydrate consumption and gout development risk.

Study covariates included gender, age, ethnicity, physical activity, body mass index (BMI), education, income, smoking status, and alcohol intake. In sensitivity analyses, researchers excluded individuals with extreme calorie intake, those receiving gout diagnosis before the final 24-hour dietary assessment or within two years of follow-up, and those completing a single diet assessment.

They restricted the analysis to individuals consuming regular diets, adjusting for diabetes, hypertension, and cardiovascular disease, and using diuretics, anti-hyperlipidemic, antidiabetic, and anti-hypertensive medications.

Results

Compared to individuals with the lowest carbohydrate consumption, those with the highest intake tended to be physically active non-alcoholics with higher calorie intake and lower income. The team found strong correlations between total carbohydrates, sugars, and starch. Over 12 years (median) of follow-up, 2,548 participants developed gout.

The total consumption of carbohydrates was related to a lowered risk of gout (HR, 0.7), as were non-added sugars, total sugars, fiber, total starch, refined starch, and whole-grain starch, with HR values of 0.7, 0.9, 0.7, 0.7, 0.9, and 0.7, respectively. In contrast, free sugars (HR, 1.2) increased gout risk. Sensitivity analyses yielded similar results. Serum urate levels significantly mediated the associations between carbohydrate intake and gout risk.

Individuals with low GRS and higher intakes of total sugars, total carbohydrates, fiber, starch, and added sugars were the least likely to develop gout. In contrast, individuals with high added sugar intake coupled with high GRS showed maximum risk. Total carbohydrate consumption and high GRS showed negative-type additive interactions, as did total starch consumption and moderate to high GRS. Serum urate levels significantly mediated the association between carbohydrate consumption and the risk of gout.

Conclusion

The study found that carbohydrates prevent gout, whereas free sugars have the opposite impact. To lower gout risk, individuals should consume meals high in useful carbohydrates and low in added sugars. Stratified management measures should be used, particularly for individuals with high genetic susceptibility. A comprehensive approach involving increasing carbohydrate consumption, plant-based food consumption, and maintaining healthy lifestyles, such as modest alcohol use, no smoking, and regular physical exercise, could assist in reducing the gout burden on society.