Uric acid is the final product of endogenous and exogenous purine nucleotide breakdown in the human body [1,2]. Approximately 70% of serum uric acid (SUA) is excreted by the kidneys, while the remaining amount is excreted by the intestinal tract [3]. High SUA level, known as hyperuricemia, is an important risk factor for various systemic diseases, including gout, hypertension, type 2 diabetes, chronic kidney disease, and cardiovascular disease [4]. In addition, low SUA level tends to be detrimental to the human body. Hypouricemia may be associated with the development of renal dysfunction [5] and neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease [6,7]. Since the SUA level outside the normal range of values is associated with diseases, maintaining a balanced SUA level may aid in preventing the onset of associated diseases.

Many studies have reported that the distribution of SUA levels can vary depending on age, sex, and environmental factors [8–11]. However, no previous study has evaluated the distribution of SUA levels among Koreans using a large-scale population-based design. We investigated the distribution of SUA levels according to age and sex in the Korean population, including the prevalence of hyper- and hypouricemia.

The flow chart capturing participant eligibility is shown in Fig. 1. A total of 172,970 participants (58,981 men and 113,989 women) were included in this study. Demographic and clinical characteristics of the participants are shown in Table 1. The mean age of men and women was 53.97 ± 8.81 and 52.63 ± 8.09 years, respectively (p < 0.001). Most of the variables had significantly higher values in men than in women (p < 0.001); however, thyroid disease and malignancy rates were higher in women than in men (p < 0.001). The mean SUA level was significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001).

We evaluated the distribution of SUA levels and prevalence of hypouricemia and hyperuricemia in the Korean population. SUA levels followed different distribution patterns according to age and sex. The prevalence of hyperuricemia was approximately 16 times higher in men than in women, while the prevalence of hypouricemia was approximately five times higher in women than in men.

In this study, the mean SUA level for men and women was 5.71 ± 1.27 and 4.21 ± 0.96 mg/dL, respectively, and both of these values were slightly lower than the values reported in a recent study based on a sample of 5,548 Koreans (5.83 and 4.36 mg/dL in men and women, respectively) [16]. Concurrently, SUA levels reported in this study were lower than those reported in recent large-scale studies in Japan (6.0 ± 1.4 and 4.5 ± 1.1 mg/dL in men and women, respectively) [19] and China (6.23 ± 1.38 and 4.38 ± 1.11 mg/dL in men and women, respectively) [20]. A study based in the United States reported that the mean SUA level was 4.4 mg/dL in white women; 4.9 mg/dL in black women; 5.8 mg/dL in white men; and 6.0 mg/dL in black men [21]. Therefore, the average SUA level may differ according to sex, race, and place of residence. Consequently, the criteria for uric acid-related diseases, including hyperuricemia or hypouricemia, may differ according to these factors.

There have been several studies on hyperuricemia (defined as SUA level ≥ 7.0 mg/dL in men and SUA level ≥ 6.0 mg/dL in women) in Korea. Among them, single-center studies using health screening data reported the prevalence of hyperuricemia in men and women as 14.3% and 2.2%, respectively, in a sample of 6,461 participants [22] and 15% and 4.1%, respectively, in a sample of 2,297 participants [23]. Meanwhile, national surveillance data-based estimates were 17.0% and 5.9%, respectively (5,548 participants) [16]. The discrepancies between these studies and the present study findings might be owing to the differences in sample composition, estimate methodology, and timeframe of the study. We believe that the present estimates based on data from 172,970 participants are a robust representation of the distribution of SUA levels in the Korean population.

Zhu et al. [8] investigated the prevalence of hyperuricemia and gout using the National Health and Nutrition Examination Survey 2007 to 2008. Although these data originated a decade ago, the prevalence of hyperuricemia was much higher in that report than in this study (overall 26.6%). The authors suggested that the prevalence of hyperuricemia increased with age and that this increase was associated with a Western diet and lifestyle, as well as complications, such as obesity and hypertension, and the use of drugs, such as diuretics and aspirin.

In our study, the prevalence of hyperuricemia was highest among men and women in their 70s; however, the pattern of age-dependent prevalence was different between men and women. The prevalence in women tended to increase gradually, but the prevalence among men decreased until the age of 60 years before it increased again over the age of 70 years. These results are comparable to the results reported by Kim et al. [16], as well as those from studies in the Chinese and Japanese populations [24,25]. Considering these findings, it is unlikely that these sex-based differences are due to nutrition, lifestyle, obesity, or medication. The reasons for the increased prevalence of hyperuricemia among middle-aged men are unclear. Future laboratory research elucidating the biological and sex- and age-specific factors determining SUA levels is warranted.

A few previous studies have reported the prevalence of hypouricemia, although there is no conclusive evidence on the relationship between hypouricemia and neurological disease [26,27]. Son et al. [18] have reported that the overall prevalence of hypouricemia was 1.39%, which differed between inpatients and outpatients treated at a single center (4.14% vs. 0.53%). This evidence indirectly suggests a relationship between hypouricemia and comorbidity. Meanwhile, Kuwabara et al. [11] showed that the prevalence of hypouricemia in patients undergoing an annual health check-up was 0.19% and 0.58% in two evaluated centers.

Considering the relatively high prevalence of CKD among older adults [28,29] and the association between CKD and SUA levels [30], CKD might be a risk factor for hyperuricemia in older age. In the present study, the relative decrease in the prevalence of hyperuricemia among older adults after excluding patients with CKD supports the hypothesis that CKD is associated with hyperuricemia. In addition, Park et al. [29] suggested that CKD prevalence in Korea (8.2%) was lower than that in the United States (13.1%) and China (10.8%). CKD prevalence might be an important factor underpinning the differences in the prevalence of hyperuricemia between countries.

Wakasugi et al. [10] conducted a population-based cross-sectional study examining the association between hypouricemia and kidney function. They reported that the prevalence of hypouricemia was 0.2% and 0.4% in men and women, respectively. In our study, the prevalence of hypouricemia was 1.10 per 1,000 persons in men and 5.57 per 1,000 persons in women. These sex-based differences in prevalence might be related to hormonal differences between men and women [31]. In addition, the prevalence in men was comparable across age groups, while the prevalence in women was the highest in the 40s age group. Previous studies have suggested that menopause may affect SUA levels; however, the exact mechanism has not been elucidated [10,32].

This study has several limitations. First, the cohort used in this study included participants aged 40 years or more, as the KoGES was established to investigate the genetic and environmental etiology of common complex diseases, such as type 2 diabetes mellitus, hypertension, obesity, metabolic syndrome, osteoporosis, cardiovascular disease, and cancer with long-term follow-up, and the causes of death among Koreans. Second, as the SUA level was only measured once, it was not possible to check whether hypouricemia or hyperuricemia was transient or persistent, which should be confirmed in a follow-up study. Third, this study did not control for medication use which might have affected the results, as certain medications can increase or decrease SUA levels. Although patients treated for gout during the study period were excluded from analysis, the possibility that the data may be distorted due to medication-related effects cannot be eliminated. Fourth, changes in environmental factors might affect the epidemiology of SUA levels during follow-up. Finally, this cohort is likely to be affected by chronic diseases, which might have impacted our findings. However, an examination of a relationship between chronic diseases and SUA levels was beyond the scope of this study.

In conclusion, this study reported the distribution of SUA levels and prevalence of hyper- and hypouricemia according to sex and age based on a large nationwide health examinee cohort. We found that the distribution of the SUA level differed according to age and sex. Therefore, prior to the study of diseases associated with SUA levels, it is necessary to establish a normal range of SUA levels according to age and sex.