The reference range for uric acid is 4.0 – 8 mg/dL for men, and 2.5 – 7 mg/dL for women. Are these values optimal for health? To answer that question, let’s have a look at how circulating levels of uric acid change during aging, and their association with risk of death for all causes.
Uric acid increases during aging in both men and women. Kuzuya et al. (2002) studied how uric acid changes during a 10-year intervals for various birth cohorts, including 32yr olds, 39yr olds, 47yr olds, 56yr olds, and 65 yr olds (1960-1969, 1950-1959, 1940-1949, 1930-1939, 1920-1929 birth cohorts, respectively). For each birth cohort, uric acid levels increased during aging for men (left image below), whereas they increased for women starting at 40 years old:
In terms of mortality risk, lowest risk of death for all causes was associated with uric acid levels of 5 – 7 mg/dL for men and 4 – 6 mg/dL for women in the 9,118 adults (average age, 43y) of Hu et al. (2019). Also note the U-shaped curve for both genders, whereas mortality risk increases at both low and high levels of uric acid:
Similarly, the lowest risk of death for all causes was associated with uric acid levels of 7 mg/dL for men, and 4 mg/dL for women in the 375,163 adults (average age, 40y) of Cho et al. (2018), with mortality risk significantly increasing at uric levels < 3.5 and > 9.5 mg/dL for men, < 2.5 and > 7.5 mg/dL for women. Collectively, these 2 studies in middle-aged adults suggest that uric acid levels ~ 4 mg/dL for women and ~7 for men may be optimal for reducing risk of disease for all causes. It’s also important to note that both low and higher values are associated with an increased mortality risk.
The data for the Hu and Chu studies are in younger adults, so how does the data look in older adults? Lowest all-cause mortality risk was associated with uric acid levels between 4 – 5 mg/dL in the 121, 771 older adults (average age, 73y) of Tseng et al. (2018), with mortality risk significantly increasing below 4 and > 8:
What are my uric acid levels? From 2016 to 2018, I measured it 15x, and although my average value of 5.2 mg/dL is not too low or too high in terms of an increased all-cause mortality risk, it increased during that 3-year period (R2 = 0.2886). When considering that uric acid increases during aging, can I reduce it with diet?
Because I track my daily nutritional intake, I can look for correlations between my dietary intake with circulating biomarkers. Interestingly, a moderately strong correlation between my lycopene intake with uric acid (R2 = 0.3343, p=0.024) was present from 2016 to 2018:
Lycopene is found almost exclusively in tomatoes and watermelon. If these foods are related to my increasing levels of uric acid, if I ate less of them, I’d expect to see a corresponding decrease in uric acid. So, in 2019, I ate less of these foods, thereby reducing my average lycopene intake from 11,585 to 9,132 micrograms per day. How did that affect circulating levels of uric acid?
In 6 measurements for 2019, my average uric acid level was 4.6 mg/dL, a value that was significantly different (p=0.02) from the 2016-2018 average of 5.2 mg/dL. Whether eating less watermelon and tomatoes caused the decrease is unknown, but it’s good to know that uric acid can be potentially modified with dietary change!
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Cho SK, Chang Y, Kim I, Ryu S. U-Shaped Association Between Serum Uric Acid Level and Risk of Mortality: A Cohort Study. Arthritis Rheumatol. 2018 Jul;70(7):1122-1132. doi: 10.1002/art.40472.
Hu L, Hu G, Xu BP, Zhu L, Zhou W, Wang T, Bao H, Cheng X. U-Shaped Association of Serum Uric Acid with All-cause and Cause-Specific Mortality in US Adults: A Cohort Study. J Clin Endocrinol Metab. 2019 Oct 25. pii: dgz068. doi: 10.1210/clinem/dgz068.
Kuzuya M, Ando F, Iguchi A, Shimokata H. Effect of aging on serum uric acid levels: longitudinal changes in a large Japanese population group. J Gerontol A Biol Sci Med Sci. 2002 Oct;57(10):M660-4.
Tseng WC, Chen YT, Ou SM, Shih CJ, Tarng DC; Taiwan Geriatric Kidney Disease (TGKD) Research Group. U-Shaped Association Between Serum Uric Acid Levels With Cardiovascular and All-Cause Mortality in the Elderly: The Role of Malnourishment. J Am Heart Assoc. 2018 Feb 10;7(4). pii: e007523. doi: 10.1161/JAHA.117.007523.