Uric Acid Production Peaks in Early Morning Hours
Uric acid production and serum levels are highest in the early morning (around 7 AM) and lowest in the late evening (around 11 PM), following a circadian rhythm that affects both serum concentration and renal clearance patterns. 1
Circadian Pattern of Uric Acid Metabolism
In gout patients on controlled hypopurine diets, serum uric acid concentration peaks at 7 AM and reaches its nadir at 11 PM, demonstrating a clear diurnal variation 1
Renal clearance of uric acid follows an inverse pattern, with highest clearance values occurring from 7 AM to 3 PM and lowest clearance from 11 PM to 7 AM 1
This circadian rhythm means that morning measurements will typically show the highest serum uric acid levels, while evening measurements may underestimate the patient's peak uric acid burden 1
Clinical Implications for Testing and Monitoring
The timing of serum uric acid testing does not require fasting, but consistency in testing conditions (including time of day) is more important than fasting status for monitoring treatment efficacy 2
Serum uric acid levels can be misleadingly normal or even low during acute gout attacks, as uric acid behaves as a negative acute phase reactant during episodes of inflammation 3, 2, 4
Approximately 10% of patients with crystal-proven gout have normal serum uric acid levels during acute attacks, so the diagnostic value of serum uric acid is particularly limited during flares 3, 4
Important Caveats About Uric Acid Fluctuations
Multiple factors beyond circadian rhythm affect serum uric acid levels, including inflammatory state, renal excretion changes, recent dietary modifications (especially alcohol and purine-rich foods), and medication effects (particularly diuretics) 2
Do not rule out gout based solely on normal serum uric acid levels, especially during an acute attack, as the temporary lowering effect of inflammation can mask underlying hyperuricemia 2
For treatment monitoring in patients on urate-lowering therapy, the target remains <6 mg/dL (360 μmol/L) regardless of time of day, with a lower target of <5 mg/dL (300 μmol/L) for severe gout with tophi or chronic arthropathy 2