Combined Supplementation with Glycine and Tryptophan Reduces Purine-Induced Serum Uric Acid Elevation by Accelerating Urinary Uric Acid Excretion: A Randomized, Single-Blind, Placebo-Controlled, Crossover Study

Abstract

The authors previously confirmed the serum uric acid-lowering effects of the combination of glycine and tryptophan in subjects with mild hyperuricemia. This study examined whether combined supplementation with glycine and tryptophan suppressed the elevation in serum uric acid levels caused by purine ingestion and accelerated urinary uric acid excretion in subjects with lower urate excretion using a randomized, single-blind, placebo-controlled, crossover clinical trial design. Healthy Japanese adult males with lower urate excretion ingested water containing purines in addition to dextrin (placebo), tryptophan, glycine, or a glycine and tryptophan mixture. The combined supplementation with glycine and tryptophan significantly reduced the elevated serum uric acid levels after purine ingestion. Glycine alone and in combination with tryptophan significantly increased urinary uric acid excretion and urate clearance compared with the effects of the placebo. Urinary pH increased by the ingestion of the mixture. These results suggested that the improved water solubility of uric acid due to increased urinary pH contributed to the increase of urinary uric acid excretion.

Enhancing effect of glycine and tryptophan mixture on estimated glomerular filtration rate in healthy participants: A randomized, double-blind, placebo-controlled parallel study

“…The current study demonstrated that the combined oral administration of glycine and tryptophan significantly elevated the eGFR of healthy participants. This mixture also decreased the serum uric acid levels, consistent with our previous reports[20,21]. No differences were observed in the effect of glycine and tryptophan supplementation between males and females, although the previous studies included mostly male participants.…”

“…In our two previous clinical trials, the oral administration of the combined dose of glycine and tryptophan led to a decreased concentration of serum uric acid because of the increased urate excretion into the urine [20,21]. A recent prospective cohort study suggested that serum uric acid levels are independently associated with the incidence of impaired renal function and renal progression [22], and a meta-analysis reported that uric acid-lowering therapy effectively regards CKD progression [23].…”

“…AA are not yet clearly distinguished. In our two previous trials, the combined dose of glycine and tryptophan was orally administered; consequently, the excretion of urates into the urine was enhanced, leading to the decreased concentration of serum uric acid[20,21]. The AA may have an effect on renal function.…”

Purification, identification, and computational analysis of xanthine oxidase inhibitory peptides from kidney bean

“…The major amino acids of kidney bean protein were Glu, Asp, Leu, Lys, Val, and Phe. It was previously confirmed that the combined supplementation with glycine and tryptophan significantly reduced the elevated serum uric acid levels after purine ingestion (Oshima, Shiiya, & Nakamura, 2019). Dipeptide Asp‐Asn could inhibit relevant enzyme activity and activate some endogenous XO inhibitors, presenting strong uric acid lowering activity (Murota et al., 2014).…”

“…A previous report showed that the purified XO inhibitor from Pleurotus ostreatus was a tripeptide and the amino acid sequence was phenylalanine–cysteine–histidine (Jang et al., 2014). It was also found that the combination of glycine and tryptophan could reduce the purine‐induced serum uric acid elevation by accelerating uric acid excretion (Oshima et al., 2019). In a research of milk‐derived dipeptides, tryptophan was confirmed to have a negative effect on XO activity.…”