Tier 3 — preclinical

Relationship of Protein Intake to Urinary Oxalate and Glycolate Excretion

Ross P. Holmes, Harold O. Goodman, Lois J. Hart, Dean G. Assimos
Kidney International 1993 44(2):366-372

Bibliography

PubMed
PMID 8377380
Funding
No funding source is disclosed in the article (it predates routine funding-disclosure requirements).
Competing interests
Not disclosed; the article predates standard competing-interest reporting requirements. Authors are affiliated with the Department of Urology, Bowman Gray School of Medicine, Wake Forest University, with no apparent commercial ties.

Study snapshot

DesignObservational cohort study on self-selected diets (Study I), plus a controlled-diet crossover study (Study II)
ModelHealthy, unrelated Caucasian adults with no history of renal, hepatic or intestinal disease, or urolithiasis
SampleStudy I (self-selected diets): n=101 (54 men, 47 women). Study II (controlled diets): n=11 completing (5 men, 6 women); one additional male excluded as a statistical outlier.
InterventionStudy I: self-selected diets with detailed dietary records over multiple 24-hour urine collections. Study II: a controlled low-protein diet (0.6 g/kg body weight/day) for 10 days, then a high-protein diet (1.8 g/kg body weight/day) for 10 days, separated by a 12-day washout. This is a study of general dietary protein intake — not hydrolysed collagen peptide supplementation specifically.
DurationStudy I: up to 1 week of urine collections. Study II: 10 days per diet phase, separated by a 12-day washout period.
Endpoints24-hour urinary oxalate excretion; 24-hour urinary glycolate excretion; 24-hour urinary urea-nitrogen excretion; Urinary calcium, urate and citrate excretion (Study II)

What the study showed, in plain terms

This is an older, general-nutrition study, not a collagen-peptide trial — it is included as background for a question readers sometimes ask: does eating a lot of extra protein (as gram-scale collagen peptide supplements effectively are) raise the risk of kidney stones via oxalate?

In a large observational group, protein intake was not correlated with urinary oxalate or glycolate excretion. In a smaller, tightly controlled crossover study, switching from a low-protein to a high-protein diet significantly raised glycolate excretion in both sexes, and raised oxalate excretion by 20% in women but not men.

The authors also found striking day-to-day and person-to-person variability in oxalate excretion, even on identical controlled diets, suggesting genetics and hormonal factors matter more than diet alone. The effect of higher protein intake on oxalate was real but modest, and its practical significance for kidney stone risk is described by the authors as unresolved.

Key findings

  • On self-selected diets, neither urinary oxalate nor glycolate excretion was significantly correlated with protein intake in either sex.
  • On controlled diets, mean oxalate excretion in women was 20% higher on the high-protein diet (1.8 g/kg/day) than the low-protein diet (0.6 g/kg/day; p=0.02); no significant difference was seen in men.
  • Glycolate excretion was significantly higher on the high-protein diet than the low-protein diet in both sexes (p<0.001).
  • A pronounced inter- and intra-individual variability in oxalate excretion was observed even on tightly controlled diets, exceeding the variability explained by protein intake alone.
  • In males (but not females) on self-selected diets, oxalate excretion correlated significantly with urea-nitrogen excretion, suggesting a possible metabolic link between protein catabolism and oxalate synthesis specific to men.

What this study can and cannot tell us

  • Studies general dietary protein (mixed macronutrient diets), not hydrolysed collagen peptide supplementation specifically; extrapolation to gram-scale collagen peptide dosing is inferential, not directly tested.
  • The controlled-diet crossover arm was small (n=11), and oxalate excretion is subject to considerable individual variability that the study itself documents.
  • This is a 1993 paper; it predates modern collagen peptide supplement formulations and does not reflect current products' hydroxyproline/glycine content or dosing conventions.
  • The clinical significance of the observed 20% rise in oxalate excretion in women on a high-protein diet — whether it translates into meaningfully higher kidney stone risk — is not established by this study design.

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