Schedule of taking calcium supplement and the risk of nephrolithiasis

Kidney Int. 2004 May;65(5):1835-41. doi: 10.1111/j.1523-1755.2004.00587.x.


Background: Variation in the timing of calcium supplement may affect gastrointestinal absorption of both calcium and oxalate differently and may associate with variable risk of calcium oxalate nephrolithiasis. There are few human studies addressing specifically the appropriate time for taking calcium supplement. Therefore, this study was performed to compare calcium bioavailability and the risk of calcium oxalate stone formation for calcium supplement taken with meal vs. taken at bedtime.

Methods: Thirty-two healthy male navy privates, 22.7 +/- 1.9 years old (mean +/- SD), who had normal renal function (serum creatinine less than 150 umol/L) and no history of renal stone, participated in the study. The subjects were randomly allocated into two groups of 16 each. Group A took 1 g of calcium carbonate with meal, 3 times/day; and group B took 3 g/day of calcium carbonate at bedtime. After taking the regimens for 1 week, followed by 1 month of washout period, crossover between both groups was done. The diet was controlled throughout the study. Twenty-four-hour urine collections for the determination of urinary constituents were obtained at baseline and after taking both regimens of calcium supplement. Activity product for calcium oxalate was determined to assess the risk of calcium oxalate stone formation.

Results: Urinary excretions of calcium were significantly elevated above the baseline values when taking calcium supplement both with meal (3.48 +/- 2.13 mmol/day vs. 5.17 +/- 2.61 mmol/day, P < 0.05) and at bedtime (3.09 +/- 1.70 mmol/day vs. 5.08 +/- 2.34 mmol/day, P < 0.05). There was no difference between the two regimens in the urinary calcium excretions. The urinary oxalate was decreased significantly when the subjects took calcium supplement with meal compared with the corresponding baseline value (0.13 +/- 0.05 vs. 0.17 +/- 0.07 mmol/d, P= 0.01). In contrast, there was no alteration in urinary oxalate when calcium supplement was taken at bedtime compared to the baseline values (0.15 +/- 0.05 mmol/day vs. 0.15 +/- 0.06 mmol/day, P= 0.9). Compared with the corresponding baseline values, there was no significant increase in the activity product for calcium oxalate when taking calcium with meal (0.54 +/- 0.25 vs. 0.57 +/- 0.22, P= 0.54), but it was increased significantly when calcium supplement was taken at bedtime (0.47 +/- 0.21 vs. 0.72 +/- 0.27, P < 0.01).

Conclusion: Calcium supplement should be taken with meal in order to avoid increasing the risk of calcium oxalate nephrolithiasis.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Availability
  • Calcium / urine
  • Calcium Oxalate / analysis
  • Calcium Oxalate / urine
  • Calcium, Dietary / administration & dosage*
  • Calcium, Dietary / adverse effects*
  • Calcium, Dietary / pharmacokinetics
  • Citric Acid / urine
  • Drug Administration Schedule
  • Humans
  • Kidney Calculi / chemistry
  • Kidney Calculi / etiology*
  • Male
  • Oxalic Acid / urine
  • Risk Factors


  • Calcium, Dietary
  • Calcium Oxalate
  • Citric Acid
  • Oxalic Acid
  • Calcium