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To the Editor:

Heaney et al.(1) previously reported that fractional calcium absorption was an inverse function of load size. The slope of the relationship was large enough to suggest that divided doses of calcium would lead to usefully higher absorption, and this finding has been the basis for recommendations that calcium be given in divided doses throughout the day. We recently had an opportunity to test this hypothesis directly, and we report the results here.

Four adult men in good health were studied twice, one week apart, receiving 1000 mg of calcium either in a single dose at breakfast or in divided doses extending over an 8-h period. We deliberately employed an extreme regimen, i.e., 17 doses of 58.8 mg each given at 30-minute intervals. This was to ensure minimal variation in rate of flow past the upper small intestinal absorptive site. The calcium source was the carbonate salt, prepared as previously described(1) in a single batch, containing45Ca tracer at a level of approximately 8 μCi/1000 mg Ca. The labeled carbonate was packed loosely into individually weighed gelatin capsules for oral administration. Meals were designedly low in calcium so as to minimize interference from unlabeled calcium sources. Blood was drawn at 0, 1, 3, 5, 7, 12, and 24 h and analyzed for total and radioactive calcium. In the second test of the series, the zero-time blood was used to adjust subsequent samples for residual radioactivity from the first test.

Serum calcium specific activity curves for the two dosing regimens are shown in Fig. 1. As can be seen, the divided dose regimen produced higher mean specific activity values at all time points after 5 h. Peak levels under both dosing regimens occurred 4 to 5 h after the total load had been ingested. Moreover, initial slopes for both dosing regimens were essentially identical. This suggests that absorption was still capacity limited, even in the divided dose regimen.

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Figure Figure 1. Time course through 24 h for the mean specific activity values for both dosing regimens.

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Mean AUC was 2.095 for the single dose regimen and 3.902 for the divided dose. Mean ratio of AUC values, within subject, was 1.974 ± 0.210. Despite the small sample size, this ratio was significantly different (p = 0.025) from 1.0 (the zero-difference ratio). The equation describing the load-absorption curve published by Heaney and Weaver(1) predicts a ratio for the two regimens of 1.83, a value well within the confidence interval of the value reported here.

Whereas our explicit dosing regimen would be clinically unrealistic, it is doubtful that, in its effect, it differs very much from a four to five times a day, divided dose regimen, because gastric mixing and slowed emptying after meals containing a fraction of the total calcium supplement dose would likely have produced much the same smoothing of the flow of calcium-containing digestate past the absorptive surface.

In brief, this confirmation of our earlier prediction demonstrates that a divided dose regimen can, for the same ingested total load as in a single dose regimen, deliver as much as 80%-100% more calcium into the body. This means that a divided regimen is to be preferred; any division will be better than none. It means also that in either planning or evaluating studies of calcium supplementation, it is important to give consideration to the dosing regimen. Different regimens will deliver effectively very different doses for the same total intake.

References

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  • 1
    Heaney RP, Weaver CM, Fitzsimmons ML 1990 The influence of calcium load on absorption fraction. J Bone Miner Res 11:11351138.