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Creighton University, 601 North 30th Street, Suite 4841, Omaha, NE 68131, E-mail: rheaney{at}creighton.edu
Dear Sir:
In a recent issue of the Journal, Martini and Wood (1) concluded that calcium carbonate, milk, and calcium-fortified orange juice are approximately equivalent with regard to calcium bioavailability. Their conclusion was based mainly on the results of the use of a pharmacodynamic method, ie, a decrease in serum parathyroid hormone (PTH) in response to the absorptive calcemia produced by each of the 3 sources. Although their conclusion may well be correct, it is questionable whether their data are adequate to support it.
It is troubling that their measurements of serum calcium did not detect the absorptive calcemia responsible for the decrease in PTH. Others (2, 3) have shown that calcemia is detectable, with a 1% change in serum calcium evoking an 10% change in PTH. Thus, the decrease in PTH 2 h after intake of the calcium carbonate and orange juice sources (36%) should have been associated with a 3–4% increase in serum calcium. Although the data of Martini and Wood fail to show even a hint of an increase in serum calcium, such an increase must have occurred, as indicated not only by the PTH response they described but also by the increase in urinary calcium excretion found at the 4-h time point.
The authors reported decremental areas under the curve (AUCs) for PTH (as a percentage of baseline). An equivalent treatment is to normalize each set to its own baseline. The time course of such relative PTH values for the 4 h over which Martini and Wood conducted their experiment is shown in Figure 1; these values are derived from the data in their Table 2. As is visually evident, the time course for milk differs considerably from that of the other 2 sources. As can be calculated from the data in Table 2 of their article, the decremental relative AUCs for the 3 sources are -1.00 for calcium carbonate, -0.67 for milk, and -1.14 for the calcium-fortified orange juice. These values cannot be easily converted to the percentage decrements reported in their article, and it is not possible to harmonize the reported decrements with the data in Figure 1. As is evident in Figure 1, calcium carbonate and fortified orange juice cannot have the same AUC value, as Martini and Wood reported. Moreover, the difference between milk and calcium-fortified orange juice is substantial. In this case, it looks as if milk is being absorbed more slowly than are the other sources, and one can only wonder what the time course of PTH might have looked like after the 4-h time point at which Martini and Wood stopped their measurements.
FIGURE 1. . Time course of relative parathyroid hormone (PTH) values for 3 calcium sources: calcium carbonate, milk, and calcium-fortified orange juice (OJ).
On the basis of the data in Figure 1 and on the results of other similar studies, 4 h is not long enough to assess AUC accurately. Factors that change the rate of gastric emptying, for example, will hasten or delay calcium entry into the system, and an adequate comparison between sources requires following the PTH curve until it returns to a value similar to baseline.
My extensive laboratory experience with the PTH response during absorptive calcemia over the past several years has convinced me that, although it greatly amplifies the calcemic signal, the PTH response is sufficiently variable from person to person and from time to time to be relatively insensitive as a means of detecting differences in absorption between calcium sources. This is certainly even more true if the time course is not long enough to capture the full AUC.
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