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Letter to the Editor |
1 Jean Mayer USDA Human Nutrition Research, Center on Aging at Tufts University, Mineral Bioavailability Laboratory, 711 Washington Street, Boston, MA 02111, E-mail: rwood{at}hnrc.tufts.edu
2 School of Public Health, University of Sao Paulo, Sao Paulo, Brazil
Dear Sir:
In his letter about our recent article (1), Heaney points out his concern that acute postprandial suppression of parathyroid hormone (PTH) concentrations should not be used as a measure of calcium bioavailability. We had similar concerns, which led us to measure a battery of potential calcium-dependent biomarkers as indicators of calcium bioavailability. We measured serum calcium, urinary calcium, plasma PTH, serum 1,25-dihydroxyvitamin D, and serum and urinary N-telopeptide collagen cross-links, as markers of bone-resorption response, in postmenopausal women both after an acute calcium load and after 7 d of a high calcium intake from 3 different sources. Thus, as we stated in the Discussion of our article (1) "on the basis of our acute and longer-term studies of several biomarkers of calcium and bone metabolism, we conclude that calcium bioavailability from milk, calcium-fortified orange juice, and a calcium carbonate supplement is equivalent." Despite apparent (but not statistically significant) differences in the acute PTH response between milk and the other 2 dietary calcium sources, we have yet to see compelling enough evidence that collectively would cause us to change these conclusions.
In addition, Heaney’s letter points out that we observed a postprandial decrease in the plasma PTH concentration of 
36%, with no evident increase in serum calcium. He suggests that we should have seen a 3–4% increase in postprandial serum calcium associated with the observed change in PTH. As stated in our article, we also expected to see a reciprocal relation between the changes in serum calcium and PTH. We note, however, that the relation between serum calcium and PTH can be more complex than Heaney’s suggestion of a 1% increase in serum calcium to a 10% decrease in PTH. For example, in a study of calcium bioavailability from calcium carbonate, Heller et al (2) reported a decrease in PTH in postmenopausal women 1 h after the consumption of a calcium carbonate supplement (Os-Cal; Smith-Kline-Beecham, Pittsburgh) but no concomitant increase in serum calcium. Moreover, in the same study, a modest increase (0.2 mg/dL) in serum calcium was observed at later time points; however, little additional decreases in PTH were evident. The change in the relation between serum calcium and PTH in Heaney et al’s (3) calcium bioavailability study in postmenopausal women suggests that this association can be complex. A compilation of data from the study of Heaney et al is shown in Table 1
, which illustrates the association observed after the consumption of calcium carbonate.
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, an increase in serum calcium of < 2% was observed within 1 h after consumption of the calcium supplement; however, a striking 40% decrease in PTH was observed. If one then examines the data in the third column of Table 1, which shows the postprandial response at 3 h, serum calcium is 6% greater than the baseline value (ie, 3 times the observed increase at 1 h); however, PTH decreased to only slightly more than its nadir, ie, to 48% of baseline. Finally, by 5 h postprandially (column 4 of Table 1), PTH began to return toward baseline, despite no change in serum calcium between 3 and 5 h. Our conclusion from the data of both Heller et al (2) and Heaney et al (3) is that the relation of serum calcium and PTH can be complex and that PTH can change with no or little observed change in serum calcium.
The degree of absorptive calcemia after consumption of a calcium-supplement source may be influenced by the composition of the test meal. For example, Heaney et al (3) found a 0.15-mg/dL change in serum calcium 1 h after ingestion of the calcium carbonate supplement and a 0.6-mg/dL increase at 3 h. In contrast, Heller et al (2) found no increase in serum calcium 1 h after the ingestion of a calcium carbonate supplement. By 2 and 5 h postprandially, Heller et al’s (2) observed calcemic response (0.2–0.3 mg/dL above baseline) was much lower than that observed by Heaney et al (3). A comparison of the 2 studies indicated that the simpler test meal (white bread, butter, and beverage) was used by Heaney et al (3), which was associated with the highest calcemic response (0.6 mg/dL compared with 0.2 mg/dL), perhaps reflecting the more complex meal (farina, sugar, egg, bread, and beverage) used by Heller et al (2). In our own study (1), the largest calcemic difference was only 0.12 mg/dL above baseline serum calcium concentrations 2 and 4 h after ingestion of the calcium carbonate supplement. Our test meal was the most complex (wheat bread, jelly, butter, eggs, mushrooms, green peppers, soybean oil, seasoning, and beverage) and may have influenced the poor calcemic response to calcium supplementation. Finally, additional undetected factors in a group of study subjects may affect the mean postprandial calcemic response observed in any study. For example, Heller et al (2) noted that one-third of their older subjects had acute serum calcium responses after calcium carbonate treatment that were not different from the response to placebo. Unfortunately, it was not possible to determine from the published data whether the same subjects would also be classified as nonresponders on the basis of other biomarkers of calcium absorption.
REFERENCES
This article has been cited by other articles:
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  C. W Gunther, R. M Lyle, P. A Legowski, J. M James, L. D McCabe, G. P McCabe, M. Peacock, and D. Teegarden Fat oxidation and its relation to serum parathyroid hormone in young women enrolled in a 1-y dairy calcium intervention Am. J. Clinical Nutrition, December 1, 2005; 82(6): 1228 - 1234. [Abstract] [Full Text] [PDF]
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 R. P. Hanzlik, S. C. Fowler, and D. H. Fisher Relative Bioavailability of Calcium from Calcium Formate, Calcium Citrate, and Calcium Carbonate J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1217 - 1222. [Abstract] [Full Text] [PDF]
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