Calcium Citrate Shown to Have Superior Bioavailability and Protects Against Bone Loss

November 21, 2000

New York (MedscapeWire) Nov 21 — An important follow-up study that reaffirms calcium citrate's superior bioavailability when compared with calcium carbonate also provides new evidence of calcium citrate's role in protecting against bone loss.

The study, published in the November issue of the Journal of Clinical Pharmacology, used 3 measures to determine calcium bioavailability — serum calcium, urinary calcium, and serum parathyroid hormone (PTH). This randomized crossover study compared the single-dose bioavailability and effects on PTH of commercial calcium citrate 250 mg (Citracal, Mission Pharmacal) and calcium carbonate 500 mg (Os-Cal, SmithKline Beecham) supplements in postmenopausal women.

"The initial study we conducted in 1999 showed that calcium citrate is more readily available to the body than calcium carbonate," explained study author Howard J. Heller, MD, assistant professor at the Center for Mineral Metabolism and Clinical Research at the University of Texas Southwestern Medical Center in Dallas. "We expanded the trial and our measurement methods to determine if one form of these commercially available calcium supplements was a better choice in postmenopausal women. We found that the tablet formulation of calcium citrate in the form of Citracal was more bioavailable than calcium carbonate, even when given with a meal. Several studies have established that calcium citrate is more bioavailable than calcium carbonate when the subject is fasting; however, some authors have previously suggested that the two forms of calcium are equally bioavailable when given with a meal.

"Moreover," Dr. Heller continued, "calcium citrate produced greater suppression of serum PTH by more than 50% over calcium carbonate. This provides physiological evidence that calcium citrate was better absorbed. We additionally found that calcium citrate may be particularly advantageous in those who absorb calcium poorly from calcium carbonate."

Parathyroid suppression is critical in maintaining bone because PTH is responsible for age-related bone loss. When the body senses a deficit in calcium, it responds to the challenge by increasing PTH levels and leaching calcium from the bones.

In another study from Mayo clinic, researchers found that calcium citrate supplementation effectively lowered serum PTH values to those found in premenopausal women, ultimately protecting them against bone loss.

Dr. Heller and his colleagues compared the calcium absorption of calcium citrate 350 mg (Citracal) and calcium carbonate 500 mg (Os-Cal) after a single oral load (500 mg calcium), taken with a meal, by calculating the peak and cumulative change in serum calcium from baseline, offering a direct measure of calcium bioavailability. Similarly, the curve of decline in serum PTH from baseline over time was used to assess the ability of calcium supplements to suppress parathyroid function. To adjust for daily biological variation and the effect of the meal alone, the value from the placebo phase was subtracted from the corresponding value for calcium citrate and calcium carbonate, allowing their actions to be compared independent of these variables.

Research participants were involved in 3 phases of randomized study. For 1 week prior to each phase, their diets contained an average amount of calcium (400 mg/day), were restricted in sodium (100 meq/day), and caffeine was not allowed. The purpose of these standardized diets was to reduce the influence of the diet on response. In 1 phase, subjects ingested a single dose, 500 mg calcium citrate. In another phase, research participants took a single dose of calcium carbonate. In the third phase, 2 placebo tablets were taken. In all phases, subjects were given the calcium supplement or placebo at the same time each morning with a standard breakfast in the clinical research setting. The participant's blood was drawn at baseline and obtained every hour for 6 hours to obtain a calcium bioavailability profile. Fasting and post-load urine samples were also collected.

This study was conducted as a follow-up to a previous study by Dr. Heller, published in the November 1999 issue of the Journal of Clinical Pharmacology, which was the first direct comparison of commercially available calcium supplements. In that study, it was proven that the calcium supplement formulation calcium citrate was 2.5 times more bioavailable than calcium carbonate, even when given with a meal, the optimum method of ensuring calcium carbonate absorption.

"It is very important for postmenopausal women to have sufficient intake of calcium (1200 to 1500 mg/day) and vitamin D (600 to 800 IU/day) in combination with a healthy, well-balanced diet and regular weight-bearing exercise," noted Dr. Heller. "However, since a serving of dairy only provides about 300 mg of calcium and up to 100 IU of vitamin D, most women are unable to achieve proper calcium and vitamin D intake via the diet alone. Our data suggests that there is an important difference in bioavailability between calcium supplements in postmenopausal women. Careful long-term studies should be done to determine if there is an equal difference in protection against bone loss and fracture."

J Clin Pharmacol. 2000;40:1237-12

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