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Calcium formate shows promise

The preeminent supplement and food enrichment form of calcium is the carbonate salt. Calcium carbonate enjoys a high percent (approximately 40 per cent) of calcium content by weight, and is one of the least expensive forms of calcium. Much research and development capital has been directed to the pursuit of superior forms in relation to bioavailability.

Calcium citrate, a more soluble form of calcium, has about half of the elemental calcium concentration (20-24 per cent) of calcium carbonate. Numerous studies have assessed the acute bioavailability of these two widely utilised calcium forms, with the evidence being contested and equivocal,1,2 due in part to the economic interests of marketers of branded products using calcium as carbonate or citrate.

The pursuit of other forms of calcium with high elemental calcium and enhanced solubility profiles has illuminated a novel form of calcium for human nutrition — calcium formate. This form exhibits high solubility and is approximately 31 per cent calcium by weight. A recent study conducted among 14 young (19-33 years; 51-93kg body weight) premenopausal women assessed the bioavailability of a single dose of calcium (1,200mg elemental calcium) from three different sources: calcium formate; a branded formulation of calcium carbonate (Caltrate, Whitehall-Robbins); and calcium citrate (Citracal, Mission Pharmacal).3 A methyl cellulose placebo was also employed.

During the seven days prior to the dosing periods, and during the study, no dietary supplements (of calcium or vitamin D metabolism-modifying agents) were used. The subjects were not randomly assigned to a treatment but followed an order of supplement dose testing: placebo, calcium formate, calcium carbonate and calcium citrate. Each treatment was taken with only a single glass of water in the morning, and blood was collected for 4.5 hours post-dose, with only water allowed during this period. At least 48 hours intervened between each treatment.

Increases in serum calcium and decreases in parathyroid hormone (a protein hormone that promotes bone breakdown and liberation of calcium into the circulation) were significantly greater during the formate dose compared to the other treatments. Serum calcium excursions reached a peak at a substantially greater rate and were sustained at a concentration up to twice that of calcium citrate and thrice that of calcium carbonate.

Depressions in circulating parathyroid hormone, a normal compensatory response to elevations in serum calcium,2 manifested a significantly earlier onset (30 minutes post-dose) and greater drop (approximately 55 per cent of baseline) after the formate dose, which persisted through the blood-collection phase. For comparison, the calcium citrate results displayed a maximum decline of about 40 per cent at three hours post-dose.

The authors of this study attributed the rapid and dramatic excursions in serum calcium and parathyroid hormone to the rapid and extensive absorption of calcium when presented as formate. Formate research was led by Dr Hector Deluca (University of Wisconsin), who in his patent filings and awards showed that calcium from formate is very soluble in an aqueous solution at neutral pH.4 The solubility feature suggests that calcium formate may be well suited for individuals with compromised gastric acidification capacity, either endogenously or from acid suppressant agent use.

This study used high single doses of calcium, and away from meals, the latter being capable of influencing bioavailability. What remains to be shown by independent investigators (the lead author of this study has an economic interest in a company with the rights to Deluca?s patents claiming the use of calcium formate as a dietary supplement) is a significantly greater effect on bone turnover indices, either biochemical or, ideally, bone density and fracture incidence after chronic use. Lastly, unaddressed remains a concern of chronic ingestion of large amounts of formate, a metabolite of methanol. However, a single-dose study with the same female population as described above did suggest rapid absorption as well as clearance of formate.5

Anthony Almada, MSc, is president and chief scientific officer of IMAGINutrition Inc. Respond:

1. Sakhaee K, et al. Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate. Am J Ther 1999; 6:313?21.
2. Heaney RP, et al. Absorbability and cost effectiveness in calcium supplementation. J Am Coll Nutr 2001; 20:239-46.
3. Hanzlik RP, et al. Relative bioavailability of calcium from calcium formate, calcium citrate and calcium carbonate. JPET 2005; 313: 1217-22.
4. DeLuca HF. Calcium formate for use as a dietary supplement. US patent 6,528,542. 2003; March 4.
5. Hanzlik RP, et al. Absorption and elimination of formate following oral administration of calcium formate in female human subjects. Drug Metab Dispos 2005; 33:282-6.

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