Effects of Calcium Source on Calcium-Metabolic Parameters in Healthy Women and Men

Research Article

Austin J Endocrinol Diabetes. 2021; 8(2): 1085.

Effects of Calcium Source on Calcium-Metabolic Parameters in Healthy Women and Men

Hitz MF1,2*, Dahl M2,3 and Jørgensen NR2,4

1National Research Center for Bone Health, Medical Department, Zealand University Hospital, Denmark

2Department of Clinical Medicine, University of Copenhagen, Denmark

3Department of Clinical Biochemistry, Zealand University Hospital, Denmark

4Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Denmark

*Corresponding author: Mette Friberg Hitz, Associated Professor, National Research Center for Bone Health, Medical Department, Zealand University Hospital, Lykkebaekvej 1, 4600 Koege, Denmark

Received: May 20, 2021; Accepted: June 22, 2021; Published: June 29, 2021


Background/Objectives: Calcium and vitamin D are important for bone health. We compared 24-hour urinary calcium-excretion (Uca/24hrs), during dietary calcium steady-state condition, for different calcium-sources and effects of vitamin D, age and sex.

Subjects/Methods: Fifty-two healthy pre- and postmenopausal women and men completed the regimens: placebo, calcium carbonate (400mg) +18μg vitamin D, calcium carbonate (400mg) +38μg vitamin D and 400mg calcium phosphate (milk). Uca/24hrs was measured during dietary calcium steady state as a surrogate measure of calcium-absorption. Serum-calcium, parathyroid hormone (PTH), 25-hydroxy-vitamin D, Procollagen Type 1 N-terminal Pro- Peptide (P1NP) and C-terminal Telopeptide of type 1 collagen (CTX) were measured.

Results: Mean daily intake of calcium for the study group ± SD was 1105 ±396 mg. Mean-Uca ± SD: placebo 5.19 ± 2.04 mmol/24hrs, milk 5.88 ± 2.39 mmol/24hrs, (CaCO3+D) 6.19 ± 2.34 mmol/24hrs and (CaCO3 + DD) 6.26 ± 2.32 mmol/day. Uca were higher for all regimens compared to placebo (p <0.001), no difference was found between regimens. CTX was lower during all regimens compared to placebo (p <0.001): placebo 450 ± 243 μg/L, Milk 377 ± 248 μg/L, (CaCO3+D) 392 ± 266 μg/L and (CaCO3+DD) 361 ± 232 μg/L.

Conclusions: Uca was higher during supplementation with calcium compared to placebo. Supplementation with calcium reduced bone resorption significantly without effecting PTH. Menopausal status, sex and supplement with vitamin d demonstrated no effect on calcium excretion.

Keywords: Calcium absorption; Calcium carbonate; Biochemical markers of bone turnover; Bone health


CaCO3+D: Calcium Carbonate with 18 Microgram Vitamin D; CaCO3+DD: Calcium Carbonate with 38 Microgram Vitamin D; CTX: C-Terminal Telepeptide of Type 1 Collagen; CV: Coefficient of Variation; IGF-1: Insulin Growth Factor 1; P1NP: Procollagen Type 1 N-Termial Propeptide; PTH: Parathyroid Hormone; SD: Standard Deviation; Uca: Urinary Calcium; Uca/24hrs: Urinary Calcium Excretion over 24 hour


Calcium is largely absorbed in the proximal part of the small intestine via both an active transcellular mechanism and a passive para-cellular route [1].

The ability to absorb calcium may decline with age, postmenopausal status and vitamin D deficiency, since both activated vitamin D and estrogen stimulate the synthesis of important calcium binding proteins responsible for active calcium absorption [2,3].

A sufficient intake of calcium and vitamin D prevents secondary hyperparathyroidism, reduce bone turnover, bone loss, and is the first choice of prophylactic treatment of osteopenia and the basis of medical treatment for osteoporosis [4,5]. Calcium may originate from the diet or be taken as a supplement. There are different calcium salts available on the market; calcium carbonate, -citrate, -citrate-malate and lactate-gluconate. There is a small-demonstrated difference in fractional calcium absorption between the different salts, which is of little practical significance for individuals with normal gastric acidic environment. Thus choice of supplement may in large depend on patient preference [6,7].

The main source of calcium in the diet originates from dairy products but other food substances contribute as well, such as vegetables [8]. The bioavailability of calcium constitutes the fraction of calcium available for systemic circulation after absorption. For calcium supplementation, the bioavailability of calcium from food depends largely on the presence of other factors such as oxalic acid, phytic acid, lactose, fibers and oligosaccharides [8,9].

The milk protein casein is known to form Caseinophosphopeptides (CPP) during digestion, which have been shown to improve bioavailability of calcium from milk. Furthermore, casein acts as a calcium binding protein, which also facilitates calcium absorption [11]. The results are conflicting and most studies are animal studies [12]. In clinical studies, CPP has been demonstrated to inhibit bone turnover in postmenopausal women and elderly men and increase Insulin Growth Fractor 1 (IGF-1).

Activated vitamin D stimulates the synthesis of calcium binding transport proteins in the intestine. It has previously been speculated whether ingested vitamin D (cholecalciferol) has a direct effect on calcium absorption from the luminal side [13].

The aim of this study was to compare the urinary excretion of calcium from the sources calcium carbonate and milk as a surrogate measure of calcium absorption. To investigate if supplementation with vitamin D in an increasing dose could reduce bone turnover markers and to investigate if ingestion of calcium from milk could demonstrate an improved bioavailability of calcium compared to calcium carbonate evaluated by the ability to suppress bone turnover markers as well as PTH.

The study was conducted in a group of healthy pre- and postmenopausal women and men.

Materials and Methods

Participants were 52 healthy men and women invited to participate in the study after advertisements in the local press in Zealand County, Denmark. One hundred-fourth-eight participants were eligible, of these 31 did not meet inclusion criteria and 65 chose not to participate due to study design; before (61) or during the study (4) (Figure 1).