Fatty acids, C9-13-neo-, calcium salts

Endpoint summary

Description of key information

Bioaccumulation potential is not relevant since Ca is an essential element in human nutrition.

Additional information

Information taken from EFSA (2006):

Absorption and regulation of absorption

Calcium must be in a soluble form or bound to soluble organic molecules to be absorbable. However, undissociated low-molecular-weight salts of calcium can also be absorbed independent of vitamin D by paracellular routes or pinocytosis. Depending on solubility, chemical form and on other factors of the food between 10 to 40% of dietary calcium is absorbed. The bulk of unabsorbed calcium is complexed to bile acids, free fatty acids, oxalic acid and excreted with the faeces (Heaney, 2002a). Lactose in the food, vitamin D, inulin, fructooligosaccharides and some casein phosphopeptides increase absorption, the latter by preventing precipitation of calcium by phosphates. Most calcium salts used in fortified foods or dietary supplements are absorbed to a similar extent as calcium from dairy foods. The absorbability of calcium citrate malate is higher (Weaver, 2001). Phytates, and especially oxalate inhibit calcium absorption. Fibre consumed without phytates does not have a negative influence. A combined high intake of predominantly insoluble fibre and phytate in the form of wheat bran over four weeks had no adverse effects on bone turnover markers in 19 healthy young women. The observed decrease in urinary calcium excretion sufficiently compensated for the reduced net absorption of dietary calcium without changing calcium retention (Zitterman et al, 1999). Both the protein and the sodium content of diets have a negative effect on calcium retention by increasing urinary calcium losses. The effect of higher protein intakes on increased urinary calcium losses appears only to result in negative effects on bone status if the calcium intake is inadequate (Heaney, 2002a). There are two kinds of calcium transport in the intestine: a) Active transport in the duodenum and upper jejunum is saturable and regulated by dietary intake and the needs of the body. Active transport involves three stages, namely entry across the brush border of the enterocyte via calcium channels and membrane-binding transport proteins, diffusion across the cytoplasm attached to calcium binding protein calbindin-D9K, and secretion across the basolateral membrane into the extracellular fluid against an electrochemical gradient either in exchange for sodium or via a calcium pump, a Ca-ATPase activated by calbindin, calcium and calmodulin. Active transport is negatively correlated with dietary calcium intake. This control is mediated via parathyroid hormone and 1,25(OH)2D. The renal production of 1,25(OH)2D is stimulated by increased parathyroid hormone secretion in response to a decrease in Ca2+ in blood and it stimulates the expression of the gene encoding calbindin, thereby enhancing calcium absorption in the intestine. Both parathyroid hormone and 1,25(OH)2D also increase renal reabsorption of calcium and bone resorption. b) Passive diffusion down an electrochemical gradient together with water, sodium and glucose via intercellular junctions or spaces occurs in all parts of the gut and is predominantly dependent on the calcium concentration in the gut lumen. This process is independent of vitamin D and age (Bronner, 1992). Passive diffusion requires that calcium is kept in solution, which can be enhanced by casein phosphopeptides (Mykkänen et al, 1980), by chelating with some amino acids (lysine and arginine) (Bronner, 1987), and by high doses of lactose (50 g/day) (Pansu et al, 1979). Increases in the osmolarity of the luminal contents of the intestine stimulate passive diffusion. Except in premature infants passive calcium absorption accounts for not more than 8 to 23% of the total calcium absorbed (McCormick, 2002). Fractional calcium absorption, is highest (about 60%) in breastfed infants (Abrams et al, 1996). Net calcium absorption, defined as intake minus faecal excretion in percent of intake, is lower in infants fed cows’ milk formula, decreases in young childhood, shows a rise in puberty, decreases to 15 to 20% in young adults (Matkovic, 1991; Miller et al, 1988; Peacock, 1991) and declines gradually thereafter (Heaney et al, 1989). Calcium absorption is increased in pregnant and lactating women compared to non-pregnant women (Moser-Veillon et al, 2001). Calcium absorption is under genetic control. The FF genotype for the Fok 1 polymorphism, a C → T transition in the vitamin D receptor translation initiation site, was related to increased calcium absorption in 72 children 7 to 12 years of age and it was associated with greater bone mineral density (Ames et al, 1999a), but these findings were not confirmed in another study with 99 girls 16.9 ± 1.2 years old (Lorentzon et al, 2001).

Calcium losses

The majority of absorbed calcium is stored in the skeleton. Excess absorbed calcium is excreted in urine, faeces, and sweat. Calcium balance is positive in healthy children, adolescents and young adults before bone growth and modelling cease, provided that they have an adequate calcium intake. Renal calcium excretion is the result of glomerular filtration (about 8 to 10 g calcium per day in adults) and tubular reabsorption (normal over 98% of the filtered load), which is primarily passive in the proximal tubules and for 20% active in the distal part of the convoluted tubules and connecting tubules. Active transport is under the control of parathyroid hormone, calcitonin and 1,25(OH)2D (Hoenderop et al, 2002). Average 24-hour excretion of calcium is 40 mg in young children, 80 mg in prepubertal children and reaches about 150-200 mg in adults. It is not strongly related to dietary calcium intake (Charles et al, 1991; Matkovic, 1991) in healthy persons. Calcium excretion is increased in hyperparathyroidism and decreased in untreated osteomalacia. Urinary calcium excretion is increased by dietary sodium intake (30 to 40 mg of calcium excreted per each two grams of dietary sodium) (Matkovic et al, 1995), by caffeine (Massey and Whiting, 1993) and in chronic metabolic acidosis (Bushinsky, 2001). Calcium excretion rises with excess dietary protein intake (by 0.5 mg for each gram of dietary protein, when intake was above 47 g/day) (Walker and Linkswiler, 1972; Whiting et al, 1998). This effect can be offset by simultaneous phosphorus intake (Guéguen and Pointillart, 2000).

Increased calcium excretion is also observed in idiopathic (hypocalcaemic) hypercalciuria, a genetic disorder of heterogeneous pathogenesis (absorptive, renal or dietary) observed in 2.2 to 6.4% of children and adults (Kruse et al, 1984; Moore et al, 1978) and which is the most frequent risk factor for nephrolithiasis. Idiopathic hypercalciuria could be the result of a defective renal epithelial Ca2+-channel leading to decreased active renal reabsorption of calcium or to an increased intestinal activity of the epithelial Ca2+-channel with augmented intestinal calcium absorption (Hoenderop et al, 2002). Hypercalciuric stone formers are more sensitive to dietary sodium chloride than individuals without stones with respect to calcium excretion (Massey and Whiting, 1995) and than normocalciuric stone formers (Burtis et al, 1994). Sodium restriction and/or protein restriction with a normal calcium intake reduces or normalises calcium excretion in hypercalciuric stone formers, whereas calcium restriction does not (Borghi et al, 2002). Calcium losses via the skin are between 4 and 96 mg/day in normal individuals, calculated from combined calcium balance and kinetic studies with 47Ca in 11 subjects (Charles et al, 1991). The authors consider the minimal obligatory loss to be 3 to 40 mg calcium per day. The amount rises with increasing serum calcium levels. Calcium is also secreted throughout the gastrointestinal tract, where about 85% is available for reabsorption with the same absorption efficiency as dietary calcium. Faecal secretory calcium loss has been estimated to be 80 to 224 mg/day in normal individuals.