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The effect of conjugated linoleic acid (CLA) on postmenopausal bone metabolism has not been investigated. Therefore, forty-three adult ovariectomised (OVX) rats (8-9 rats per group) were fed either a control diet containing 40 g/kg soyabean oil (SBO diet) or the SBO diet with 0 (control OVX), 2.5, 5 or 10 g/kg of CLA (replacing soybean oil) for 9 weeks. A group of sham-operated (SH) rats were fed the SBO diet. OVX rats had significantly (P<0.05) lower femoral bone mineral density and macromineral concentration, and intestinal Ca absorption compared to SH rats. CLA supplementation had no effect on these parameters. Ex vivo PGE(2) biosynthesis by bone and urinary Pyr and Dpyr (markers of bone resorption) were significantly higher (P<0.001) in control OVX rats compared with SH rats, and were significantly (P<0.001) lowered by CLA supplementation with 5 and 10, but not 2.5 g/kg diet in OVX rats. In conclusion, CLA supplementation appeared to reduce the rate of bone resorption in adult OVX rats.

Background: There is a high prevalence of osteopenia among patients with Crohn's disease (CD). There is some evidence that a deficiency of certain bone-active nutrients (including vitamins K and D) may have a partial role in this bone loss., Aims: To compare the intake and the status of vitamin K in CD patients, currently in remission, with age- and sex-matched controls, and furthermore to investigate the relationship between vitamin K status and bone turnover in these patients., Subjects: CD patients (n = 44; mean age: 36.9 yr) and matched controls (n = 44) were recruited from the Cork University Hospital and Cork City area, respectively., Methods: Bloods were analyzed for the total and undercarboxylated (Glu)-osteocalcin and urine analyzed for cross-linked N-telopeptides of type I collagen (NTx). Vitamin K(1) intake was estimated by food frequency questionnaire., Results: Vitamin K(1) intake in CD patients tended to be lower than that of controls (mean (SD), 117 (82) vs 148 (80) mug/d, respectively; p= 0.059). Glu and NTx concentrations in CD patients were higher than controls (mean (SD), 5.1 (3.1) vs 3.9 (2.1) ng/ml, respectively; p= 0.03 for Glu; and 49 (41) vs 25.8 (19.5) nM BCE/mM creatinine, respectively; p= 0.001 for NTx). In CD patients, Glu was significantly correlated with NTx (r= 0.488; p < 0.001), even after controlling for age, gender, vitamin D status, calcium intake, and corticosteroid use., Conclusion: Vitamin K status of CD patients was lower than that of the healthy controls. Furthermore, the rate of bone resorption in the CD was inversely correlated with vitamin K status, suggesting that it might be another etiological factor for CD-related osteopenia.

Objective: To estimate vitamin D intakes in a representative sample of Irish adults and to assess the contribution of foods to these intake estimates., Design: Vitamin D intakes in 1379, 18-64-y-old adults from the North/South Ireland Food Consumption Survey were estimated using a combination of new analytical data for vitamin D in foods, determined by HPLC, and used to revise recipe calculations, together with existing data from McCance and Widdowson's The Composition of Foods, 5th Edition plus supplements., Results: The total mean daily intake (MDI) of vitamin D (1 microg=40 IU) from all sources was 4.2 microg. The MDI was significantly higher (P<0.001) when the contribution from nutritional supplements was included (4.2 microg) compared with food sources only (3.2 microg). Men had significantly higher intakes (4.4 microg) than women (4.0 microg; P<0.001), which increased significantly (P<0.001) with age in both sexes. Meat/meat products (30.1%), fish/fish products (14.3%) and eggs/egg dishes (9.1%) were the main contributors to vitamin D intake. Supplements contributed 6.8 and 12% to MDI in men and women, respectively. In all, 74% of adults had an MDI of vitamin D that was less than the median (5 microg) of the recommended daily range of 0-10 microg., Conclusion: The findings of this study suggest that a large number of Irish adults have low vitamin D intakes. This, along with emerging evidence of low vitamin D status in at least some population subgroups, suggests that strategies to increase vitamin D intakes, including fortification of food, should be investigated.

Ca absorption has been shown to be unaffected by high luminal concentrations of two commonly consumed soyabean phyto-oestrogens (PO) (genistein and daidzein) in Caco-2 cells grown under oestrogen-depleted conditions. However, these compounds exhibit dose-dependent biphasic effects in some tissues, such as reproductive tissue and bone. Thus, in light of this biphasic activity, the effect of lower concentrations of genistein and daidzein on Ca absorption requires further investigation. Therefore, the aim of the present study was to investigate the effect of a range of concentrations of genistein and daidzein on Ca absorption in the human Caco-2 intestinal-like cell model. Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On day 21, the Caco-2 monolayers (n 12 per treatment), grown in oestrogen-deplete media, were then exposed to 10 nm-1,25-dihydroxycholecalciferol (1,25 (OH)2D3), or 1, 10 and 50 microm-genistein or -daidzein for 24 h. After exposure, transepithelial and transcellular transport of (45)Ca and fluorescein transport were measured. As expected, 1,25 (OH)2D3 stimulated Ca absorption in Caco-2 cells, by up regulating transcellular transport. Ca absorption was unaffected by either PO at luminal concentrations of 1, 10 or 50 microm, typical of intakes by Western and Asian populations as well as supplemental levels, respectively. The results of this model suggest that the proposed beneficial effects of supplemental levels of these PO compounds on bone mass in postmenopausal women more probably arise from direct effects on bone cells, and not by an indirect effect of these compounds on Ca absorption.

Recent data from a randomized, double-blind, placebo-controlled, yearlong clinical trial suggest that supplementation with the dietary phytoestrogen genistein (54 mg/day) may be as effective as hormone replacement therapy in attenuating menopause-related bone loss without causing the associated side effects. These findings may have implications for the development of diet-based strategies aimed at osteoporosis prevention.

The effect of polyunsaturated fatty acids (PUFA), in particular conjugated linoleic acid (CLA), on Ca and bone metabolism is unclear. In a 2x2 factorial design study, forty male 4-week-old rats were fed a control diet containing 70 g added fat (soyabean oil (SBO; n-6 PUFA-rich diet) or menhaden oil-safflower oil (MSO; n-3 PUFA-rich diet))/kg diet with 0 or 10 g CLA/kg for 8 weeks. Ex vivo prostaglandin E2 biosynthesis by bone organ culture was significantly higher (P<0.001) in rats consuming SBO compared with MSO, irrespective of CLA. Addition of the CLA treatment to either diet further lowered (P<0.05) ex vivo prostaglandin E2 production. Neither PUFA type nor CLA altered circulating or femoral mRNA levels of osteocalcin (a marker of bone formation) or insulin-like growth factor-I (a mediator of bone metabolism). While urinary pyridinium crosslinks levels (markers of bone resorption) were unaffected by CLA irrespective of PUFA type, they were significantly higher (P<0.05) in rats consuming SBO compared with MSO irrespective of CLA. Net fractional (%) and absolute (mg) Ca absorption were significantly (P<0.01 and P<0.05 respectively) higher in CLA-supplemented than unsupplemented animals fed on the n-3 PUFA-rich diet, whereas CLA had no effect in animals fed the n-6 PUFA-rich diet. There was no effect of CLA supplementation on bone mineral mass. In conclusion, CLA supplementation over 8 weeks appeared to enhance Ca absorption in young growing rats fed an n-3 PUFA-rich diet, but had no measurable effect on bone metabolism or bone mass over this time frame.

The beneficial effect of bovine whey protein (WP) on bone metabolism has been shown in adult human subjects and ovariectomised rats. However, its effect on bone formation in earlier life, particularly during periods of bone mineral accrual, has not been investigated. Twenty-one male rats (4 weeks old, Wistar strain) were randomised by weight into three groups of seven rats each and fed ad libitum on a semi-purified low-Ca diet (3.0 g Ca/kg diet) containing 0 (control), 10 (diet WP1) or 20 (diet WP2) g bovine WP/kg for 47 d. On day 34 of the dietary intervention, all rats had two gelatine capsules containing demineralised bone powder implanted subcutaneously in the thorax region (a well-established in vivo model of ectopic bone formation). At 14 d after implantation, alkaline phosphatase activity (reflective of bone formation) in the bone implants from animals fed WP1 and -2 diets was almost 2-fold (P<0.01) that of control animals. Insulin-like growth factor (IGF)-I mRNA levels were about 3-fold (P<0.05) higher in implants from animals fed the WP diets compared with those from control animals. Serum- and urine-based biomarkers of bone metabolism and bone mineral composition in intact femora were unaffected by WP supplementation. In conclusion, the present findings suggest that bovine WP can enhance the rate of ectopic bone formation in young growing rats fed a Ca-restricted diet. This effect may be mediated by an increased synthesis of IGF-I in growing bone. The effect of WP on bone formation warrants further investigation.

Recently, dietary phyto-oestrogens (PO) have been suggested as possible alternatives to oestrogen therapy (hormone replacement therapy) as a means of preventing bone loss associated with ovarian hormone deficiency. While PO, which exhibit oestrogen-like activity, act directly on bone cells, their protective effect on bone may be partly due to their ability to enhance Ca absorption. Therefore, the aim of the present study was to investigate the effect of 17beta-oestradiol and two commonly consumed soyabean PO (genistein and daidzein) on Ca absorption in the human Caco-2 intestinal-like cell model. Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers. On day 21, the Caco-2 monolayers (n 8-18 per treatment), grown in oestrogen-replete or -deplete media, were then exposed to 10 nm-17beta-oestradiol, 1 nm-1,25-dihydroxycholecalciferol, or 50 micro m-genistein or -daidzein for 24 h. After exposure, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured. As expected, 1,25-dihydroxycholecalciferol stimulated Ca absorption in Caco-2 cells, by up-regulating transcellular transport, whereas 17beta-oestradiol had no effect on Ca absorption. Unexpectedly, both PO decreased Ca absorption (by about 17-19 % compared with control, P<0.05), by reducing transcellular Ca transport in Caco-2 cells grown in oestrogen-replete media. This inhibitory effect disappeared when monolayers were grown in oestrogen-deplete media. In conclusion, PO at high luminal concentrations either had no effect or reduced Ca absorption in Caco-2 cells, dependent on oestrogen status. The effect of lower concentrations of these compounds needs to be investigated.

A high-salt diet increases urinary calcium excretion. Its effect on bone, however, is less clear. Recent research suggests that a high-salt diet increases the rate of bone resorption in postmenopausal women over a 4-week period, but increased potassium intake (as potassium citrate) ameliorates this adverse effect. These findings may have implications for the development of dietary guidelines for osteoporosis prevention.

Hypertension has been associated with abnormalities of Ca and bone metabolism. Consequently, dietary strategies aimed at reducing blood pressure may also benefit bone health; however, this issue has received little attention. Therefore, the objective of the present study was to investigate the effect of two antihypertensive-type diets on blood pressure and bone metabolism and composition in normotensive (Wistar-Kyoto NHsd, WKY) and hypertensive (spontaneously hypertensive NHsd, SHR) rats. Thirty WKY and thirty SHR male rats, 14 weeks old, were separately randomized by weight into three groups of ten rats each. One group from each strain was given a control diet while the other two groups were fed two anti-hypertensive (high fruit and vegetable (F/V) and high fruit and vegetable and low-fat dairy produce (combination)) diets for 8 weeks. SHR rats were significantly (P<0.01) heavier than WKY rats. Blood pressure and femoral length, width, dry weight, ash, Ca, Mg, P and bone mineral mass were significantly (P<0.0001) greater in SHR than WKY rats, but were unaffected by diet, irrespective of strain. While markers of bone formation (serum osteocalcin) and bone resorption (urinary pyridinoline and deoxypyridinoline) were similar in both strains, these markers were significantly (P<0.05) lower (28-31, 16-23, 31-33 % respectively) in the SHR rats fed the combination diet relative to those fed the control and F/V diets. Bone turnover in WKY rats was unaffected by diet. In conclusion, these findings suggest that the combination diet may benefit bone metabolism in hypertensive animals. However, as blood pressure was unaffected by this diet, the mechanism by which it reduced bone turnover requires further investigation.

Capric (10:0) and lauric (12:0) acid and conjugated linoleic acid (CLA) have been shown to increase paracellular permeability across human intestinal-like Caco-2 cell monolayers. While this has generated interest in terms of improved drug absorption and delivery, little has been done in terms of their potential effect on nutrient transport across the intestinal epithelium. Therefore, the objective of the present study was to investigate the effect of these fatty acids on transepithelial Ca transport in Caco-2 cells. Cells were seeded onto permeable transport membranes and allowed to differentiate, over 21 d, into intestinal-like cell monolayers. Monolayers (n 9 per treatment) were exposed to 0 (control) or 80 microm-10:0, 80 microm-12:0, 80 microm-18:2, 80 microm-CLA (mixed isomers), 80 microm-cis-9,trans-11 CLA or 80 microm-trans-10,cis-12 CLA for 22 d after seeding (chronic effect) or for 24 h before Ca transport studies (acute effect) on day 22. After exposure, transepithelial and transcellular transport of 45Ca, fluorescein transport (a marker of paracellular Ca transport) and transepithelial electrical resistance (TEER, an indicator of permeability) were measured. Overall Ca transport and TEER in Caco-2 cells were unaffected by exposure to any of the fatty acids for 24 h, or to 18:2, CLA blend or cis-9,trans-11 CLA for 22 d. Paracellular (but not total transepithelial and transcellular) Ca transport across Caco-2 cells was significantly increased (P<0.01, by about 1.5-fold relative to the control value) by exposure to 10:0, 12:0 and trans-10,cis-12 CLA for 22 d, suggesting that these non-esterified fatty acids could potentially enhance Ca absorption in vivo.

Calcium accounts for 1-2 % of adult human body weight. Over 99 % of total body Ca is found in the teeth and bones. Therefore, in addition to the obvious structural role of the skeleton, it also serves as a reservoir for Ca. Dietary Ca intake has an important impact on bone metabolism and bone health. Chronic Ca deficiency resulting from inadequate intake or poor intestinal absorption is one of several important causes of reduced bone mass and osteoporosis. It is vital, therefore, that adequate dietary Ca is consumed at all stages of life - in early life so that the genetically programmed peak bone mass can be reached and in later adulthood so that the skeletal mass can be maintained and age-related bone loss minimised. Unfortunately, there is wide variation in the estimates of daily Ca requirements made by different expert authorities. Furthermore, there is evidence that many individuals are not consuming these recommended levels. The consequence of this for bone health will be discussed in the present review. Besides the amount of Ca in the diet, the absorption of dietary Ca in foods is also a critical factor in determining the availability of Ca for bone development and maintenance. Thus, there is a need to identify food components and/or functional food ingredients that may positively influence Ca absorption in order to ensure that Ca bioavailability from foods can be optimised. This approach may be of particular value in individuals who fail to achieve the dietary recommended level of Ca.

Background: Sub-optimal selenium status may have a role in the aetiology of various pathologies. Selenium status depends on adequate selenium in the diet. A relatively high proportion of Irish adults (17% men; 46% women) have an inadequate dietary intake., Aim: A study was designed to examine the selenium status of healthy Irish adults., Methods: Ninety-one healthy Irish adults, aged 18-67 years, were recruited from the Cork City area. A fasting blood sample was collected from each subject and each was assayed for serum selenium an index of serum selenium., Results: Mean (+/- SD) serum selenium concentration in healthy Irish adults was 76 (+/- 21)microg/l. There was no significant difference in values between males and females or between postmenopausal and premenopausal women or between the three main age categories., Conclusion: Current serum selenium values of Irish adults would not appear to be sufficient to achieve optimal activity of glutathione peroxidase, which occurs at serum selenium concentration around 95microg/l. Sub-optimal selenium status may increase susceptibility to various chronic disorders.

A low Ca intake by both rats and man increases bone resorption, decreases bone mass and increases the risk of osteoporosis. The skeletal effect of high Ca intakes is less clear, particularly during periods of bone mineral accrual. Twenty-four female 5-week-old rats, Wistar strain, were randomized by weight into three groups of eight rats each and fed ad libitum a semi-purified diet containing 2 (Ca-restricted), 5 (normal) or 20 (Ca-supplemented) g Ca/kg for 3 weeks. When compared with the normal Ca diet, urinary Ca excretion was unaffected by the dietary restriction of Ca for 3 weeks, but was greater (P<0.001) in Ca-supplemented rats. Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) levels were significantly greater during weeks 2 (Pyr P<0.05, Dpyr P<0.001) and 3 (Pyr P<0.01, Dpyr, P<0.001) of dietary Ca restriction, but were unaffected by Ca supplementation. Femoral dry weight and the concentration of Mg and P in femora were unaffected by dietary Ca concentration. Femoral Ca concentration was reduced (P<0.05) in the Ca-restricted group compared with the other two groups. In conclusion, these results suggest that increasing dietary Ca intake, well above the recommended level, had no effect on bone mineral composition or bone resorption (as assessed with urinary pyridinium crosslinks) in young growing female rats. In addition, these results confirm the findings of previous studies which have shown that bone Ca content in young growing rats was reduced by dietary Ca restriction and that this reduction results, at least in part, from an increased rate of bone resorption.

In 1992 a significant relationship between bone turnover and the vitamin D receptor (VDR) genotype was reported in Australian subjects of UK-Irish decent. Since then, several groups have investigated the relationship between VDR and other bone-related genotypes, bone mass and bone turnover in several populations. However, the results of these studies are conflicting. Therefore, our aim was to determine bone-related genotypes in a population of healthy Irish adults and relate these genotypes to the rate of bone turnover. One hundred and eighteen healthy Irish adults (aged 19-67 yr) were recruited and fasting blood and first void urines were collected from each subject. Bone-related genotype frequencies in healthy Irish adults were similar to those reported in other Caucasian populations and were in Hardy-Weinberg equilibrium. Estrogen receptor (Pvu II or Xba I), apolipoprotein E and collagen IA1 genotypes were not related to bone turnover. The tt VDR genotype was associated with significantly higher serum osteocalcin (29% and 40%) compared with the Tt and TT genotypes, respectively. The ff VDR genotype was associated with significantly higher urinary pyridinoline (by approximately 44% and approximately 29%) and deoxypyridinoline (by approximately 76% and approximately 58%) levels and higher serum osteocalcin (by approximately 25% and approximately 53%) compared with the Ff or FF genotypes, respectively. These findings suggest that healthy Irish adults with either the tt or ff VDR genotype have higher rates of bone turnover than those with Tt or TT, or Ff or FF genotypes, respectively, and therefore may have a higher risk of low bone mineral density and osteoporosis in later life.

The effects of salt (NaCl) supplementation of rat diets (50 g/kg diet), with normal (200 g/kg) or high (500 g/kg) dietary casein content, were studied in 3-week-old male rats over a 3-week period. Weight gain was reduced by dietary salt but was unaffected by dietary casein. Salt-supplemented rats exhibited a two- and three-fold increase in urinary Mg and Ca excretion respectively, irrespective of dietary casein content. Dietary casein had no effect on urinary Ca or Mg. Salt reduced femoral mass but not femoral mass expressed relative to body weight, but neither variable was affected by dietary casein. Femoral Mg and P contents and concentrations were unaffected by dietary salt or casein. While femoral Ca concentration was unaffected by dietary salt, the Ca content was reduced by salt supplementation, irrespective of dietary casein content. Neither the content nor concentration of Ca in femora was affected by dietary casein. Urinary pyridinoline and deoxypyridinoline levels were increased by salt supplementation, irrespective of dietary casein content, but were unaffected by casein. Net Ca absorption was unaffected by dietary salt or casein. In conclusion, these results show that salt supplementation over the short-term increased the rate of bone resorption in rats. This was as a consequence of Na-induced calciuria. On the other hand, a high dietary protein intake had no effect on Ca metabolism, bone composition or bone resorption, nor did it augment the Na-induced calciuria or increased rate of bone resorption.

The effect of the level or source of dietary protein or protein-derived peptides on Ca absorption is not well understood. We determined, therefore, the influence of habitual dietary casein level, meal casein and meal casein phosphopeptide (CPP) on Ca absorption in the rat. True fractional Ca absorption was investigated in male 7-week-old rats, Wistar strain, in three separate studies using a faecal 47Sc: 47Ca ratio method. In studies A and C, rats (n 8 per group) were fed on a purified diet containing 200 g casein/kg for 2 weeks. Rats were then given a 47Ca-labelled meal (10 g) containing (per kg) either 0, 100, 200, or 300 g casein (study A) or 0, 100, 200, 350 or 500 g CPP (study C). In study B, rats (n 24 per group) were fed on a purified diet containing (per kg) either 200, 350 or 500 g casein for 2 weeks. Each group was then further randomized into three groups (n 8 per group) and given a 47Ca-labelled meal (10 g of the same diet) containing (per kg) either 200, 350 or 500 g casein. Ca absorption from a meal was unaffected by increasing meal casein concentration from 0 to 300 g/kg (study A), but was increased with a meal casein content of 500 g/kg (study B). Fractional Ca absorption decreased with increasing usual dietary casein intake in the range 200-500 g/kg (study B), suggesting intestinal adaptation. Ca absorption was unaffected by inclusion of 100 g CPP/kg in a single meal but was significantly (P < 0.001) reduced by 200, 350 and 500 g CPP/kg meal, with no evident dose-relationship. Thus, while Ca absorption was enhanced by high-casein meals, the mechanism remains unclear.

Background: In spite of the strong evidence for the beneficial health effects of dietary fibres, one of the potential nutritional disadvantages of high fibre diets is the adverse effect on the bioavailability of micronutrients, especially minerals and trace elements. With regard to Ca, there is considerable evidence that phytate, which is associated with fibre in many foods, such as cereals and soya products, inhibits Ca absorption. However, there is some doubt as to whether fibres per se have an influence on Ca absorption., Aim of the Study: Therefore, the purpose of this study was to investigate the effect on Ca absorption of two cereal-based fibre extracts (wheat bran and barley hull). In addition, in order to distinguish between the effect of the fibre components per se and the associated phytate content in these fibre extracts, we investigated the effect of dephytinised wheat and barley fibre extracts and the effect of phytate, as sodium phytate at levels present in the fibre extracts, on Ca absorption. Ca absorption was assessed in Caco-2 cells, as a model for studying Ca absorption in humans., Methods: The effect of wheat and barley fibre extracts, dephytinised wheat and barley fibre extracts, cellulose, and of sodium phytate on transepithelial 45Ca transport and 45Ca uptake was studied in differentiated Caco-2 cells grown on permeable filter supports. Wheat and barley fibre extracts were dephytinised with wheat phytase., Results: Wheat fibre extract had a 3.2-fold higher phytate content (48.0 mmol/kg) than barley fibre extract (15.1 mmol/kg). Enzymatic dephytinisation of both fibre extracts reduced the phytate content to undetectable levels. The rate of transepithelial 45Ca transport across Caco-2 cell monolayers and the uptake of 45Ca into Caco-2 cells were unaffected by cellulose or barley fibre extract. On the other hand, inclusion of wheat fibre extract in the Ca transport buffer (50 g fibre/l) significantly reduced the rate of 45Ca transport (by 17 and 19% respectively) and the uptake of 45Ca (by 24 and 25% respectively) relative to a fibre-free buffer and a control fibre (cellulose) transport buffer. Increasing the phytate concentration of the transport buffer from 0 to 2 mM (a level close to that in the wheat fibre containing buffer) significantly reduced the rate of 45Ca transport (by 16%) and 45Ca uptake (by 26%). Dephytinisation of the wheat fibre extract removed its inhibitory effects on 45Ca transport and e.g. 45Ca uptake., Conclusion: The results from the present study in Caco-2 cells suggest that it is the phytate in wheat fibre extract which is the major inhibitory factor of Ca absorption and that wheat fibre per se has little if any inhibitory effect on Ca absorption. In addition, the results of this study support the usefulness of Caco-2 cells for investigating the effects of dietary factors on the cellular uptake and transepithelial intestinal transport of Ca.

The availability of calcium from semi-synthetic meals and model food systems was studied by an in vitro method using equilibrium dialysis after simulating gastric digestion. Twelve different food components (phytate, oxalate, wheat fibre- and barley fibre-extract, D-sorbitol, xylitol, galactitol, casein, three different casein phosphopeptide preparations, and lactose) were added to the semi-synthetic meal and their effect on the relative index of availability of 45Ca was studied. Phytate, oxalate, wheat fibre-extract and barley fibre-extract, and, surprisingly, casein had a negative effect on availability of calcium. The most pronounced effect was observed for the addition of phytate. The other dietary factors had no effect on calcium availability. Therefore, this rapid and inexpensive in vitro model could be a useful screening method for factors affecting calcium absorption, especially inhibitory factors, in future human calcium bioavailability studies.

In the past, a major challenge for nutrition research was in defining indicators of nutritional adequacy. More recently, the research base related to the role of nutrition in chronic disease has expanded sufficiently to permit moving beyond deficiency indicators to other indicators with broader functional significance. Thus, nutrition research is faced with the new challenge of defining 'optimal nutrition'. One definition of optimal nutrition with respect to any particular nutrient could be when a functional marker reaches an 'optimal value' or plateau beyond which it is not longer affected by intake or stores of the nutrient. A functional marker of nutrient status could be defined as a physiological or biochemical factor which (1) is related to function or effect of the nutrient in target tissue(s) and (2) is affected by dietary intake or stores of the nutrient (which may include markers of disease risk). Examples of such indicators or markers are those related to risk of chronic diseases such as osteoporosis, CHD, or hypertension. The present review focuses on the concept of optimal nutrition with respect to three nutrients, Ca, Mg and P. However, for P and Mg there are as yet no functional indicators which respond to dietary intake, and in such cases nutrient requirements are established using more traditional approaches, e.g. balance data. For Ca, there has been interest in using maximal Ca retention, which is based on balance data, bone mass measurements and biomarkers of bone turnover as useful functional indicators of the adequacy of Ca intake.

Fifty-four male and forty-five female 7-week-old rats, Wistar strain, average weights 190 g and 140 g respectively, were randomized by weight into three groups of eighteen rats each (males) and three groups of fifteen rats each (females) and fed on a semi-purified diet containing (per kg) 2 (low), 5 (normal) or 20 g (high) Ca as CaCO3 for 2 weeks. Each group was then further randomized into three groups of six rats each (males) and five rats each (females) and given a meal (10 g of the same diet) containing either 2, 5 or 20 g Ca as 47CaCO3. 47Ca was determined in quantitative daily collections of faeces over 7 d and fractional absorption of 47Ca estimated by extrapolating the linear portion (days 3-7) of the plot of log 47Ca retention v. time back to the time of isotope administration. Absorption of meal Ca was higher in males than in females and was affected similarly in males and females by previous dietary Ca intake and meal Ca content. Fractional absorption of meal Ca decreased with increasing previous dietary Ca intake and with increasing meal Ca content, and the combined effect of these two variables caused fractional Ca absorption to vary from 11-89%. Absolute absorption of meal Ca decreased with increasing previous dietary Ca intake and increased with increasing meal Ca content. The influence on Ca absorption of variations in meal Ca content (load effect) was greater than that of variations in previous dietary Ca intake (adaptive effect). These results show that previous dietary Ca intake and meal Ca content are both major determinants of Ca absorption from meals in intact rats fed in the normal way and that the rat responds to these factors in a manner similar to that reported for humans. This study provides further evidence of similarities between rats and humans in dietary Ca absorption.