Vitamin D status and current policies to achieve adequate vitamin D intake in the Nordic countries.

Aims: Nordic countries share fairly similar food culture and geographical location as well as common nutrition recommendations. The aim of this paper was to review the latest data on vitamin D status and intake and to describe the national supplementation and food fortification policies to achieve adequate vitamin D intake in the Nordic countries. Methods: The data are based on results derived from a literature search presented in a workshop held in Helsinki in November 2018 and completed by recent studies. Results: Vitamin D policies and the implementation of the recommendations differ among the Nordic countries. Vitamin D fortification policies can be mandatory or voluntary and widespread, moderate or non-existent. Vitamin D supplementation recommendations differ, ranging from all age groups being advised to take supplements to only infants. In the general adult population of the Nordic countries, vitamin D status and intake are better than in the risk groups that are not consuming vitamin D supplements or foods containing vitamin D. Non-Western immigrant populations in all Nordic countries share the problem of vitamin D insufficiency and deficiency. Conclusions: Despite the common nutrition recommendations, there are differences between the Nordic countries in the implementation of the recommendations and policies to achieve adequate vitamin D intake and status. There is a need for wider Nordic collaboration studies as well as strategies to improve vitamin D status, especially in risk groups.

Development and validation of an interview-administered FFQ for assessment of vitamin D and calcium intakes in Finnish women.

Increased vitamin D fortification of dairy products has increased the supply of vitamin D-containing products with different vitamin D contents on the market in Finland. The authors developed a ninety-eight-item FFQ with eight food groups and with a question on supplementation to assess dietary and supplemental vitamin D and Ca intakes in Finnish women (60ºN). The FFQ was validated in subgroups with different habitual vitamin D supplement use (0-57·5 µg/d) against the biomarker serum 25-hydroxyvitamin D (S-25(OH)D) and against 3-d food records (FR) (n 29-67). Median total vitamin D intake among participants was 9·4 (range 1·6-30·5) µg/d. Spearman's correlations for vitamin D and Ca ranged from 0·28 (P 0·146, FFQ v. S-25(OH)D, persons not using supplements) to 0·75 (P<0·001, FFQ v. FR, supplement use included). The correlations between the FFQ and S-25(OH)D concentrations improved within increasing supplement intake. The Bland-Altman analysis showed wide limits of agreement between FFQ and FR: for vitamin D between -7·8 and 8·8 µg/d and for Ca between -938 and 934 mg/d, with mean differences being 0·5 µg/d and 2 mg/d, respectively. The triads method was used to calculate the validity coefficients of the FFQ for vitamin D, resulting in a mean of 1·00 (95 % CI 0·59, 1·00) and a range from 0·33 to 1·00. The perceived variation in the estimates could have been avoided with a longer FR period and larger number of participants. The results are comparable with earlier studies, and the FFQ provides a reasonable estimation of vitamin D and Ca intakes.

Mono- and polyphosphates have similar effects on calcium and phosphorus metabolism in healthy young women.

PURPOSE: Phosphate (Pi) salts, often mono- (MP) or polyphosphates (PP), are commonly used as additives in the food industry. Previous studies have shown that the effects of MP and PP on calcium (Ca) and phosphorus (P) metabolism may differ. The aim of this study was to determine whether the effects of MP and PP salts differ on markers of Ca and P metabolism in young women. METHODS: Fourteen healthy women 19-31 years of age were randomized into three controlled 24-h study sessions, each subject serving as her own control. During each session, the subjects received three doses of MP, PP or a placebo with meals in randomized order. Both Pi salts provided 1,500 mg P/d, and the diet during each session was identical. Markers of Ca and P metabolism were followed six times over 24 h. RESULTS: During both MP and PP sessions, we found an increase in serum phosphate (S-Pi, p = 0.0001), urinary phosphate (U-Pi, p = 0.0001) and serum parathyroid hormone (S-PTH, p = 0.048 MP, p = 0.012 PP) relative to the control session. PP decreased U-Ca more than did MP (p = 0.014). CONCLUSIONS: The results suggest that PP binds Ca in the intestine more than does MP. Based on the S-Pi, U-Pi and S-PTH results, both Pi salts are absorbed with equal efficiency. In the long run, increased S-PTH, caused by either an MP or PP salt, could have negative effects on bone metabolism.

Associations among total and food additive phosphorus intake and carotid intima-media thickness--a cross-sectional study in a middle-aged population in Southern Finland.

BACKGROUND: Dietary phosphorus (P) intake in Western countries is 2- to 3-fold higher than recommended, and phosphate is widely used as a food additive in eg. cola beverages and processed meat products. Elevated serum phosphate concentrations have been associated with cardiovascular disease (CVD) risk factors and CVD itself in several studies in patients with renal dysfunction and in a few studies in the general population. Carotid intima-media thickness (IMT) is a CVD risk factor, thus the aim of the study was to determine if an association between dietary P, especially food additive phosphate (FAP), intake, and IMT exists. METHODS: Associations among total phosphorus (TP) and FAP intake and carotid IMT were investigated in a cross-sectional study of 37- to 47-year-old females (n = 370) and males (n = 176) in Finland. Associations among TP intake, FAP intake, and IMT were tested by analysis of covariance (ANCOVA) in quintiles (TP) and sextiles (FAP) using sex, age, low-density/high-density lipoprotein cholesterol ratio, smoking status, and IMT sonographer as covariates. RESULTS: No significant associations were present between TP or FAP intake and IMT (p > 0.05, ANCOVA), but in between-group comparisons some differences were found indicating higher IMT among subjects with higher P intake. When testing for a significant linear trend with contrast analysis, a positive trend was observed between energy-adjusted TP intake and IMT among all subjects (p = 0.039), and among females a tendency for a trend existed (p = 0.067). Among all subjects, a significant positive linear trend was also present between FAP intake and IMT (p = 0.022); this trend was also seen in females (p = 0.045). In males, no significant associations or trends were noted between TP or FAP intake and IMT (p > 0.05). CONCLUSIONS: Our results indicate that a significant linear trend exists between energy-adjusted TP intake and FAP intake, and IMT among all subjects. Based on these results, high dietary P intake should be further investigated due to its potential association with adverse cardiovascular health effects in the general population.

Low calcium:phosphorus ratio in habitual diets affects serum parathyroid hormone concentration and calcium metabolism in healthy women with adequate calcium intake.

Excessive dietary P intake alone can be deleterious to bone through increased parathyroid hormone (PTH) secretion, but adverse effects on bone increase when dietary Ca intake is low. In many countries, P intake is abundant, whereas Ca intake fails to meet recommendations; an optimal dietary Ca:P ratio is therefore difficult to achieve. Our objective was to investigate how habitual dietary Ca:P ratio affects serum PTH (S-PTH) concentration and other Ca metabolism markers in a population with generally adequate Ca intake. In this cross-sectional analysis of 147 healthy women aged 31-43 years, fasting blood samples and three separate 24-h urinary samples were collected. Participants kept a 4-d food record and were divided into quartiles according to their dietary Ca:P ratios. The 1st quartile with Ca:P molar ratio < or = 0.50 differed significantly from the 2nd (Ca:P molar ratio 0.51-0.57), 3rd (Ca:P molar ratio 0.58-0.64) and 4th (Ca:P molar ratio > or = 0.65) quartiles by interfering with Ca metabolism. In the 1st quartile, mean S-PTH concentration (P = 0.021) and mean urinary Ca (U-Ca) excretion were higher (P = 0.051) than in all other quartiles. These findings suggest that in habitual diets low Ca:P ratios may interfere with homoeostasis of Ca metabolism and increase bone resorption, as indicated by higher S-PTH and U-Ca levels. Because low habitual dietary Ca:P ratios are common in Western diets, more attention should be focused on decreasing excessively high dietary P intake and increasing Ca intake to the recommended level.

Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women.

Both K and Ca supplementation may have beneficial effects on bone through separate mechanisms. K in the form of citrate or bicarbonate affects bone by neutralising the acid load caused by a high protein intake or a low intake of alkalising foods, i.e. fruits and vegetables. Ca is known to decrease serum parathyroid hormone (S-PTH) concentration and bone resorption. We compared the effects of calcium carbonate, calcium citrate and potassium citrate on markers of Ca and bone metabolism in young women. Twelve healthy women aged 22-30 years were randomised into four controlled 24 h study sessions, each subject serving as her own control. At the beginning of each session, subjects received a single dose of calcium carbonate, calcium citrate, potassium citrate or a placebo in randomised order. The diet during each session was identical, containing 300 mg Ca. Both the calcium carbonate and calcium citrate supplement contained 1000 mg Ca; the potassium citrate supplement contained 2250 mg K. Markers of Ca and bone metabolism were followed. Potassium citrate decreased the bone resorption marker (N-terminal telopeptide of type I collagen) and increased Ca retention relative to the control session. Both Ca supplements decreased S-PTH concentration. Ca supplements also decreased bone resorption relative to the control session, but this was significant only for calcium carbonate. No differences in bone formation marker (bone-specific alkaline phosphatase) were seen among the study sessions. The results suggest that potassium citrate has a positive effect on the resorption marker despite low Ca intake. Both Ca supplements were absorbed well and decreased S-PTH efficiently.

Habitual high phosphorus intakes and foods with phosphate additives negatively affect serum parathyroid hormone concentration: a cross-sectional study on healthy premenopausal women.

OBJECTIVE: Foods can contain natural phosphorus (NP) and phosphate-containing food additives (AP). The main objective of the present study was to investigate whether NP and AP of habitual diets differ in their effects on markers of Ca metabolism. We also investigated the impact of total habitual dietary P intake on markers of Ca metabolism. DESIGN: Cross-sectional study. Fasting blood samples were collected and participants kept a 4 d food record, from which dietary intake of total P and the consumption of NP (milk and cheese, excluding processed cheese) and AP (processed cheese) sources were calculated. Participants were divided into groups according to their NP- and AP-containing food consumption and into quartiles according to their total P intake. SETTING: Southern Finland. SUBJECTS: One hundred and forty-seven healthy premenopausal women aged 31-43 years. RESULTS: Relative to the lowest total dietary P quartile, mean serum parathyroid hormone (S-PTH) concentration was higher (P = 0.048, analysis of covariance (ANCOVA)) and the mean serum ionized Ca concentration lower (P = 0.016, ANCOVA) in the highest P intake quartile. Mean S-PTH concentrations were higher among participants who consumed processed cheese (P = 0.027, ANCOVA) and less milk and other cheese than processed cheese (P = 0.030, ANCOVA). CONCLUSIONS: High total habitual dietary P intake affected S-PTH unfavourably. Furthermore, phosphate additives may have more harmful effects on bone than other P sources, as indicated by higher mean S-PTH concentration among participants who consumed AP-containing foods. Because of the high dietary P intake and current upward trend in consumption of processed foods in Western countries, these findings may have important public health implications.

Effects of phosphodiesterase 7 inhibition by RNA interference on the gene expression and differentiation of human mesenchymal stem cell-derived osteoblasts.

The second messenger molecule cyclic adenosine monophosphate (cAMP) plays an important role in the hormonal regulation of bone metabolism. cAMP is inactivated by the cyclic nucleotide phosphodiesterases (PDEs), a superfamily of enzymes divided into 11 known families designated PDE 1-11. The aim of this study was to investigate the effect of PDE7 and PDE8 inhibition on the gene expression and differentiation of human osteoblasts. Osteoblasts differentiated from human mesenchymal stem cells (hMSC) were cultured and treated with short interfering RNAs (siRNAs) generated from PDE7 and PDE8 PCR products. Total RNA was isolated from the cells, and gene expression was assayed with cDNA microarray and quantitative real-time PCR. bALP measurements were assayed during differentiation, and mineralization was determined by quantitative Alizarin red S staining. PDE7 and PDE8 inhibition by RNA interference decreased the gene expression of PDE7A by 60-70%, PDE7B by 40-50%, and PDE8A by 30%. PDE7 silencing increased the expression of beta-catenin, osteocalcin, caspase-8, and cAMP-responsive element-binding protein 5 (CREB-5) genes and decreased the expression of the 1, 25-dihydroxyvitamin D3 receptor gene. PDE8A silencing increased the expression of anti-apoptotic genes, but decreased the expression of osteoglycin (osteoinductive factor) and bone morphogenetic protein 1 (BMP-1). PDE7 silencing increased bALP and mineralization up to three-fold compared to controls. Treatment with the PDE7-selective PDE inhibitor BRL-50481 had similar effects on mineralization as the gene silencing. The PDE7 silencing also increased forskolin stimulated cAMP response, but had no effect on the proliferation rate. Furthermore, osteocalcin expression was increased by PDE7 silencing by a mechanism dependent on protein kinase A. Our results show that specific gene silencing with the RNAi method is a useful tool for inhibiting the gene expression of specific PDEs and that PDE7 silencing upregulates several osteogenic genes and increases mineralization. PDE7 may play an important role in the regulation of osteoblastic differentiation.

Long-term effects of tripeptide Ile-Pro-Pro on osteoblast differentiation in vitro.

Bone mineralization is a result of the function of bone-forming osteoblasts. Osteoblast differentiation from their precursors is a carefully controlled process that is affected by many signaling molecules. Protein-rich food-derived bioactive peptides are reported to express a variety of functions in vivo. We studied the long-term in vitro effect of bioactive tripeptide Ile-Pro-Pro (IPP) on osteoblasts differentiated from human mesenchymal stem cells. Osteoblast bone alkaline phosphatase activity (bALP), bone-forming capacity and gene expression were investigated. Treatment with 50 microM IPP had no effect on bALP activity, but osteoblast mineralization was increased. Gene expression of beta-catenin, Cbfa1/Runx2, PTHrP, CREB-5, osteoglycin, osteocalcin, caspase-8, osteoprotegerin (OPG) and RANKL was analyzed by quantitative real-time PCR on Days 13, 17 and 20 of culture. The results indicate that IPP increased mineral formation due to enhanced cell survival and matrix formation. In addition, IPP reduced the RANKL/OPG ratio. Bioactive peptides, such as IPP, could be one method by which a protein-rich diet promotes bone integrity.

Vitamin D Fortification of Fluid Milk Products and Their Contribution to Vitamin D Intake and Vitamin D Status in Observational Studies-A Review.

Fluid milk products are systematically, either mandatorily or voluntarily, fortified with vitamin D in some countries but their overall contribution to vitamin D intake and status worldwide is not fully understood. We searched the PubMed database to evaluate the contribution of vitamin D-fortified fluid milk products (regular milk and fermented products) to vitamin D intake and serum or plasma 25-hydroxyvitamin D (25(OH)D) status in observational studies during 1993⁻2017. Twenty studies provided data on 25(OH)D status (n = 19,744), and 22 provided data on vitamin D intake (n = 99,023). Studies showed positive associations between the consumption of vitamin D-fortified milk and 25(OH)D status in different population groups. In countries with a national vitamin D fortification policy covering various fluid milk products (Finland, Canada, United States), milk products contributed 28⁻63% to vitamin D intake, while in countries without a fortification policy, or when the fortification covered only some dairy products (Sweden, Norway), the contribution was much lower or negligible. To conclude, based on the reviewed observational studies, vitamin D-fortified fluid milk products contribute to vitamin D intake and 25(OH)D status. However, their impact on vitamin D intake at the population level depends on whether vitamin D fortification is systematic and policy-based.

High dietary phosphate intake reduces bone strength in the growing rat skeleton.

UNLABELLED: Nutrition influences peak bone mass development in early adulthood. The effect of high dietary phosphate intake on the growing skeleton of 1-month-old male rats (n = 30) was assessed in an 8-week intervention. High dietary phosphate intake increased bone remodeling and impaired bone material properties, diminishing bone mechanical strength. INTRODUCTION: High dietary phosphate intake is typical in the Western diet. Abundant phosphate intake enhances parathyroid secretion and bone metabolism. To study the influence of high dietary phosphate intake on growing bone homeostasis and structure, we submitted growing rats to experimental diets that varied in their phosphate content. MATERIALS AND METHODS: One-month-old intact male rats (n = 30) were fed a control diet (Ca:P 1:1) or an experimental diet of either Ca:P 1:2 or Ca:P 1:3 for 8 weeks. At the beginning and the end of the study period, the right femurs were measured using DXA. Double labeling with tetracycline injection was performed 12 and 2 days before death. After death, hind legs were cut loose. Left femurs were processed for histomorphometry. Right femurs were measured with pQCT. Mechanical testing was performed on the right femoral neck and tibial shaft. Six right tibias were analyzed with microCT. Serum PTH, calcium, and phosphate contents were analyzed. RESULTS: High-phosphate intake impaired growth of the animal, limited bone longitudinal growth, and restricted femur BMC and BMD build-up. Osteoclast number, osteoblast perimeter, and mineral apposition rate were increased, and trabecular area and width were decreased. Phosphate decreased femur midshaft total bone BMD, cortical bone BMD, and mean cortical thickness. High-phosphate diet reduced femoral neck and tibial shaft ultimate strength and tibia stiffness and toughness. In addition, serum PTH increased. CONCLUSIONS: High dietary phosphate intake reduced growth, skeletal material, and structural properties and decreased bone strength in growing male rats. Adequate calcium could not overcome this.

Letter to the Editor Re: McClure et al. Nutrients 2017, 9, 95.

n/a.

Dietary phosphorus intake is negatively associated with bone formation among women and positively associated with some bone traits among men-a cross-sectional study in middle-aged Caucasians.

High dietary phosphorus (P) intake has acute negative effects on calcium (Ca) and bone metabolism, but long-term clinical data are contradictory. We hypothesized that high P intake is associated with impaired bone health as suggested by earlier short-term studies on bone metabolism. In this cross-sectional study, we investigated associations between dietary P intake, bone traits in the radius and tibia, and bone turnover in a population-based sample of 37- to 47-year-old Caucasian premenopausal women (n=333) and men (n=179) living in Southern Finland (60°N). We used various regression models in an "elaboration approach" to elucidate the role of P intake in bone traits and turnover. The addition of relevant covariates to the models mainly removed the significance of P intake as a determinant of bone traits. In the final regression model (P intake, weight, height, age, Ca intake, serum 25-hydroxyvitamin D, physical activity, smoking, contraceptive use in women), P intake was slightly positively associated only with bone mineral content and cross-sectional cortical bone area in the tibia of men. Among women, inclusion of Ca removed all existing significance in the crude models for any bone trait. In women P intake was negatively associated with the bone formation marker serum intact pro-collagen type I amino-terminal propeptide, whereas no association was present between P intake and bone turnover in men. In conclusion, these findings disagree with the hypothesis; P intake was not deleteriously associated with bone traits; however, P intake may negatively contribute to bone formation among women.

Prolonged increase in dietary phosphate intake alters bone mineralization in adult male rats.

Excessive intake of dietary phosphate without the company of calcium causes serum parathyroid hormone (s-PTH) concentration to rise. We investigated the effect of a modest but prolonged increase in dietary intake of inorganic phosphate on the bone quantitative factors of mature male rats. Twenty Wistar rats were divided into two groups and fed a high-phosphate diet (1.2% phosphate) or a control diet (0.6% phosphate) for 8 weeks. In the beginning and at the end of the study period, femur and lumbar bone mineral density (BMD), bone mineral content and area were measured using DXA, s-PTH was analyzed from the blood sample, and after sacrifice, right femur was cut loose and processed into paraffin cuts. Bone diameter, inner diameter and cortical width was measured from the hematoxylin- and eosin-dyed femur cuts. Tibias were degraded and calcium and phosphate content was analyzed by inductively coupled plasma-mass spectrometer. Femoral BMD increased significantly more in the control group than in the phosphate group (P=.005). Lumbar BMD values decreased in both groups, and the fall was greater in the control group (P=.007). The phosphate group had significantly higher s-PTH values (P=.0135). Femoral histomorphometric values or tibial mineral contents did not differ between groups. In conclusion, increase in dietary phosphate intake caused s-PTH to rise and hindered mineral deposition into cortical bone, leading to lower BMD. The effect on trabecular bone was opposing as mineral loss was less in the lumbar spine of phosphate group animals. These results are in concurrence with the data stating that skeletal response to PTH is complex and site dependent.

Calcium intake in health maintenance - a systematic review.

BACKGROUND: Calcium (Ca) is an essential nutrient for the human body. Despite lively research, there is uncertainty about Ca requirements in terms of desirable health outcomes including an upper intake level above which the potential for harm increases. OBJECTIVES: The aim was to conduct a review to update requirements and desirable or harmful health effects of Ca on the current scientific evidence. METHODS: We searched Medline and Swemed from January 2000 to December 2011 and included all systematic reviews that reported Ca supplementation or usual Ca intake on health outcomes. Meta-analyses, randomized clinical trials and cohort studies were included in the second search between May 2009 and March 2011 and an additional search covering studies till the end of 2011. This review concentrated on studies reporting independent effects of Ca, although a few recent trials report sole effects of Ca on health outcomes, most trials use Ca in combination with vitamin D vs. placebo. RESULTS: In total, we reviewed 38 studies addressing the effects of Ca on bone, pregnancy-related outcomes, cancers, cardiovascular outcomes, obesity, and mortality. There was a lot of heterogeneity in the study protocols, which made it difficult to draw any strong conclusions. According to the literature, high Ca intake seems to have a small positive effect on bone mineral content (BMC) or bone mineral density (BMD) in children and postmenopausal women. We did not find any consistent evidence on the effects of Ca on bone health in premenopausal women or men. Also, the evidence that Ca supplementation reduces fracture incidence is scarce and inconsistent. Maternal diet may influence the peak bone mass of offspring but more studies are required. There was no overall effect of Ca intake on cancers. Ca was associated with a decreased risk of breast cancer and a slightly increased risk of prostate cancer in two of the three studies. No associations were found with other cancers. We found no consistent association between cardiovascular outcomes and Ca intake except for blood pressure. A small decrease of 2-4 mmHg in systolic blood pressure was found in pregnant and in hypertensive subjects with Ca supplementation. Reviewed studies did not show consistent evidence relating Ca intake to either mortality or obesity. CONCLUSION: Based on this evidence, there is no need to change the Nordic recommendations for Ca intake. However, due to heterogeneity in the studies it is difficult to interpret the results and provide single summary statement.

Associations of genetic lactase non-persistence and sex with bone loss in young adulthood.

Some studies have reported that after attainment of peak bone mass (PBM), slow bone loss may occur in both men and women; however, findings are inconsistent. Genetic factors play a significant role in bone loss, but the available evidence is conflicting. Genetic lactase non-persistence (lactase C/C(-13910) genotype) is suggested to increase risk for inadequate calcium intake predisposing to poorer bone health. We investigated whether this genotype is associated with PBM and bone loss in young Finnish adults. Subjects belong to the Cardiovascular Risk in Young Finns Study that is an ongoing multi-centre follow-up of atherosclerosis risk factors. From the original cohort, randomly selected subjects aged 20-29 participated in baseline bone mineral density (BMD) measurements (n=358), and in follow-up measurements 12 years later (n=157). Bone mineral content (BMC) and BMD at lumbar spine (LS) and femoral neck (FN) were measured at baseline and follow-up with dual energy X-ray absorptiometry (DXA). Lactase C/T(-13910) polymorphism was determined by PCR and allele-specific fluorogenic probes. Information on lifestyle was elicited with questionnaires. During the follow-up, bone loss at both bone sites was greater in males (LS BMD: -1.1%, FN BMD: -5.2%) than in females (LS BMD: +2.1%, FN BMD: -0.7%) (both bone sites p=0.001). Younger age predicted greater loss of FN BMC and BMD in females (p=0.013 and p=0.001, respectively). Increased calcium intake predicted FN BMD gain in both sexes (in females B=0.007 g/cm(2)/mg, p=0.002; in males B=0.006, p=0.045), and increased physical activity LS BMD gain in females (B=0.091 g/cm(2)/physical activity point, p=0.023). PBM did not differ between the lactase genotypes, but males with the CC(-13910) genotype seemed to be prone to greater bone loss during the follow-up (LS BMD: C/C vs. T/T p=0.081). In conclusion, bone loss in young adulthood was more common in males than in females and seemed to occur mainly at the femoral neck. Young males with the lactase CC(-13910) genotype may be more susceptible to bone loss; however, calcium intake predicts changes in bone mass more than the lactase genotype.

Increased calcium intake does not completely counteract the effects of increased phosphorus intake on bone: an acute dose-response study in healthy females.

A high dietary P intake is suggested to have negative effects on bone through increased parathyroid hormone secretion, as high serum parathyroid hormone (S-PTH) concentration increases bone resorption. In many countries the P intake is 2- to 3-fold above dietary guidelines, whereas Ca intake is too low. This combination may not be optimal for bone health. In a previous controlled study, we found that dietary P dose-dependently increased S-PTH and bone resorption and decreased bone formation. The aim of the present study was to investigate the dose-response effects of Ca intake on Ca and bone metabolism with a dietary P intake higher than recommended. Each of the twelve healthy female subjects aged 21-40 years attended three 24-h study sessions, which were randomized with regard to a Ca dose of 0 (control day), 600 or 1200 mg, and each subject served as her own control. The meals on each study day provided 1850 mg P and 480 mg Ca. S-PTH concentration decreased (P < 0.001) and serum ionized Ca concentration increased (P < 0.001) with increasing Ca doses. The bone formation marker, serum bone-specific alkaline phosphatase, did not differ significantly (P = 0.4). By contrast, the bone resorption marker, urinary N-terminal telopeptide of collagen type I, decreased significantly with both Ca doses (P = 0.008). When P intake was above current recommendations, increased Ca intake was beneficial for bone, as indicated by decreased S-PTH concentration and bone resorption. However, not even a high Ca intake could affect bone formation when P intake was excessive.