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.

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.

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.

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.

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.

Prevalence of vitamin D deficiency and secondary hyperparathyroidism during winter in pre-menopausal Bangladeshi and Somali immigrant and ethnic Finnish women: associations with forearm bone mineral density.

Secondary hyperparathyroidism (SHPT) is one of the outcomes of vitamin D deficiency that negatively affects bone metabolism. We studied the ethnic differences in vitamin D status in Finland and its effect on serum intact parathyroid hormone (S-iPTH) concentration and bone traits. The study was done in the Helsinki area (60°N) during January-February 2008. A total of 143 healthy women (20-48 years of age) from two groups of immigrant women (Bangladeshi, n 34 and Somali, n 48), and a group of ethnic Finnish women (n 61) were studied in a cross-sectional setting. Serum concentrations of 25-hydroxyvitamin D (S-25OHD) and S-iPTH were measured. Peripheral quantitative computed tomography measurements were taken at 4 and 66 % of the forearm length. In all groups, the distribution of S-25OHD was shifted towards the lower limit of the normal range. A high prevalence of vitamin D insufficiency (S-25OHD < 50 nmol/l) was observed (89·6 %) in the Somali group. The prevalence of SHPT (S-iPTH>65 ng/l) was higher (79·1 %) in Somali women than in Finnish women (16 %). There was a significant association between S-25OHD and S-iPTH (r - 0·49, P < 0·001). Ethnicity and S-25OHD together explained 30 % of the variation in S-iPTH. The total bone mass at all sites of the forearm, fracture load and stress-strain index was higher (P < 0·001) in Bangladeshi and Finnish women than in Somali women. The high prevalence of hypovitaminosis D, SHPT and low bone status in Somali women indicates a higher risk of osteoporosis.

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.

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.

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.

High phosphorus intakes acutely and negatively affect Ca and bone metabolism in a dose-dependent manner in healthy young females.

Ca and P are both essential nutrients for bone and are known to affect one of the most important regulators of bone metabolism, parathyroid hormone (PTH). Too ample a P intake, typical of Western diets, could be deleterious to bone through the increased PTH secretion. Few controlled dose-response studies are available on the effects of high P intake in man. We studied the short-term effects of four P doses on Ca and bone metabolism in fourteen healthy women, 20-28 years of age, who were randomized to four controlled study days; thus each study subject served as her own control. P supplement doses of 0 (placebo), 250, 750 or 1500 mg were taken, divided into three doses during the study day. The meals served were exactly the same during each study day and provided 495 mg P and 250 mg Ca. The P doses affected the serum PTH (S-PTH) in a dose-dependent manner (P=0.0005). There was a decrease in serum ionized Ca concentration only in the highest P dose (P=0.004). The marker of bone formation, bone-specific alkaline phosphatase, decreased (P=0.05) and the bone resorption marker, N-terminal telopeptide of collagen type I, increased in response to the P doses (P=0.05). This controlled dose-response study showed that P has a dose-dependent effect on S-PTH and increases PTH secretion significantly when Ca intake is low. Acutely high P intake adversely affects bone metabolism by decreasing bone formation and increasing bone resorption, as indicated by the bone metabolism markers.

Bread fortified with cholecalciferol increases the serum 25-hydroxyvitamin D concentration in women as effectively as a cholecalciferol supplement.

Fortification of foods is a feasible way of preventing low vitamin D status. Bread could be a suitable vehicle for fortification because it is a common part of diets worldwide. The bioavailability of cholecalciferol from bread is not known. We studied cholecalciferol stability, the concentration of the added cholecalciferol, the dispersion of cholecalciferol in bread, and the bioavailability of cholecalciferol from fortified bread. Three batches of fortified low-fiber wheat and high-fiber rye breads were baked; from each batch, 3 samples of dough and bread were analyzed for their cholecalciferol content. In a single-blind bioavailability study, 41 healthy women, 25-45 y old, with mean serum 25-hydroxyvitamin D concentration 29 nmol/L (range 12-45 nmol/L), were randomly assigned to 4 study groups. Each group consumed fortified wheat bread, fortified rye bread, regular wheat bread (control), or regular wheat bread and a cholecalciferol supplement (vitamin D control) daily for 3 wk. The daily dose of vitamin D was 10 mug in all groups except the control group. The vitamin dispersed evenly in the breads and was stable. Both fortified breads increased serum 25-hydroxyvitamin D concentration as effectively as the cholecalciferol supplement. Supplementation or fortification did not affect serum intact parathyroid hormone concentration or urinary calcium excretion. In conclusion, fortified bread is a safe and feasible way to improve vitamin D nutrition.

Vitamin D receptor gene start codon polymorphism (FokI) is associated with forearm bone mineral density and calcaneal ultrasound in Finnish adolescent boys but not in girls.

We examined the association between vitamin D receptor (VDR) gene FokI polymorphism and bone mineral density and quantitative ultrasound parameters in Finnish adolescents. We assessed bone mineral density at the distal sites of radius and ulna, quantitative ultrasound of the calcaneus, serum concentration of 25-hydroxyvitamin D (25-OHD), calcium intake, physical activity, and BsmI and FokI polymorphisms of the vitamin D receptor gene in 86 girls and 38 boys aged 14 to 16 years. In girls, FokI polymorphism was not significantly associated with bone mineral density or quantitative ultrasound parameters. In adolescent boys, the Ff genotype was associated with higher forearm BMD and calcaneal ultrasound values, when adjusted for body and bone size, BsmI polymorphism, calcium intake, vitamin D status, smoking, and physical activity.