Ravinnon fosforin ja kalsium-fosforisuhteen vaikutukset kalsiumin ja luun aineenvaihduntaan terveillä 20 43-vuotiailla suomalaisilla naisilla

Dietary habits have changed during the past decades towards an increasing consumption of processed foods, which has notably increased not only total dietary phosphorus (P) intake, but also intake of P from phosphate additives. While the intake of calcium (Ca) in many Western countries remains below recommended levels (800 mg/d), the usual daily P intake in a typical Western diet exceeds by 2- to 3-fold the dietary guidelines (600 mg/d). The effects of high P intake in healthy humans have been investigated seldom. In this thesis healthy 20- to 43-year-old women were studied. In the first controlled study (n = 14), we examined the effects of P doses, and in a cross-sectional study (n = 147) the associations of habitual P intakes with Ca and bone metabolism. In this same cross-sectional study, we also investigated whether differences exist between dietary P originating from natural P sources and phosphate additives. The second controlled study (n = 12) investigated whether by increasing the Ca intake, the effects of a high P intake could be reduced. The associations of habitual dietary calcium-to-phosphorus ratios (Ca:P ratio) with Ca and bone metabolism were determined in a cross-sectional study design (n = 147). In the controlled study, the oral intake of P doses (495, 745, 1245 and 1995 mg/d) with a low Ca intake (250 mg/d) increased serum parathyroid hormone (S-PTH) concentration in a dose-dependent manner. In addition, the highest P dose decreased serum ionized calcium (S-iCa) concentration and bone formation and increased bone resorption. In the second controlled study with a dietary P intake of 1850 mg/d, by increasing the Ca intake from 480 mg/d to 1080 mg/d and then to 1680 mg/d, the S-PTH concentration decreased, the S-iCa concentration increased and bone resorption decreased dose-dependently. However, not even the highest Ca intake could counteract the effect of high dietary P on bone formation, as indicated by unchanged bone formation activity. In the cross-sectional studies, a higher habitual dietary P intake (>1650 mg/d) was associated with lower S-iCa and higher S-PTH concentrations. The consumption of phosphate additive-containing foods was associated with a higher S-PTH concentration. Moreover, habitual low dietary Ca:P ratios (≤0.50, molar ratio) were associated with higher S-PTH concentrations and 24-h urinary Ca excretions, suggesting that low dietary Ca:P ratios may interfere with homeostasis of Ca metabolism and increase bone resorption. In summary, excessive dietary P intake in healthy Finnish women seems to be detrimental to Ca and bone metabolism, especially when dietary Ca intake is low. The results indicate that by increasing dietary Ca intake to the recommended level, the negative effects of high P intake could be diminished, but not totally prevented. These findings imply that phosphate additives may be more harmful than natural P. Thus, reduction of an excessively high dietary P intake is also beneficial for healthy individuals.Fosfori ja kalsium ovat luun perusrakennusaineita, joita tarvitaan kestävän luuston muodostumiseen ja ylläpitoon läpi elämän. Samanaikaisesti, kun kalsiumin saanti ravinnosta monilla länsimaalaisilla jää liian vähäiseksi, saadaan fosforia ravinnosta 2-3-kertaisesti yli ravitsemussuositusten (600 mg/vrk). Suomalaiset työikäiset naiset saavat ravinnosta keskimäärin 1360 mg/vrk ja miehet 1780 mg/vrk fosforia. Tähän mennessä ravinnon fosforiin liittyviä tutkimuksia on tehty vain muutamia terveillä ihmisillä. Tässä väitöskirjatyössä tutkittiin, onko ravinnon fosforimäärällä ja fosforilähteillä (ruoan luontaisesti sisältämä fosfori ja ruokaan lisäaineena lisätty fosfori) sekä ruokavalion kalsium-fosforisuhteella vaikutusta kalsiumin ja luun aineenvaihduntaan. Väitöskirjatyö perustui kahteen kokeelliseen tutkimukseen sekä poikkileikkaustutkimukseen terveillä suomalaisilla 20 43-vuotiailla naisilla. Ensimmäisessä tutkimuksessa havaittiin, että mitä suurempi ravinnon fosforimäärä (495, 745, 1245 ja 1995 mg/vrk) sitä enemmän kohosi verinäytteistä määritetyn keskeisen kalsiumin ja luun aineenvaihdunnan merkkiaineen, seerumin lisäkilpirauhashormonin (S-PTH), pitoisuus. Lisäksi suurin fosforiannos vähensi luun muodostusta ja lisäsi luun hajoamista. Toisessa tutkimuksessa ravinnon fosforin saannin ollessa runsasta (1850 mg/vrk) kalsiumin lisääminen ruokavalioon laski S-PTH pitoisuutta ja luun hajoamista ja täten vaikutti edullisesti kalsiumin ja luun aineenvaihduntaan. Kalsiumlisällä ei havaittu olevan vaikutusta luun muodostukseen, mikä viittaa siihen, että tutkimuksessa käytetyillä kalsiumannoksilla (1080 ja 1680 mg/vrk) ei pystytty vähentämään kaikkia runsaan fosforin saannin aiheuttamia haitallisia vaikutuksia. Poikkileikkaustutkimuksessa runsas ravinnon fosforin saanti (>1650 mg/vrk) ja ruoan, joka sisälsi lisäaineena lisättyä fosforia, käyttö olivat yhteydessä kohonneisiin S-PTH-pitoisuuksiin. Lisäksi saatiin viitteitä siitä, että alhainen ruokavalion kalsium-fosforisuhde (≤0.50) voi häiritä kalsiumaineenvaihduntaa ja mahdollisesti tätä kautta lisätä myös luun hajoamista. Tämän väitöskirjatyön tutkimusten perusteella terveiden suomalaisnaisten runsas fosforin saanti näyttää olevan haitallista kalsiumin ja luun aineenvaihdunnalle, varsinkin, jos kalsiumin saanti ravinnosta on vähäistä. Nämä tutkimustulokset viittaavat myös siihen, että lisäaineista peräisin oleva fosfori on haitallisempaa kuin elintarvikkeen luontaisesti sisältämä fosfori. Vaikka näissä tutkimuksissa havaittiin, että ravinnon runsaan fosforin saannin haitallisia vaikutuksia voidaan vähentää, niin silti niitä ei voida kokonaan poistaa ruokavaliolla, joka sisältää riittävästi kalsiumia. Runsaan fosforin saannin vähentäminen näyttäisi olevan perustelua myös terveillä ihmisillä

Serum parathyroid hormone is related to genetic variation in vitamin D binding protein with respect to total, free, and bioavailable 25-hydroxyvitamin D in middle-aged Caucasians – a cross-sectional study

Peer reviewe

Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians. A complex association with bone?

Background Studies have shown altered vitamin D metabolism in obesity. We assessed differences between obese and normal-weight subjects in total, free, and bioavailable 25-hydroxyvitamin D (25(OH) D, 25(OH) D-Free, and 25(OH) D-Bio, respectively), vitamin D binding protein (DBP), parathyroid hormone (PTH) and bone traits. Methods 595 37-47-year-old healthy Finnish men and women stratified by BMI were examined in this cross-sectional study. Background characteristic and intakes of vitamin D and calcium were collected. The concentrations of 25(OH) D, PTH, DBP, albumin and bone turnover markers were determined from blood. 25(OH) D-Free and 25(OH) D-Bio were calculated. pQCT was performed at radius and tibia. Results Mean +/- SE (ANCOVA) 25(OH) D-Free (10.8 +/- 0.6 vs 12.9 +/- 0.4 nmol/L; P = 0.008) and 25(OH) DBio (4.1 +/- 0.3 vs 5.1 +/- 0.1 nmol/L; P = 0.003) were lower in obese than in normal-weight women. In men, 25(OH) D (48.0 +/- 2.4 vs 56.4 +/- 2.0 nmol/L, P = 0.003), 25(OH) D-Free (10.3 +/- 0.7 vs 12.5 +/- 0.6 pmol/L; P = 0.044) and 25(OH) D-Bio (4.2 +/- 0.3 vs 5.1 +/- 0.2 nmol/L; P = 0.032) were lower in obese. Similarly in all subjects, 25(OH) D, 25(OH) D-Free and 25(OH) D-Bio were lower in obese (P Conclusions The associations between BMI and 25(OH) D, 25(OH) D-Free, and 25(OH) D-Bio, DBP, and PTH suggest that obese subjects may differ from normal-weight subjects in vitamin D metabolism. BMI associated positively with trabecular bone traits and CSI in our study, and slightly negatively with cortical bone traits. Surprisingly, there was a negative association of free and bioavailable 25(OH) D and some of the bone traits in obese women.Peer reviewe

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 degrees 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. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians. A complex association with bone?

<div><p>Background</p><p>Studies have shown altered vitamin D metabolism in obesity. We assessed differences between obese and normal-weight subjects in total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D, 25(OH)D_Free, and 25(OH)D_Bio, respectively), vitamin D binding protein (DBP), parathyroid hormone (PTH) and bone traits.</p><p>Methods</p><p>595 37-47-year-old healthy Finnish men and women stratified by BMI were examined in this cross-sectional study. Background characteristic and intakes of vitamin D and calcium were collected. The concentrations of 25(OH)D, PTH, DBP, albumin and bone turnover markers were determined from blood. 25(OH)D_Free and 25(OH)D_Bio were calculated. pQCT was performed at radius and tibia.</p><p>Results</p><p>Mean±SE (ANCOVA) 25(OH)D_Free (10.8±0.6 vs 12.9±0.4 nmol/L; P = 0.008) and 25(OH)D_Bio (4.1±0.3 vs 5.1±0.1 nmol/L; P = 0.003) were lower in obese than in normal-weight women. In men, 25(OH)D (48.0±2.4 vs 56.4±2.0 nmol/L, P = 0.003), 25(OH)D_Free (10.3±0.7 vs 12.5±0.6 pmol/L; P = 0.044) and 25(OH)D_Bio (4.2±0.3 vs 5.1±0.2 nmol/L; P = 0.032) were lower in obese. Similarly in all subjects, 25(OH)D, 25(OH)D_Free and 25(OH)D_Bio were lower in obese (P<0.001). DBP (399±12 vs 356±7mg/L, P = 0.008) and PTH (62.2±3.0 vs 53.3±1.9 ng/L; P = 0.045) were higher in obese than in normal-weight women. In all subjects, PTH and DBP were higher in obese (P = 0.047and P = 0.004, respectively). In obese women, 25(OH)D was negatively associated with distal radius trabecular density (R² = 0.089, P = 0.009) and tibial shaft cortical strength index (CSI) (R² = 0.146, P = 0.004). 25(OH)D_Free was negatively associated with distal radius CSI (R² = 0.070, P = 0.049), radial shaft cortical density (CorD) (R² = 0.050, P = 0.045), and tibial shaft CSI (R² = 0.113, P = 0.012). 25(OH)D_Bio was negatively associated with distal radius CSI (R² = 0.072, P = 0.045), radial shaft CorD (R² = 0.059, P = 0.032), and tibial shaft CSI (R² = 0.093, P = 0.024).</p><p>Conclusions</p><p>The associations between BMI and 25(OH)D, 25(OH)D_Free, and 25(OH)D_Bio, DBP, and PTH suggest that obese subjects may differ from normal-weight subjects in vitamin D metabolism. BMI associated positively with trabecular bone traits and CSI in our study, and slightly negatively with cortical bone traits. Surprisingly, there was a negative association of free and bioavailable 25(OH)D and some of the bone traits in obese women.</p></div

Low free 25-hydroxyvitamin D and high vitamin D binding protein and parathyroid hormone in obese Caucasians:a complex association with bone?

Abstract Background: Studies have shown altered vitamin D metabolism in obesity. We assessed differences between obese and normal-weight subjects in total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D, 25(OH)DFree, and 25(OH)DBio, respectively), vitamin D binding protein (DBP), parathyroid hormone (PTH) and bone traits. Methods: 595 37–47-year-old healthy Finnish men and women stratified by BMI were examined in this cross-sectional study. Background characteristic and intakes of vitamin D and calcium were collected. The concentrations of 25(OH)D, PTH, DBP, albumin and bone turnover markers were determined from blood. 25(OH)DFree and 25(OH)DBio were calculated. pQCT was performed at radius and tibia. Results: Mean±SE (ANCOVA) 25(OH)DFree (10.8±0.6 vs 12.9±0.4 nmol/L; P = 0.008) and 25(OH)DBio (4.1±0.3 vs 5.1±0.1 nmol/L; P = 0.003) were lower in obese than in normal-weight women. In men, 25(OH)D (48.0±2.4 vs 56.4±2.0 nmol/L, P = 0.003), 25(OH)DFree (10.3±0.7 vs 12.5±0.6 pmol/L; P = 0.044) and 25(OH)DBio (4.2±0.3 vs 5.1±0.2 nmol/L; P = 0.032) were lower in obese. Similarly in all subjects, 25(OH)D, 25(OH)DFree and 25(OH)DBio were lower in obese (P&lt;0.001). DBP (399±12 vs 356±7mg/L, P = 0.008) and PTH (62.2±3.0 vs 53.3±1.9 ng/L; P = 0.045) were higher in obese than in normal-weight women. In all subjects, PTH and DBP were higher in obese (P = 0.047and P = 0.004, respectively). In obese women, 25(OH)D was negatively associated with distal radius trabecular density (R²2 = 0.089, P = 0.009) and tibial shaft cortical strength index (CSI) (R² = 0.146, P = 0.004). 25(OH)DFree was negatively associated with distal radius CSI (R² = 0.070, P = 0.049), radial shaft cortical density (CorD) (R² = 0.050, P = 0.045), and tibial shaft CSI (R² = 0.113, P = 0.012). 25(OH)DBio was negatively associated with distal radius CSI (R² = 0.072, P = 0.045), radial shaft CorD (R² = 0.059, P = 0.032), and tibial shaft CSI (R² = 0.093, P = 0.024). Conclusions: The associations between BMI and 25(OH)D, 25(OH)DFree, and 25(OH)DBio, DBP, and PTH suggest that obese subjects may differ from normal-weight subjects in vitamin D metabolism. BMI associated positively with trabecular bone traits and CSI in our study, and slightly negatively with cortical bone traits. Surprisingly, there was a negative association of free and bioavailable 25(OH)D and some of the bone traits in obese women